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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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Bender BF, Berry JA. Trends in Passive IoT Biomarker Monitoring and Machine Learning for Cardiovascular Disease Management in the U.S. Elderly Population. ADVANCES IN GERIATRIC MEDICINE AND RESEARCH 2023; 5:e230002. [PMID: 37274061 PMCID: PMC10237513 DOI: 10.20900/agmr20230002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
It is predicted that the growth in the U.S. elderly population alongside continued growth in chronic disease prevalence will further strain an already overburdened healthcare system and could compromise the delivery of equitable care. Current trends in technology are demonstrating successful application of artificial intelligence (AI) and machine learning (ML) to biomarkers of cardiovascular disease (CVD) using longitudinal data collected passively from internet-of-things (IoT) platforms deployed among the elderly population. These systems are growing in sophistication and deployed across evermore use-cases, presenting new opportunities and challenges for innovators and caregivers alike. IoT sensor development that incorporates greater levels of passivity will increase the likelihood of continued growth in device adoption among the geriatric population for longitudinal health data collection which will benefit a variety of CVD applications. This growth in IoT sensor development and longitudinal data acquisition is paralleled by the growth in ML approaches that continue to provide promising avenues for better geriatric care through higher personalization, more real-time feedback, and prognostic insights that may help prevent downstream complications and relieve strain on the healthcare system overall. However, findings that identify differences in longitudinal biomarker interpretations between elderly populations and relatively younger populations highlights the necessity that ML approaches that use data from newly developed passive IoT systems should collect more data on this target population and more clinical trials will help elucidate the extent of benefits and risks from these data driven approaches to remote care.
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Affiliation(s)
| | - Jasmine A. Berry
- Robotics Institute, University of Michigan, College of Engineering, Ann Arbor, MI 48109, USA
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Zheng T, Tang AM, Huang YL, Chen J. Non-linear association of cystatin C and all-cause mortality of heart failure: A secondary analysis based on a published database. Front Cardiovasc Med 2022; 9:930498. [PMID: 36148067 PMCID: PMC9488665 DOI: 10.3389/fcvm.2022.930498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 08/08/2022] [Indexed: 11/30/2022] Open
Abstract
Background Prior reports have revealed that basal Cystatin-C (CysC) is positively associated with all-cause death in patients with heart failure (HF). Yet, this positive association is not necessarily generalizable to Chinese HF patients due to methodological limitations and lack of data from Chinese patients. Materials and methods We performed secondary data mining based on a retrospective cohort dataset published on the internet. This dataset contains 2008 patients with HF who were admitted to a tertiary hospital in Sichuan Province, China from 2016 to 2019. The exposure variable was baseline CysC and the outcome variable was all-cause death on day 28, day 90, and month 6. Covariates were baseline measurements, including demographic data, drug use, comorbidity score, organ function status (heart, kidney), and severity of heart failure. Results Among 1966 selected participants, the mortality rates at 28 days, 90 days and 6 months were 1.83% (36/1966), 2.09% (41/1966) and 2.85% (56/1966) respectively. After adjustment for confounders, the non-linear associations between CysC and all-cause deaths were observed. We calculated the inflection points were about 2.5 mg/L of CysC. On the right of inflection point, each increase of 1 mg/L in CysC was associated with an increase in the risk of 28-day mortality (Relative risk [RR], 2.07; 95% confidence interval [CI], 1.09 to 3.93; P = 0.0266), 90-day mortality (RR, 2.51; 95% CI, 1.38 to 4.57; P = 0.003), and 6-month mortality (RR,2.25; 95% CI, 1.37 to 3.70; P < 0.001). Conclusion Our findings suggest that values about 2.5 mg/l of cystatin could be a danger threshold for the short-term risk of death in heart failure. Exceeding this threshold, for every 1 mg/L increase in CysC, the risk of all-cause mortality increased by more than one time.
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Affiliation(s)
- Tao Zheng
- Department of Cardiology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - A-Mei Tang
- Department of Cardiology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - Yuan-Lei Huang
- Department of Cardiology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - Jin Chen
- Department of Cardiology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
- *Correspondence: Jin Chen,
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Tariq H, Ramakrishnan M, Gupta A. Insights into Cognitive Brain Health in Chronic Kidney Disease. GERONTOLOGY & GERIATRICS : RESEARCH 2022; 8:1074. [PMID: 37671071 PMCID: PMC10478617 DOI: 10.26420/gerontolgeriatrres.2022.1074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/07/2023]
Abstract
Cognitive impairment and Chronic Kidney Disease (CKD) are common in older adults. With advances in medicine, the average lifespan is expected to increase, further increasing the prevalence of both conditions. The mechanisms underlying cognitive impairment in CKD are unclear. While mild-moderately low estimated glomerular filtration rate (eGFR) may not be associated with cognitive impairment, severely decreased eGFR and albuminuria do. Patients on dialysis have a high prevalence of cognitive impairment. Cognitive function improves after kidney transplantation. However, some residual cognitive deficits persist after transplantation, indicating that restoring the kidney function alone may not be enough to restore cognitive function, and other etiological factors may play a role. Albuminuria, another marker of CKD is also associated with cognitive impairment. However, albuminuria is often undiagnosed. Improving early identification and management of patients with albuminuria may be a good population-based dementia prevention strategy. Other factors associated with cognitive impairment in CKD include anemia and other metabolic derangements commonly observed in CKD. In this article, we reviewed the prevalence of cognitive impairment in CKD, the potential mechanisms underlying cognitive impairment in CKD, andthecurrent evidence on the association between cognitive impairment and eGFR and albuminuria.
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Affiliation(s)
- H Tariq
- Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, USA
| | - M Ramakrishnan
- Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, USA
| | - A Gupta
- Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, USA
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Obert LA, Elmore SA, Ennulat D, Frazier KS. A Review of Specific Biomarkers of Chronic Renal Injury and Their Potential Application in Nonclinical Safety Assessment Studies. Toxicol Pathol 2021; 49:996-1023. [PMID: 33576319 DOI: 10.1177/0192623320985045] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
A host of novel renal biomarkers have been developed over the past few decades which have enhanced monitoring of renal disease and drug-induced kidney injury in both preclinical studies and in humans. Since chronic kidney disease (CKD) and acute kidney injury (AKI) share similar underlying mechanisms and the tubulointerstitial compartment has a functional role in the progression of CKD, urinary biomarkers of AKI may provide predictive information in chronic renal disease. Numerous studies have explored whether the recent AKI biomarkers could improve upon the standard clinical biomarkers, estimated glomerular filtration rate (eGFR), and urinary albumin to creatinine ratio, for predicting outcomes in CKD patients. This review is an introduction to alternative assays that can be utilized in chronic (>3 months duration) nonclinical safety studies to provide information on renal dysfunction and to demonstrate specific situations where these assays could be utilized in nonclinical drug development. Novel biomarkers such as symmetrical dimethyl arginine, dickkopf homolog 3, and cystatin C predict chronic renal injury in animals, act as surrogates for GFR, and may predict changes in GFR in patients over time, ultimately providing a bridge from preclinical to clinical renal monitoring.
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Affiliation(s)
- Leslie A Obert
- 549350GlaxoSmithKline (GSK), Nonclinical Safety, Collegeville, PA, USA
| | - Susan A Elmore
- Cellular and Molecular Pathology Branch, National Toxicology Program (NTP), 6857National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA
| | - Daniela Ennulat
- 549350GlaxoSmithKline (GSK), Nonclinical Safety, Collegeville, PA, USA
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Bidin MZ, Shah AM, Stanslas J, Seong CLT. Blood and urine biomarkers in chronic kidney disease: An update. Clin Chim Acta 2019; 495:239-250. [PMID: 31009602 DOI: 10.1016/j.cca.2019.04.069] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Revised: 04/17/2019] [Accepted: 04/17/2019] [Indexed: 01/11/2023]
Abstract
INTRODUCTION Chronic kidney disease (CKD) is a silent disease. Most CKD patients are unaware of their condition during the early stages of the disease which poses a challenge for healthcare professionals to institute treatment or start prevention. The trouble with the diagnosis of CKD is that in most parts of the world, it is still diagnosed based on measurements of serum creatinine and corresponding calculations of eGFR. There are controversies with the current staging system, especially in the methodology to diagnose and prognosticate CKD. OBJECTIVE The aim of this review is to examine studies that focused on the different types of samples which may serve as a good and promising biomarker for early diagnosis of CKD or to detect rapidly declining renal function among CKD patient. METHOD The review of international literature was made on paper and electronic databases Nature, PubMed, Springer Link and Science Direct. The Scopus index was used to verify the scientific relevance of the papers. Publications were selected based on the inclusion and exclusion criteria. RESULT 63 publications were found to be compatible with the study objectives. Several biomarkers of interest with different sample types were taken for comparison. CONCLUSION Biomarkers from urine samples yield more significant outcome as compare to biomarkers from blood samples. But, validation and confirmation with a different type of study designed on a larger population is needed. More comparison studies on different types of samples are needed to further illuminate which biomarker is the better tool for the diagnosis and prognosis of CKD.
