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Zhang F, Chu A, Bai Y, Huang L, Zhong Y, Li Y. Association of sarcopenia index, a surrogate marker of muscle mass, and incident chronic kidney disease. Clin Nutr ESPEN 2025; 67:184-191. [PMID: 40112920 DOI: 10.1016/j.clnesp.2025.03.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 02/12/2025] [Accepted: 03/13/2025] [Indexed: 03/22/2025]
Abstract
BACKGROUND Sarcopenia, characterized by loss of muscle mass and strength, has been linked to various health outcomes, including chronic kidney disease (CKD). This study aims to investigate the association of sarcopenia index, based on serum creatinine and cystatin C levels, with incident CKD in middle-aged and older adults. METHODS This study extracted data from a nation cohort, including age ≥45 years adults without CKD at baseline. Sarcopenia index was calculated based on serum creatinine and cystatin C levels, and incident CKD was assessed through follow-up surveys. Cox proportional hazards regression models were used to analyze the association between sarcopenia index and incident CKD, adjusting for potential confounders, with hazard ratio (HR) with 95 % confidence interval (95 % CI) reported. RESULTS A total of 8618 participants were included in the analysis. The median age was 61.0 years, and 44.7 % were male. During a mean follow-up period of 5.0 years, 514 cases of incident CKD were identified. After adjusting for covariates, compared with participants in the lowest tertile, the corresponding CKD HRs (95 % CIs) for participants in the medium and highest tertile were 0.701 (95 % CI: 0.558-0.880, P = 0.002), 0.784 (95 % CI: 0.618-0.994; P = 0.045). Restricted cubic spline curves revealed that incident rate decreased with increase in sarcopenia index. CONCLUSION This study provides national longitudinal evidence on the association of higher sarcopenia index with lower incident CKD. Our findings suggest that sarcopenia index may be a useful biomarker for predicting the risk of CKD in this population.
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Affiliation(s)
- Fan Zhang
- Department of Nephrology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Aojiao Chu
- Department of Nephrology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yan Bai
- Department of Nephrology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Liuyan Huang
- Department of Nephrology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yifei Zhong
- Department of Nephrology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China.
| | - Yi Li
- Department of Nephrology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China.
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Makmun A, Satirapoj B, Tuyen DG, Foo MWY, Danguilan R, Gulati S, Kim S, Bavanandan S, Chiu YW, Tang SCW. The burden of chronic kidney disease in Asia region: a review of the evidence, current challenges, and future directions. Kidney Res Clin Pract 2025; 44:411-433. [PMID: 39384350 PMCID: PMC12066349 DOI: 10.23876/j.krcp.23.194] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 04/12/2024] [Accepted: 05/07/2024] [Indexed: 10/11/2024] Open
Abstract
The disease burden of chronic kidney disease (CKD) and its impact on healthcare systems has been poorly studied in Asia, a socioeconomically diverse region with wide variations in availability, access, and quality of CKD care. The high CKD burden in this region is predominantly driven by an increased prevalence of risk factors including diabetes mellitus, hypertension, obesity, and use of traditional medicines and is further aggravated by challenges associated with effective implementation of population-based screening and surveillance systems in early detection and intervention of CKD. The Asian continent mostly comprised of low- and middle-income countries with resource restraints lacks robust population-based CKD registries resulting in a paucity of data on CKD incidence and prevalence, various treatment modalities, uptake of current guidelines, and the overall impact of implementation of developmental programs. There is an urgent need for a collaborative action plan between the healthcare community and governments in this region to detect CKD in its early stages and prevent its complications including kidney failure, cardiovascular disease, and death. Research- based evidence on the impact of early detection, sustainable treatment options, quality of life, delay or avoidance of dialysis, and related cost analysis is the need of the hour. We highlight successful implementation of strategic and policy-sharing programs adopted in a few countries; also, consolidate available region-specific data, quantify estimates of CKD burden and propose strategies with a multidisciplinary approach involving patients, the healthcare community and governmental bodies to combat CKD and its complications.
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Affiliation(s)
- Afiatin Makmun
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Padjadjaran University, Bandung, Indonesia
| | - Bancha Satirapoj
- Division of Nephrology, Department of Medicine, Phramongkutkloa Hospital, Bangkok, Thailand
| | - Do Gia Tuyen
- Division of Nephrology, Department of Internal Medicine, Hanoi Medical University, Hanoi, Vietnam
| | - Marjorie W. Y. Foo
- Department of Renal Medicine, Singapore General Hospital, Duke-NUS Medical School, Singapore
| | - Romina Danguilan
- National Kidney and Transplant Institute, Quezon, the Philippines
| | - Sanjeev Gulati
- Nephrology and Kidney Transplant Fortis Group of Hospitals, New Delhi, India
- Department of Nephrology, Manipal University, Manipal, India
| | - Sejoong Kim
- Division of Nephrology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sunita Bavanandan
- Department of Nephrology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia
| | - Yi-Wen Chiu
- Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Sydney C. W. Tang
- Division of Nephrology, Department of Medicine, Queen Mary Hospital, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China
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Kristensen T, Oturai PS, Haddock BT, Biering‐Sørensen F, Kruuse C, Andersen UB. Feasibility of replacing 99mTc-DTPA GFR measurements with eGFR from cystatin C in individuals with spinal cord injuries. Physiol Rep 2025; 13:e70315. [PMID: 40356291 PMCID: PMC12069801 DOI: 10.14814/phy2.70315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Revised: 03/13/2025] [Accepted: 03/28/2025] [Indexed: 05/15/2025] Open
Abstract
In individuals with spinal cord injury (SCI) and neurogenic bladder dysfunction, guidelines recommend regular monitoring of kidney function by measuring the glomerular filtration rate using an externally administered filtration markers such as 99mTc-DTPA, since creatinine-based eGFR models are inaccurate due to lower muscle mass in these individuals. To examine the feasibility of substituting GFR measurements with eGFR based on s-cystatin C, simultaneous 99mTc-DTPA clearance (mGFR) and cystatin C-based clearance (eGFRcys) measures were evaluated in 248 individuals with SCI. In a subgroup of 26 participants, the test-retest variability of eGFRcys was assessed. Finally, long-term (1-3 years) repeatability of simultaneously measured mGFR and eGFRcys was evaluated in 40 individuals. We could demonstrate a very good correlation between mGFR and eGFRcys, with an intraclass correlation (ICC) of 0.92, a very good test-retest variation of eGFRcys (ICC: 0.98) and a very good long-term repeatability of eGFRcys and mGFR (ICC 0.92 and 0.94, respectively). We conclude that in individuals with SCI, eGFR calculated from a single sample of cystatin C can replace measurements of GFR using an externally administered substance. Using a fixed normal limit rather than an age-corrected normal material for p-cystatin C or eGFRCYS will misclassify many individuals as having chronic kidney disease.
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Affiliation(s)
- Tatiana Kristensen
- Department of Clinical Physiology and Nuclear MedicineCopenhagen University Hospital ‐ Rigshospitalet; GlostrupCopenhagenDenmark
| | - Peter S. Oturai
- Department of Clinical Physiology and Nuclear MedicineCopenhagen University Hospital ‐ Rigshospitalet; GlostrupCopenhagenDenmark
| | - Bryan T. Haddock
- Department of Clinical Physiology and Nuclear MedicineCopenhagen University Hospital ‐ Rigshospitalet; GlostrupCopenhagenDenmark
| | - Fin Biering‐Sørensen
- Department of Brain and Spinal Cord Injury, Neuroscience CenterCopenhagen University Hospital ‐ Rigshospitalet; GlostrupCopenhagenDenmark
- Institute of Clinical Medicine, University of CopenhagenCopenhagenDenmark
| | - Christina Kruuse
- Department of Brain and Spinal Cord Injury, Neuroscience CenterCopenhagen University Hospital ‐ Rigshospitalet; GlostrupCopenhagenDenmark
- Institute of Clinical Medicine, University of CopenhagenCopenhagenDenmark
| | - Ulrik B. Andersen
- Department of Clinical Physiology and Nuclear MedicineCopenhagen University Hospital ‐ Rigshospitalet; GlostrupCopenhagenDenmark
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Cipulli F, Balzani E, Marini G, Lassola S, De Rosa S, Bellani G. ICU 'Magic Numbers': The Role of Biomarkers in Supporting Clinical Decision-Making. Diagnostics (Basel) 2025; 15:975. [PMID: 40310334 PMCID: PMC12025389 DOI: 10.3390/diagnostics15080975] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2025] [Revised: 03/24/2025] [Accepted: 04/09/2025] [Indexed: 05/02/2025] Open
Abstract
Critical care medicine is a highly complex field where diagnosing diseases and selecting effective therapies pose daily challenges for clinicians. In critically ill patients, biomarkers can play a crucial role in identifying and addressing clinical problems. Selecting the right biomarkers and utilizing them effectively can lead to more informed decisions, ultimately impacting patient outcomes. However, each biomarker has its strengths and limitations, making a thorough understanding essential for accurate diagnosis and treatment management. For instance, neuron-specific enolase (NSE) is commonly used to predict outcomes in out-of-hospital cardiac arrest (OHCA), procalcitonin (PCT) levels strongly correlate with bacterial infections, and NT-proBNP serves as a reliable indicator of cardiac stress. Additionally, serum creatinine (SCr) remains fundamental in renal diagnostics, while prealbumin helps differentiate catabolic and anabolic phases in critically ill patients. This narrative review highlights a carefully selected set of biomarkers known for their clinical utility and reliability in guiding critical care decisions. Further refining the application of biomarkers-especially by integrating them into a multimodal approach-will enhance clinicians' ability to navigate the challenges of critical care, always striving to improve patient outcomes.
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Affiliation(s)
- Francesco Cipulli
- Anesthesia and Intensive Care 1, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Largo Medaglie d’Oro 9, 38112 Trento, Italy; (G.M.); (S.L.); (S.D.R.); (G.B.)
| | - Eleonora Balzani
- Centre for Medical Sciences-CISMed, University of Trento, Via S. Maria Maddalena 1, 38122 Trento, Italy;
| | - Giuseppe Marini
- Anesthesia and Intensive Care 1, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Largo Medaglie d’Oro 9, 38112 Trento, Italy; (G.M.); (S.L.); (S.D.R.); (G.B.)
| | - Sergio Lassola
- Anesthesia and Intensive Care 1, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Largo Medaglie d’Oro 9, 38112 Trento, Italy; (G.M.); (S.L.); (S.D.R.); (G.B.)
| | - Silvia De Rosa
- Anesthesia and Intensive Care 1, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Largo Medaglie d’Oro 9, 38112 Trento, Italy; (G.M.); (S.L.); (S.D.R.); (G.B.)
- Centre for Medical Sciences-CISMed, University of Trento, Via S. Maria Maddalena 1, 38122 Trento, Italy;
| | - Giacomo Bellani
- Anesthesia and Intensive Care 1, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Largo Medaglie d’Oro 9, 38112 Trento, Italy; (G.M.); (S.L.); (S.D.R.); (G.B.)
- Centre for Medical Sciences-CISMed, University of Trento, Via S. Maria Maddalena 1, 38122 Trento, Italy;
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Sulleyx S, Zhou Y, Ndanga M, Saka A. Integrating aging biomarkers and immune function to predict kidney health: insights from the future of families and child wellbeing study. GeroScience 2025; 47:1989-1997. [PMID: 39432148 PMCID: PMC11979024 DOI: 10.1007/s11357-024-01402-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Accepted: 10/15/2024] [Indexed: 10/22/2024] Open
Abstract
Biomarkers of biological aging predict health outcomes more accurately than chronological age. This study examines the relationship between aging biomarkers, immune function, and kidney health using the Future of Families and Child Wellbeing Study Biomarker Dataset. Using Wave 5 (year 9) and Wave 6 (year 15), we examined biomarker data from a total of 4898 individuals. The panel of aging biomarkers, comprised of epigenetic clocks (GrimAge, Horvath), immune function markers (CD8 + T cells, plasmablasts), and metabolic indicators (GDF-15, leptin), was evaluated in depth. We used principal component analysis (PCA) and K-means clustering for subtype identification. A random forest regressor was employed to predict kidney function using Cystatin C levels, and the importance of features was assessed. Three clusters with unique biological age and immune function profiles were identified. Cluster 1 had younger biological age markers. In Cluster 2, both GrimAge and GDF-15 levels were significantly increased, indicating an elevated risk for age-related diseases. According to predictive modeling, GrimAge, Pack Years, and immune function markers had the strongest influence on Cystatin C levels (R2 = 0.856). The incorporation of immune aging markers enhanced the predictive power, emphasizing the importance of immunosenescence in renal health. Aging biomarkers and immune function significantly impact kidney health prediction. The study results call for the utilization of extensive biomarker tests for individualized elderly care and early recognition of kidney deterioration. Clinical practice can be improved by incorporating biological age assessments for the prevention and management of age-related diseases.
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Affiliation(s)
- Saanie Sulleyx
- National Healthy Start Association, NW Suite 500, 1325 G Street, Washington, DC, 20005, USA.
- Pathology and Laboratory Medicine, Boston University, Boston, USA.
- Health Information Management and Health Services Administration, CUNY School of Professional Studies, New York, NY, USA.
| | - Yan Zhou
- Pathology and Laboratory Medicine, Boston University, Boston, USA
| | - Memory Ndanga
- Health Information Management and Health Services Administration, CUNY School of Professional Studies, New York, NY, USA
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Rong X, Yang G, Xu Y, Chen H, Wang X, Fu J, Li L, Pan X. Efficacy and Safety of Tenofovir Amibufenamide and Tenofovir Alafenamide for First-Time HBV-Related Decompensated Cirrhosis. J Viral Hepat 2025; 32:e14029. [PMID: 39469961 DOI: 10.1111/jvh.14029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 10/02/2024] [Accepted: 10/10/2024] [Indexed: 10/30/2024]
Abstract
Clinical studies of tenofovir amibufenamide (TMF) and tenofovir alafenamide (TAF) treatment in patients with HBV-related decompensated cirrhosis (HBV-DC) are limited. This study evaluated the efficacy and safety of TMF versus TAF in naive-treated patients with first-time HBV-DC. Based on the antiviral drug used, patients were categorised into the TMF group and the TAF group. Virological and serological responses, hepatic and renal functions and blood lipid changes in both groups were evaluated during 48 weeks of treatment. A total of 98 patients were enrolled, 45 in the TMF group and 53 in the TAF group. At 48 weeks of treatment, the proportions of patients who achieved complete virological response (CVR) were 85.7% and 90.7%, respectively (p = 0.791). Improvement of at least 2 points in Child-Turcotte-Pugh scores was observed in 64.3% versus 79.1% (p = 0.169) of the patients. There were no significant changes in serum creatinine, estimated glomerular filtration rate or total cholesterol from baseline to week 48 between the two groups. Cystatin C remained stable in the TMF group but increased over time in the TAF group (p < 0.001). Low-density lipoprotein cholesterol remained stable in the TMF group but increased significantly in the TAF group at week 48 (p = 0.015). These results suggest that both TMF and TAF can rapidly suppress HBV replication, improve hepatic function and have no negative effects on renal function among patients with HBV-DC. Regarding lipid metabolism, both showed a better safety, while regular monitoring of blood lipid levels is recommended.
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Affiliation(s)
- Xinxin Rong
- Department of Infectious Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Guangde Yang
- Department of Infectious Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Yuanyuan Xu
- Department of Infectious Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - He Chen
- Department of Infectious Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Xia Wang
- Department of Infectious Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Juanjuan Fu
- Department of Infectious Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Li Li
- Department of Infectious Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Xiucheng Pan
- Department of Infectious Diseases, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
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McCoy IE, Go AS, Hsu JY, Zhang X, Muiru AN, Shah VO, Weir M, Rincon-Choles H, Cohen DL, Anderson A, Jaar B, Sondheimer J, Rao PS, Srivastava A, Dember LM, He J, Chen J, Hsu CY. Differential Effect of Hospitalization on Cystatin C- and Creatinine-Based Estimated GFR. J Am Soc Nephrol 2025:00001751-990000000-00582. [PMID: 40067355 DOI: 10.1681/asn.0000000670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 03/06/2025] [Indexed: 04/11/2025] Open
Abstract
Background Cystatin C has entered mainstream clinical care as a measure of kidney function, joining serum creatinine, which has been used for almost a century. However, many physicians notice that estimation of GFR from serum creatinine (eGFRCr) and estimation of GFR by cystatin C (eGFRCys) values can differ considerably. Hospitalization with critical illness is known to acutely decrease eGFRdiff (eGFRCys−eGFRCr). However, whether this effect occurs in all-cause hospitalizations and persists after hospitalization is unknown. Methods Among 5599 adult participants in the Chronic Renal Insufficiency Cohort study with serum creatinine and cystatin C measurements, we estimated the association of six categories of total days of hospitalization between annual study visits (never hospitalized, hospitalized <7, 7 to <14, 14 to <28, 28 to <42, and ≥42 days) and changes in eGFRCr, eGFRCys, and eGFRdiff between those study visits. Results Compared with no hospitalization between study visits, increasing days of hospitalization were associated with decreases in eGFRCys (e.g., −3.30 [95% confidence interval, −5.48 to −1.13] ml/min per 1.73 m2 for ≥42 days of hospitalization, test for trend P < 0.001), while eGFRCr remained relatively stable (e.g., −1.12 [−2.77 to 0.53] ml/min per 1.73 m2 for ≥42 days of hospitalization, test for trend P = 0.21). The differential effect resulted in eGFRdiff becoming progressively more negative with more total days of hospitalization (test for trend P < 0.001). Conclusions Prolonged or repeated hospitalization was associated with larger decreases in eGFRCys compared with eGFRCr on measurements months after hospital discharge.
