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Garofolo M, Vitale M, Penno G, Solini A, Orsi E, Grancini V, Bonora E, Fondelli C, Trevisan R, Vedovato M, Nicolucci A, Pugliese G. Prognostic impact of switching to the 2021 chronic kidney disease epidemiology collaboration creatinine-based equation in Caucasian patients with type 2 diabetes: the Renal Insufficiency and Cardiovascular events (RIACE) Italian Multicenter Study. Cardiovasc Diabetol 2024; 23:377. [PMID: 39449120 PMCID: PMC11515406 DOI: 10.1186/s12933-024-02450-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Accepted: 09/19/2024] [Indexed: 10/26/2024] Open
Abstract
BACKGROUND A Chronic Kidney Disease (CKD) Epidemiology Collaboration (EPI) formula not including a Black race coefficient has been recently developed and is now recommended in the US. The new (2021) equation was shown to yield higher estimated glomerular filtration rate (eGFR) values than the old (2009) one in a non-Black general population sample, thus reclassifying a significant number of individuals to a better eGFR category. However, reclassified individuals were previously shown to have a lower risk of progression to end-stage kidney disease, but higher adjusted risks for all-cause death and morbidity and mortality from cardiovascular disease than those not reclassified. This study evaluated the prognostic impact of switching from the 2009 to the 2021 CKD-EPI equation in non-Black individuals with type 2 diabetes. METHODS The Renal Insufficiency And Cardiovascular Events (RIACE) was a prospective cohort study enrolling 15,773 Caucasian patients in 19 Italian centers in 2006-2008. Cardiometabolic risk profile, treatments, complications, and comorbidities were assessed at baseline and eGFR was calculated with the two equations. Vital status was retrieved on 31 October 2015 for 15,656 participants (99.3%). RESULTS With the 2021 equation, the eGFR value increased in all patients, except for 293 individuals with a 2009 eGFR ≥ 105 ml·min- 1·1.73 m- 2. The median difference was 4.10 ml·min- 1·1.73 m- 2 and was higher in males, older individuals and those in the G2 category. Reclassification decreased the percentage of patients with reduced eGFR from 17.28 to 13.96% and with any CKD from 36.23 to 34.03%. Reclassified individuals had better cardiometabolic risk profile and lower prevalence of complications and use of medications than non-reclassified individuals. Risk of death versus the 2009 G1 category was lower for reclassified than non-reclassified participants in all eGFR categories and, particularly, in each 2009 eGFR category, though difference was significant only in the G4-G5 category. The Receiver Operator Characteristic curves were statistically, but not clinically different with the two equations. CONCLUSION Changing from the 2009 to the 2021 CKD-EPI equation results in higher eGFR and lower CKD prevalence, with a lower risk of death in reclassified patients with an eGFR < 30 ml·min- 1·1.73 m- 2, but virtually no impact on mortality prediction. TRIAL REGISTRATION ClinicalTrials.gov, NCT00715481, retrospectively registered 15 July, 2008.