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Affiliation(s)
- Mohammad Zulkarnain Bidin
- Nephrology Unit, Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
| | - Anim Md Shah
- Nephrology Unit, Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; Nephrology Department, Serdang Hospital, Selangor, Malaysia
| | - J Stanslas
- Pharmacotherapeutics Unit, Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia
| | - Christopher Lim Thiam Seong
- Nephrology Unit, Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; Nephrology Department, Serdang Hospital, Selangor, Malaysia.
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Cystatin C for predicting all-cause mortality and rehospitalization in patients with heart failure: a meta-analysis. Biosci Rep 2019; 39:BSR20181761. [PMID: 30643006 PMCID: PMC6361773 DOI: 10.1042/bsr20181761] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Revised: 11/09/2018] [Accepted: 11/27/2018] [Indexed: 12/23/2022] Open
Abstract
Circulating cystatin C (cys-C/CYC) has been identified as an independent predictor of all-cause mortality in patients with coronary artery disease and the general population. This meta-analysis aimed to systematically evaluate the association between elevated cys-C level and all-cause mortality and rehospitalization risk amongst patients with heart failure (HF). PubMed and Embase databases were searched until December 2017. All prospective observational studies that reported a multivariate-adjusted risk estimate of all-cause mortality and/or rehospitalization for the highest compared with lowest cys-C level in HF patients were included. Ten prospective studies involving 3155 HF patients were included. Meta-analysis indicated that the highest compared with lowest cys-C level was associated with an increased risk of all-cause mortality (hazard ratio (HR): 2.33; 95% confidence intervals (CI): 1.67-3.27; I2 = 75.0%, P<0.001) and combination of mortality/rehospitalization (HR: 2.06; 95%CI: 1.58-2.69; I2 = 41.6%, P=0.181). Results of stratified analysis indicated that the all-cause mortality risk was consistently found in the follow-up duration, cys-C cut-off value or type of HF subgroup. Elevated cys-C level is possibly associated with an increased risk of all-cause mortality and rehospitalization in HF patients. This increased risk is probably independent of creatinine or estimated glomerular filtration rate (eGFR).
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Karger AB, Inker LA, Coresh J, Levey AS, Eckfeldt JH. Novel Filtration Markers for GFR Estimation. EJIFCC 2017; 28:277-288. [PMID: 29333147 PMCID: PMC5746837] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Abstract
Creatinine-based glomerular filtration rate estimation (eGFRcr) has been improved and refined since the 1970s through both the Modification of Diet in Renal Disease (MDRD) Study equation in 1999 and the CKD Epidemiology Collaboration (CKD-EPI) equation in 2009, with current clinical practice dependent primarily on eGFR for accurate assessment of GFR. However, researchers and clinicians have recognized limitations of relying on creatinine as the only filtration marker, which can lead to inaccurate GFR estimates in certain populations due to the influence of non-GFR determinants of serum or plasma creatinine. Therefore, recent literature has proposed incorporation of multiple serum or plasma filtration markers into GFR estimation to improve precision and accuracy and decrease the impact of non-GFR determinants for any individual biomarker. To this end, the CKD-EPI combined creatinine-cystatin C equation (eGFRcr-cys) was developed in 2012 and demonstrated superior accuracy to equations relying on creatinine or cystatin C alone (eGFRcr or eGFRcys). Now, the focus has broadened to include additional novel filtration markers to further refine and improve GFR estimation. Beta-2-microglobulin (B2M) and beta-trace-protein (BTP) are two filtration markers with established assays that have been proposed as candidates for improving both GFR estimation and risk prediction. GFR estimating equations based on B2M and BTP have been developed and validated, with the CKD-EPI combined BTP-B2M equation (eGFRBTP-B2M) demonstrating similar performance to eGFR and eGFR. Additionally, several studies have demonstrated that both B2M and BTP are associated with outcomes in CKD patients, including cardiovascular events, ESRD and mortality. This review will primarily focus on these two biomarkers, and will highlight efforts to identify additional candidate biomarkers through metabolomics-based approaches.
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Affiliation(s)
- Amy B. Karger
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA,Department of Laboratory Medicine and Pathology University of Minnesota 420 Delaware St SE MMC 609, Minneapolis, MN 55455 United States of America
| | - Lesley A. Inker
- William B. Schwartz Division of Nephrology, Tufts Medical Center, Department of Medicine, Tufts University School of Medicine, Boston, MA, USA
| | - Josef Coresh
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | - Andrew S. Levey
- William B. Schwartz Division of Nephrology, Tufts Medical Center, Department of Medicine, Tufts University School of Medicine, Boston, MA, USA
| | - John H. Eckfeldt
- Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
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Predictive value of cystatin C in people with suspected or established coronary artery disease: A meta-analysis. Atherosclerosis 2017; 263:60-67. [PMID: 28599259 DOI: 10.1016/j.atherosclerosis.2017.05.025] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2017] [Revised: 04/28/2017] [Accepted: 05/18/2017] [Indexed: 11/21/2022]
Abstract
BACKGROUND AND AIMS Circulating cystatin C has been recognized as an independent predictor of cardiovascular and all-cause mortality in the general population. We aimed to evaluate the prognostic value of baseline circulating cystatin C levels in people with suspected or established coronary artery disease (CAD) by conducting a meta-analysis. METHODS We searched Pubmed and Embase databases up to October 2016 for prospective observational studies investigating the predictive value of elevated circulating cystatin C levels in people with suspected or established CAD. Adverse vascular outcomes included all-cause mortality, cardiovascular mortality, or total adverse vascular events consisting of death, myocardial infarction, revascularization, stroke, and heart failure. RESULTS Ten studies involving participants with known or suspected CAD were included in this meta-analysis. When comparing the highest with the lowest cystatin C levels, the pooled hazard ratio (HR) was 2.27 (95% confidence interval [CI] 1.86-2.78) for all-cause mortality, 2.24 (95% CI 1.69-2.97) for cardiovascular mortality, and 1.87 (95% CI 1.57-2.24) for total adverse vascular events, respectively. Subgroup analysis results showed that this association was not influenced by follow-up duration, region, or CAD type. CONCLUSIONS Elevated circulating cystatin C is independently associated with adverse vascular outcomes in people with suspected or established CAD in terms of all-cause mortality, cardiovascular mortality, and total adverse vascular events. This increased risk is probably independent of creatinine/estimated glomerular filtration rate.
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Kwon YE, Lee MJ, Park KS, Han SH, Yoo TH, Oh KH, Lee J, Lee KB, Chung W, Kim YH, Ahn C, Choi KH. Cystatin C is Better than Serum Creatinine for Estimating Glomerular Filtration Rate to Detect Osteopenia in Chronic Kidney Disease Patients. Yonsei Med J 2017; 58:380-387. [PMID: 28120569 PMCID: PMC5290018 DOI: 10.3349/ymj.2017.58.2.380] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Revised: 08/30/2016] [Accepted: 09/13/2016] [Indexed: 11/27/2022] Open
Abstract
PURPOSE Recent studies have reported that loss of bone mass is associated with renal function decline and increased fracture risks in chronic kidney disease (CKD) patients. The aim of this study was to investigate the best estimated glomerular filtration rate (eGFR) equation to detect osteopenia in CKD patients. MATERIALS AND METHODS This was a cross-sectional study, and 780 patients aged 50 years or above were classified into normal bone mass or osteopenia groups according to the -1.0 of T-scores at total hip and femur neck. Comparisons of area under the receiver operating characteristic (ROC) curves (AUC) were performed to investigate significant differences among three eGFR formulas: Modification of Diet in Renal Disease, CKD-Epidemiology Collaboration (EPI) creatinine, and CKD-EPI cystatin C (CKD-EPI-Cys). RESULTS The mean age was 61 years old and the proportion of females was 37.3%. The total hip osteopenia group showed lower CKD-EPI-Cys eGFR levels (osteopenia group, 33.3±19.0 mL/min/1.73 m²; normal group, 48.1±26.2 mL/min/1.73 m², p<0.001). In multiple logistic regression analysis, CKD-EPI-Cys eGFR was independently associated with osteopenia at the total hip (per 1 mL/min/1.73 m² increase, odds ratio 0.98, 95% confidence interval 0.97-0.99, p=0.004) after adjusting for confounding variables. ROC curve analyses indicated that CKD-EPI-Cys shows the largest AUC for osteopenia at the total hip (AUC=0.678, all p<0.01) and the femur neck (AUC=0.665, all p<0.05). CONCLUSION Decreased renal function assessed by CKD-EPI-Cys equation correlates with osteopenia better than creatinine-based methods in CKD patients, and the CKD-EPI-Cys formula might be a useful tool to assess skeletal-related event risks.