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Affiliation(s)
- Ian E McCoy
- Division of Nephrology, University of California San Francisco, San Francisco, California
| | - Alan S Go
- Division of Research, Kaiser Permanente Northern California, Oakland, California
| | - Jesse Y Hsu
- Division of Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Xiaoming Zhang
- Division of Biostatistics, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Anthony N Muiru
- Division of Nephrology, University of California San Francisco, San Francisco, California
| | - Vallabh O Shah
- Division of Nephrology, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico
| | - Matthew Weir
- Division of Nephrology, University of Maryland School of Medicine, Baltimore, Maryland
| | | | - Debbie L Cohen
- Renal, Electrolyte and Hypertension Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Amanda Anderson
- Department of Epidemiology, University of Alabama, Birmingham, Alabama
| | - Bernard Jaar
- Division of Nephrology, Johns Hopkins University, Baltimore, Maryland
| | - James Sondheimer
- Division of Nephrology and Hypertension, Wayne State University School of Medicine, Detroit, Michigan
| | - Panduranga S Rao
- Division of Nephrology, University of Michigan, Ann Arbor, Michigan
| | - Anand Srivastava
- Division of Nephrology, University of Illinois Chicago, Chicago, Illinois
| | - Laura M Dember
- Renal, Electrolyte and Hypertension Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Jiang He
- Department of Epidemiology, Peter O'Donnell Jr. School of Public Health, UT Southwestern Medical Center, Dallas, Texas
| | - Jing Chen
- Department of Epidemiology, Peter O'Donnell Jr. School of Public Health, UT Southwestern Medical Center, Dallas, Texas
- Division of Nephrology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, Texas
| | - Chi-Yuan Hsu
- Division of Nephrology, University of California San Francisco, San Francisco, California
- Division of Research, Kaiser Permanente Northern California, Oakland, California
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Budhiraja P, Butterfield R, Hommos M, Heilman RL, Cheungpasitporn W, Alajous S, Me HM, Chakkera HA, Corey RL, Abu Jawdeh BG, Khamash HA. Performance of Glomerular Filtration Rate Estimating Equations in Kidney Transplant Recipients of Various Races: A Retrospective Cohort Study. Transplant Proc 2025; 57:230-240. [PMID: 39837671 DOI: 10.1016/j.transproceed.2024.12.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 11/18/2024] [Accepted: 12/05/2024] [Indexed: 01/23/2025]
Abstract
BACKGROUND We assessed the accuracy of different GFR estimating equations in kidney transplant recipients across diverse racial backgrounds, addressing the previously identified validation gap in multiethnic populations predominantly studied in White cohorts. METHODS In this single-center study, eGFR was compared to the measured GFR (mGFR) one year following kidney transplantation. RESULTS The 1-year eGFR and mGFR data from 1145 participants (54% Whites, 23% Hispanics, 9% Blacks, 7% Native Americans, and 6% Asians) revealed varied correlations across racial groups. For Whites, the combined 2021 CKD-EPI creatinine-cystatin C formulas demonstrated a stronger correlation (r = 0.72, [0.65, 0.78]) compared to the 2021 CKD-EPI creatinine and EKFC cystatin C equation. This equation also achieved the highest accuracy (P30: 77.1%). In Black recipients, both the 2009 CKD-EPI (r = 0.56 [0.42, 0.68]) and the 2021 CKD-EPI creatinine (r = 0.56 [0.41, 0.68]) exhibited modest correlations. The 2021 CKD-EPI creatinine-cystatin C equation showed improved correlation (r = 0.63 (0.43, 0.77)] and an accuracy of 62.7% (P30), which was slightly lower than the EKFC cystatin C equation (P30: 64.7%). However, neither the EKFC (rescaled) cystatin C nor the race-free kidney-specific equations outperformed existing eGFR equations for Black participants In Hispanic patients, combined creatinine-cystatin C equations outperformed creatinine-only equations. Among Native Americans, the combined creatinine-cystatin, EKFC (rescaled) cystatin C, and race-free kidney-specific equations achieved an accuracy rate exceeding 85%. In Asians, the CKD-EPI creatinine-cystatin C equation showed the highest correlation, while the race-free kidney-specific equation had the most accuracy. CONCLUSION Our findings indicate that creatinine-cystatin C combined equations outperformed single-marker formulas across all racial groups, with negligible differences between the 2009 CKD EPI and the race-neutral 2021 CKD-EPI version.
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Affiliation(s)
- Pooja Budhiraja
- Division of Medicine, Mayo Clinic Arizona, Phoenix, Arizona.
| | | | - Musab Hommos
- Division of Medicine, Mayo Clinic Arizona, Phoenix, Arizona
| | | | | | - Salah Alajous
- Division of Medicine, Mayo Clinic Arizona, Phoenix, Arizona
| | - Hay Me Me
- Division of Medicine, Mayo Clinic Arizona, Phoenix, Arizona
| | | | - Rebecca L Corey
- Department of Pharmacy, Mayo Clinic Arizona, Phoenix, Arizona
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Williams VL, Gerlach AT. Establishing discordance rate of estimated glomerular filtration rate between serum creatinine-based calculations and cystatin-C-based calculations in critically ill patients. Pharmacotherapy 2025; 45:161-168. [PMID: 39945448 PMCID: PMC11905338 DOI: 10.1002/phar.70000] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Revised: 01/03/2025] [Accepted: 01/17/2025] [Indexed: 03/14/2025]
Abstract
INTRODUCTION The use of serum creatinine (SCr) for drug dosing has significant limitations and is influenced by many non-kidney factors. Cystatin C (cysC) is an alternative or additional marker of kidney function that is less affected by non-kidney factors. Although cysC may be useful in hospitalized patients, the use of cysC to calculate drug dosing in critically ill patients has been incompletely investigated. OBJECTIVE The objective of this study was to determine the rate of discordance in estimated glomerular filtration rate (eGFR) between SCr-based calculations and SCr/cysC-based calculations that affect drug dosing in critically ill patients. METHODS This was a single-center, retrospective, observational cohort study at an academic medical center including critically ill adult patients admitted in 2023 with SCr and cysC ordered. Data were collected via chart review. Demographic data were analyzed via descriptive statistics. Discordance, defined as the percentage of times at which there is at least one discrepancy in kidney dosing for a medication using Cockcroft-Gault (CG) creatinine clearance versus Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR creatinine-cystatin C (eGFRcr-cys) equations, was analyzed via Wilcoxon matched pair signed ranked sum. eGFR calculations were normalized for patients' body surface area for comparison. RESULTS The study population included 232 patients (53.02% female; mean age 58.7 +/- 14.9 years; with 62.5% in medical, 23.28% in surgical, and 8.62% in neurological intensive care) with a median SCr of 0.94 mg/dL IQR [0.57-1.58] and median cysC of 1.92 mg/L IQR [1.27-2.77]. The median clearance rates were 68.5 mL/min (45.3-111.5) for CG and 53.9 mL/min (30.9-80.7) for CKD-EPI eGFRcr-cys; p < 0.001. The discordance rate across all study drugs was 32.3% (75/232). The four most common study drugs demonstrating discordance were cefepime 40.6% (52/128), vancomycin 38.3% (46/120), levetiracetam 35.1% (13/37), and piperacillin/tazobactam 11.6% (5/43). CONCLUSION Clinically significant discordance exists between SCr and SCr/cysC-based estimates of kidney function. This study established a discordance rate, as defined by drug dosing, of 32.3% in adult patients admitted to the ICU.
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Guzmán Núñez APM, Filler G, Barbier OC, Rojas Lima E, Mendez-Hernández P, Ortega-Romero M, Díaz González de Ferris ME, Medeiros M. Switching to the CKD-EPI but Not Modified FAS eGFR Formula Underdetects CKD Among Adolescents and Young Adults in México. CHILDREN (BASEL, SWITZERLAND) 2025; 12:239. [PMID: 40003341 PMCID: PMC11854586 DOI: 10.3390/children12020239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 02/05/2025] [Accepted: 02/07/2025] [Indexed: 02/27/2025]
Abstract
BACKGROUND Guidelines recommend switching the glomerular filtration rate (eGFR) estimation from the CKiD-U25 to the CKD-EPI formula at age 18. We investigated how this would affect chronic kidney disease (CKD) classification. METHODS Serum creatinine was enzymatically measured in 1061 samples from 914 community-based 10-23-year-olds from Tlaxcala, Mexico, a region where urinary biomarkers demonstrated early kidney damage associated with exposure to inorganic toxins in a pediatric population. We calculated their eGFR using CKiD-U25, modified Schwartz, the first and modified Pottel full-age spectrum (FAS), and CKD-EPI formulae. Correlation analysis characterized the CKD stage stratified by age and sex. RESULTS At baseline, the median age was 13 (IQR: 12, 15) years, and 55% were female. Median CKiD-U25 eGFR was 96.9 (IQR: 83.3, 113.3) mL/min/1.73 m2, significantly lower than the CKD-EPI eGFR, which was 140.8 (IQR: 129.9, 149.3) mL/min/1.73 m2 (p < 0.0001, Wilcoxon rank test). The mean bias was 36.99 ± 12.89 mL/min/1.73 m2. Pearson correlation was r = 0.8296 (95% confidence interval 0.0898-0.8474). There was a better correlation between the modified Schwartz (r = 0.9421 (0.9349, 0.9485)) and the Pottel FAS (r = 0.9299 (0.9212, 0.9376)) formulae. Agreement was deficient when the eGFR was >75 mL/min/1.73 m2 in younger age and female sex. Modified Schwartz identified 281 (26.4%) measurements as having CKD 2 and 3 (2+), U25 identified 401 (37.7%) measurements as having CKD 2+, FAS identified 267 (25.1%) and modified FAS identified 282 (30%) measurements as having CKD 2+, and CKD-EPI identified 51 (4.8%) measurements as having CKD 2+, respectively. CONCLUSIONS In this population, there needed to be better agreement between the various eGFR formulae. CKD-EPI identifies substantially fewer at-risk participants as having CKD.
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Affiliation(s)
| | - Guido Filler
- Department of Paediatrics, Western University, London, ON N6A 3K7, Canada
- Department of Medicine, Western University, London, ON N6A 3K7, Canada
- The Lilibeth Caberto Kidney Clinical Research Unit, Western University, London, ON N6A 3K7, Canada
- Children’s Health Research Institute, London, ON N6C 4V3, Canada
| | - Olivier C. Barbier
- Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City 07360, Mexico; (O.C.B.); (E.R.L.)
| | - Elodia Rojas Lima
- Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City 07360, Mexico; (O.C.B.); (E.R.L.)
| | - Pablo Mendez-Hernández
- Jefatura de Educación, Investigación y Capacitación del Hospital General Tlaxcala, Secretaría de Salud de Tlaxcala, Santa Ana Chiautempan 90800, Mexico;
- Facultad de Ciencias de la Salud, Universidad Autónoma de Tlaxcala, Tlaxcala de Xicohténcatl 90000, Mexico
| | - Manolo Ortega-Romero
- Unidad de Investigación en Nefrología y Metabolismo Mineral Óseo, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico; (M.O.-R.); (M.M.)
| | | | - Mara Medeiros
- Unidad de Investigación en Nefrología y Metabolismo Mineral Óseo, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico; (M.O.-R.); (M.M.)
- Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico
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11
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Tran TTT, Ha TK, Phan NM, Le MV, Nguyen TH. Detection of decline in estimated glomerular filtration rate in patients with type 2 diabetes by cystatin C-based equations. World J Nephrol 2024; 13:95761. [PMID: 39723358 PMCID: PMC11572656 DOI: 10.5527/wjn.v13.i4.95761] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 09/15/2024] [Accepted: 10/15/2024] [Indexed: 11/07/2024] Open
Abstract
BACKGROUND Aging population is a significant issue in Viet Nam and across the globe. Elderly individuals are at higher risk of chronic kidney disease (CKD), especially those with diabetes. Several studies found that the estimated glomerular filtration rate (eGFR) determined using creatinine-based equations was not as accurate as that determined using cystatin C-based equations. Cystatin C-based equations may be beneficial in elderly patients with an age-associated decline in kidney function. Early determination of eGFR decline and associated factors would aid in appropriate interventions to improve kidney function in elderly patients with diabetes. AIM To determine the utility of cystatin C-based equations in early detection of eGFR decline and to explore factors associated with eGFR decline in elderly patients with diabetes. METHODS This cross-sectional study included 93 participants aged ≥ 60 years evaluated in Can Tho University of Medicine and Pharmacy Hospital between October 2022 and July 2023, including 47 and 46 participants with and without diabetes respectively, according to the American Diabetes Association criteria for diabetes. The kappa coefficient, Student's t, Mann-Whitney, χ 2, Pearson's correlation, multivariate logistic regression, and multiple linear regression analyses were employed. RESULTS The eGFRs were lower with the cystatin C-based equations than with the creatinine-based equations. Good agreement was found between the Modification of Diet in Renal Disease (MDRD) and CKD Epidemiology Collaboration (CKD-EPI) 2021 creatinine-cystatin C equations (kappa = 0.66). In the diabetes group, 30% of the participants had low eGFR. Both plasma glucose and glycated hemoglobin were associated with an increased risk of eGFR decline (P < 0.05) and negatively correlated with eGFR (P = 0.001). By multivariate logistic regression, total cholesterol, and exercise were independently associated with low eGFR. By multiple linear regression, higher plasma glucose levels were correlated with lower eGFR (P = 0.026, r = -0.366). CONCLUSION Cystatin C-based equations were superior in the early detection of a decline in eGFR, and the MDRD equation may be considered as an alternative to the CKD-EPI 2021 creatinine-cystatin C equation. Exercise, plasma glucose, and total cholesterol were independently associated with eGFR in patients with diabetes.
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Affiliation(s)
- Tam Thai Thanh Tran
- Department of Physiology, Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho 900000, Viet Nam
- Department of Functional Exploration, Can Tho University of Medicine and Pharmacy Hospital, Can Tho 900000, Viet Nam
| | - Tien Kim Ha
- School of Medicine and Pharmacy, The University of Da Nang, Da Nang 550000, Viet Nam
| | - Nhut Minh Phan
- Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho 900000, Viet Nam
| | - Minh Van Le
- Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho 900000, Viet Nam
| | - Tin Hoang Nguyen
- Department of Physiology, Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho 900000, Viet Nam
- Department of Functional Exploration, Can Tho University of Medicine and Pharmacy Hospital, Can Tho 900000, Viet Nam
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12
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Nizhamuding X, Liu Y, Zeng J, Zhao H, Zhang T, Zhang C. Challenges and Perspectives on the Adoption of Cystatin C testing in China: A laboratory technician's perspective. Clin Biochem 2024; 133-134:110839. [PMID: 39489391 DOI: 10.1016/j.clinbiochem.2024.110839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 10/29/2024] [Accepted: 10/31/2024] [Indexed: 11/05/2024]
Abstract
Cystatin C (CysC) belongs to the cysteine protease inhibitor superfamily and is produced by all nucleated cells in the body in very stable amounts independent of age, sex, diet, and muscle mass. CysC is considered an ideal biomarker for assessing glomerular filtration rate (GFR) compared to traditional biomarkers for assessing GFR, such as creatinine. However, CysC is not sufficiently utilized for GFR assessment by clinicians, probably for various reasons such as insufficient understanding among clinicians or a lack of standardized quantitative methods. This review discusses and analyzes the aforementioned issues from the perspective of laboratory technicians.
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Affiliation(s)
- Xiaerbanu Nizhamuding
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/ National Center of Gerontology, PR China; Chinese Academy of Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, PR China.
| | - Yang Liu
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/ National Center of Gerontology, PR China; Chinese Academy of Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, PR China
| | - Jie Zeng
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/ National Center of Gerontology, PR China
| | - Haijian Zhao
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/ National Center of Gerontology, PR China
| | - Tianjiao Zhang
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/ National Center of Gerontology, PR China; Chinese Academy of Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, PR China.
| | - Chuanbao Zhang
- National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/ National Center of Gerontology, PR China; Chinese Academy of Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, PR China.
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13
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Banerjee S, Garimella PS, Hong KN, Bullen AL, Daniels LB, Wettersten N. Association between Proenkephalin A and cardiovascular outcomes in ambulatory Veterans. IJC HEART & VASCULATURE 2024; 55:101557. [PMID: 39633843 PMCID: PMC11615503 DOI: 10.1016/j.ijcha.2024.101557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 11/08/2024] [Accepted: 11/11/2024] [Indexed: 12/07/2024]
Abstract
Proenkephalin (PENK) is a novel biomarker of kidney function associated with cardiovascular risk in patients with cardiovascular disease. Its association with cardiovascular outcomes in ambulatory individuals is less described. In an observational study of 199 ambulatory Veterans enrolled from April to September 2010, we assessed PENK's association with major adverse cardiac events (MACE - cardiovascular death, heart failure [HF] hospitalization, myocardial infarction [MI], or stroke) and individual outcomes of all-cause mortality, incident HF, and cardiovascular death using Cox regression. We also assessed the association of PENK with left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and left ventricular mass index (LVMi) with linear regression. The mean age was 66 ± 12 years, 99 % were men, and 76 % were White, with median follow-up of 12.7 years. Each two-fold higher PENK was associated with a 73 % higher risk of MACE in unadjusted analysis (HR 1.73; 95 % CI 1.00, 2.99; p = 0.043), though this association lost significance after adjusting for confounders (HR 1.69; 95 % CI 0.90-3.15; p = 0.098). PENK was not associated with all-cause mortality, incident HF or cardiovascular death, although risk estimates were elevated with wide confidence intervals for incident HF and cardiovascular death. PENK was not associated with LVMi or LVEDd but had a non-linear relationship with LVEF with low and high PENK associated with lower LVEF. In conclusion, PENK may be associated with a higher risk of MACE in ambulatory Veterans with diverse health statuses; however, further studies are needed. Abbreviations: PENK: Proenkephalin A; MACE: Major Adverse Cardiac Events.