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MESH Headings
- Aged
- Female
- Humans
- Male
- Middle Aged
- Biomarkers/blood
- Cardiovascular Diseases/diagnosis
- Cardiovascular Diseases/mortality
- Cardiovascular Diseases/epidemiology
- Cardiovascular Diseases/ethnology
- Creatinine/blood
- Decision Support Techniques
- Diabetes Mellitus, Type 2/diagnosis
- Diabetes Mellitus, Type 2/mortality
- Diabetes Mellitus, Type 2/ethnology
- Diabetes Mellitus, Type 2/epidemiology
- Diabetes Mellitus, Type 2/blood
- Diabetic Nephropathies/diagnosis
- Diabetic Nephropathies/mortality
- Diabetic Nephropathies/epidemiology
- Diabetic Nephropathies/ethnology
- Diabetic Nephropathies/physiopathology
- Glomerular Filtration Rate
- Italy/epidemiology
- Kidney/physiopathology
- Models, Biological
- Predictive Value of Tests
- Prognosis
- Prospective Studies
- Race Factors
- Renal Insufficiency, Chronic/diagnosis
- Renal Insufficiency, Chronic/mortality
- Renal Insufficiency, Chronic/physiopathology
- Renal Insufficiency, Chronic/epidemiology
- Renal Insufficiency, Chronic/ethnology
- Risk Assessment
- Risk Factors
- Time Factors
- White People
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Affiliation(s)
- Monia Garofolo
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Martina Vitale
- Department of Clinical and Molecular Medicine, "La Sapienza" University, Via di Grottarossa, Rome, 1035-1039 - 00189, Italy
| | - Giuseppe Penno
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Anna Solini
- Department of Surgical, Medical, Molecular and Critical Area Pathology, University of Pisa, Pisa, Italy
| | - Emanuela Orsi
- Diabetes Unit, Fondazione IRCCS "Cà Granda - Ospedale Maggiore Policlinico", Milan, Italy
| | - Valeria Grancini
- Diabetes Unit, Fondazione IRCCS "Cà Granda - Ospedale Maggiore Policlinico", Milan, Italy
| | - Enzo Bonora
- Division of Endocrinology, Diabetes and Metabolism, University and Hospital Trust of Verona, Verona, Italy
| | | | - Roberto Trevisan
- Endocrinology and Diabetes Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
| | - Monica Vedovato
- Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy
| | - Antonio Nicolucci
- Center for Outcomes Research and Clinical Epidemiology (CORESEARCH), Pescara, Italy
| | - Giuseppe Pugliese
- Department of Clinical and Molecular Medicine, "La Sapienza" University, Via di Grottarossa, Rome, 1035-1039 - 00189, Italy.
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Li JJ, Sa RL, Zhang Y, Yan ZL. Evaluating new biomarkers for diabetic nephropathy: Role of α2-macroglobulin, podocalyxin, α-L-fucosidase, retinol-binding protein-4, and cystatin C. World J Diabetes 2024; 15:1212-1225. [PMID: 38983807 PMCID: PMC11229980 DOI: 10.4239/wjd.v15.i6.1212] [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: 01/07/2024] [Revised: 02/27/2024] [Accepted: 04/30/2024] [Indexed: 06/11/2024] Open
Abstract
BACKGROUND The intricate relationship between type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) presents a challenge in understanding the significance of various biomarkers in diagnosis. AIM To elucidate the roles and diagnostic values of α2-macroglobulin (α2-MG), podocalyxin (PCX), α-L-fucosidase (AFU), retinol-binding protein-4 (RBP-4), and cystatin C (CysC) in DN. METHODS From December 2018 to December 2020, 203 T2DM patients were enrolled in the study. Of these, 115 were diagnosed with DN (115 patients), while the remaining 88 patients were classified as non-DN. The urinary levels of α2-MG, PCX, and AFU and the serum concentrations RBP-4 and CysC were measured in conjunction with other relevant clinical indicators to evaluate their potential correlations and diagnostic utility. RESULTS After adjustments for age and gender, significant positive correlations were observed between the biomarkers CysC, RBP-4, α2-MG/urinary creatinine (UCr), PCX/UCr, and AFU/UCr, and clinical indicators such as urinary albumin-to-creatinine ratio (UACR), serum creatinine, urea, 24-h total urine protein, and neutrophil-to-lymphocyte ratio (NLR). Conversely, these biomarkers exhibited negative correlations with the estimated glomerular filtration rate (P < 0.05). Receiver operating characteristic (ROC) curve analysis further demonstrated the diagnostic performance of these biomarkers, with UACR showcasing the highest area under the ROC curve (AUCROC) at 0.97. CONCLUSION This study underscores the diagnostic significance of α2-MG, PCX, and AFU in the development of DN. The biomarkers RBP-4, CysC, PCX, AFU, and α2-MG provide promising diagnostic insights, while UACR is the most potent diagnostic biomarker in assessing DN.