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Affiliation(s)
- Young Eun Kwon
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Mi Jung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Kyoung Sook Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Seung Hyeok Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Tae Hyun Yoo
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Kook Hwan Oh
- Department of Internal Medicine, Seoul National University, Seoul, Korea
| | - Joongyub Lee
- Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Korea
| | - Kyu Beck Lee
- Department of Internal Medicine, Kangbuck Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Wookyung Chung
- Division of Nephrology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea
| | - Yeong Hoon Kim
- Department of Nephrology, College of Medicine, Inje University, Busan, Korea
| | - Curie Ahn
- Department of Internal Medicine, Seoul National University, Seoul, Korea
| | - Kyu Hun Choi
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
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Verdelli C, Corbetta S. MECHANISMS IN ENDOCRINOLOGY: Kidney involvement in patients with primary hyperparathyroidism: an update on clinical and molecular aspects. Eur J Endocrinol 2017; 176:R39-R52. [PMID: 27601015 DOI: 10.1530/eje-16-0430] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2016] [Revised: 08/12/2016] [Accepted: 09/02/2016] [Indexed: 12/27/2022]
Abstract
Primary hyperparathyroidism (PHPT) is the third most common endocrine disease. Kidney is a target of both chronic elevated PTH and calcium in PHPT. The classic PHPT complications of symptomatic kidney stones and nephrocalcinosis have become rare and the PHPT current presentation is asymptomatic with uncertain and long-lasting progression. Nonetheless, the routine use of imaging and of biochemical determinations have revealed the frequent occurrence of asymptomatic kidney stones, hypercalciuria and reduced kidney function in asymptomatic PHPT patients. Though the pathogenesis is far from being elucidated, PHPT is associated with reduced renal function, in terms of estimated glomerular filtration rate, and related increased morbidity and mortality. In the last decade, the effort of the Kidney Disease: Improving Global Outcomes (KDIGO) panel of experts highlighted that even mild reduction of kidney function is associated with increased risk of cardiovascular disease. These considerations provided the basis for the Fourth Workshop recommendations of a more extensive diagnostic workout about kidney features and of wider criteria for parathyroid surgery including asymptomatic kidney disease. Moreover, kidney involvement in PHPT is likely to be affected by variants of genes coding the key molecules regulating the calcium and ions renal handling; these features might have clinical relevance and should be considered both during diagnostic workout and follow-up. Finally, the effects of parathyroid surgery and of medical treatment on kidney involvement of PHPT are reviewed.
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Affiliation(s)
- C Verdelli
- Laboratory of Experimental EndocrinologyIRCCS Istituto Ortopedico Galeazzi, Milan, Italy
| | - S Corbetta
- Laboratory of Experimental EndocrinologyIRCCS Istituto Ortopedico Galeazzi, Milan, Italy
- Endocrinology ServiceDepartment of Biomedical Sciences for Health, University of Milan, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
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12
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Ermetici F, Filopanti M, Verga U, Passeri E, Dito G, Malavazos AE, Mapelli C, Raggi ME, Spada A, Corbetta S. Estimated glomerular filtration rate by serum cystatin C correlates with cardiometabolic parameters in patients with primary hyperparathyroidism. Eur J Endocrinol 2015; 173:441-6. [PMID: 26194503 DOI: 10.1530/eje-15-0341] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2015] [Accepted: 07/20/2015] [Indexed: 01/05/2023]
Abstract
OBJECTIVE Patients with primary hyperparathyroidism (PHPT) are at risk of chronic kidney disease (CKD). Cystatin C (Cys-C) is considered a more reliable tool to assess glomerular filtration rate (GFR) than creatinine. The study aimed to assess circulating Cys-C and its relationships with biochemical PHPT and cardiometabolic parameters. DESIGN AND METHODS The present cross-sectional study was performed in academic endocrine units on PHPT patients (n=190) and non-hypertensive, non-diabetic, age- and sex-matched healthy controls (n=135) with no established CKD. The main outcomes were creatinine by alkaline picrate method, Cys-C by immunonephelometry and calculation of estimated GFR based on creatinine and Cys-C (eGFRcr-cys) using the CKD-EPI equation. RESULTS In PHPT patients, circulating Cys-C ranged 0.45-3.13 mg/l and correlated with creatinine, age and BMI. Mean Cys-C level was higher in PHPT patients than in controls (0.93±0.02 vs 0.78±0.14 mg/l; P=0.03). Cys-C levels in PHPT patients were predicted by age, BMI, ionized calcium, hypertension and HDL-cholesterol, the most significant determinant being ionized calcium. Cys-C positively correlated with cardiovascular disease (CVD) occurrence. Overall, 18.4% of PHPT patients with eGFRcr >60 ml/min per 1.73 m(2) (n=169) had Cys-C levels higher than the 95th percentile in controls (1.03 mg/l), consistent with a preclinical CKD, which was associated with hypertension and insulin resistance. Considering eGFRcr-cys, CKD (stages G3a, G3b, 4) was diagnosed in 13.7% of PHPT patients. Estimated GFRcr-cys, but not eGFR based on creatinine, was predicted by insulin resistance and hypertension and positively correlated with CVD. CONCLUSIONS Elevated Cys-C levels were associated with ionized calcium, cardiometabolic risk factors and CVD, and identified preclinical CKD in PHPT patients.
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Affiliation(s)
- Federica Ermetici
- Diabetology and Metabolic Disease UnitIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyEndocrine and Diabetology UnitFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Milan, ItalyEndocrinology UnitIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyClinical Pathology LaboratoryIRCCS E. Medea, Bosisio Parini, Lecco, ItalyEndocrine and Diabetology UnitDepartment of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Milan, ItalyEndocrinology UnitDepartment of Biomedical Sciences for Health, University of Milan, IRCCS Policlinico San Donato, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy
| | - Marcello Filopanti
- Diabetology and Metabolic Disease UnitIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyEndocrine and Diabetology UnitFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Milan, ItalyEndocrinology UnitIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyClinical Pathology LaboratoryIRCCS E. Medea, Bosisio Parini, Lecco, ItalyEndocrine and Diabetology UnitDepartment of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Milan, ItalyEndocrinology UnitDepartment of Biomedical Sciences for Health, University of Milan, IRCCS Policlinico San Donato, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy
| | - Uberta Verga
- Diabetology and Metabolic Disease UnitIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyEndocrine and Diabetology UnitFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Milan, ItalyEndocrinology UnitIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyClinical Pathology LaboratoryIRCCS E. Medea, Bosisio Parini, Lecco, ItalyEndocrine and Diabetology UnitDepartment of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Milan, ItalyEndocrinology UnitDepartment of Biomedical Sciences for Health, University of Milan, IRCCS Policlinico San Donato, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy
| | - Elena Passeri
- Diabetology and Metabolic Disease UnitIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyEndocrine and Diabetology UnitFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Milan, ItalyEndocrinology UnitIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyClinical Pathology LaboratoryIRCCS E. Medea, Bosisio Parini, Lecco, ItalyEndocrine and Diabetology UnitDepartment of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Milan, ItalyEndocrinology UnitDepartment of Biomedical Sciences for Health, University of Milan, IRCCS Policlinico San Donato, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy
| | - Giorgia Dito
- Diabetology and Metabolic Disease UnitIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyEndocrine and Diabetology UnitFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Milan, ItalyEndocrinology UnitIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyClinical Pathology LaboratoryIRCCS E. Medea, Bosisio Parini, Lecco, ItalyEndocrine and Diabetology UnitDepartment of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Milan, ItalyEndocrinology UnitDepartment of Biomedical Sciences for Health, University of Milan, IRCCS Policlinico San Donato, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy
| | - Alexis Elias Malavazos
- Diabetology and Metabolic Disease UnitIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyEndocrine and Diabetology UnitFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Milan, ItalyEndocrinology UnitIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyClinical Pathology LaboratoryIRCCS E. Medea, Bosisio Parini, Lecco, ItalyEndocrine and Diabetology UnitDepartment of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Milan, ItalyEndocrinology UnitDepartment of Biomedical Sciences for Health, University of Milan, IRCCS Policlinico San Donato, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy
| | - Chiara Mapelli
- Diabetology and Metabolic Disease UnitIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyEndocrine and Diabetology UnitFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Milan, ItalyEndocrinology UnitIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyClinical Pathology LaboratoryIRCCS E. Medea, Bosisio Parini, Lecco, ItalyEndocrine and Diabetology UnitDepartment of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Milan, ItalyEndocrinology UnitDepartment of Biomedical Sciences for Health, University of Milan, IRCCS Policlinico San Donato, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy