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Affiliation(s)
- Shreya Banerjee
- Department of Medicine, University of California, 9500 Gilman Drive, UC, La Jolla, San Diego, CA 92037, USA
| | - Pranav S. Garimella
- Division of Nephrology-Hypertension, University of California, 9300 Campus Point Drive #7424 La Jolla, San Diego, CA 92037, USA
| | - Kimberly N. Hong
- Division of Cardiovascular Medicine, University of California, 9300 Campus Point Drive #7424 La Jolla, San Diego, CA 92037, USA
| | - Alexander L. Bullen
- Division of Nephrology-Hypertension, University of California, 9300 Campus Point Drive #7424 La Jolla, San Diego, CA 92037, USA
- Nephrology Section, Veterans Affairs San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA
| | - Lori B. Daniels
- Division of Cardiovascular Medicine, University of California, 9300 Campus Point Drive #7424 La Jolla, San Diego, CA 92037, USA
| | - Nicholas Wettersten
- Division of Cardiovascular Medicine, University of California, 9300 Campus Point Drive #7424 La Jolla, San Diego, CA 92037, USA
- Division of Cardiovascular Medicine, San Diego Veterans Affairs Medical Center, 3350 La Jolla Village Drive, San Diego, CA 92161, USA
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14
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Nasuuna EM, Tomlinson LA, Kalyesubula R, Dziva Chikwari C, Castelnuovo B, Manabe YC, Nakanjako D, Weiss HA. Comparison of the prevalence and associated factors of chronic kidney disease diagnosed by serum creatinine or cystatin C among young people living with HIV in Uganda. BMC Nephrol 2024; 25:422. [PMID: 39587464 PMCID: PMC11590532 DOI: 10.1186/s12882-024-03865-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Accepted: 11/15/2024] [Indexed: 11/27/2024] Open
Abstract
INTRODUCTION Young people living with HIV (YPLHIV) are at increased risk of developing chronic kidney disease (CKD) which is associated with high mortality and morbidity. Early diagnosis is important to halt progression. We aimed to estimate the prevalence and factors associated with CKD among YPLHIV in Kampala, Uganda, and to compare serum creatinine and cystatin C for early diagnosis of CKD in this population. METHODS A cross-sectional study with YPLHIV aged 10 to 24 years was conducted in seven HIV clinics. Participants provided a urine and blood sample to measure urinary albumin, proteinuria, serum creatinine and cystatin C levels at baseline and after three months. The estimated glomerular filtration rate (eGFR) was calculated using CKDEPI 2021, Cockroft-Gault and bedside Schwartz equations using creatinine or cystatin C. The albumin creatinine ratio (ACR) and proteinuria were measured. CKD was defined as either eGFR < 60 ml/min/1.73m2 or < 90 ml/min/1.73m2 or ACR above 30 mg/g on two separate occasions. Univariable and multivariable logistic regression were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for factors associated with CKD. RESULTS A total of 500 participants were enrolled. Most were female (56%; n = 280) and aged 10 to 17 years (66.9%; n = 335). CKD prevalence ranged from 0 to 23% depending on the criteria, equation and biomarker used. Cystatin C-based equations estimated higher prevalence of CKD compared to creatinine-based ones. Prevalence of ACR above 30 mg/g was 10.1% and of proteinuria 29%. Factors independently associated with CKD were age (aOR = 1.42; 95% CI:1.30-1.51) and male sex (aOR = 3.02; 95% CI:1.68-5.43). CONCLUSION CKD prevalence among YPLHIV varied substantially depending on definitions used and the current definition would likely lead to missed cases of CKD among YPLHIV. Estimating equations should be validated against measured GFR in YPLHIV and the optimal definition of CKD in this vulnerable population should be revised to optimise detection and opportunities for reducing disease progression. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Esther M Nasuuna
- Non-communicable Diseases Program, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
- Infectious Diseases Institute, Makerere University, College of Health Sciences, Kampala, Uganda.
| | - Laurie A Tomlinson
- Department of non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
| | - Robert Kalyesubula
- Non-communicable Diseases Program, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
- Departments of Physiology and Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | - Chido Dziva Chikwari
- Biomedical Research and Training Institute, Harare, Zimbabwe
- MRC International Statistics and Epidemiology Group, London School of Hygiene & Tropical Medicine, London, UK
| | - Barbara Castelnuovo
- Infectious Diseases Institute, Makerere University, College of Health Sciences, Kampala, Uganda
| | - Yukari C Manabe
- Infectious Diseases Institute, Makerere University, College of Health Sciences, Kampala, Uganda
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Damalie Nakanjako
- Infectious Diseases Institute, Makerere University, College of Health Sciences, Kampala, Uganda
- Department of Medicine, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Helen A Weiss
- MRC International Statistics and Epidemiology Group, London School of Hygiene & Tropical Medicine, London, UK
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15
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Katz-Agranov N, Rieu-Werden ML, Thacker A, Lykken JM, Sise ME, Shah SJ. Large Discordance between Creatinine-Based and Cystatin C-Based eGFRs is Associated with Falls, Hospitalizations, and Death in Older Adults. Clin J Am Soc Nephrol 2024; 19:1275-1283. [PMID: 39146034 PMCID: PMC11469786 DOI: 10.2215/cjn.0000000000000523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 08/12/2024] [Indexed: 08/17/2024]
Abstract
Key Points A large eGFR discordance (i.e ., cystatin C–based eGFR >30% lower than creatinine-based eGFR) is common in older adults and increased with age. A large eGFR discordance was associated with increased risk of falls, hospitalization, and death, independent of kidney function. There are multiple ways to measure differences in creatinine and cystatin C; all produce similar associations with aging-related adverse outcomes. Background eGFR calculated using creatinine and cystatin C often differ in older adults. We hypothesized that older adults with cystatin C–based eGFR (eGFRcys) values significantly lower than creatinine-based eGFR (eGFRcr) values may have higher risk of aging-related adverse outcomes, independent of kidney function. Methods We conducted a longitudinal cohort study of adults 65 years and older from the Health and Retirement Study, a cohort of older American adults, to determine the relationship between eGFR discordance and aging-related adverse outcomes. We calculated eGFRcr and eGFRcys using baseline creatinine and cystatin C measurements. A large eGFR discordance was defined as eGFRcys >30% lower than eGFRcr. We assessed four aging-related adverse outcomes over a 2-year follow-up: falls, hip fractures, hospitalizations, and death. We fit separate multivariable regression models to determine the association between having a large eGFR discordance and each outcome adjusting for confounders, including kidney function. Results Of 5574 older adults, 1683 (30%) had a large eGFR discordance. Those with a large eGFR discordance were more likely to be older, female, and White. The prevalence of a large eGFR discordance increased with age, from 20% among those 65–69 years to 44% among those 80 years and older. Over a 2-year follow-up, there were 305 deaths (5.5%), 2013 falls (39.2%), 69 hip fractures (1.3%), and 1649 hospitalizations (32.2%). In adjusted analyses, large eGFR discordance was associated with a higher hazard ratio for death (hazard ratio, 1.43; 95% confidence interval [CI], 1.12 to 1.82) and significantly higher odds of falls (odds ratio, 1.32; 95% CI, 1.16 to 1.51) and hospitalizations (odds ratio, 1.32; 95% CI, 1.15 to 1.51). A large eGFR discordance was not associated with hip fractures. Conclusions In a large, nationally representative cohort of older adults, prevalence of eGFR discordance increased with age and was associated with higher risk of falls, hospitalization, and death, independent of kidney function.
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Affiliation(s)
- Nurit Katz-Agranov
- Renal Division, Department of Medicine, VA Boston Healthcare System, Boston, MA
| | | | - Ayush Thacker
- Center for Aging and Serious Illness, Massachusetts General Hospital, Boston, MA
| | - Jacquelyn M. Lykken
- Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA
| | - Meghan E. Sise
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA
| | - Sachin J. Shah
- Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA
- Center for Aging and Serious Illness, Massachusetts General Hospital, Boston, MA
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Maringhini S, Zoccali C. Chronic Kidney Disease Progression-A Challenge. Biomedicines 2024; 12:2203. [PMID: 39457516 PMCID: PMC11505431 DOI: 10.3390/biomedicines12102203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 09/20/2024] [Accepted: 09/25/2024] [Indexed: 10/28/2024] Open
Abstract
Chronic kidney disease (CKD) is a progressive condition characterized by a continuous decline in renal function, independent of the initial cause of damage or external factors such as infection, inflammation, or toxins. The accurate measurement of renal function, typically assessed using the glomerular filtration rate (GFR), is crucial for managing CKD. The most accepted hypothesis for CKD progression is glomerular damage caused by hyperfiltration. Various factors can accelerate CKD progression, and several biomarkers have been identified to monitor this progression. Numerous studies have explored the risk factors associated with CKD progression, and some of these factors can be modified. Additionally, several drugs are now available that can reduce CKD progression. This review summarizes recent publications and highlights potential future research directions in CKD progression. It discusses the evolution of GFR measurement methods, the mechanisms driving CKD progression, and the latest findings on biomarkers and risk factors. Furthermore, it explores therapeutic strategies, including dietary modifications and pharmacological interventions, to slow CKD progression. Understanding these mechanisms and interventions is crucial for developing effective therapeutic strategies to prevent or slow CKD progression.
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Affiliation(s)
- Silvio Maringhini
- Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione (ISMETT), 90127 Palermo, Italy
| | - Carmine Zoccali
- Renal Research Institute, New York, NY 10065, USA;
- Institute of Molecular Biology and Genetics (Biogem), 83031 Ariano Irpino, Italy
- Associazione Ipertensione Nefrologia Trapianto Renale (IPNET), c/o Nefrologia, Grande Ospedale Metropolitano, 89124 Reggio Calabria, Italy
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17
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Ma H, Wang P, Hou Z, Zhou H, Lv D, Cui F, Shuang W. Preoperative Serum Cystatin C as an Independent Prognostic Factor for Survival in Patients with Renal Cell Carcinoma. J Cancer 2024; 15:5978-5985. [PMID: 39440052 PMCID: PMC11493004 DOI: 10.7150/jca.97711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Accepted: 09/10/2024] [Indexed: 10/25/2024] Open
Abstract
Purpose: This study aims to evaluate the prognostic significance of preoperative serum cystatin C (Cys-C) in patients with renal cell carcinoma (RCC). Methods: We analyzed clinicopathological data and follow-up information of 624 RCC patients who underwent partial or radical nephrectomy at our institution. The optimal cutoff value of Cys-C was determined using X-tile software. Survival outcomes, including overall survival (OS) and cancer-specific survival (CSS), were evaluated using the Kaplan-Meier method and log-rank test. To avoid overfitting and collinearity, we used LASSO-based multivariable Cox regression analysis to identify independent predictors of OS and CSS. The predictive accuracy of the established model, including preoperative serum Cys-C, was evaluated using the time-dependent receiver operating characteristic (ROC) curves and the area under the curve (AUC). Results: The median follow-up period was 40 months. The optimal cutoff value of preoperative serum Cys-C levels was 0.95 mg/L. Compared with the low Cys-C group, patients in the high Cys-C group had significantly shorter OS and CSS. Multivariable Cox regression analysis indicated that elevated preoperative serum Cys-C level was an independent adverse predictor for RCC patients post-nephrectomy. After adjusting for all covariates, high preoperative serum Cys-C level was associated with worse OS (hazard ratio [HR]: 2.254; 95% confidence interval [CI]: 1.144, 4.439; P = 0.019) and CSS (HR: 3.621; 95% CI: 1.386, 9.456; P = 0.009). Time-dependent ROC analysis demonstrated that our model, including preoperative serum Cys-C, performed well in predicting accuracy of survival. Conclusions: Preoperative serum Cys-C level is an effective prognostic indicator for OS and CSS in RCC patients undergoing nephrectomy.
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Affiliation(s)
- Hui Ma
- School of Public Health, Shanxi Medical University, Taiyuan 030001, China
- Grand Hospital of Shuozhou, Shuozhou 036000, China
- Department of Urology, The First Hospital of Shanxi Medical University, No. 85, JieFang South Road, Yingze District, Taiyuan 030001, China
| | - Peipei Wang
- School of Public Health, Shanxi Medical University, Taiyuan 030001, China
| | - Zhao Hou
- Academy of Medical Sciences, Shanxi Medical University, Taiyuan 030001, China
| | - Huiyu Zhou
- First Clinical Medical College, Shanxi Medical University, Taiyuan 030001, China
| | - Dingyang Lv
- First Clinical Medical College, Shanxi Medical University, Taiyuan 030001, China
| | - Fan Cui
- Assisted Reproductive Center, Taiyuan Hospital of Peking University First Hospital, Taiyuan 030032, Shanxi, China
| | - Weibing Shuang
- School of Public Health, Shanxi Medical University, Taiyuan 030001, China
- First Clinical Medical College, Shanxi Medical University, Taiyuan 030001, China
- Department of Urology, The First Hospital of Shanxi Medical University, No. 85, JieFang South Road, Yingze District, Taiyuan 030001, China
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Yadav AK, Ghosh A, Kumar V, Parameswaran S, Kar SS, Thakur JS, Kohli HS, Dalton NR, Jafar TH, Levey AS, Jha V. Development and Validation of an Accurate Creatinine-Based Equation to Estimate Glomerular Filtration Rate for the Adult Indian Population: Design and Methods. Indian J Nephrol 2024; 0:1-8. [PMID: 39937212 PMCID: PMC7616642 DOI: 10.25259/ijn_221_2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/13/2025] Open
Abstract
Background Existing creatinine-based equations to estimate glomerular filtration rate (GFR), developed primarily in populations of European and African American ancestry, do not accurately reflect the GFR in the Indian population due to differences in body composition, diet, and other factors. This manuscript describes the rationale and methodology for developing a creatinine-based equation for more accurate GFR estimation in Indian subjects. Materials and Methods This cross-sectional study will be conducted in India's two geographically and demographically diverse locations: Chandigarh (north) and Puducherry (south). Participants will include a representative sample from the general population and subjects with chronic kidney disease (CKD), with the latter being recruited from outpatient clinics. A total of 1558 subjects will be enrolled in the discovery and cross-validation cohort and 620 subjects in the external validation cohort. The reference standard for measured GFR (mGFR) will be the plasma clearance of iohexol. Stepwise multiple regression on log-transformed data will determine a set of variables that jointly predict mGFR and identify factors influencing mGFR and estimated (eGFR) in the study population. This study will also explore the performance of mGFR by iohexol measurement from dried blood spots against mGFR from plasma clearance of iohexol. Conclusion Developing a more reliable and accurate creatinine-based GFR estimating equation will improve CKD diagnosis, classification, and management. The findings will have substantial implications for CKD research in India and other regions with similar populations.
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Affiliation(s)
- Ashok Kumar Yadav
- Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Arpita Ghosh
- George Institute for Global Health India, New Delhi, India
- Manipal Academy of Higher Education, Manipal, India
- University of New South Wales, Sydney, New South Wales, Australia
| | - Vivek Kumar
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Sreejith Parameswaran
- Departments of Nephrology, Jawaharlal Institute of Postgraduate Medical Education & Research, Pondicherry, India
| | - Sitanshu Sekhar Kar
- Department of Preventive & Social Medicine, Jawaharlal Institute of Postgraduate Medical Education & Research, Pondicherry, India
| | - Jarnail Singh Thakur
- Department of Community Medicine, School of Public Health, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Harbir Singh Kohli
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Neil R Dalton
- WellChild Laboratory, Evelina London Children’s Hospital, Guy’s and St Thomas NHS Foundation Trust, UK
| | - Tazeen H Jafar
- Program in Health Services & Systems Research, Duke-NUS Medical School, Singapore
| | - Andrew S Levey
- Division of Nephrology, Tufts Medical Center, Boston, Massachusetts, USA
| | - Vivekanand Jha
- George Institute for Global Health India, New Delhi, India
- Manipal Academy of Higher Education, Manipal, India
- University of New South Wales, Sydney, New South Wales, Australia
- School of Public Health, Imperial College, London, UK
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19
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Nasuuna EM, Tomlinson LA, Kalyesubula R, Chikwari CD, Castelnuovo B, Manabe YC, Nakanjako D, Weiss HA. Comparison of the prevalence and associated factors of chronic kidney disease diagnosed by serum creatinine or cystatin C among young people living with HIV in Uganda. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2024:2024.09.02.24312932. [PMID: 39281729 PMCID: PMC11398437 DOI: 10.1101/2024.09.02.24312932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 09/18/2024]
Abstract
Introduction Young people living with HIV (YPLHIV) are at increased risk of developing chronic kidney disease (CKD) which is associated with high mortality and morbidity. Early diagnosis is important to halt progression. We aimed to estimate the prevalence and factors associated with CKD among YPLHIV in Kampala, Uganda, and to compare serum creatinine and cystatin C for early diagnosis of CKD in this population. Methods A cross-sectional study with YPLHIV aged 10 to 24 years was conducted in seven HIV clinics. Participants provided a urine and blood sample to measure urinary albumin, proteinuria, serum creatinine and cystatin C levels at baseline and after three months. The estimated glomerular filtration rate (eGFR) was calculated using CKDEPI 2021, Cockroft-Gault and bedside Schwartz equations using creatinine or cystatin C. The albumin creatinine ratio (ACR) and proteinuria were measured. CKD was defined as either eGFR <60ml/min/1.73m2 or <90ml/min/1.73m2 or ACR above 30mg/g on two separate occasions. Univariable and multivariable logistic regression were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for factors associated with CKD. Results A total of 500 participants were enrolled. Most were female (56%; n=280) and aged 10 to 17 years (66.9%; n=335). CKD prevalence ranged from 0-23% depending on the criteria, equation and biomarker used. Cystatin C-based equations estimated higher prevalence of CKD compared to creatinine-based ones. Prevalence of ACR above 30mg/g was 10.1% and of proteinuria 29%. Factors independently associated with CKD were age (aOR=1.42; 95% CI:1.30-1.51) and male sex (aOR=3.02; 95% CI:1.68-5.43). Conclusion CKD prevalence among YPLHIV varied substantially depending on definitions used and the current definition would likely lead to missed cases of CKD among YPLHIV. Estimating equations should be validated against measured GFR in YPLHIV and the optimal definition of CKD in this vulnerable population should be revised to optimise detection and opportunities for reducing disease progression.