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Affiliation(s)
- Jing-Jing Li
- Department of Infectious Diseases, Inner Mongolia Medical University, Hohhot First Hospital, Hohhot 010000, Inner Mongolia Autonomous Region, China
| | - Ru-La Sa
- Department of Endocrinology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010000, Inner Mongolia Autonomous Region, China
| | - Yu Zhang
- Department of Dermatology, Inner Mongolia Autonomous Region People’s Hospital, Hohhot 010000, Inner Mongolia Autonomous Region, China
| | - Zhao-Li Yan
- Department of Endocrinology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010000, Inner Mongolia Autonomous Region, China
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Williams P. Retaining Race in Chronic Kidney Disease Diagnosis and Treatment. Cureus 2023; 15:e45054. [PMID: 37701164 PMCID: PMC10495104 DOI: 10.7759/cureus.45054] [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: 09/08/2023] [Indexed: 09/14/2023] Open
Abstract
The best overall measure of kidney function is glomerular filtration rate (GFR) as commonly estimated from serum creatinine concentrations (eGFRcr) using formulas that correct for the higher average creatinine concentrations in Blacks. After two decades of use, these formulas have come under scrutiny for estimating GFR differently in Blacks and non-Blacks. Discussions of whether to include race (Black vs. non-Black) in the calculation of eGFRcr fail to acknowledge that the original race-based eGFRcr provided the same CKD treatment recommendations for Blacks and non-Blacks based on directly (exogenously) measured GFR. Nevertheless, the National Kidney Foundation and the American Society of Nephrology Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease removed race in CKD treatment guidelines and pushed for the immediate adoption of a race-free eGFRcr formula by physicians and clinical laboratories. This formula is projected to negate CKD in 5.51 million White and other non-Black adults and reclassify CKD to less severe stages in another 4.59 million non-Blacks, in order to expand treatment eligibility to 434,000 Blacks not previously diagnosed and to 584,000 Blacks previously diagnosed with less severe CKD. This review examines: 1) the validity of the arguments for removing the original race correction, and 2) the performance of the proposed replacement formula. Excluding race in the derivation of eGFRcr changed the statistical bias from +3.7 to -3.6 ml/min/1.73m2 in Blacks and from +0.5 to +3.9 in non-Blacks, i.e., promoting CKD diagnosis in Blacks at the cost of restricting diagnosis in non-Blacks. By doing so, the revised eGFRcr greatly exaggerates the purported racial disparity in CKD burden. Claims that the revised formulas identify heretofore undiagnosed CKD in Blacks are not supported when studies that used kidney failure replacement therapy and mortality are interpreted as proxies for baseline CKD. Alternatively, a race-stratified eGFRcr (i.e., separate equations for Blacks and non-Blacks) would provide the least biased eGFRcr for both Blacks and non-Blacks and the best medical treatment for all patients.
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Affiliation(s)
- Paul Williams
- Life Sciences, Lawrence Berkeley National Laboratory, Berkeley, USA
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Hayat M, Ahmad N, Khan SLA, Mohkumuddin S, Siddique W, Khan A, Atif M. Pattern, frequency and factors associated with inappropriate high dosing in chronic kidney disease patients at a tertiary care hospital in Pakistan. BMC Nephrol 2023; 24:118. [PMID: 37127612 PMCID: PMC10150458 DOI: 10.1186/s12882-023-03167-5] [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: 12/16/2022] [Accepted: 04/13/2023] [Indexed: 05/03/2023] Open
Abstract
BACKGROUND Patients with chronic kidney diseases (CKD) are susceptible to the toxic drug effects if given unadjusted doses. Although Pakistan harbors a high burden of CKD patients, there is limited information available on the frequency, pattern and factors associated with unadjusted drug doses among CKD patients. METHODS This cross-sectional study conducted at Sandeman Provincial Hospital, Quetta included 303 non-dialysis ambulatory CKD patients (glomerular filtration rate < 60 ml/min/1.73m2). The patients' data were collected through a purpose designed data collection form. The appropriateness of doses was checked against the renal drug handbook-2018, Kidney Disease Improving