| | - Maria Elisabetta Raggi
- Diabetology and Metabolic Disease UnitIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyEndocrine and Diabetology UnitFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Milan, ItalyEndocrinology UnitIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyClinical Pathology LaboratoryIRCCS E. Medea, Bosisio Parini, Lecco, ItalyEndocrine and Diabetology UnitDepartment of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Milan, ItalyEndocrinology UnitDepartment of Biomedical Sciences for Health, University of Milan, IRCCS Policlinico San Donato, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy
| | - Anna Spada
- Diabetology and Metabolic Disease UnitIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyEndocrine and Diabetology UnitFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Milan, ItalyEndocrinology UnitIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyClinical Pathology LaboratoryIRCCS E. Medea, Bosisio Parini, Lecco, ItalyEndocrine and Diabetology UnitDepartment of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Milan, ItalyEndocrinology UnitDepartment of Biomedical Sciences for Health, University of Milan, IRCCS Policlinico San Donato, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy
| | - Sabrina Corbetta
- Diabetology and Metabolic Disease UnitIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyEndocrine and Diabetology UnitFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Milan, ItalyEndocrinology UnitIRCCS Policlinico San Donato, San Donato Milanese, Milan, ItalyClinical Pathology LaboratoryIRCCS E. Medea, Bosisio Parini, Lecco, ItalyEndocrine and Diabetology UnitDepartment of Clinical Sciences and Community Health, University of Milan, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Milan, ItalyEndocrinology UnitDepartment of Biomedical Sciences for Health, University of Milan, IRCCS Policlinico San Donato, Via Morandi 30, 20097 San Donato Milanese, Milan, Italy
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Riverol M, Becker JT, López OL, Raji CA, Thompson PM, Carmichael OT, Gach HM, Longstreth WT, Fried L, Tracy RP, Kuller LH. Relationship between Systemic and Cerebral Vascular Disease and Brain Structure Integrity in Normal Elderly Individuals. J Alzheimers Dis 2015; 44:319-28. [PMID: 25213770 DOI: 10.3233/jad-141077] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Cerebral white matter lesions (WMLs) are considered a reflection of cerebral and systemic small vessel disease (SVD), and are associated with reductions in brain volume. Like the brain, the kidney is also sensitive to factors that affect vasculature. Glomerular dysfunction due to renal vascular damage can be measured with different biochemical parameters, such as creatinine or cystatin C, although cystatin C is considered to be more accurate than creatinine in the elderly. The purpose of the study was to determine whether manifestations of SVD in the kidney can predict SVD-based damage to the brain. We examined the relationship between glomerular dysfunction as a measure of SVD on WMLs, gray matter (GM) volume, and cognition in 735 cognitively normal participants from the Cardiovascular Health Study Cognition Study. The multivariate analyses controlled for demographic characteristics, hypertension, heart disease, diabetes, Apolipoprotein 4 allele, C reactive protein, lipids, physical activity, smoking, and body mass index (BMI). Elevated cystatin C levels were associated with lower neuropsychological test scores, the presence of MRI-identified brain infarcts, the severity of WMLs, and GM atrophy five years later. In adjusted models, GM volume was significantly associated with cystatin-C only until BMI and severity of WMLs were added to the model, meaning that the effect of SVD on GM volume is mediated by these two variables. These findings suggest that age-related SVD is a process that leads to altered brain structure, and creates a vulnerability state for cognitive decline.
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Affiliation(s)
- Mario Riverol
- Department of Neurology, University of Navarra, Pamplona, Spain Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA
| | - James T Becker
- Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Oscar L López
- Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Cyrus A Raji
- Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA
| | - Paul M Thompson
- Laboratory of Neuro Imaging, UCLA School of Medicine, Los Angeles, CA, USA
| | - Owen T Carmichael
- Department of Neurology, University of California Davis, Davis, CA, USA
| | - H Michael Gach
- Department of Radiology, University of Pittsburgh, Pittsburgh, PA, USA Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA
| | - William T Longstreth
- Departments of Neurology and Epidemiology, University of Washington, Seattle, WA, USA
| | - Linda Fried
- Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA Renal Section, VA Pittsburgh Medical Center, Pittsburgh, PA, USA
| | | | - Lewis H Kuller
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA
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Luo J, Wang LP, Hu HF, Zhang L, Li YL, Ai LM, Mu HY, Kun-Wang. Cystatin C and cardiovascular or all-cause mortality risk in the general population: A meta-analysis. Clin Chim Acta 2015; 450:39-45. [PMID: 26192218 DOI: 10.1016/j.cca.2015.07.016] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2015] [Revised: 07/10/2015] [Accepted: 07/16/2015] [Indexed: 11/25/2022]
Abstract
BACKGROUND Elevated cystatin C level was associated with excessive risk of cardiovascular events and mortality in the highly cardiovascular risk populations. We conducted this meta-analysis to investigate the relationship between serum cystatin C level and cardiovascular or all-cause mortality risk in the general population. METHODS We searched for all relevant studies published through May 2015 using PubMed, Embase, and Cochrane Library. Prospective studies that assessed the relationship between serum cystatin C level and cardiovascular or all-cause mortality risk in the general population were selected. Pooled adjust hazard risk (HR) and the corresponding 95% confidence intervals (CI) were calculated for continuous and category of cystatin C level. RESULTS Nine studies composed of 38,854 participants were analyzed. Elevated serum cystatin C level was associated with excessive risk of all-cause mortality (HR 1.72; 95% CI 1.37-2.16) and cardiovascular mortality (HR 2.74; 95% CI 2.04-3.68) comparing the highest to lowest category of cystatin C. Each standard deviation increment in serum cystatin C level increased 32% all-cause (HR 1.32; 95% CI 1.12-1.55) and 57% cardiovascular mortality (HR 1.57; 95% CI 1.31-1.88) risk. CONCLUSIONS Elevated serum cystatin C level is independently associated with excessive cardiovascular and all-cause mortality risk in elderly persons.
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Affiliation(s)
- Jian Luo
- Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi 830000, China
| | - Ling-Peng Wang
- Department of Internal Medicine (VIP) of The First Affiliated Hospital, Xinjiang Medical University, Urumqi 830000, China
| | - Hai-Feng Hu
- Department of Heart and Renal of The Sixth People's Hospital in Xinjiang Uygur Autonomous Region, Urumqi 830000, China
| | - Li Zhang
- Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi 830000, China
| | - Ya-Li Li
- Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi 830000, China
| | - Li-Man Ai
- Department of Internal Medicine (VIP) of The First Affiliated Hospital, Xinjiang Medical University, Urumqi 830000, China
| | - Hu-Yati Mu
- Department of Internal Medicine (VIP) of The First Affiliated Hospital, Xinjiang Medical University, Urumqi 830000, China.
| | - Kun-Wang
- Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi 830000, China.
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Lopez-Giacoman S, Madero M. Biomarkers in chronic kidney disease, from kidney function to kidney damage. World J Nephrol 2015; 4:57-73. [PMID: 25664247 PMCID: PMC4317628 DOI: 10.5527/wjn.v4.i1.57] [Citation(s) in RCA: 212] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2014] [Revised: 10/21/2014] [Accepted: 11/10/2014] [Indexed: 02/06/2023] Open
Abstract
Chronic kidney disease (CKD) typically evolves over many years, with a long latent period when the disease is clinically silent and therefore diagnosis, evaluation and treatment is based mainly on biomarkers that assess kidney function. Glomerular filtration rate (GFR) remains the ideal marker of kidney function. Unfortunately measuring GFR is time consuming and therefore GFR is usually estimated from equations that take into account endogenous filtration markers like serum creatinine (SCr) and cystatin C (CysC). Other biomarkers such as albuminuria may precede kidney function decline and have demonstrated to have strong associations with disease progression and outcomes. New potential biomarkers have arisen with the promise of detecting kidney damage prior to the currently used markers. The aim of this review is to discuss the utility of the GFR estimating equations and biomarkers in CKD and the different clinical settings where these should be applied. The CKD-Epidemiology Collaboration equation performs better than the modification of diet in renal disease equation, especially at GFR above 60 mL/min per 1.73 m2. Equations combining CysC and SCr perform better than the equations using either CysC or SCr alone and are recommended in situations where CKD needs to be confirmed. Combining creatinine, CysC and urine albumin to creatinine ratio improves risk stratification for kidney disease progression and mortality. Kidney injury molecule and neutrophil gelatinase-associated lipocalin are considered reasonable biomarkers in urine and plasma to determine severity and prognosis of CKD.