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Affiliation(s)
- Esther M Nasuuna
- Non-communicable Diseases Program, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe Uganda
- Infectious Diseases Institute, Makerere University, College of Health Sciences, Kampala, Uganda
| | - Laurie A Tomlinson
- Department of non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT, UK
| | - Robert Kalyesubula
- Non-communicable Diseases Program, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe Uganda
- Departments of Physiology and Medicine, Makerere University College of Health Sciences, Kampala, Uganda
| | - Chido Dziva Chikwari
- Biomedical Research and Training Institute, Harare, Zimbabwe
- MRC International Statistics and Epidemiology Group, London School of Hygiene & Tropical Medicine, London, UK
| | - Barbara Castelnuovo
- Non-communicable Diseases Program, Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe Uganda
| | - Yukari C Manabe
- Infectious Diseases Institute, Makerere University, College of Health Sciences, Kampala, Uganda
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Damalie Nakanjako
- Infectious Diseases Institute, Makerere University, College of Health Sciences, Kampala, Uganda
- Department of Medicine, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda
| | - Helen A Weiss
- MRC International Statistics and Epidemiology Group, London School of Hygiene & Tropical Medicine, London, UK
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Xiao Z, Riletu A, Yan X, Meng Q, Zhang W, Zhang N, Ma C, Guo X, Han J, Nie H, Deng H, Liu J, Chen J, Dong Y, Liu T. Association of serum cystatin C level and major adverse cardiovascular events in patients with percutaneous coronary intervention. Cardiovasc Diagn Ther 2024; 14:621-629. [PMID: 39263480 PMCID: PMC11384458 DOI: 10.21037/cdt-23-482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 06/07/2024] [Indexed: 09/13/2024]
Abstract
Background Recurrent acute myocardial infarction requiring unplanned percutaneous coronary intervention (PCI) is one of the major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS) after PCI. There is a continuing controversy about the association between serum cystatin C, a biomarker for the evaluation of renal function, and the prognosis of ACS patients following PCI. The retrospective study evaluated the association between serum cystatin C level and MACE in ACS patients after PCI. Methods Data were retrieved for 330 patients with ACS for primary PCI in a single center. Serum cystatin C levels were measured before PCI. All patients underwent regular follow-ups after PCI, and the studied endpoint was MACE, defined as the need for a repeat revascularization in the heart. The predictive value of serum cystatin C for MACE was analyzed using univariate and multivariate analysis. Restricted cubic spline (RCS) analysis was applied to evaluate the dose-response relationship between serum cystatin C level and MACE in ACS patients following PCI. Results After a median follow-up of 63 months (range, 1-148 months), 121 of the 330 patients experienced MACE. Compared to patients who did not have MACE, patients who had MACE showed a significant decrease in serum cystatin C levels (0.99±0.32 vs. 1.15±0.78 mg/L, P=0.03). In multivariate regression analysis, serum cystatin C level was an independent risk factor for MACE. According to the serum cystatin C level, patients were divided into 4 categories, Cox regression analysis illustrated that the second quartile of serum cystatin C level indicated an increased risk of MACE in patients with PCI for primary ACS compared to the highest quartile [Q2: adjusted hazard ratio (HR) =2.109; 95% confidence interval (CI): 1.193-3.727; P=0.01]. RCS analysis showed a significant U-shaped dose-response relationship between cystatin C level and MACE in patients with PCI for ACS (P for non-linearity =0.004). Conclusions These results indicated an association between serum cystatin C level and post-PCI MACE in ACS patients.
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Affiliation(s)
- Zhibin Xiao
- Department of Clinical Pharmacy, College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Aoge Riletu
- Department of Pharmacy, Inner Mongolian International Mongolian Hospital, Hohhot, China
| | - Xiaoyu Yan
- Department of Clinical Pharmacy, College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Qi Meng
- Department of Clinical Pharmacy, College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Weiru Zhang
- Department of Clinical Pharmacy, College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Na Zhang
- Department of Clinical Pharmacy, College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Chi Ma
- Department of Clinical Pharmacy, College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Xin Guo
- Department of Clinical Pharmacy, College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Jiatong Han
- Department of Clinical Pharmacy, College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Huijuan Nie
- Department of Cardiology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Hui Deng
- Department of Neurology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Jing Liu
- Department of Pharmacy, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Jianping Chen
- College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
| | - Yu Dong
- Department of Natural Medicinal Chemistry, College of Pharmacy, Inner Mongolia Medical University, Hohhot, China
- Engineering Technology Research Center of Pharmacodynamic Substance and Quality Control of Mongolian Medicine in Inner Mongolia, Inner Mongolia Medical University, Hohhot, China
| | - Tianlong Liu
- Department of Pharmacy, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
- Key Laboratory of Clinical and Basic Research on Cardiovascular Diseases, Basic Research Team of Cardiovascular Diseases, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
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21
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Skidmore M, Spencer S, Desborough R, Kent D, Bhandari S. Cystatin C as a Marker of Kidney Function in Children. Biomolecules 2024; 14:938. [PMID: 39199326 PMCID: PMC11352255 DOI: 10.3390/biom14080938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 07/25/2024] [Accepted: 07/31/2024] [Indexed: 09/01/2024] Open
Abstract
This review examines the reliability of cystatin C as a biomarker for kidney function in paediatric populations. Chronic kidney disease (CKD) affects a significant number of children globally, leading to severe health complications such as anaemia, hypertension, and growth disorders. Traditionally, kidney function has been assessed using the estimated glomerular filtration rate derived from serum creatinine, though this method is flawed due to variability in muscle mass, age, gender, and diet. Cystatin C offers an alternative as it is less influenced by these factors. Evidence from various studies indicates that cystatin C provides a more accurate assessment of kidney function, especially in neonates and children with urinary tract malformations. Additionally, it is more reliable in early detection of acute kidney injury in paediatric intensive care units. Despite its potential, cystatin C is not yet widely adopted in clinical guidelines, primarily due to a lack of large-scale paediatric studies. Nonetheless, existing research supports its utility in providing a consistent and precise measure of kidney function across different paediatric age groups, suggesting that it could enhance early diagnosis and management of CKD in children if more extensive validation studies are conducted.
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Affiliation(s)
- Megan Skidmore
- Faculty of Medicine, Hull York Medical School, Hull HU6 7RU, UK
| | - Sebastian Spencer
- Faculty of Medicine, Hull York Medical School, Hull HU6 7RU, UK
- School of Medical Sciences, University of Hull, Hull HU6 7RX, UK
- Academic Renal Research, Hull University Teaching Hospitals NHS Trust, Hull HU3 2JZ, UK
| | - Robert Desborough
- Faculty of Medicine, Hull York Medical School, Hull HU6 7RU, UK
- Academic Renal Research, Hull University Teaching Hospitals NHS Trust, Hull HU3 2JZ, UK
| | - David Kent
- Faculty of Medicine, Hull York Medical School, Hull HU6 7RU, UK
- Paediatric Department, Clarendon Wing, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust, Leeds LS1 3EX, UK
| | - Sunil Bhandari
- Faculty of Medicine, Hull York Medical School, Hull HU6 7RU, UK
- Academic Renal Research, Hull University Teaching Hospitals NHS Trust, Hull HU3 2JZ, UK
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22
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Bainaud M, Try M, Zaidan M. [Nephroprotection: General principles and application to the patients with cancers - when nephroprotection is essential for oncological care plan]. Bull Cancer 2024; 111:675-686. [PMID: 37827963 DOI: 10.1016/j.bulcan.2023.05.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 05/04/2023] [Accepted: 05/22/2023] [Indexed: 10/14/2023]
Abstract
Nephroprotection is a set of recommendations that aim to prevent the risks of acute and/or chronic renal failure and to limit the progression of renal failure towards an end stage. Nephroprotection is not limited to nephrology and applies to all patients at risk of renal failure. Cancer patients are particularly at risk of developing intrinsic and extrinsic renal failure, as well as the toxicity of specific treatments. However, they are poorly included in nephroprotection studies. Thus, current guidelines have not been adapted to these pathologies and oncology-specific comorbidities, such as malnutrition or prognosis, are often not taken into account. In this article, we review the established recommendations by transposing them to the cancer patient as a whole. In addition to the reminder of hygiene and dietary rules to control blood pressure and diabetes, we discuss the importance of therapeutic education, iatrogeny and treatment options to control renal failure in this context. The lack of clearly established data in cancer confirms the needs to strengthen links between oncologists, hematologists and nephrologists and reinforces the emergence of onco-nephrology as a new discipline.
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Affiliation(s)
- Matthieu Bainaud
- Centre hospitalier universitaire de Poitiers, service d'oncologie médicale, Poitiers, France; Groupe de recherche interdisciplinaire francophone en onco-néphrologie, Paris, France.
| | - Melanie Try
- Groupe de recherche interdisciplinaire francophone en onco-néphrologie, Paris, France; Assistance publique-Hôpitaux de Paris (AP-HP), centre hospitalier universitaire de Bicêtre, université de Paris-Saclay, service de néphrologie, dialyse et transplantation, Le Kremlin-Bicêtre, France
| | - Mohamad Zaidan
- Assistance publique-Hôpitaux de Paris (AP-HP), centre hospitalier universitaire de Bicêtre, université de Paris-Saclay, service de néphrologie, dialyse et transplantation, Le Kremlin-Bicêtre, France
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23
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Palomo-Piñón S, Aguilar-Alonso JA, Chávez-Iñiguez JS, Hernández-Arellanes FE, Mariano-Murga JA, Flores-Rodríguez JC, Pérez-López MJ, Pazos-Pérez F, Treviño-Becerra A, Guillen-Graf AE, Ramos-Gordillo JM, Trinidad-Ramos P, Antonio-Villa NE. Strategies to address diabetic kidney disease burden in Mexico: a narrative review by the Mexican College of Nephrologists. Front Med (Lausanne) 2024; 11:1376115. [PMID: 38962740 PMCID: PMC11219582 DOI: 10.3389/fmed.2024.1376115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 06/07/2024] [Indexed: 07/05/2024] Open
Abstract
Chronic kidney disease (CKD) is a growing global public health challenge worldwide. In Mexico, CKD prevalence is alarmingly high and remains a leading cause of morbidity and mortality. Diabetic kidney disease (DKD), a severe complication of diabetes, is a leading determinant of CKD. The escalating diabetes prevalence and the complex regional landscape in Mexico underscore the pressing need for tailored strategies to reduce the burden of CKD. This narrative review, endorsed by the Mexican College of Nephrologists, aims to provide a brief overview and specific strategies for healthcare providers regarding preventing, screening, and treating CKD in patients living with diabetes in all care settings. The key topics covered in this review include the main cardiometabolic contributors of DKD (overweight/obesity, hyperglycemia, arterial hypertension, and dyslipidemia), the identification of kidney-related damage markers, and the benefit of novel pharmacological approaches based on Sodium-Glucose Co-Transporter-2 Inhibitors (SGLT2i) and Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA). We also address the potential use of novel therapies based on Mineralocorticoid Receptor Antagonists (MRAs) and their future implications. Emphasizing the importance of multidisciplinary treatment, this narrative review aims to promote strategies that may be useful to alleviate the burden of DKD and its associated complications. It underscores the critical role of healthcare providers and advocates for collaborative efforts to enhance the quality of life for millions of patients affected by DKD.
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Affiliation(s)
- Silvia Palomo-Piñón
- Vicepresidente del Colegio de Nefrólogos de México AC, Mexico City, Mexico
- Directora General del Registro Nacional de Hipertensión Arterial México (RIHTA) Grupo de Expertos en Hipertensión Arterial México (GREHTA), Mexico City, Mexico
| | | | | | - Felipe Ericel Hernández-Arellanes
- Departamento de Nefrología, Hospital de Especialidades Dr. Antonio Fraga Mouret, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | | | | | - María Juana Pérez-López
- Departamento de Nefrología, Hospital de Especialidades Dr. Antonio Fraga Mouret, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | - Fabiola Pazos-Pérez
- Nefrología, UMAE Hospital de Especialidades Dr. Bernardo Sepúlveda Gutiérrez, Centro Medico Siglo XXI, Mexico City, Mexico
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24
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Khan H, Abu-Raisi M, Feasson M, Shaikh F, Saposnik G, Mamdani M, Qadura M. Current Prognostic Biomarkers for Abdominal Aortic Aneurysm: A Comprehensive Scoping Review of the Literature. Biomolecules 2024; 14:661. [PMID: 38927064 PMCID: PMC11201473 DOI: 10.3390/biom14060661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 05/29/2024] [Accepted: 06/03/2024] [Indexed: 06/28/2024] Open
Abstract
Abdominal aortic aneurysm (AAA) is a progressive dilatation of the aorta that can lead to aortic rupture. The pathophysiology of the disease is not well characterized but is known to be caused by the general breakdown of the extracellular matrix within the aortic wall. In this comprehensive literature review, all current research on proteins that have been investigated for their potential prognostic capabilities in patients with AAA was included. A total of 45 proteins were found to be potential prognostic biomarkers for AAA, predicting incidence of AAA, AAA rupture, AAA growth, endoleak, and post-surgical mortality. The 45 proteins fell into the following seven general categories based on their primary function: (1) cardiovascular health, (2) hemostasis, (3) transport proteins, (4) inflammation and immunity, (5) kidney function, (6) cellular structure, (7) and hormones and growth factors. This is the most up-to-date literature review on current prognostic markers for AAA and their functions. This review outlines the wide pathophysiological processes that are implicated in AAA disease progression.
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Affiliation(s)
- Hamzah Khan
- Division of Vascular Surgery, St. Michael’s Hospital, Toronto, ON M5B 1W8, Canada
- Li Ka Shing Knowledge Institute, St Michael’s Hospital, Unity Health Toronto, Toronto, ON M5B 1W8, Canada
| | - Mohamed Abu-Raisi
- Division of Vascular Surgery, St. Michael’s Hospital, Toronto, ON M5B 1W8, Canada
- Li Ka Shing Knowledge Institute, St Michael’s Hospital, Unity Health Toronto, Toronto, ON M5B 1W8, Canada
| | - Manon Feasson
- Li Ka Shing Knowledge Institute, St Michael’s Hospital, Unity Health Toronto, Toronto, ON M5B 1W8, Canada
| | - Farah Shaikh
- Division of Vascular Surgery, St. Michael’s Hospital, Toronto, ON M5B 1W8, Canada
- Li Ka Shing Knowledge Institute, St Michael’s Hospital, Unity Health Toronto, Toronto, ON M5B 1W8, Canada
| | - Gustavo Saposnik
- Li Ka Shing Knowledge Institute, St Michael’s Hospital, Unity Health Toronto, Toronto, ON M5B 1W8, Canada
- Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON M5S 1A1, Canada
| | - Muhammad Mamdani
- Li Ka Shing Knowledge Institute, St Michael’s Hospital, Unity Health Toronto, Toronto, ON M5B 1W8, Canada
| | - Mohammad Qadura
- Division of Vascular Surgery, St. Michael’s Hospital, Toronto, ON M5B 1W8, Canada
- Li Ka Shing Knowledge Institute, St Michael’s Hospital, Unity Health Toronto, Toronto, ON M5B 1W8, Canada
- Department of Surgery, University of Toronto, Toronto, ON M5T 1P5, Canada
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25
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Zoccali C, Mallamaci F. The evolving scenario of estimated glomerular filtration rate in clinical practice: the European kidney function consortium formulas. J Nephrol 2024; 37:1193-1195. [PMID: 38771518 DOI: 10.1007/s40620-024-01957-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Accepted: 04/11/2024] [Indexed: 05/22/2024]
Affiliation(s)
- Carmine Zoccali
- Renal Research Institute, New York, NY, USA.
- Institute of Molecular Biology and Genetics (Biogem), Ariano Irpino, Italy.