Global Outcomes guidelines, British National Formulary-2022, and manufacturer leaflets. Data were analysed by SPSS 23 and multiple binary logistic regression analysis was used to assess the factors associated with receiving inappropriate high doses. A p-value < 0.05 was considered statistically significant. RESULTS The patients received a total of 2265 prescription lines, with a median of eight different drugs per patient (interquartile range: 6-9 drugs). A total of 34.5% (783/2265) drugs required dose adjustment. Of these, doses were not adjusted for 56.1% (440) drugs in 162 (53.4%) patients. The most common pharmacological class of drugs requiring dose adjustment were antibiotics (79.1%), followed by antidiabetics (59.2%), diuretics (57.0%), angiotensin converting enzyme inhibitors (56.9%), beta blockers (56.9%), analgesics (56.0%), angiotensin receptor blockers (55.2%), domperidone (53.9%) and antihyperlipidmics (46.1%). Patient's age of 41-60 (OR = 5.76) and > 60 years (OR = 9.49), hypertension (OR = 2.68), diabetes mellitus (OR = 3.47) and cardiovascular diseases (OR = 2.82) had statistically significant association (p-value < 0.05) with inappropriate high doses. CONCLUSION The high frequency of inappropriate high doses suggests an important quality gap in medication dosing for patients with ND-CKD at the study site. Special attention should be paid to the drugs and patients with identified risk factors for receiving inappropriate high doses.
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Affiliation(s)
- Muhammad Hayat
- Department of Pharmacy Practice, Faculty of Pharmacy and Health Sciences, University of Balochistan, Quetta, Pakistan
| | - Nafees Ahmad
- Department of Pharmacy Practice, Faculty of Pharmacy and Health Sciences, University of Balochistan, Quetta, Pakistan.
| | | | - Syed Mohkumuddin
- Department of Nephrology, Bolan Medical College, Quetta, Pakistan
| | - Wajeeha Siddique
- Department of Pharmacy Practice, Faculty of Pharmacy and Health Sciences, University of Balochistan, Quetta, Pakistan
| | - Amjad Khan
- Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan
| | - Muhammad Atif
- Department of Pharmacy Practice, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
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Escribano-Serrano J, Jiménez-Varo E, Escribano-Cobalea M, López-Ceres A, Casto-Jarillo C, Hormigo-Pozo A, Michán-Doña A. Is the use of the new Chronic Kidney Disease Epidemiology Consortium (CKD-EPI 2021) formula appropriate for the Spanish population? Rev Clin Esp 2023; 223:144-153. [PMID: 36796634 DOI: 10.1016/j.rceng.2023.02.002] [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: 10/31/2022] [Accepted: 11/17/2022] [Indexed: 02/16/2023]
Abstract
INTRODUCTION United States nephrology societies recommend changing from the CKD-EPI 2009 equation to the new CKD-EPI 2021 equation, which does not include the race coefficient, for calculating estimated glomerular filtration rate (eGFR). It is unknown how this change might affect the distribution of kidney disease in the predominantly Caucasian Spanish population. METHODS Two databases of adults from the province of Cádiz, DB-SIDICA (N=264,217) and DB-PANDEMIA (N=64,217), that had plasma creatinine measurements recorded between 2017 and 2021 were studied. Changes in eGFR and the consequent reclassification into different categories of the KDIGO 2012 classification resulting from substituting the CKD-EPI 2009 equation for the 2021 equation were calculated. RESULTS Compared to the 2009 equation, CKD-EPI 2021 yielded a higher eGFR, with a median of 3.8mL/min/1.73m2 (IQR 2.98-4.48) in DB-SIDICA and 3.89mL/min/1.73m2 (IQR 3.05-4.55) in DB-PANDEMIA. The first consequence was that 15.3% of the total population in DB-SIDICA and 15.1% of the total population in DB-PANDEMIA were reclassified into a higher category of eGFR, as were 28.1% and 27.3%, respectively, of the population with CKD (G3-G5); no subjects were classified into the more severe category. The second consequence was that the prevalence of kidney disease decreased from 9% to 7.5% in both cohorts. CONCLUSIONS Implementing the CKD-EPI 2021 equation in the Spanish population, which is predominantly Caucasian, would increase eGFR by a modest amount (greater in men and those who are older or have a higher GFR). A significant proportion of the population would be classified into a higher eGFR category, with a consequent decrease in the prevalence of kidney disease.