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Ho LC, Sung JM, Tsai YS, Wang HH, Li YC, Chen YT, Chang MY, Hung SY. Cystatin C as a Predictor for Outcomes in Patients with Negligible Renal Function. Blood Purif 2014; 38:81-8. [DOI: 10.1159/000365837] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2014] [Accepted: 07/08/2014] [Indexed: 11/19/2022]
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Comparison of CKD-EPI Cystatin C and Creatinine Glomerular Filtration Rate Estimation Equations in Asian Indians. Int J Nephrol 2014; 2014:746497. [PMID: 24868463 PMCID: PMC4020461 DOI: 10.1155/2014/746497] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2014] [Accepted: 03/11/2014] [Indexed: 11/18/2022] Open
Abstract
Background. Chronic kidney disease (CKD) is identified in the general population using estimated glomerular filtration rates (eGFR) calculated from a serum creatinine-based equation, the chronic kidney disease-epidemiology collaboration (CKD-EPI) equation. Using serum cystatin C in combination may improve eGFR accuracy. We evaluated the new CKD-EPI equations incorporating cystatin C in a population of Asian Indians in classifying CKD across body mass index, diabetes, and hypertension status. Methods. We retrieved standardized serum creatinine and serum cystatin C data from a cohort of 2877 Asian Indians aged 40–80 years from the Singapore Indian Eye Study and calculated eGFR (in mL/min/1.73 m2) with the new CKD-EPI equations and serum creatinine only equation. Results. The creatinine only equation mean eGFR (88 ± 17) was similar to using spline Log cystatin C (88 ± 22). The lowest mean eGFR (81 ± 21) was obtained with the spline Log cystatin C—age, sex, and weight equation. The creatinine only equation had the fewest participants (7.1%) with eGFR <60 and spline Log cystatin C—age, sex, and weight equation had the most (16.1%). Conclusions. Using serum cystatin C resulted in widely varying eGFR which significantly affected the classification of chronic kidney disease.
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Comparison of CKD-EPI Cystatin C and Creatinine Glomerular Filtration Rate Estimation Equations in Asian Indians. Int J Nephrol 2014. [PMID: 24868463 DOI: 10.1155/746497] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background. Chronic kidney disease (CKD) is identified in the general population using estimated glomerular filtration rates (eGFR) calculated from a serum creatinine-based equation, the chronic kidney disease-epidemiology collaboration (CKD-EPI) equation. Using serum cystatin C in combination may improve eGFR accuracy. We evaluated the new CKD-EPI equations incorporating cystatin C in a population of Asian Indians in classifying CKD across body mass index, diabetes, and hypertension status. Methods. We retrieved standardized serum creatinine and serum cystatin C data from a cohort of 2877 Asian Indians aged 40-80 years from the Singapore Indian Eye Study and calculated eGFR (in mL/min/1.73 m(2)) with the new CKD-EPI equations and serum creatinine only equation. Results. The creatinine only equation mean eGFR (88 ± 17) was similar to using spline Log cystatin C (88 ± 22). The lowest mean eGFR (81 ± 21) was obtained with the spline Log cystatin C-age, sex, and weight equation. The creatinine only equation had the fewest participants (7.1%) with eGFR <60 and spline Log cystatin C-age, sex, and weight equation had the most (16.1%). Conclusions. Using serum cystatin C resulted in widely varying eGFR which significantly affected the classification of chronic kidney disease.
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Sabanayagam C, Wong TY, Liao J, Sethi S, Teo BW. Body mass index and preclinical kidney disease in Indian adults aged 40 years and above without chronic kidney disease. Clin Exp Nephrol 2014; 18:919-24. [PMID: 24526413 DOI: 10.1007/s10157-014-0945-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2013] [Accepted: 01/22/2014] [Indexed: 10/25/2022]
Abstract
BACKGROUND Obesity is associated with diabetes and hypertension, two major risk factors for chronic kidney disease (CKD). Recently, it has been shown that obesity is associated with preclinical kidney disease defined by elevated levels of cystatin C among those without CKD in US adults. However, the association of obesity with cystatin C is not known in industrialized Asian populations. METHODS We examined 2,052 Indian adults aged 40-80 years in Singapore who were free of CKD defined as a serum creatinine-based estimated glomerular filtration rate (eGFRcr) <60 mL/min/1.73 m(2) and/or the presence of microalbuminuria. Body mass index (BMI) values were categorized into normal (18.5-24.9), overweight (25-29.9) and obese (≥30 kg/m(2)). Elevated serum cystatin C was defined as cystatin C ≥1 mg/L. RESULTS Overweight and obesity were significantly associated with elevated levels of cystatin C after adjusting for potential confounders including diabetes and hypertension and eGFRcr. Compared to those with normal weight, the odds ratio (95 % confidence interval) of elevated cystatin C was 1.49 (1.17-1.88) for overweight and 3.20 (2.33-4.39) for obese. This association was consistently present when BMI was analyzed as a continuous variable and also in subgroups of men, women and in those without diabetes mellitus or hypertension. CONCLUSIONS Higher BMI levels are associated with preclinical kidney disease in Indian adults aged 40 years and above without CKD.
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Affiliation(s)
- Charumathi Sabanayagam
- Singapore Eye Research Institute, 11 Third Hospital Avenue, #06-13, SNEC Bldg, Singapore, 168751, Singapore,
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Togashi Y, Imura N, Miyamoto Y. Urinary cystatin C as a renal biomarker and its immunohistochemical localization in anti-GBM glomerulonephritis rats. ACTA ACUST UNITED AC 2013; 65:1137-43. [DOI: 10.1016/j.etp.2013.05.005] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2013] [Revised: 04/09/2013] [Accepted: 05/14/2013] [Indexed: 01/18/2023]
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Fu Z, Xue H, Guo J, Chen L, Dong W, Gai L, Liu H, Sun Z, Chen Y. Long-term prognostic impact of cystatin C on acute coronary syndrome octogenarians with diabetes mellitus. Cardiovasc Diabetol 2013; 12:157. [PMID: 24182196 PMCID: PMC4176996 DOI: 10.1186/1475-2840-12-157] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2013] [Accepted: 10/20/2013] [Indexed: 12/22/2022] Open
Abstract
Objective Cystatin C (Cys C) is a marker of renal dysfunction. Prior studies have shown that blood Cys C is related to the prognosis of coronary heart disease. The aim of the present study was to evaluate the long-term prognostic impact of Cys C on acute coronary syndrome (ACS) octogenarians with diabetes mellitus (DM). Methods We enrolled 660 consecutive ACS octogenarians who underwent coronary angiography and were classified into two groups based on diabetes. The baseline characters and Cys C level were measured on admission. Survival curve was calculated using the Kaplan-Meier method. Multivariate Cox regression was used to identify predictors of mortality and of major adverse cardiac events (MACE) rate. Results There were 223 and 398 patients in groups DM and non-DM who fulfilled the follow-up. The average follow-up period was 28 (IQR 16–38) months. Diastolic blood pressure (DBP) was lower, ratios of hypertension and chronic renal failure (CRF), fasting blood glucose, HbA1c and Cys C levels were higher in DM group than those in non-DM group (P<0.01). The cumulative survival of DM group was significantly lower than that of non-DM group in the long term (P = 0.018). All cause mortality and MACE of DM group were higher than those of non-DM group (P<0.05). The plasma Cys C concentration (OR = 3.32, 95% CI = 1.18-10.92, P = 0.023) was the uniqueness independent predictor for long-term all cause mortality. The plasma Cys C concentration (OR = 2.47, 95% CI = 1.07-7.86, P = 0.029) and Genesis score (OR = 1.01, 95% CI = 1.00-1.03, P = 0.043) were independent predictors for MACE in DM group. ROC curve analysis showed that the predictive cut-off value of Cys C for mortality of DM group was 1.605 (0.718, 0.704). Conclusions Cys C is an independent predictor for long-term mortality and MACE of ACS octogenarians with DM.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Yundai Chen
- Department of Cardiology, Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Beijing, Haidian District 100853, People's Republic of China.