- Associazione Ipertensione Nefrologia Trapianto Renal (IPNET), C/O Nefrologia, Grande Ospedale Metropolitano, 8914, Reggio Calabria, Italy.
| | - Francesca Mallamaci
- Nephrology, Dialysis and Transplantation Unit Azienda Ospedaliera, Bianchi-Melacrino-Morelli", Reggio Calabria, Italy
- Institute of Clinical Physiology, Research Unit of Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension of Reggio Calabria, CNR-IFC, Reggio Calabria, Italy
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26
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Huang C, Lu J, Yang J, Wang Z, Hang D, Fu Z. Associations of serum cystatin C concentrations with total mortality and mortality of 12 site-specific cancers. Front Mol Biosci 2024; 11:1209349. [PMID: 38725873 PMCID: PMC11079135 DOI: 10.3389/fmolb.2024.1209349] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 03/25/2024] [Indexed: 05/12/2024] Open
Abstract
Purpose Cystatin C (CysC), beyond its biomarker role of renal function, has been implicated in various physical and pathological activities. However, the impact of serum CysC on cancer mortality in a general population remains unknown. We aimed to examine the associations of serum CysC concentrations with total mortality and mortality of 12 site-specific cancers. Methods We included 241,008 participants of the UK Biobank cohort with CysC measurements who had normal creatinine-based estimated glomerular filtration rates and were free of cancer and renal diseases at baseline (2006-2010). Death information was obtained from the National Health Service death records through 28 February 2021. Multivariable Cox proportional hazards models were used to compute hazard ratios (HR) per one standard deviation increase in log-transformed CysC concentrations and 95% confidence intervals (95% CI) for mortality. Results Over a median follow-up of 12.1 (interquartile range, 11.3-12.8) years, 5,744 cancer deaths occurred. We observed a positive association between serum CysC concentrations and total cancer mortality (HR = 1.16, 95% CI: 1.12-1.20). Specifically, participants with higher serum CysC concentrations had increased mortality due to lung cancer (HR = 1.12, 95% CI: 1.05-1.20), blood cancer (HR = 1.29, 95% CI: 1.16-1.44), brain cancer (HR = 1.19, 95% CI: 1.04-1.36), esophageal cancer (HR = 1.20, 95% CI: 1.05-1.37), breast cancer (HR = 1.18, 95% CI: 1.03-1.36), and liver cancer (HR = 1.49, 95% CI: 1.31-1.69). Conclusion Our findings indicate that higher CysC concentrations are associated with increased mortality due to lung, blood, brain, esophageal, breast, and liver cancers. Future studies are necessary to clarify underlying mechanisms.
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Affiliation(s)
- Changzhi Huang
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jiayi Lu
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Jing Yang
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Zhenling Wang
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Dong Hang
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China
| | - Zan Fu
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Fu EL, Levey AS, Coresh J, Grams ME, Faucon AL, Elinder CG, Dekker FW, Delanaye P, Inker LA, Carrero JJ. Accuracy of GFR estimating equations based on creatinine, cystatin C or both in routine care. Nephrol Dial Transplant 2024; 39:694-706. [PMID: 37813817 DOI: 10.1093/ndt/gfad219] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Indexed: 10/11/2023] Open
Abstract
BACKGROUND New equations to estimate glomerular filtration rate based on creatinine (eGFRcr), cystatin C (eGFRcys) or both (eGFRcr-cys) have been developed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the European Kidney Function Consortium (EKFC). There is a need to evaluate the performance of these equations in diverse European settings to inform implementation decisions, especially among people with key comorbid conditions. METHODS We performed a cross-sectional study including 6174 adults referred for single-point plasma clearance of iohexol in Stockholm, Sweden, with 9579 concurrent measurements of creatinine and cystatin C. We assessed the performance of the CKD-EPI 2009/2012/2021, EKFC 2021/2023, revised Lund-Malmö (RLM) 2011 and Caucasian, Asian, Pediatric and Adult (CAPA) 2014 equations against measured GFR (mGFR). RESULTS Mean age was 56 years, median mGFR was 62 mL/min/1.73 m2 and 40% were female. Comorbid conditions were common: cardiovascular disease (30%), liver disease (28%), diabetes (26%) and cancer (26%). All eGFRcr-cys equations had small bias and P30 (the percentage of estimated values within 30% of mGFR) close to 90%, and performed better than eGFRcr or eGFRcys equations. Among eGFRcr equations, CKD-EPI 2009 and CKD-EPI 2021 showed larger bias and lower P30 than EKFC 2021 and RLM. There were no meaningful differences in performance across eGFRcys equations. Findings were consistent across comorbid conditions, and eGFRcr-cys equations showed good performance in patients with liver disease, cancer and heart failure. CONCLUSIONS In conclusion, eGFRcr-cys equations performed best, with minimal variation among equations in this Swedish cohort. The lower performance of CKD-EPI eGFRcr equations compared with EKFC and RLM may reflect differences in population characteristics and mGFR methods. Implementing eGFRcr equations will require a trade-off between accuracy and uniformity across regions.
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Affiliation(s)
- Edouard L Fu
- Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Andrew S Levey
- Division of Nephrology, Department of Internal Medicine, Tufts Medical Center, Boston, MA, USA
| | - Josef Coresh
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA
| | - Morgan E Grams
- Division of Precision Medicine, Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA
| | - Anne-Laure Faucon
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
- INSERM UMR 1018, Department of Clinical Epidemiology, Paris-Saclay University, Paris, France
| | - Carl-Gustaf Elinder
- Division of Renal Medicine, Department of Clinical Intervention, and Technology, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden
| | - Friedo W Dekker
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Pierre Delanaye
- Department of Nephrology-Dialysis-Transplantation, University of Liège, CHU Sart Tilman, Liège, Belgium
- Department of Nephrology-Dialysis-Apheresis, Hôpital Universitaire Carémeau, Nîmes, France
| | - Lesley A Inker
- Division of Nephrology, Department of Internal Medicine, Tufts Medical Center, Boston, MA, USA
| | - Juan-Jesus Carrero
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
- Division of Nephrology, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden
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Liu D, Li N, Zhou Y, Wang M, Song P, Yuan C, Shi Q, Chen H, Zhou K, Wang H, Li T, Pan XF, Tian H, Li S. Sex-specific associations between skeletal muscle mass and incident diabetes: A population-based cohort study. Diabetes Obes Metab 2024; 26:820-828. [PMID: 37997500 DOI: 10.1111/dom.15373] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 10/31/2023] [Accepted: 11/04/2023] [Indexed: 11/25/2023]
Abstract
AIMS To investigate the sex-specific associations between predicted skeletal muscle mass index (pSMI) and incident type 2 diabetes in a retrospective longitudinal cohort of Chinese men and women. MATERIALS AND METHODS We enrolled Chinese adults without diabetes at baseline from WATCH (West chinA adulT health CoHort), a large health check-up-based database. We calculated pSMI to estimate skeletal muscular mass, and measured blood glucose variables and assessed self-reported history to identify new-onset diabetes. The nonlinear association between pSMI and incident type 2 diabetes was modelled using the penalized spline method. The piecewise association was estimated using segmented linear splines in weighted Cox proportional hazards regression models. RESULTS Of 47 885 adults (53.2% women) with a median age of 40 years, 1836 developed type 2 diabetes after a 5-year median follow-up. In women, higher pSMI was associated with a lower risk of incident type 2 diabetes (Pnonlinearity = 0.09, hazard ratio [HR] per standard deviation increment in pSMI: 0.79 [95% confidence interval {CI} 0.68, 0.91]). A nonlinear association of pSMI with incident type 2 diabetes was detected in men (Pnonlinearity < 0.001). In men with pSMI lower than 8.1, higher pSMI was associated with a lower risk of incident type 2 diabetes (HR 0.58 [95% CI 0.40, 0.84]), whereas pSMI was not significantly associated with incident diabetes in men with pSMI equal to or greater than 8.1 (HR 1.08 [95% CI 0.93, 1.25]). CONCLUSIONS In females, a larger muscular mass is associated with a lower risk of type 2 diabetes. For males, this association is significant only among those with diminished muscle mass.
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Affiliation(s)
- Dan Liu
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China
| | - Nan Li
- Department of Informatics, West China Hospital, Sichuan University, Chengdu, China
| | - Yiling Zhou
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China
| | - Miye Wang
- Department of Informatics, West China Hospital, Sichuan University, Chengdu, China
| | - Peige Song
- School of Public Health, Zhejiang University, Hangzhou, China
| | - Changzheng Yuan
- School of Public Health, Zhejiang University, Hangzhou, China
| | - Qingyang Shi
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China
| | - Hui Chen
- School of Public Health, Zhejiang University, Hangzhou, China
| | - Kaixin Zhou
- College of Life Sciences, University of the Chinese Academy of Sciences, Beijing, China
- College of Public Health, Guangzhou Medical University, Guangzhou, China
| | - Huan Wang
- Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, UK
| | - Tao Li
- Department of Anesthesiology, Laboratory of Mitochondria and Metabolism, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China
| | - Xiong-Fei Pan
- Section of Epidemiology and Population Health, Ministry of Education Key Laboratory of Birth Defects and Related Diseases of Women and Children, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Haoming Tian
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China
| | - Sheyu Li
- Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China
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Choi MC, Kim DG, Yim SH, Kim HJ, Kim HW, Yang J, Kim BS, Huh KH, Kim MS, Lee J. Creatinine-cystatin C ratio and death with a functioning graft in kidney transplant recipients. Sci Rep 2024; 14:1966. [PMID: 38263396 PMCID: PMC10806062 DOI: 10.1038/s41598-024-52649-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Accepted: 01/22/2024] [Indexed: 01/25/2024] Open
Abstract
Death with a functioning graft is important cause of graft loss after kidney transplantation. However, little is known about factors predicting death with a functioning graft among kidney transplant recipients. In this study, we evaluated the association between post-transplant creatinine-cystatin C ratio and death with a functioning graft in 1592 kidney transplant recipients. We divided the patients into tertiles based on sex-specific creatinine-cystatin C ratio. Among the 1592 recipients, 39.5% were female, and 86.1% underwent living-donor kidney transplantation. The cut-off value for the lowest creatinine-cystatin C ratio tertile was 0.86 in males and 0.73 in females. The lowest tertile had a significantly lower 5-year patient survival rate and was independently associated with death with a functioning graft (adjusted hazard ratio 2.574, 95% confidence interval 1.339-4.950, P < 0.001). Infection was the most common cause of death in the lowest tertile group, accounting for 62% of deaths. A low creatinine-cystatin C ratio was significantly associated with an increased risk of death with a functioning graft after kidney transplantation.
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Affiliation(s)
- Mun Chae Choi
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
- The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Deok Gie Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
- The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seung Hyuk Yim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
- The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hyun Jeong Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
- The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hyoung Woo Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jaeseok Yang
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Beom Seok Kim
- The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kyu Ha Huh
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
- The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Myoung Soo Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea
- The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Juhan Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
- The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Republic of Korea.
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Avendanha RA, Campos GFC, Branco BC, Ishii NC, Gomes LHN, de Castro AJ, Leal CRV, Simões E Silva AC. Potential urinary biomarkers in preeclampsia: a narrative review. Mol Biol Rep 2024; 51:172. [PMID: 38252179 DOI: 10.1007/s11033-023-09053-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Accepted: 10/30/2023] [Indexed: 01/23/2024]
Abstract
INTRODUCTION Preeclampsia (PE) is a highly relevant pregnancy-related disorder. An early and accurate diagnosis is crucial to prevent major maternal and neonatal complications and mortality. Due to the association of kidney dysfunction with the pathophysiology of the disease, urine samples have the potential to provide biomarkers for PE prediction, being minimally invasive and easy to perform. Therefore, searching for novel biomarkers may improve outcomes. This narrative review aimed to summarize the scientific literature about the traditional and potential urinary biomarkers in PE and to investigate their applicability to screen and diagnose the disorder. METHODS A non-systematic search was performed in PubMed/MEDLINE, Scopus, and SciELO databases. RESULTS There is significant divergence in the literature regarding traditionally used serum markers creatinine, cystatin C, and albuminuria, accuracy in PE prediction. As for the potential renal biomarkers investigated, including vascular epithelial growth factor (VEGF), placental growth factor (PlGF), and soluble fms-like tyrosine kinase (sFlt-1), urinary levels of PlGF and sFtl-1/PlGF ratio in urine seem to be the most promising as screening tests. The assessment of the global load of misfolded proteins through urinary congophilia, podocyturia, and nephrinuria has also shown potential for screening and diagnosis. Studies regarding the use of proteomics and metabolomics have shown good accuracy, sensitivity, and specificity for predicting the development and severity of PE. CONCLUSION However, there are still many divergences in the literature, which requires future and more conclusive research to confirm the predictive role of urinary biomarkers in pregnant women with PE.
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Affiliation(s)
- Renata Araujo Avendanha
- Liga Acadêmica de Pesquisa Científica, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil
| | | | - Beatriz Castello Branco
- Liga Acadêmica de Pesquisa Científica, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil
- Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, UFMG, Belo Horizonte, MG, Brazil
| | - Nicolle Coimbra Ishii
- Liga Acadêmica de Pesquisa Científica, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil
- Universidade Federal de Juiz de Fora (UFJF), Juiz de Fora, Minas Gerais, Brazil
| | - Luiz Henrique Nacife Gomes
- Liga Acadêmica de Pesquisa Científica, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil
- Faculdade de Ciências Médicas de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
| | - Ailton José de Castro
- Liga Acadêmica de Pesquisa Científica, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil
| | - Caio Ribeiro Vieira Leal
- Departamento de Ginecologia e Obstetrícia, Faculdade de Medicina, UFMG, Belo Horizonte, Minas Gerais, Brazil
| | - Ana Cristina Simões E Silva
- Liga Acadêmica de Pesquisa Científica, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
- Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina, UFMG, Belo Horizonte, MG, Brazil.
- Faculdade de Medicina, UFMG, Avenida Alfredo Balena, 190, 2o andar, sala 281. Bairro Santa Efigênia, Belo Horizonte, CEP 30130-100, MG, Brazil.
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Delanaye P, Cavalier E, Stehlé T, Pottel H. Glomerular Filtration Rate Estimation in Adults: Myths and Promises. Nephron Clin Pract 2024; 148:408-414. [PMID: 38219717 DOI: 10.1159/000536243] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 12/23/2023] [Indexed: 01/16/2024] Open
Abstract
BACKGROUND In daily practice, glomerular filtration rate (GFR) is estimated with equations including renal biomarkers. Among these biomarkers, serum creatinine remains the most used. However, there are many limitations with serum creatinine, which we will discuss in the current review. We will also discuss how creatinine-based equations have been developed and what we can expect from them in terms of performance to estimate GFR. SUMMARY Different creatinine-based equations have been proposed. We will show the advantages of the recent European Kidney Function Consortium equation. This equation can be used in children and adults. This equation can also be used with some flexibility in different populations. KEY MESSAGES GFR is estimated by creatinine-based equations, but the most important for nephrologists is probably to know the limitations of these equations.
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Affiliation(s)
- Pierre Delanaye
- Department of Nephrology-Dialysis-Transplantation, University of Liège, CHU Sart Tilman, Liège, Belgium
- Department of Nephrology-Dialysis-Apheresis, Hôpital Universitaire Carémeau, Nîmes, France
| | - Etienne Cavalier
- Department of Clinical Chemistry, University of Liège, CHU Sart Tilman, Liège, Belgium
| | - Thomas Stehlé
- Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Henri Mondor, Service de Néphrologie et Transplantation, Fédération Hospitalo-Universitaire "Innovative Therapy for Immune Disorders", Créteil, France
| | - Hans Pottel
- Department of Public Health and Primary Care, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
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Mondal A, Kobe C, Mariani LH, Zee J. Evaluation of Biomarker-Based Glomerular Filtration Rate Estimating Equations in Glomerular Disease. GLOMERULAR DISEASES 2024; 4:119-128. [PMID: 39015840 PMCID: PMC11250572 DOI: 10.1159/000539353] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Accepted: 04/29/2024] [Indexed: 07/18/2024]
Abstract
Introduction Glomerular filtration rate (GFR) is typically estimated with equations that use biomarkers such as serum creatinine and/or cystatin-C. The impact of these different biomarkers on GFR estimates in glomerular disease patients is unclear. In this study, we compared the different GFR estimating equations in the Cure Glomerulonephropathy (CureGN) cohort of children and adults with glomerular disease. Methods All available cystatin-C measurements from CureGN study participants were matched to same-day serum creatinine measurements to estimate GFR. To explore the strength of agreement between eGFR values obtained from the "Under 25" (U25) and Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equations, we used intraclass correlation coefficients. Multivariable linear mixed effects models were used to determine which factors were independently associated with differences in eGFR values. Results A total of 928 cystatin-C measurements were matched to same-day serum creatinine measurements from N = 332 CureGN study participants (58% male, 69% White/Caucasian, 20% Black/African American). Among 628 measurements collected while study participants were under 25 years old, there was moderate agreement (0.731) in serum creatinine versus cystatin-C U25 equations. Models showed that higher eGFR values were associated with larger differences between the two equations (p < 0.001). Among 253 measurements collected while study participants were at least 18 years old, there was excellent agreement (0.891-0.978) among CKD-Epi equations using serum creatinine alone, cystatin-C alone, or the combination of both. Younger age was associated with larger differences between CKD-Epi equations (p = 0.06 to p = 0.016). Conclusion Excellent agreement between CKD-Epi equations indicates continued use of serum creatinine alone for GFR estimation could be appropriate for adults. In contrast, only moderate agreement between U25 equations indicates a need for more frequent measurement of cystatin-C among children and young adults, especially as eGFR increases.