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Affiliation(s)
- J Escribano-Serrano
- Unidad de Gestión Clínica San Roque, Área de Gestión Sanitaria Campo de Gibraltar Este, Cádiz, Spain; Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain.
| | - E Jiménez-Varo
- Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain; Unidad de Gestión Clínica Laboratorio Análisis Clínicos, Hospital La Línea, Área de Gestión Sanitaria Campo de Gibraltar Este, Cádiz, Spain
| | - M Escribano-Cobalea
- Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain; Unidad de Gestión Clínica Obstetricia y Ginecología, Hospital Punta Europa de Algeciras, Área de Gestión Clínica Campo de Gibraltar Oeste, Cádiz, Spain
| | - A López-Ceres
- Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain; Unidad de Gestión Clínica Laboratorio Análisis Clínicos, Hospital La Línea, Área de Gestión Sanitaria Campo de Gibraltar Este, Cádiz, Spain
| | - C Casto-Jarillo
- Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain; Unidad de Gestión Clínica Laboratorio Análisis Clínicos, Hospital La Línea, Área de Gestión Sanitaria Campo de Gibraltar Este, Cádiz, Spain
| | - A Hormigo-Pozo
- Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain; Unidad de Gestión Clínica San Andrés-Torcal, Área de Gestión Sanitaria Málaga Guadalhorce, Málaga, Spain
| | - A Michán-Doña
- Instituto de Investigación e Innovación Biomédica de Cádiz (INIBICA), Cádiz, Spain; Departamento de Medicina, Hospital Universitario de Jerez, Área de Gestión Sanitaria Norte de Cádiz, Cádiz, Spain
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Escribano-Serrano J, Jiménez-Varo E, Escribano-Cobalea M, López-Ceres A, Casto-Jarillo C, Hormigo-Pozo A, Michán-Doña A. ¿Es apropiada la aplicación de la nueva ecuación Chronic Kidney Disease Epidemiology Consortium (CKD-EPI 2021) en la población española? Rev Clin Esp 2023. [DOI: 10.1016/j.rce.2022.11.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
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Hsu CY, Go AS. The race coefficient in glomerular filtration rate-estimating equations and its removal. Curr Opin Nephrol Hypertens 2022; 31:527-533. [PMID: 36093899 PMCID: PMC9645369 DOI: 10.1097/mnh.0000000000000833] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
PURPOSE OF REVIEW To review new publications about the use of the race coefficient in glomerular filtration rate (GFR)-estimating equations since this topic was last reviewed a year ago in Current Opinion in Nephrology and Hypertension . RECENT FINDINGS Accounting for race (or genetic ancestry) does improve the performance of GFR-estimating equations when serum creatinine (SCr) is used as the filtration marker but not when cystatin C is used. The National Kidney Foundation (NKF)-American Society of Nephrology (ASN) Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease recommended immediate adoption of a new refitted SCr-based equation without race and increased use of cystatin C. This report has created consensus but the endorsed new SCr equation without race underestimates GFR in Black Americans and overestimates GFR in non-Black Americans, which may result in diminished ability to detect racial disparities. SUMMARY The approach recommended by the NKF-ASN Task Force represents a compromise attempting to balance a number of competing values, including racial justice, benefit of classifying more Black Americans as having (more severe) chronic kidney disease, accuracy compared with measured GFR, and financial cost. The full implications of adopting the race-free refitted CKD-EPI SCr equation are yet to be known.
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Affiliation(s)
- Chi-yuan Hsu
- Division of Nephrology, University of California, San Francisco, San Francisco, CA, USA
| | - Alan S Go
- Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA
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