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Jeong M, Kim YW, Min JR, Kwon M, Han BS, Kim JG, Jeong SH. Change in kidney damage biomarkers after 13weeks of exposing rats to the complex of Paecilomyces sinclairii and its host Bombyx mori larvae. Food Chem Toxicol 2013; 59:177-86. [DOI: 10.1016/j.fct.2013.05.041] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2012] [Revised: 05/22/2013] [Accepted: 05/24/2013] [Indexed: 12/28/2022]
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Togashi Y, Miyamoto Y. Urinary cystatin C as a biomarker for diabetic nephropathy and its immunohistochemical localization in kidney in Zucker diabetic fatty (ZDF) rats. ACTA ACUST UNITED AC 2013; 65:615-22. [DOI: 10.1016/j.etp.2012.06.005] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2012] [Revised: 05/18/2012] [Accepted: 06/20/2012] [Indexed: 11/29/2022]
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Jeong M, Kim YW, Min JR, Kwon M, Han BS, Kim JG, Jeong SH. Kidney Toxicity Induced by 13 Weeks Exposure to the Fruiting Body of Paecilomyces sinclairii in Rats. Toxicol Res 2012; 28:179-85. [PMID: 24278608 PMCID: PMC3834420 DOI: 10.5487/tr.2012.28.3.179] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2012] [Revised: 09/22/2012] [Accepted: 09/25/2012] [Indexed: 11/30/2022] Open
Abstract
Paecilomyces sinclairiis (PS) is known as a functional food or human health supplement. However concerns have been raised about its kidney toxicity. This study was performed to investigate the kidney toxicity of PS by 13 week-oral administration to rats. Blood urea nitrogen (BUN), serum creatinine, and kidney damage biomarkers including beta-2-microglobulin (β2m), glutathione S-transferase alpha (GST-α), kidney injury molecule 1 (KIM-1), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) and osteopontin were measured during or after the treatment of PS. BUN, creatinine and kidney damage biomarkers in serum were not changed by PS. However, kidney cell karyomegaly and tubular hypertrophy were observed dose-dependently with higher severity in males. KIM-1, TIMP-1 and osteopontin in kidney and urine were increased dose dependently in male or at the highest dose in female rats. Increased urinary osteopontin by PS was not recovered at 2 weeks of post-exposure in both genders. Cystatin C in kidney was decreased at all treatment groups but inversely increased in urine. The changes in kidney damage biomarkers were more remarkable in male than female rats. These data indicate that the PS may provoke renal cell damage and glomerular filtration dysfunction in rats with histopathological lesions and change of kidney damage biomarkers in kidney or urine. Kidney and urinary KIM-1 and cystatin C were the most marked indicators, while kidney weight, BUN and creatinine and kidney damage biomarkers in serum were not influenced.
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Affiliation(s)
- Mihye Jeong
- Agro-Material Safety Evaluating Division, National Academy of Agricultural Science, Rural Development Administration, Suwon 441-707, Korea
| | - Young-Won Kim
- Department of Bio Applied Toxicology, Hoseo Toxicology Research Center, Hoseo University, Asan 336-795, Korea
| | - Jeong-Ran Min
- Department of Bio Applied Toxicology, Hoseo Toxicology Research Center, Hoseo University, Asan 336-795, Korea
| | - Min Kwon
- Department of Bio Applied Toxicology, Hoseo Toxicology Research Center, Hoseo University, Asan 336-795, Korea
| | - Beom-Suk Han
- Department of Bio Applied Toxicology, Hoseo Toxicology Research Center, Hoseo University, Asan 336-795, Korea
| | - Jeong-Gyu Kim
- Environmental Science and Ecological Engineering, Korea University 136-701, Korea
| | - Sang-Hee Jeong
- Department of Bio Applied Toxicology, Hoseo Toxicology Research Center, Hoseo University, Asan 336-795, Korea
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Battistoni A, Rubattu S, Volpe M. Circulating biomarkers with preventive, diagnostic and prognostic implications in cardiovascular diseases. Int J Cardiol 2012; 157:160-8. [DOI: 10.1016/j.ijcard.2011.06.066] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2011] [Revised: 04/27/2011] [Accepted: 06/12/2011] [Indexed: 12/22/2022]
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Overton ET, Patel P, Mondy K, Bush T, Conley L, Rhame F, Kojic EM, Hammer J, Henry K, Brooks, for the SUN Study Investiga JT. Cystatin C and baseline renal function among HIV-infected persons in the SUN Study. AIDS Res Hum Retroviruses 2012; 28:148-55. [PMID: 21480819 DOI: 10.1089/aid.2011.0018] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
In the combination antiretroviral therapy (cART) era, renal dysfunction remains common. The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN) (ClinicalTrials.gov number, NCT00146419) is a prospective observational cohort study of HIV-infected adults. At baseline, comprehensive data were collected, including cystatin C and measures of renal function. Univariate and multivariate regression analyses were performed to identify factors associated with baseline renal dysfunction [estimated glomerular filtration rate (eGFR) < 90 ml/min/1.73 m(2) calculated using the simplified Modification of Diet in Renal Disease equation] and elevated cystatin C (>1.0 mg/liter) in a cross-sectional analysis. Among 670 subjects with complete data (mean age 41 years, mean CD4 cell count 530 cells/mm(3), 79% prescribed cART), the mean eGFR was 96.8 ml/min/1.73 m(2). Forty percent of subjects had renal dysfunction; 3.3% had chronic kidney disease (eGFR < 60 ml/min/1.73 m(2)). Elevated cystatin C was present in 18% of subjects. In multivariate analysis, renal dysfunction was associated with older age, non-Hispanic white race/ethnicity, higher body mass index (BMI), hypertension, higher cystatin C levels, and current prescription of ritonavir. Factors associated with elevated cystatin C included hepatitis C coinfection, hypertension, current smoking, older age, current tenofovir use, detectable plasma HIV RNA, and elevated microalbuminuria. The prevalence of chronic kidney disease (CKD) was low in this contemporary HIV cohort. However, mild to moderate renal dysfunction was common despite the widespread use of cART.
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Affiliation(s)
| | - Pragna Patel
- Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Kristin Mondy
- University of Texas Medical Branch, Austin Programs, Austin, Texas
| | - Tim Bush
- Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Lois Conley
- Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Frank Rhame
- Abbott Northwestern Hospital, Minneapolis, Minnesota
- University of Minnesota, Minneapolis, Minnesota
| | | | - John Hammer
- Denver Infectious Disease Consultants, Denver, Colorado
| | - Keith Henry
- University of Minnesota, Minneapolis, Minnesota
- HIV Program, Hennepin County Medical Center, Minneapolis, Minnesota
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Lertnawapan R, Bian A, Rho YH, Raggi P, Oeser A, Solus JF, Gebretsadik T, Shintani A, Stein CM. Cystatin C is associated with inflammation but not atherosclerosis in systemic lupus erythematosus. Lupus 2011; 21:279-87. [PMID: 22072023 DOI: 10.1177/0961203311425527] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Even mild renal impairment is associated with increased atherosclerosis and cardiovascular mortality. Cystatin C, a novel measure of renal function, is more sensitive than conventional creatinine-based measures for the detection of subtle renal impairment. Increased cystatin concentrations are also associated with cardiovascular risk, independently of conventional measures of renal function. This study examined the hypothesis that cystatin C is elevated in systemic lupus erythematosus (SLE) and is associated with coronary atherosclerosis. METHODS Serum cystatin C, creatinine, tumor necrosis factor (TNF)-α, interleukin (IL)-6, coronary artery calcium score (CACS), Framingham risk score (FRS), Modified Diet in Renal Disease estimated glomerular filtration rate (MDRD-eGFR), and other clinical parameters were measured in 118 patients with SLE and 83 control subjects. The independent association between concentrations of cystatin C and SLE was evaluated using multivariable linear regression models, and the relationship between renal measures and coronary calcium was assessed with multivariable proportional odds logistic regression models. RESULTS Cystatin C, but not other measures of renal function, was significantly higher in patients with SLE than in controls (1.09 [interquartile range, IQR: 0.85-1.28] mg/l vs. 0.89 [IQR: 0.76-0.99] mg/l; p < 0.001 after adjustment for age, race, sex and MDRD-eGFR). Cystatin C was significantly associated with SLICC (p = 0.04), erythrocyte sedimentation rate (ESR) (p = 0.02), TNF-α (p = 0.008) and IL-6 (p = 0.01) after adjustment for age, race, and sex. Cystatin C was not significantly correlated with coronary calcium score in SLE (rho=0.096, p = 0.31) and the association remained non-significant after adjustment for age, race, sex, and Framingham risk score (p = 0.99). CONCLUSIONS Cystatin C was higher in patients with SLE than in control subjects even after adjustment for conventional measures of renal function. Cystatin C was significantly correlated with several markers of inflammation in SLE but was not associated with coronary atherosclerosis. Subtle renal dysfunction does not appear to be directly associated with accelerated atherosclerosis in SLE.