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Affiliation(s)
- Antara Mondal
- Division of Biostatistics, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, USA
- Department of Biomedical and Health Informatics, Data Science and Biostatistics Unit, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
| | - Christina Kobe
- Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Laura H. Mariani
- Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Jarcy Zee
- Division of Biostatistics, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, USA
- Department of Pediatrics, Children’s Hospital of Philadelphia Research Institute, Philadelphia, PA, USA
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Saeed D, Reza T, Shahzad MW, Karim Mandokhail A, Bakht D, Qizilbash FH, Silloca-Cabana EO, Ramadhan A, Bokhari SFH. Navigating the Crossroads: Understanding the Link Between Chronic Kidney Disease and Cardiovascular Health. Cureus 2023; 15:e51362. [PMID: 38292979 PMCID: PMC10825078 DOI: 10.7759/cureus.51362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/30/2023] [Indexed: 02/01/2024] Open
Abstract
Chronic Kidney Disease (CKD) has emerged as a global healthcare challenge affecting a significant portion of the world's population. This comprehensive narrative review delves into the intricate relationship between CKD and cardiovascular disease (CVD). CKD is characterized by kidney damage persisting for at least three months, often with or without a decline in glomerular filtration rate (GFR). It is closely linked with CVD, as individuals with CKD face a high risk of cardiovascular events, making cardiovascular-associated mortality a significant concern in advanced CKD stages. The review emphasizes the importance of precise risk assessment using biomarkers, advanced imaging, and tailored medication strategies to mitigate cardiovascular risks in CKD patients. Lifestyle modifications, early intervention, and patient-centered care are crucial in managing both conditions. Challenges in awareness and recognition of CKD and the need for comprehensive interdisciplinary care are highlighted. Recent advances in research offer promising therapies, such as SGLT2 inhibitors, MRAs, GLP-1R agonists, and selective endothelin receptor antagonists. Stem cell-based therapies, gene editing, and regenerative approaches are under investigation. Patient-physician "risk discussions" and tailored risk assessments are essential for improving patient outcomes. In conclusion, the review underscores the complexity of the interconnected CKD and cardiovascular health domains. Ongoing research, innovative therapies, and personalized healthcare will be instrumental in addressing the challenges, reducing the disease burden, and enhancing well-being for individuals facing CKD and cardiovascular issues. Recognizing the intricate connections between these conditions is imperative for healthcare providers, policymakers, and researchers as they seek to improve the quality of care and outcomes for affected individuals.
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Affiliation(s)
- Danish Saeed
- Internal Medicine, Shaikh Zayed Medical Complex, Lahore, PAK
| | - Taufiqa Reza
- Internal Medicine, Avalon University School of Medicine, Youngstown, USA
| | | | | | - Danyal Bakht
- Medicine and Surgery, Mayo Hospital, Lahore, PAK
| | | | | | - Afif Ramadhan
- General Practice, Faculty of Medicine, Public Health, and Nursing, Gadjah Mada University, Yogyakarta, IDN
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Lee S, Lee S, Jo S, Kim KA, Yang YJ, Lee JJ, Kim E, Park Y, Kyong T, Kim JH. Calf Circumference as an Indicator for Cystatin C Testing in Hospitalized Elderly Male Patients for Detecting Hidden Renal Impairment. J Clin Med 2023; 12:6899. [PMID: 37959364 PMCID: PMC10647781 DOI: 10.3390/jcm12216899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 10/26/2023] [Accepted: 10/31/2023] [Indexed: 11/15/2023] Open
Abstract
Serum creatinine is used to measure the estimated glomerular filtration rate (eGFR); however, it is influenced by muscle mass and may therefore overestimate renal function in patients with sarcopenia. We examined calf circumference (CC) as a convenient muscle mass evaluation tool that can potentially indicate the need to test for cystatin C instead of creatinine in elderly inpatients. We retrospectively reviewed the electronic health record of 271 inpatients aged 65 or over. CC was determined by measuring the thickest part of the nondominant calf. eGFRcys and eGFRcr were calculated using cystatin C and creatinine levels, respectively. We evaluated optimum CC cutoff values using the eGFRcys/eGFRcr ratio for detecting hidden renal impairment (HRI, defined as eGFRcr ≥ 60 mL/min/1.73 m2 but eGFRcys < 60 mL/min/1.73 m2). CC showed a significant positive correlation with the eGFRcys/eGFRcr ratio in both sexes. The areas under the receiver operating characteristic curve were 0.725 and 0.681 for males and females, respectively. CC cutoffs with a sensitivity or specificity of 90% or 95% might be used to detect HRI in males. In conclusion, utilizing the optimum cutoff, CC could be a cost-effective screening tool for detecting HRI in elderly male patients using cystatin C as an add-on test.
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Affiliation(s)
- Sunghwan Lee
- Department of Laboratory Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, 363 Dongbaekjukjeon-daero, Giheung-gu, Yongin-si 16995, Gyeonggi-do, Republic of Korea; (S.L.); (K.-A.K.)
| | - Seul Lee
- Department of Hospital Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, 363 Dongbaekjukjeon-daero, Giheung-gu, Yongin-si 16995, Gyeonggi-do, Republic of Korea; (S.L.); (S.J.)
| | - Sunhee Jo
- Department of Hospital Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, 363 Dongbaekjukjeon-daero, Giheung-gu, Yongin-si 16995, Gyeonggi-do, Republic of Korea; (S.L.); (S.J.)
| | - Kyung-Ah Kim
- Department of Laboratory Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, 363 Dongbaekjukjeon-daero, Giheung-gu, Yongin-si 16995, Gyeonggi-do, Republic of Korea; (S.L.); (K.-A.K.)
| | - Yu Jin Yang
- Department of Nutrition, Yongin Severance Hospital, Yonsei University College of Medicine, 363 Dongbaekjukjeon-daero, Giheung-gu, Yongin-si 16995, Gyeonggi-do, Republic of Korea; (Y.J.Y.); (J.J.L.)
| | - Jung Joo Lee
- Department of Nutrition, Yongin Severance Hospital, Yonsei University College of Medicine, 363 Dongbaekjukjeon-daero, Giheung-gu, Yongin-si 16995, Gyeonggi-do, Republic of Korea; (Y.J.Y.); (J.J.L.)
| | - Eunsung Kim
- Department of Inpatient Nursing, Yongin Severance Hospital, Yonsei University College of Medicine, 363 Dongbaekjukjeon-daero, Giheung-gu, Yongin-si 16995, Gyeonggi-do, Republic of Korea;
| | - Yongjung Park
- Department of Laboratory Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211, Eonju-ro, Gangnam-gu, Seoul 06273, Republic of Korea;
| | - Taeyoung Kyong
- Department of Hospital Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, 363 Dongbaekjukjeon-daero, Giheung-gu, Yongin-si 16995, Gyeonggi-do, Republic of Korea; (S.L.); (S.J.)
| | - Jeong-Ho Kim
- Department of Laboratory Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, 363 Dongbaekjukjeon-daero, Giheung-gu, Yongin-si 16995, Gyeonggi-do, Republic of Korea; (S.L.); (K.-A.K.)
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Liao J, Xiao F, Yang L, Wei Y, Song C, Li J, Yu S, Lu Y, Zhang J, Dai L, Liang W, Li T, Xiong Z, Wu Y, Jardine MJ, Carrero JJ, Shan Y, Huang X. Cystatin C-based estimated glomerular filtration rate and risk of stroke in the general population: a prospective cohort study. Clin Kidney J 2023; 16:2059-2071. [PMID: 37915909 PMCID: PMC10616444 DOI: 10.1093/ckj/sfad188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Indexed: 11/03/2023] Open
Abstract
Background Previous results on the association between the estimated glomerular filtration rate (eGFR) and stroke are mixed. Most studies derived the eGFR from serum creatinine, which is affected by non-kidney determinants and thus has possibly biased the association with stroke risk. Methods In this cohort study, we included 429 566 UK Biobank participants (94.5% white, 54% women, age 56 ± 8 years) free of stroke at enrollment. The eGFRcys and eGFRcr were calculated with serum cystatin C and creatinine, respectively. Outcomes of interest were risk of total stroke and subtypes. We investigated the linear and nonlinear associations using Cox proportional hazards models and restricted cubic splines, corrected for regression dilution bias. Results During an average follow-up of 10.11 years, 4427 incident strokes occurred, among which 3447 were ischemic and 1163 were hemorrhagic. After adjustment for confounders, the regression dilution-corrected hazard ratios (95% confidence intervals) for every 10 mL/min/1.73 m2 decrement in eGFRcys were 1.10 (1.05-1.14) for total stroke and 1.11 (1.08-1.15) for ischemic stroke. A similar pattern was observed with eGFRcr, although the association was weaker. When either type of eGFR was below 75 mL/min/1.73 m2, the risks of total and ischemic stroke increased exponentially as eGFR decreased. A U-shaped relationship was witnessed if eGFRcr was used instead. There was a null association between eGFR and hemorrhagic stroke. Conclusions The risks of total stroke and ischemic stroke increased exponentially when the eGFRcys fell below 75 mL/min/1.73 m2.
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Affiliation(s)
- Jinlan Liao
- Renal Division, Peking University Shenzhen Hospital, Peking University, Shenzhen, Guangdong Province, China
| | - Fei Xiao
- Renal Division, Peking University Shenzhen Hospital, Peking University, Shenzhen, Guangdong Province, China
- Shantou University Medical College, Shantou, Guangdong Province, China
| | - Liuqiao Yang
- BGI-Shenzhen, Shenzhen, Guangdong Province, China
| | - Yanling Wei
- Clinical Research Academy, Peking University Shenzhen Hospital, Peking University, Shenzhen, Guangdong Province, China
| | - Congying Song
- Clinical Research Academy, Peking University Shenzhen Hospital, Peking University, Shenzhen, Guangdong Province, China
| | - Jing Li
- Renal Division, Peking University Shenzhen Hospital, Peking University, Shenzhen, Guangdong Province, China
| | - Sike Yu
- BGI-Shenzhen, Shenzhen, Guangdong Province, China
| | - Yueqi Lu
- BGI-Shenzhen, Shenzhen, Guangdong Province, China
| | - Jingwen Zhang
- Renal Division, Peking University Shenzhen Hospital, Peking University, Shenzhen, Guangdong Province, China
| | - Liang Dai
- Clinical Research Academy, Peking University Shenzhen Hospital, Peking University, Shenzhen, Guangdong Province, China
| | - Wei Liang
- Renal Division, Peking University Shenzhen Hospital, Peking University, Shenzhen, Guangdong Province, China
| | - Tao Li
- BGI-Shenzhen, Shenzhen, Guangdong Province, China
| | - Zuying Xiong
- Renal Division, Peking University Shenzhen Hospital, Peking University, Shenzhen, Guangdong Province, China
| | - Yangfeng Wu
- Peking University Clinical Research Institute, Peking University, Beijing, China
| | - Meg J Jardine
- The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia
- Concord Repatriation General Hospital, Sydney, New South Wales, Australia
- Department of Medicine, Stanford Centre for Clinical Research, Stanford University School of Medicine, Stanford, CA, USA
| | - Juan Jesus Carrero
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
- Division of Nephrology, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm 182 88, Sweden
| | - Ying Shan
- BGI-Shenzhen, Shenzhen, Guangdong Province, China
- Clinical Research Academy, Peking University Shenzhen Hospital, Peking University, Shenzhen, Guangdong Province, China
| | - Xiaoyan Huang
- Renal Division, Peking University Shenzhen Hospital, Peking University, Shenzhen, Guangdong Province, China
- Clinical Research Academy, Peking University Shenzhen Hospital, Peking University, Shenzhen, Guangdong Province, China
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Pinsino A, Carey MR, Husain S, Mohan S, Radhakrishnan J, Jennings DL, Nguonly AS, Ladanyi A, Braghieri L, Takeda K, Faillace RT, Sayer GT, Uriel N, Colombo PC, Yuzefpolskaya M. The Difference Between Cystatin C- and Creatinine-Based Estimated GFR in Heart Failure With Reduced Ejection Fraction: Insights From PARADIGM-HF. Am J Kidney Dis 2023; 82:521-533. [PMID: 37086965 DOI: 10.1053/j.ajkd.2023.03.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Accepted: 03/02/2023] [Indexed: 04/24/2023]
Abstract
RATIONALE & OBJECTIVE The clinical implications of the discrepancy between cystatin C (cysC)- and serum creatinine (Scr)-estimated glomerular filtration rate (eGFR) in patients with heart failure (HF) and reduced ejection fraction (HFrEF) are unknown. STUDY DESIGN Post-hoc analysis of randomized trial data. SETTING & PARTICIPANTS 1,970 patients with HFrEF enrolled in PARADIGM-HF with available baseline cysC and Scr measurements. EXPOSURE Intraindividual differences between eGFR based on cysC (eGFRcysC) and Scr (eGFRScr; eGFRdiffcysC-Scr). OUTCOMES Clinical outcomes included the PARADIGM-HF primary end point (composite of cardiovascular [CV] mortality or HF hospitalization), CV mortality, all-cause mortality, and worsening kidney function. We also examined poor health-related quality of life (HRQoL), frailty, and worsening HF (WHF), defined as HF hospitalization, emergency department visit, or outpatient intensification of therapy between baseline and 8-month follow-up. ANALYTICAL APPROACH Fine-Gray subdistribution hazard models and Cox proportional hazards models were used to regress clinical outcomes on baseline eGFRdiffcysC-Scr. Logistic regression was used to investigate the association of baseline eGFRdiffcysC-Scr with poor HRQoL and frailty. Linear regression models were used to assess the association of WHF with eGFRcysC, eGFRScr, and eGFRdiffcysC-Scr at 8-month follow-up. RESULTS Baseline eGFRdiffcysC-Scr was higher than +10 and lower than-10mL/min/1.73m2 in 13.0% and 35.7% of patients, respectively. More negative values of eGFRdiffcysC-Scr were associated with worse outcomes ([sub]hazard ratio per standard deviation: PARADIGM-HF primary end point, 1.18; P=0.008; CV mortality, 1.34; P=0.001; all-cause mortality, 1.39; P<0.001; worsening kidney function, 1.31; P=0.05). For a 1-standard-deviation decrease in eGFRdiffcysC-Scr, the prevalences of poor HRQoL and frailty increased by 29% and 17%, respectively (P≤0.008). WHF was associated with a more pronounced decrease in eGFRcysC than in eGFRScr, resulting in a change in 8-month eGFRdiffcysC-Scr of-4.67mL/min/1.73m2 (P<0.001). LIMITATIONS Lack of gold-standard assessment of kidney function. CONCLUSIONS In patients with HFrEF, discrepancies between eGFRcysC and eGFRScr are common and are associated with clinical outcomes, HRQoL, and frailty. The decline in kidney function associated with WHF is more marked when assessed with eGFRcysC than with eGFRScr. PLAIN-LANGUAGE SUMMARY Kidney function assessment traditionally relies on serum creatinine (Scr) to establish an estimated glomerular filtration rate (eGFR). However, this has been challenged with the introduction of an alternative marker, cystatin C (cysC). Muscle mass and nutritional status have differential effects on eGFR based on cysC (eGFRcysC) and Scr (eGFRScr). Among ambulatory patients with heart failure enrolled in PARADIGM-HF, we investigated the clinical significance of the difference between eGFRcysC and eGFRScr. More negative values (ie, eGFRScr>eGFRcysC) were associated with worse clinical outcomes (including mortality), poor quality of life, and frailty. In patients with progressive heart failure, which is characterized by muscle loss and poor nutritional status, the decline in kidney function was more pronounced when eGFR was estimated using cysC rather than Scr.
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Affiliation(s)
- Alberto Pinsino
- Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center; Division of Critical Care Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY.
| | - Matthew R Carey
- Department of Medicine, Columbia University Irving Medical Center
| | - Syed Husain
- Department of Medicine, Division of Nephrology, Columbia University Irving Medical Center
| | - Sumit Mohan
- Department of Medicine, Division of Nephrology, Columbia University Irving Medical Center; Department of Epidemiology, Mailman School of Public Health, Columbia University Irving Medical Center
| | - Jai Radhakrishnan
- Department of Medicine, Division of Nephrology, Columbia University Irving Medical Center
| | - Douglas L Jennings
- Department of Pharmacy, Columbia University Irving Medical Center; Department of Pharmacy Practice, Long Island University College of Pharmacy, New York
| | - Austin S Nguonly
- Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center
| | - Annamaria Ladanyi
- Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center
| | - Lorenzo Braghieri
- Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center; Department of Medicine, Cleveland Clinic, Cleveland, OH
| | - Koji Takeda
- Department of Surgery, Division of Cardiac Surgery, Columbia University Irving Medical Center
| | | | - Gabriel T Sayer
- Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center
| | - Nir Uriel
- Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center
| | - Paolo C Colombo
- Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center
| | - Melana Yuzefpolskaya
- Department of Medicine, Division of Cardiology, Columbia University Irving Medical Center
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Yim J, Son NH, Kyong T, Park Y, Kim JH. Muscle mass has a greater impact on serum creatinine levels in older males than in females. Heliyon 2023; 9:e21866. [PMID: 38027624 PMCID: PMC10663898 DOI: 10.1016/j.heliyon.2023.e21866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Revised: 10/06/2023] [Accepted: 10/30/2023] [Indexed: 12/01/2023] Open
Abstract
Background and aims We analyzed the effects of age and sex on the relationship between muscle mass and serum creatinine levels in an apparently healthy population, including older adults. Materials and methods We retrospectively evaluated 1,502 individuals from the Korea National Health and Nutrition Examination Survey (KNHANES) and 4,586 individuals from the Health Check (HC) groups. We utilized data from the KNHANES and HC groups on serum creatinine levels and skeletal muscle mass index (SMI), determined using dual X-ray absorptiometry or bioelectric impedance analysis. Results A significant negative correlation between SMI and age was observed in both the KNHANES and HC groups in males but not in females. In males, serum creatinine levels showed a significant negative correlation with age in both the KNHANES (r = -0.522, P < 0.0001) and HC groups (r = -0.451, P < 0.0001). In females, there was no significant correlation between serum creatinine levels and age in the KNHANES (r = -0.016, P = 0.5985) and HC group (r = -0.011, P = 0.5618). Conclusions Serum creatinine levels decrease more significantly in older males than in older females due to sex-specific muscle mass decline.
