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Sex-specific shifts in CKD classification using European Kidney Function Consortium (EKFC) as compared to CKD
Ulla T Schultheiss1, Jakob Möller2, Thomas McDonnell3
1Institute of Epidemiology and Prevention, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany; Department of Medicine IV, Nephrology and Primary Care, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany; SYNLAB MVZ Humangenetik Freiburg GmbH, Freiburg, Germany.
Introduction:
Chronic kidney disease (CKD) is more prevalent in women than men, but men progress faster to kidney failure (KF). Equations may estimate glomerular filtration rate (eGFR) differently by sex. This study assessed sex-specific reclassification using the creatinine- and cystatin C-based European Kidney Function Consortium (EKFC) versus the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR equations and evaluated KF prediction.
Methods:
We compared classification in Kidney Disease: Improving Global Outcomes (KDIGO) GFR stages at baseline by sex based on GFR estimated with EKFC vs CKD-EPI equations in the German CKD study (GCKD) (5085 persons). Findings were validated in the National Unified Renal Translational Research Enterprise (NURTuRE)-CKD cohort (2589 persons) and the population-based RENIS-3 (Renal Iohexol Clearance Survey) study (1383 persons), the latter with gold-standard measured GFR (mGFR).
Results:
Among GCKD participants, men (60%) had a higher urine albumin-to-creatinine ratio (UACR), whereas women had higher eGFR. Over 8.5 years, 181 women (3.6%) and 459 men (9.0%) developed KF. Using EKFC formulas based on cystatin C only or combined with creatinine, women were consistently and more frequently reclassified into milder eGFR stages and 4- to 5.7-fold more frequently classified as not having CKD than men. Sex-specific reclassification patterns were replicated in NURTuRE-CKD (2589 persons). In RENIS-3, comparison with mGFR showed sex-specific misclassification for both equations, with better alignment in the lower eGFR ranges for EKFC. Predictive performance for progression to KF was similar between the EKFC and CKD-EPI equations and became equivalent after adjusting for age, sex, and UACR.
Conclusions:
Women were more frequently reclassified into a less severe stage of CKD using the EKFC eGFR than the CKD-EPI equation, yet the prognostic performance for KF did not differ significantly between the two equations for both women and men. This suggests that the reclassification has limited clinical influence on KF risk prediction.
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