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Affiliation(s)
- R Lertnawapan
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University, Nashville, TN 37232-6602, USA
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Bhavsar NA, Appel LJ, Kusek JW, Contreras G, Bakris G, Coresh J, Astor BC. Comparison of measured GFR, serum creatinine, cystatin C, and beta-trace protein to predict ESRD in African Americans with hypertensive CKD. Am J Kidney Dis 2011; 58:886-93. [PMID: 21944667 DOI: 10.1053/j.ajkd.2011.07.018] [Citation(s) in RCA: 65] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2011] [Accepted: 07/22/2011] [Indexed: 01/02/2023]
Abstract
BACKGROUND Identification of persons with chronic kidney disease (CKD) who are at highest risk to progress to end-stage renal disease (ESRD) is necessary to reduce the burden of kidney failure. The relative utility of traditional markers of kidney function, including estimated glomerular filtration rate (eGFR) and serum creatinine level, and emerging markers of kidney function, including cystatin C and beta-trace protein (BTP) levels, to predict ESRD and mortality has yet to be established. STUDY DESIGN Randomized clinical trial followed by an observational cohort study. SETTING & PARTICIPANTS 865 African American individuals with hypertensive CKD enrolled in a clinical trial of 2 levels of blood pressure control and 3 different antihypertensive drugs as initial therapy and subsequently followed by an observational cohort study. PREDICTORS Quintile of measured GFR (mGFR) by iothalamate clearance, serum creatinine, serum creatinine-based eGFR, cystatin C, and BTP values. OUTCOMES & MEASUREMENTS Incidence of ESRD and mortality. RESULTS 246 participants reached ESRD during a median follow-up of 102 months. The incidence rate of ESRD was higher with higher quintiles of each marker. The association between higher BTP level and ESRD was stronger than those for the other markers, including mGFR. All markers remained significantly associated with ESRD after adjustment for mGFR and relevant covariates (all P < 0.05), with BTP level retaining the strongest association (HR for highest vs lowest quintile, 5.7; 95% CI, 2.2-14.9). Associations with the combined end point of ESRD or mortality (n = 390) were weaker, but remained significant for cystatin C (P = 0.05) and BTP levels (P = 0.004). LIMITATIONS The ability of these markers to predict ESRD and mortality in other racial and ethnic groups and in individuals with CKD due to other causes is unknown. CONCLUSIONS Plasma BTP and cystatin C levels may be useful adjuncts to serum creatinine level and mGFR in evaluating risk of progression of kidney disease.
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Affiliation(s)
- Nrupen A Bhavsar
- Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD, USA
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Sanders JL, Boudreau RM, Fried LP, Walston JD, Harris TB, Newman AB. Measurement of organ structure and function enhances understanding of the physiological basis of frailty: the Cardiovascular Health Study. J Am Geriatr Soc 2011; 59:1581-8. [PMID: 21883106 DOI: 10.1111/j.1532-5415.2011.03557.x] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
OBJECTIVES To determine whether disease burden is associated with frailty independent of diagnosed chronic disease and whether physiological measurements provide greater understanding of the etiology of frailty. DESIGN Cross-sectional. SETTING Community. PARTICIPANTS Two thousand four hundred thirty-seven participants in the Cardiovascular Health Study, 1992/93 examination (mean age 74.8 ± 4.8, 43.4% male, 95.8% white). MEASUREMENTS Disease burden and frailty were tabulated using 10-point scales (0 = healthy, 10 = unhealthy). Disease burden was the sum of measurements characterizing the vasculature, brain, kidneys, lungs, and glucose metabolism. Frailty was assessed using the frailty index reported by Fried. Multivariate linear models were used to determine the association between disease burden (predictor) and frailty (outcome). RESULTS Unadjusted, 1-point-higher disease burden was associated with a 0.28-point-higher frailty score (P < .001). White matter grade, forced vital capacity, and cystatin-C were particularly strongly and significantly associated with frailty. Disease burden attenuated the association between frailty and age by 29%, and disease burden and age had similar associations with frailty. Disease burden attenuated the association between frailty and fibrinogen, Factor VIII, and C-reactive protein by 32%, 56%, and 83%, respectively. Frailty was associated with diagnosed depression, stroke, cognitive impairment, arthritis, and pulmonary disease but not coronary heart disease, diabetes mellitus, or kidney disease in the presence of a summary of disease burden. In the adjusted model, disease burden remained significantly associated with frailty (β = 0.11, P < .001). CONCLUSION Disease burden was independently and significantly associated with frailty. These results emphasize that typically unrecognized physiological changes may contribute significantly to frailty.
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Affiliation(s)
- Jason L Sanders
- Medical Scientist Training Program, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
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Saito M, Nemoto T, Tobimatsu S, Ebata M, Le Y, Nakajima K. Coffee consumption and cystatin-C-based estimated glomerular filtration rates in healthy young adults: results of a clinical trial. J Nutr Metab 2011; 2011:146865. [PMID: 21773013 PMCID: PMC3136094 DOI: 10.1155/2011/146865] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2011] [Revised: 03/20/2011] [Accepted: 04/17/2011] [Indexed: 01/02/2023] Open
Abstract
Recently it has been reported that the estimated glomerular filtration rate (eGFR) is higher in habitual coffee consumers than in noncoffee consumers. However, the causality remains unclear. Therefore, we conducted a clinical trial to investigate the effects of coffee consumption on kidney function. Nineteen asymptomatic nonsmokers aged 21-27 years old participated in this study. They consumed coffee (18 g coffee beans/450 mL per day) or green tea as a comparator for 2 weeks in a crossover design. Although creatinine-based eGFR was not affected after consuming either beverage, all cystatin-C-based eGFRs determined using five different equations were significantly increased after coffee consumption (means: 5.0-7.7%), but not after green tea consumption (means: 0.1-1.6%). Serum adiponectin and magnesium levels increased significantly after coffee consumption (means: 13.6% and 4.3%, resp.), but not after green tea consumption. These findings suggest that even a short period of coffee consumption may increase cystatin-C-based eGFR, along with favorable changes in serum adiponectin, in healthy young adults.
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Affiliation(s)
- Masafumi Saito
- Division of Clinical Nutrition, Department of Medical Dietetics, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan
| | - Tohru Nemoto
- Division of Clinical Nutrition, Department of Medical Dietetics, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan
| | - Satoshi Tobimatsu
- Division of Clinical Nutrition, Department of Medical Dietetics, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan
| | - Midori Ebata
- Division of Clinical Nutrition, Department of Medical Dietetics, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan
| | - Yulan Le
- Division of Clinical Nutrition, Department of Medical Dietetics, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan
| | - Kei Nakajima
- Division of Clinical Nutrition, Department of Medical Dietetics, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan
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Efficacy and safety of aliskiren-based dual and triple combination therapies in US minority patients with stage 2 hypertension. ACTA ACUST UNITED AC 2011; 5:102-13. [PMID: 21414565 DOI: 10.1016/j.jash.2011.01.006] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2010] [Revised: 01/06/2011] [Accepted: 01/24/2011] [Indexed: 01/13/2023]
Abstract
Minority patients with hypertension generally require combination therapy to reach blood pressure (BP) goals. We examined the BP-lowering efficacy and safety of combination aliskiren/amlodipine therapy in self-identified minority patients in the United States with stage 2 hypertension and the impact of adding hydrochlorothiazide (HCTZ) to this combination. In this 8-week double-blind study, 412 patients were randomized to receive aliskiren/amlodipine (150/5 mg) or amlodipine (5 mg) with forced titration up to aliskiren/amlodipine/HCTZ (300/10/25 mg) or aliskiren/amlodipine (300/10 mg), respectively. Overall, mean age was 55.2 years, mean body mass index was 32 kg/m(2), 62.3% were black, 28.2% were Hispanic/Latino, and 69.1% had metabolic syndrome. Mean sitting systolic blood pressure (MSSBP), the primary efficacy outcome, was reduced from 167.1 mm Hg at baseline to 130.7 mm Hg at week 8 with aliskiren/amlodipine/HCTZ and from 167.4 mm Hg to 137.9 mm Hg with aliskiren/amlodipine (P < .0001 between groups). At week 8, BP goal (<140/90 mm Hg) was achieved in 72.6% and 53.2% of patients in the two treatment groups, respectively (P < .0001). Adverse events were experienced by 34.2% and 40.2%, respectively. Combination aliskiren/amlodipine therapy was effective in treating these high-risk patients but inclusion of HCTZ provided greater antihypertensive efficacy. Both treatments were similarly well tolerated.