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Affiliation(s)
- Jisook Yim
- Department of Laboratory Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Nak-Hoon Son
- Department of Statistics, Keimyung University, Daegu, Republic of Korea
| | - Taeyoung Kyong
- Department of Hospital Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Republic of Korea
| | - Yongjung Park
- Department of Laboratory Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jeong-Ho Kim
- Department of Laboratory Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Republic of Korea
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De Rosa S, Greco M, Rauseo M, Annetta MG. The Good, the Bad, and the Serum Creatinine: Exploring the Effect of Muscle Mass and Nutrition. Blood Purif 2023; 52:775-785. [PMID: 37742621 PMCID: PMC10623400 DOI: 10.1159/000533173] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 07/17/2023] [Indexed: 09/26/2023]
Abstract
Muscle wasting (sarcopenia) is one of the hallmarks of critical illness. Patients admitted to intensive care unit develop sarcopenia through increased protein catabolism, a decrease in protein syntheses, or both. Among the factors known to promote wasting are chronic inflammation and cytokine imbalance, insulin resistance, hypermetabolism, and malnutrition. Moreover, muscle wasting, known to develop in chronic kidney disease patients, is a harmful consequence of numerous complications associated with deteriorated renal function. Plenty of published data suggest that serum creatinine (SCr) reflects increased kidney damage and is also related to body weight. Based on the concept that urea and creatinine are nitrogenous end products of metabolism, the urea:creatinine ratio (UCR) could be applied but with limited clinical usability in case of kidney damage, hypovolemia, excessive, or protein intake, where UCR can be high and independent of catabolism. Recent data suggest that the sarcopenia index should be considered an alternative to serum creatinine. It is more reliable in estimating muscle mass than SCr. However, the optimal biomarker of catabolism is still an unresolved issue. The SCr is not a promising biomarker for renal function and muscle mass based on the influence of several factors. The present review highlights recent findings on the limits of SCr as a surrogate marker of renal function and the assessment modalities of nutritional status and muscle mass measurements.
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Affiliation(s)
- Silvia De Rosa
- Centre for Medical Sciences - CISMed, University of Trento, Trento, Italy
- Anesthesia and Intensive Care, Santa Chiara Regional Hospital, APSS Trento, Trento, Italy
| | - Massimiliano Greco
- Department of Anesthesiology and Intensive Care, IRCCS Humanitas Research Hospital, Milan, Italy
- Department of Biomedical Science, Humanitas University, Milan, Italy
| | - Michela Rauseo
- Department of Anesthesia and Intensive Care, University of Foggia, Policlinico Riuniti di Foggia, Foggia, Italy
| | - Maria Giuseppina Annetta
- UOC Di Anestesia, Rianimazione, Terapia Intensiva e Tossicologia Clinica, Dipartimento Di Scienze dell’Emergenza, Anestesiologiche e Della Rianimazione, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A, Rome, Italy
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Delanaye P, Cavalier E, Pottel H, Stehlé T. New and old GFR equations: a European perspective. Clin Kidney J 2023; 16:1375-1383. [PMID: 37664574 PMCID: PMC10469124 DOI: 10.1093/ckj/sfad039] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Indexed: 09/05/2023] Open
Abstract
Glomerular filtration rate (GFR) is estimated in clinical practice from equations based on the serum concentration of endogenous biomarkers and demographic data. The 2009 creatinine-based Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI2009) was recommended worldwide until 2021, when it was recalibrated to remove the African-American race factor. The CKD-EPI2009 and CKD-EPIcr2021 equations overestimate GFR of adults aged 18-30 years, with a strong overestimation in estimated GFR (eGFR) at age 18 years. CKD-EPICr2021 does not perform better than CKD-EPI2009 in US population, overestimating GFR in non-Black subjects, and underestimating it in Black subjects with the same magnitude. CKD-EPICr2021 performed worse than the CKD-EPI2009 in White Europeans, and provides no or limited performance gains in Black European and Black African populations. The European Kidney Function Consortium (EKFC) equation, which incorporates median normal value of serum creatinine in healthy population, overcomes the limitations of the CKD-EPI equations: it provides a continuity of eGFR at the transition between pediatric and adult care, and performs reasonably well in diverse populations, assuming dedicated scaling of serum creatinine (Q) values is used. The new EKFC equation based on cystatin C (EKFCCC) shares the same mathematical construction, namely, it incorporates the median cystatin C value in the general population, which is independent of sex and ethnicity. EKFCCC is therefore a sex-free and race-free equation, which performs better than the CKD-EPI equation based on cystatin C. Despite advances in the field of GFR estimation, no equation is perfectly accurate, and GFR measurement by exogenous tracer clearance is still required in specific populations and/or specific clinical situations.
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Affiliation(s)
- Pierre Delanaye
- Department of Nephrology-Dialysis-Transplantation, University of Liège, CHU Sart Tilman, Liège, Belgium
- Department of Nephrology-Dialysis-Apheresis, Hôpital Universitaire Carémeau, Nîmes, France
| | - Etienne Cavalier
- Department of Clinical Chemistry, University of Liège, CHU Sart Tilman, Liège, Belgium
| | - Hans Pottel
- Department of Public Health and Primary Care, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
| | - Thomas Stehlé
- Université Paris Est Créteil, INSERM, Institut Mondor de Recherche Biomédicale (IMRB), Créteil, France
- Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Henri Mondor, Service de Néphrologie et Transplantation, Fédération Hospitalo-Universitaire « Innovative therapy for immune disorders », Créteil, France
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Spencer S, Desborough R, Bhandari S. Should Cystatin C eGFR Become Routine Clinical Practice? Biomolecules 2023; 13:1075. [PMID: 37509111 PMCID: PMC10377068 DOI: 10.3390/biom13071075] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Revised: 06/29/2023] [Accepted: 07/03/2023] [Indexed: 07/30/2023] Open
Abstract
Kidney function assessment is crucial for diagnosing and managing kidney diseases. Glomerular filtration rate (GFR) is widely used as an indicator of kidney function, but its direct measurement is challenging. Serum creatinine, a commonly used marker for estimating GFR (eGFR), has limitations in accuracy and sensitivity. Cystatin C, a protein freely filtered by the glomerulus, has emerged as a promising alternative marker for kidney function. It is unaffected by muscle mass and shows stronger associations with cardiovascular disease and mortality than creatinine. Various equations have been developed to estimate GFR using creatinine or cystatin C alone or in combination. The CKD-EPIcreat-cys equation combining both markers demonstrates improved accuracy in GFR estimation, especially for individuals with eGFR values of 45-59 mL/min/1.73 m2. Cystatin C-based estimates of GFR outperform creatinine-based estimates in predicting clinical outcomes and identifying patients at higher risk, particularly in elderly and non-white ethnic groups. Cystatin C offers advantages over creatinine as a marker of kidney function. It is not influenced by non-kidney factors and provides more accurate estimation of GFR, aiding in the early detection of kidney disease and predicting adverse outcomes. Incorporating cystatin C into routine kidney function assessment may improve patient risk stratification and guide clinical decision-making. However, widespread adoption of cystatin C testing requires increased availability and accessibility in clinical laboratories. Further research and implementation efforts are needed to fully realize the potential of cystatin C in kidney function assessment and improving patient outcomes.
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Affiliation(s)
- Sebastian Spencer
- School of Medical Sciences, University of Hull, Hull HU6 7RX, UK
- Hull York Medical School, University of Hull, Hull HU6 7RU, UK
- Academic Renal Research, Hull University Teaching Hospitals NHS Trust, Hull HU3 2JZ, UK
| | - Robert Desborough
- Hull York Medical School, University of Hull, Hull HU6 7RU, UK
- Academic Renal Research, Hull University Teaching Hospitals NHS Trust, Hull HU3 2JZ, UK
| | - Sunil Bhandari
- Hull York Medical School, University of Hull, Hull HU6 7RU, UK
- Academic Renal Research, Hull University Teaching Hospitals NHS Trust, Hull HU3 2JZ, UK
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Fu EL, Levey AS, Coresh J, Elinder CG, Rotmans JI, Dekker FW, Paik JM, Barany P, Grams ME, Inker LA, Carrero JJ. Accuracy of GFR Estimating Equations in Patients with Discordances between Creatinine and Cystatin C-Based Estimations. J Am Soc Nephrol 2023; 34:1241-1251. [PMID: 36995139 PMCID: PMC10356168 DOI: 10.1681/asn.0000000000000128] [Citation(s) in RCA: 47] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 03/13/2023] [Indexed: 03/31/2023] Open
Abstract
SIGNIFICANCE STATEMENT Large discordances between eGFR on the basis of creatinine (eGFR cr ) or cystatin C (eGFR cys ) are common in clinical practice. However, which GFR estimating equation (eGFR cr , eGFR cys , or eGFR cr-cys ) is most accurate in these settings is not known. In this real-world study of 9404 concurrent measurements of creatinine, cystatin C, and iohexol clearance, all three equations performed similarly when eGFR cr and eGFR cys were similar (45% of cases). However, with large discordances (55% of cases), eGFR cr-cys was much more accurate than either alone. These findings were consistent among individuals with cardiovascular disease, heart failure, diabetes mellitus, liver disease, and cancer who have been underrepresented in research cohorts. Thus, when eGFR cr and eGFR cys are largely discordant in clinical practice, eGFR cr-cys is more accurate than eGFR cr or eGFR cys . BACKGROUND Cystatin C is recommended as a confirmatory test to eGFR when more precise estimates are needed for clinical decision making. Although eGFR on the basis of both creatinine and cystatin (eGFR cr-cys ) is the most accurate estimate in research studies, it is uncertain whether this is true in real-world settings, particularly when there are large discordances between eGFR based on creatinine (eGFR cr ) and that based on cystatin C (eGFR cys ). METHODS We included 6185 adults referred for measured GFR (mGFR) using plasma clearance of iohexol in Stockholm, Sweden, who had 9404 concurrent measurements of creatinine, cystatin C, and iohexol clearance. The performance of eGFR cr , eGFR cys , and eGFR cr-cys was assessed against mGFR with median bias, P30 , and correct classification of GFR categories. We stratified analyses within three categories: eGFR cys at least 20% lower than eGFR cr (eGFR cys eGFR cr ). RESULTS eGFR cr and eGFR cys were similar in 4226 (45%) samples, and among these samples all three estimating equations performed similarly. By contrast, eGFR cr-cys was much more accurate in cases of discordance. For example, when eGFR cys eGFR cr (8% of samples), the median biases were -4.5, 8.4, and 1.4 ml/min per 1.73m 2 . The findings were consistent among individuals with cardiovascular disease, heart failure, diabetes mellitus, liver disease, and cancer. CONCLUSIONS When eGFR cr and eGFR cys are highly discordant in clinical practice, eGFR cr-cys is more accurate than either eGFR cr or eGFR cys .
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Affiliation(s)
- Edouard L. Fu
- Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Andrew S. Levey
- Division of Nephrology, Department of Internal Medicine, Tufts Medical Center, Boston, Massachusetts
| | - Josef Coresh
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
| | - Carl-Gustaf Elinder
- Division of Renal Medicine, Department of Clinical Intervention and Technology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
| | - Joris I. Rotmans
- Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Friedo W. Dekker
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Julie M. Paik
- Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts
| | - Peter Barany
- Division of Renal Medicine, Department of Clinical Intervention and Technology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden
| | - Morgan E. Grams
- Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands
| | - Lesley A. Inker
- Division of Nephrology, Department of Internal Medicine, Tufts Medical Center, Boston, Massachusetts
| | - Juan-Jesus Carrero
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
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Kwon S, Hyeon JS, Jung Y, Li L, An JN, Kim YC, Yang SH, Kim T, Kim DK, Lim CS, Hwang GS, Lee JP. Urine myo-inositol as a novel prognostic biomarker for diabetic kidney disease: a targeted metabolomics study using nuclear magnetic resonance. Kidney Res Clin Pract 2023; 42:445-459. [PMID: 37551126 PMCID: PMC10407640 DOI: 10.23876/j.krcp.22.152] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2022] [Revised: 12/31/2022] [Accepted: 01/12/2023] [Indexed: 08/09/2023] Open
Abstract
BACKGROUND As a leading cause of chronic kidney disease, clinical demand for noninvasive biomarkers of diabetic kidney disease (DKD) beyond proteinuria is increasing. Metabolomics is a popular method to identify mechanisms and biomarkers. We investigated urinary targeted metabolomics in DKD patients. METHODS We conducted a targeted metabolomics study of 26 urinary metabolites in consecutive patients with DKD stage 1 to 5 (n = 208) and healthy controls (n = 26). The relationships between estimated glomerular filtration rate (eGFR) or urine protein-creatinine ratio (UPCR) and metabolites were evaluated. Multivariate Cox analysis was used to estimate relationships between urinary metabolites and the target outcome, end-stage renal disease (ESRD). C statistics and time-dependent receiver operating characteristics (ROC) were used to assess diagnostic validity. RESULTS During a median 4.5 years of follow-up, 103 patients (44.0%) progressed to ESRD and 65 (27.8%) died. The median fold changes of nine metabolites belonged to monosaccharide and tricarboxylic acid (TCA) cycle metabolites tended to increase with DKD stage. Myo-inositol, choline, and citrates were correlated with eGFR and choline, while mannose and myo-inositol were correlated with UPCR. Elevated urinary monosaccharide and TCA cycle metabolites showed associations with increased morality and ESRD progression. The predictive power of ESRD progression was high, in the order of choline, myo-inositol, and citrate. Although urinary metabolites alone were less predictive than serum creatinine or UPCR, myo-inositol had additive effect with serum creatinine and UPCR. In time-dependent ROC, myo-inositol was more predictive than UPCR of 1-year ESRD progression prediction. CONCLUSION Myo-inositol can be used as an additive biomarker of ESRD progression in DKD.
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Affiliation(s)
- Soie Kwon
- Department of Internal Medicine, Chung-Ang University Heukseok Hospital, Seoul, Republic of Korea
- Department of Clinical Medical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jin Seong Hyeon
- Western Seoul Center, Korea Basic Science Institute, Seoul, Republic of Korea
- Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea
| | - Youngae Jung
- Western Seoul Center, Korea Basic Science Institute, Seoul, Republic of Korea
| | - Lilin Li
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Critical Care Medicine, Yanbian University Hospital, Yanji, China
| | - Jung Nam An
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea
| | - Yong Chul Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Seung Hee Yang
- Kidney Research Institute, Seoul National University Medical Research Center , Seoul, Republic of Korea
| | - Tammy Kim
- Institute of Life and Death Studies, Hallym University, Chuncheon, Republic of Korea
| | - Dong Ki Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Chun Soo Lim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Department of Chemistry and Nano Science, Ewha Womans University, Seoul, Republic of Korea
| | - Geum-Sook Hwang
- Western Seoul Center, Korea Basic Science Institute, Seoul, Republic of Korea
- Division of Nephrology, Department of Internal Medicine-Nephrology, Seoul National University Boramae Medical Center, Seoul, Republic of Korea
| | - Jung Pyo Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
- Division of Nephrology, Department of Internal Medicine-Nephrology, Seoul National University Boramae Medical Center, Seoul, Republic of Korea
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Muiru A, Hsu J, Zhang X, Appel L, Chen J, Cohen DL, Drawz PE, Freedman BI, Go AS, He J, Horwitz E, Hsu RK, Lash JP, Liu KD, McCoy IE, Porter A, Rao P, Ricardo AC, Rincon-Choles H, Sondheimer J, Taliercio J, Unruh M, Hsu CY, CRIC Study Investigators. Risk for Chronic Kidney Disease Progression After Acute Kidney Injury: Findings From the Chronic Renal Insufficiency Cohort Study. Ann Intern Med 2023; 176:961-968. [PMID: 37429030 PMCID: PMC10829039 DOI: 10.7326/m22-3617] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/12/2023] Open
Abstract
BACKGROUND Prior studies associating acute kidney injury (AKI) with more rapid subsequent loss of kidney function had methodological limitations, including inadequate control for differences between patients who had AKI and those who did not. OBJECTIVE To determine whether AKI is independently associated with subsequent kidney function trajectory among patients with chronic kidney disease (CKD). DESIGN Multicenter prospective cohort study. SETTING United States. PARTICIPANTS Patients with CKD (n = 3150). MEASUREMENTS Hospitalized AKI was defined by a 50% or greater increase in inpatient serum creatinine (SCr) level from nadir to peak. Kidney function trajectory was assessed using estimated glomerular filtration rate (eGFR) based on SCr level (eGFRcr) or cystatin C level (eGFRcys) measured at annual study visits. RESULTS During a median follow-up of 3.9 years, 433 participants had at least 1 AKI episode. Most episodes (92%) had stage 1 or 2 severity. There were decreases in eGFRcr (-2.30 [95% CI, -3.70 to -0.86] mL/min/1.73 m2) and eGFRcys (-3.61 [CI, -6.39 to -0.82] mL/min/1.73 m2) after AKI. However, in fully adjusted models, the decreases were attenuated to -0.38 (CI, -1.35 to 0.59) mL/min/1.73 m2 for eGFRcr and -0.15 (CI, -2.16 to 1.86) mL/min/1.73 m2 for eGFRcys, and the CI bounds included the possibility of no effect. Estimates of changes in eGFR slope after AKI determined by either SCr level (0.04 [CI, -0.30 to 0.38] mL/min/1.73 m2 per year) or cystatin C level (-0.56 [CI, -1.28 to 0.17] mL/min/1.73 m2 per year) also had CI bounds that included the possibility of no effect. LIMITATIONS Few cases of severe AKI, no adjudication of AKI cause, and lack of information about nephrotoxic exposures after hospital discharge. CONCLUSION After pre-AKI eGFR, proteinuria, and other covariables were accounted for, the association between mild to moderate AKI and worsening subsequent kidney function in patients with CKD was small. PRIMARY FUNDING SOURCE National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health.
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Affiliation(s)
- Anthony Muiru
- Division of Nephrology, University of California, San Francisco School of Medicine, San Francisco, CA
| | - Jesse Hsu
- Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Xiaoming Zhang
- Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Larry Appel
- Division of General Internal Medicine, The Johns Hopkins University, Baltimore, MD
| | - Jing Chen
- Section of Nephrology & Hypertension, Tulane University School of Medicine, New Orleans, LA
| | - Debbie L. Cohen
- Division of Nephrology, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Paul E. Drawz
- Division of Nephrology and Hypertension, University of Minnesota Medical School, Minneapolis, MN
| | - Barry I. Freedman
- Section on Nephrology, Wake Forest University, Winston-Salem, North Carolina
| | - Alan S. Go
- Division of Research, Kaiser Permanente Northern California, Oakland, CA
| | - Jiang He
- Tulane University School of Public Health & Tropical Medicine, New Orleans, LA
| | - Ed Horwitz
- Case Western Reserve University School of Medicine, Cleveland, OH
| | - Raymond K. Hsu
- Division of Nephrology, University of California, San Francisco School of Medicine, San Francisco, CA
| | - James P. Lash
- Division of Nephrology, University of Illinois Health, Chicago, IL
| | - Kathleen D. Liu
- Division of Nephrology, University of California, San Francisco School of Medicine, San Francisco, CA
| | - Ian E. McCoy
- Division of Nephrology, University of California, San Francisco School of Medicine, San Francisco, CA
| | - Anna Porter
- Division of Nephrology, University of Illinois Health, Chicago, IL
| | - Panduranga Rao
- Division of Nephrology, University of Michigan Health, Ann Arbor, MI
| | - Ana C. Ricardo
- Division of Nephrology, University of Illinois Health, Chicago, IL
| | | | - James Sondheimer
- Division of Nephrology and Hypertension, Wayne State University School of Medicine, Detroit, MI
| | | | - Mark Unruh
- University of New Mexico Health Sciences, Albuquerque, NM
| | - Chi-yuan Hsu
- Division of Nephrology, University of California, San Francisco School of Medicine, San Francisco, CA
- Division of Research, Kaiser Permanente Northern California, Oakland, CA
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Dutta A, Saha S, Bahl A, Mittal A, Basak T. A comprehensive review of acute cardio-renal syndrome: need for novel biomarkers. Front Pharmacol 2023; 14:1152055. [PMID: 37288107 PMCID: PMC10242013 DOI: 10.3389/fphar.2023.1152055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 05/03/2023] [Indexed: 06/09/2023] Open
Abstract
Cardiorenal syndrome represents a wide-spectrum disorder involving the heart and kidneys as the primary affected organs. India has an increasingly high burden of acute CRS, coinciding with the rise in global statistics. Up to 2022, approximately 46.1% of all cardiorenal patients have been diagnosed with acute CRS in India. Acute CRS involves a sudden deterioration of kidney functionalities, referred to as acute kidney injury (AKI) in acute heart failure patients. The pathophysiology of CRS involves hyperactivation of the sympathetic nervous system (SNS) and the renin-angiotensin-aldosterone system (RAAS) following acute myocardial stress. The pathological phenotype of acute CRS is associated with perturbed inflammatory, cellular, and neurohormonal markers in circulation. These complications increase the risk of mortality in clinically diagnosed acute CRS patients, making it a worldwide healthcare burden. Hence, effective diagnosis and early prevention are crucial to prevent the progression of CRS in AHF patients. Present biomarkers, such as serum creatinine (sCr), cystatin C (CysC), glomerular filtration rate (GFR), blood urea nitrogen (BUN), serum and/or urine neutrophil gelatinase-associated lipocalin (NGAL), B-type natriuretic peptide (BNP), and NT-proBNP, are clinically used to diagnose AKI stages in CRS patients but are limitedly sensitive to the early detection of the pathology. Therefore, the need for protein biomarkers is emerging for early intervention in CRS progression. Here, we summarized the cardio-renal nexus in acute CRS, with an emphasis on the present clinicopathological biomarkers and their limitations. The objective of this review is to highlight the need for novel proteomic biomarkers that will curb the burgeoning concern and direct future research trials.
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Affiliation(s)
- Abhi Dutta
- School of Biosciences and Bioengineering, Indian Institute of Technology (IIT)-Mandi, Mandi, Himachal Pradesh, India
- BioX Center, Indian Institute of Technology (IIT)-Mandi, Mandi, Himachal Pradesh, India
| | - Shubham Saha
- School of Biosciences and Bioengineering, Indian Institute of Technology (IIT)-Mandi, Mandi, Himachal Pradesh, India
- BioX Center, Indian Institute of Technology (IIT)-Mandi, Mandi, Himachal Pradesh, India
| | - Ajay Bahl
- Department of Cardiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Anupam Mittal
- Department of Translational and Regenerative Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Trayambak Basak
- School of Biosciences and Bioengineering, Indian Institute of Technology (IIT)-Mandi, Mandi, Himachal Pradesh, India
- BioX Center, Indian Institute of Technology (IIT)-Mandi, Mandi, Himachal Pradesh, India
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Soraci L, Cherubini A, Paoletti L, Filippelli G, Luciani F, Laganà P, Gambuzza ME, Filicetti E, Corsonello A, Lattanzio F. Safety and Tolerability of Antimicrobial Agents in the Older Patient. Drugs Aging 2023; 40:499-526. [PMID: 36976501 PMCID: PMC10043546 DOI: 10.1007/s40266-023-01019-3] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/27/2023] [Indexed: 03/29/2023]
Abstract
Older patients are at high risk of infections, which often present atypically and are associated with high morbidity and mortality. Antimicrobial treatment in older individuals with infectious diseases represents a clinical challenge, causing an increasing burden on worldwide healthcare systems; immunosenescence and the coexistence of multiple comorbidities determine complex polypharmacy regimens with an increase in drug-drug interactions and spread of multidrug-resistance infections. Aging-induced pharmacokinetic and pharmacodynamic changes can additionally increase the risk of inappropriate drug dosing, with underexposure that is associated with antimicrobial resistance and overexposure that may lead to adverse effects and poor adherence because of low tolerability. These issues need to be considered when starting antimicrobial prescriptions. National and international efforts have been made towards the implementation of antimicrobial stewardship (AMS) interventions to help clinicians improve the appropriateness and safety of antimicrobial prescriptions in both acute and long-term care settings. AMS programs were shown to decrease consumption of antimicrobials and to improve safety in hospitalized patients and older nursing home residents. With the abundance of antimicrobial prescriptions and the recent emergence of multidrug resistant pathogens, an in-depth review of antimicrobial prescriptions in geriatric clinical practice is needed. This review will discuss the special considerations for older individuals needing antimicrobials, including risk factors that shape risk profiles in geriatric populations as well as an evidence-based description of antimicrobial-induced adverse events in this patient population. It will highlight agents of concern for this age group and discuss interventions to mitigate the effects of inappropriate antimicrobial prescribing.
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Affiliation(s)
- Luca Soraci
- Unit of Geriatric Medicine, IRCCS INRCA, 87100, Cosenza, Italy
| | - Antonio Cherubini
- Geriatria, Accettazione geriatrica e Centro di ricerca per l'invecchiamento, IRCCS INRCA, Ancona, Italy
| | - Luca Paoletti
- Geriatria, Accettazione geriatrica e Centro di ricerca per l'invecchiamento, IRCCS INRCA, Ancona, Italy
| | | | - Filippo Luciani
- Infectious Diseases Unit of Annunziata Hospital, Cosenza, Italy
| | - Pasqualina Laganà
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy
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Gallo G, Lanza O, Savoia C. New Insight in Cardiorenal Syndrome: From Biomarkers to Therapy. Int J Mol Sci 2023; 24:5089. [PMID: 36982164 PMCID: PMC10049666 DOI: 10.3390/ijms24065089] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 02/28/2023] [Accepted: 03/02/2023] [Indexed: 03/09/2023] Open
Abstract
Cardiorenal syndrome consists in the coexistence of acute or chronic dysfunction of heart and kidneys resulting in a cascade of feedback mechanisms and causing damage to both organs associated with high morbidity and mortality. In the last few years, different biomarkers have been investigated with the aim to achieve an early and accurate diagnosis of cardiorenal syndrome, to provide a prognostic role and to guide the development of targeted pharmacological and non-pharmacological therapies. In such a context, sodium-glucose cotransporter 2 (SGLT2) inhibitors, recommended as the first-line choice in the management of heart failure, might represent a promising strategy in the management of cardiorenal syndrome due to their efficacy in reducing both cardiac and renal outcomes. In this review, we will discuss the current knowledge on the pathophysiology of cardiorenal syndrome in adults, as well as the utility of biomarkers in cardiac and kidney dysfunction and potential insights into novel therapeutics.
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Affiliation(s)
| | | | - Carmine Savoia
- Clinical and Molecular Medicine Department, Faculty of Medicine and Psychology, Sant’Andrea Hospital, Sapienza University of Rome, 00189 Rome, Italy
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An J, Yu H, Gao Z, Hu X, Wang X. Value of cystatin C in predicting recurrence in patients with severe diabetic foot and diabetic foot ulcer. Biomark Med 2023; 17:287-296. [PMID: 37283546 DOI: 10.2217/bmm-2022-0837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023] Open
Abstract
Objective: Our objective is to investigate the risk factors and predictive ability of severe diabetic foot (DF) and diabetic foot ulcers (DFUs). Patients & methods: The efficacy of cystatin C in predicting the recurrence of DF and DFU was evaluated using a receiver operating characteristic curve. Results: The findings indicate that, in contrast to non-severe patients, severe cases exhibit elevated levels of cystatin C (p < 0.05). Additionally, a statistically significant increase in cystatin C levels was observed in the subgroup of patients with recurrent DFU (p < 0.01). Conclusion: Cystatin C emerged as a significant risk factor for severe DF and recurrent DFU, with the potential for predicting their occurrence.
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Affiliation(s)
- Jingsi An
- Endocrinology Department, Jinzhou Central Hospital, Jinzhou, Liaoning, 121000, China
- Jinzhou Medical University, Jinzhou, Liaoning, 121000, China
| | - Hongwei Yu
- Department of Cardiology, Jinzhou Central Hospital, Jinzhou, Liaoning, 121000, China
| | - Zhenyu Gao
- Department of Nephrology, Jinzhou Central Hospital, Jinzhou, Liaoning, 121000, China
| | - Xiangka Hu
- Jinzhou Medical University, Jinzhou, Liaoning, 121000, China
| | - Xueying Wang
- Endocrinology Department, Jinzhou Central Hospital, Jinzhou, Liaoning, 121000, China
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Wang J, Lu Z, Cai R, Zheng H, Yu J, Zhang Y, Gu Z. Microneedle-based transdermal detection and sensing devices. LAB ON A CHIP 2023; 23:869-887. [PMID: 36629050 DOI: 10.1039/d2lc00790h] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
Microneedles have been expected for the construction of next-generation biosensors towards personalization, digitization, and intellectualization due to their metrics of minimal invasiveness, high integration, and favorable biocompatibility. Herein, an overview of state-of-the-art microneedle-based detection and sensing systems is presented. First, the designs of microneedle devices based on extraction mechanisms are concluded, corresponding to different geometries and materials of microneedles. Second, the targets of equipment-assisted microneedle detections are summarized, as well as the objective significance, revealing the current performance and potential scenarios of these microneedles. Third, the trend towards highly integrated sensors is elaborated by emphasizing the sensing principles (colorimetric, fluorometric and electronic manner). Finally, the key challenges to be tackled and the perspectives on future development are discussed.
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Affiliation(s)
- Junxia Wang
- Zhejiang Provincial Key Laboratory for Advanced Drug Delivery Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
| | - Ziyi Lu
- Zhejiang Provincial Key Laboratory for Advanced Drug Delivery Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China
| | - Ruisi Cai
- Zhejiang Provincial Key Laboratory for Advanced Drug Delivery Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
| | - Hanqi Zheng
- Zhejiang Provincial Key Laboratory for Advanced Drug Delivery Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
| | - Jicheng Yu
- Zhejiang Provincial Key Laboratory for Advanced Drug Delivery Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China
- Jinhua Institute of Zhejiang University, Jinhua, 321299, China
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, 311121, China
| | - Yuqi Zhang
- Zhejiang Provincial Key Laboratory for Advanced Drug Delivery Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
- Department of Burns and Wound Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China
| | - Zhen Gu
- Zhejiang Provincial Key Laboratory for Advanced Drug Delivery Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China
- Jinhua Institute of Zhejiang University, Jinhua, 321299, China
- Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, 311121, China
- MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China
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Gottlieb ER, Estiverne C, Tolan NV, Melanson SE, Mendu ML. Estimated GFR With Cystatin C and Creatinine in Clinical Practice: A Retrospective Cohort Study. Kidney Med 2023; 5:100600. [PMID: 36879723 PMCID: PMC9984886 DOI: 10.1016/j.xkme.2023.100600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Rationale & Objective Estimation of glomerular filtration rate (eGFR) and staging of chronic kidney disease (CKD) are essential to guide management. Although creatinine is routinely used, a recent national task force recommended the use of cystatin C for confirmation. The objective of this study was to examine the following parameters: (1) how cystatin C correlates with creatinine eGFR; (2) how it indicates differences in CKD staging; and (3) how it may affect kidney care delivery. Study Design Retrospective observational cohort study. Setting & Participants 1,783 inpatients and outpatients who had cystatin C and creatinine levels drawn within 24 hours at Brigham Health-affiliated clinical laboratories. Predictors Serum creatinine levels, basic clinical/sociodemographic variables, and reasons for ordering cystatin C from a structured partial chart review. Analytical Approach Univariate and multivariable linear and logistic regression. Results Cystatin C-based eGFR was very strongly correlated with creatinine-based eGFR (Spearman correlation ρ = 0.83). Cystatin C eGFR resulted in a change to a later CKD stage in 27%, an earlier stage in 7%, and no change in 66% of patients. Black race was associated with a lower likelihood of change to a later stage (OR, 0.53; 95% CI [0.36, 0.75]; P < 0.001), whereas age (OR per year OR, 1.03; 95% CI [1.02, 1.04]; P < 0.001) and Elixhauser score (OR per point OR, 1.22; 95% CI [1.10, 1.36]; P < 0.001) were associated with a higher likelihood of change to a later stage. Limitations Single center, no direct measurement of clearance for comparison, and inconsistent self-identification of race/ethnicity. Conclusions Cystatin C eGFR correlates strongly with creatinine eGFR but can have a substantial effect on CKD staging. As cystatin C is adopted, clinicians must be informed on this impact.
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Affiliation(s)
- Eric Raphael Gottlieb
- Department of Medicine, Mount Auburn Hospital, Cambridge, Massachusetts
- Harvard Medical School, Boston, Massachusetts
- Laboratory for Computational Physiology, Massachusetts Institute of Technology, Cambridge, Massachusetts
| | - Christopher Estiverne
- Harvard Medical School, Boston, Massachusetts
- Division of Renal Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
| | - Nicole V. Tolan
- Harvard Medical School, Boston, Massachusetts
- Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts
| | - Stacy E.F. Melanson
- Harvard Medical School, Boston, Massachusetts
- Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts
| | - Mallika L. Mendu
- Harvard Medical School, Boston, Massachusetts
- Division of Renal Medicine, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
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Estimated GFR Accuracy When Cystatin C and Creatinine-Based Estimates Are Discrepant in Older Adults. Kidney Med 2023; 5:100628. [PMID: 37168389 PMCID: PMC10165149 DOI: 10.1016/j.xkme.2023.100628] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/14/2023] Open
Abstract
Rationale & Objective Serum creatinine and cystatin C are used to estimate glomerular filtration rate, but creatinine-based estimated glomerular filtration rate (eGFRcr), cystatin C-based estimated glomerular filtration rate (eGFRcys), and combined creatinine- and cystatin C-based estimated glomerular filtration rate (eGFRcr-cys) are often divergent, particularly in older adults. We investigated which estimated glomerular filtration rate (eGFR) was more accurate and less biased compared with measured glomerular filtration rate (mGFR). Study Design A diagnostic test study from the Berlin Initiative Study. Setting & Participants The study population included 657 individuals aged 70 years or older with iohexol plasma clearance (mGFR) and serum creatinine and cystatin C measurements: 567 community-dwelling participants and 90 with a serum creatinine of ≥1.5 mg/dL. Tests Compared We defined 3 groups on the basis of the difference eGFRcys - eGFRcr: whether < -5 mL/min/1.73 m2 (lower eGFRcys), within 5 mL/min/1.73 m2 (reference), or ≥ 5 mL/min/1.73 m2 (lower eGFRcr). eGFRcr, eGFRcys, and eGFRcr-cys were compared to mGFR to assess bias and accuracy. Outcome Median bias (eGFR minus mGFR) with 95% CIs and accuracy (percentage of eGFR values within ±30% of mGFR). Results The mean ± standard deviation age was 78 ± 6 years; the mean eGFRcys, eGFRcr, and eGFRcr-cys were 59 ± 23, 64 ± 20, and 61 ± 22 mL/min/1.73 m2, respectively, and the mean mGFR was 56 ± 19 mL/min. Half of the participants were in the lower eGFRcys group (n=337, 51%). Among them, the median bias for eGFRcys was the lowest (median bias, -2.7; 95% CI, -3.8 to -1.9) compared with the other eGFR equations. Conversely, in the lower eGFRcr group (n=121, 18%), the median bias for eGFRcr was the lowest compared with those for eGFRcys and eGFRcr-cys (2.9; [95% CI, 0.9-4.8] vs 13.8 [95% CI, 11.4-15.6] and 9.5 [95% CI, 7.7-11.0], respectively). Accuracy (percentage of eGFR values within ±30% of mGFR) was 93% for eGFRcr in the lower eGFRcr group and 92% for eGFRcys and 94% for eGFRcr-cys in the lower eGFRcys group. Limitations Untested generalizability in younger populations. Conclusions Among older adults, the lower eGFR between eGFRcys and eGFRcr was a more accurate and less biased estimate of mGFR when comparing the groups.
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