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MacIsaac RJ, Premaratne E, Jerums G. Estimating glomerular filtration rate in diabetes using serum cystatin C. Clin Biochem Rev 2011; 32:61-67. [PMID: 21611078 PMCID: PMC3100282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/30/2023]
Abstract
Chronic kidney disease (CKD) is a major public health problem, especially for people with diabetes. Not only is it a risk factor for end-stage renal disease (ESRD) but it is also a major cardiovascular disease (CVD) risk factor. Methods that accurately and simply estimate glomerular filtration rate (GFR) are therefore needed to optimise the detection and management of CKD in people with diabetes. One of the main failures of commonly used creatinine-based methods for estimating renal function is that they lack applicability across the full range of GFR values and underestimate GFR levels >60 mL/min/1.73m(2). Methods for accurately estimating an early pathological decline in GFR (i.e. ΔGFR >3.3 mL/min/year before reaching a GFR <60 mL/min/1.73m(2)) are especially needed as appropriate interventions have been shown to retard progression to ESRD and reduce CVD risk in people with diabetes. In contrast, recent studies have suggested that estimates of GFR based on serum cystatin C concentration might provide a simple and accurate method for detecting and monitoring an early decline in renal function.
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Affiliation(s)
- Richard J MacIsaac
- Department of Endocrinology and Diabetes, St Vincent’s Hospital, Fitzroy, Vic. 3065, Australia
- Endocrine Centre, Austin Health and University of Melbourne, Heidelberg West, Vic. 3081, Australia
| | - Erosha Premaratne
- Endocrine Centre, Austin Health and University of Melbourne, Heidelberg West, Vic. 3081, Australia
| | - George Jerums
- Department of Endocrinology and Diabetes, St Vincent’s Hospital, Fitzroy, Vic. 3065, Australia
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Togashi Y, Sakaguchi Y, Miyamoto M, Miyamoto Y. Urinary cystatin C as a biomarker for acute kidney injury and its immunohistochemical localization in kidney in the CDDP-treated rats. ACTA ACUST UNITED AC 2011; 64:797-805. [PMID: 21377848 DOI: 10.1016/j.etp.2011.01.018] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2010] [Accepted: 01/30/2011] [Indexed: 11/17/2022]
Abstract
Cystatin C, a cysteine protease inhibitor, is a novel biomarker of renal damage. In the present study, we examined the urinary and plasma levels of cystatin C and how useful they are for the early detection of acute kidney injury (AKI) in CDDP-treated rats in comparison with other biomarkers (β2-microglobulin, calbindin, clusterin, EGF, GST-α, GST-μ, KIM-1, NGAL, osteopontin, TIMP-1, and VEGF). The urinary levels of cystatin C, GST-α, KIM-1, and EGF changed prior to proximal tubule damage and increases in plasma urea nitrogen and creatinine levels, suggesting their usefulness for predicting AKI. On the other hand, the plasma cystatin C level hardly changed. We also investigated the localization of cystatin C in the kidney according to the progression of renal damage. Cystatin C was predominantly localized in the proximal tubule of the cortex, and its immunohistochemical expression was not affected by CDDP treatment. In addition, cystatin C was observed in the lumen of the renal tubule in the cortex, cortico-medullary junction, and medulla during the progression of renal damage, although its immunoreactive area ratio was very low. In conclusion, urinary cystatin C measurements can detect CDDP-induced AKI as early as KIM-1, GST-α, and EGF in rats, although the change ratio of the cystatin C was smaller than others. Immunohistochemical cystatin C expression in the proximal tubule of the kidney was hardly changed by the CDDP treatment, but it was newly observed in the renal tubule lumen after CDDP treatment.
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Affiliation(s)
- Yuko Togashi
- Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan
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Wilson ME, Boumaza I, Lacomis D, Bowser R. Cystatin C: a candidate biomarker for amyotrophic lateral sclerosis. PLoS One 2010; 5:e15133. [PMID: 21151566 PMCID: PMC3000338 DOI: 10.1371/journal.pone.0015133] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2010] [Accepted: 10/22/2010] [Indexed: 11/18/2022] Open
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurologic disease characterized by progressive motor neuron degeneration. Clinical disease management is hindered by both a lengthy diagnostic process and the absence of effective treatments. Reliable panels of diagnostic, surrogate, and prognostic biomarkers are needed to accelerate disease diagnosis and expedite drug development. The cysteine protease inhibitor cystatin C has recently gained interest as a candidate diagnostic biomarker for ALS, but further studies are required to fully characterize its biomarker utility. We used quantitative enzyme-linked immunosorbent assay (ELISA) to assess initial and longitudinal cerebrospinal fluid (CSF) and plasma cystatin C levels in 104 ALS patients and controls. Cystatin C levels in ALS patients were significantly elevated in plasma and reduced in CSF compared to healthy controls, but did not differ significantly from neurologic disease controls. In addition, the direction of longitudinal change in CSF cystatin C levels correlated to the rate of ALS disease progression, and initial CSF cystatin C levels were predictive of patient survival, suggesting that cystatin C may function as a surrogate marker of disease progression and survival. These data verify prior results for reduced cystatin C levels in the CSF of ALS patients, identify increased cystatin C levels in the plasma of ALS patients, and reveal correlations between CSF cystatin C levels to both ALS disease progression and patient survival.
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Affiliation(s)
- Meghan E. Wilson
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America
| | - Imene Boumaza
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America
| | - David Lacomis
- Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America
| | - Robert Bowser
- Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America
- * E-mail:
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Ma Y, Li Q, Wang J, Xu Z, Song C, Zhuang R, Yang K, Yang A, Jin B. Cystatin C, a novel urinary biomarker for sensitive detection of acute kidney injury during haemorrhagic fever with renal syndrome. Biomarkers 2010; 15:410-7. [PMID: 20450259 DOI: 10.3109/1354750x.2010.482214] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
To explore the value of cystatin C for evaluating acute kidney injury (AKI) in haemorrhagic fever with renal syndrome (HFRS), the concentrations of cystatin C in serum and urine samples from HFRS patients were determined. The serum and urinary cystatin C concentrations significantly increased in HFRS patients compared with normal controls (p < 0.001). In the acute phase of HFRS, urinary cystatin C increased to higher levels than serum creatinine, especially in severe or critical cases in the oliguric stage. Furthermore, higher levels of urinary cystatin C in the acute phase positively correlated with increased severity of the subsequent kidney injury. In conclusion, urinary cystatin C is a more sensitive clinical marker for AKI in HFRS, which may enable us to initiate treatment measures as early as possible.
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Affiliation(s)
- Ying Ma
- Department of Immunology, The Fourth Military Medical University, Xi'an, China
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Cystatin C is not a better estimator of GFR than plasma creatinine in the general population. Kidney Int 2010; 78:1305-11. [PMID: 20844470 DOI: 10.1038/ki.2010.321] [Citation(s) in RCA: 100] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Accurate measurement of glomerular filtration rate (GFR) is complicated and costly; therefore, GFR is commonly estimated by assessing creatinine or cystatin C concentrations. Because estimates based on cystatin C predict cardiovascular disease better than creatinine, these estimates have been hypothesized to be superior to those based on creatinine, when the GFR is near the normal range. To test this, we measured GFR by iohexol clearance in a representative sample of middle-aged (50-62 years) individuals in the general population, excluding those with coronary heart or kidney disease, stroke or diabetes mellitus. Bias, precision (median and interquartile range of estimated minus measured GFR (mGFR)), and accuracy (percentage of estimates within 30% of mGFR) of published cystatin C and creatinine-based GFR equations were compared in a total of 1621 patients. The cystatin C-based equation with the highest accuracy (94%) had a bias of 3.5 and precision of 18 ml/min per 1.73 m², whereas the most accurate (95%) creatinine-based equation had a bias of 2.9 and precision of 15 ml/min per 1.73 m² The best equation, based on both cystatin C and creatinine, had a bias of 7.6 ml/min per 1.73 m², precision of 15 ml/min per 1.73 m², and accuracy of 92%. Thus, estimates of GFR based on cystatin C were not superior to those based on creatinine in the general population. Hence, the better prediction of cardiovascular disease by cystatin C than creatinine measurements, found by others, may be due to factors other than GFR.
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CHA RANHUI, LEE CHUNGSIK, LIM YOUNHEE, KIM HO, LEE SEUNGHWAN, YU KYUNGSANG, KIM YONSU. Clinical usefulness of serum cystatin C and the pertinent estimation of glomerular filtration rate based on cystatin C. Nephrology (Carlton) 2010; 15:768-76. [DOI: 10.1111/j.1440-1797.2010.01344.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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Current awareness: Pharmacoepidemiology and drug safety. Pharmacoepidemiol Drug Saf 2009. [DOI: 10.1002/pds.1654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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