Discordance in Creatinine- and Cystatin C-Based eGFR and Clinical Outcomes: A Meta-Analysis

Estrella MM, Ballew SH, Sang Y, Grams ME, Coresh J, Surapaneni A, Alencar De Pinho N, Ärnlöv J, Brenner H, Carrero JJ, Chen TK, Cohen DL, Cushman M, Gansevoort RT, Hwang SJ, Inker LA, Ix JH, Kabasawa K, Konta T, Lees JS, Polkinghorne KR, Shlipak MG, Vernooij RW, Wheeler DC, Yadav AK, Levey AS, Eckardt KU (2025)

Publication Type: Journal article

Publication year: 2025

Journal

DOI: 10.1001/jama.2025.17578

Abstract

Importance: Estimated glomerular filtration rates (eGFRs) can differ according to whether creatinine or cystatin C is used for the eGFR calculation, but the prevalence and importance of these differences remain unclear. Objectives: To evaluate the prevalence of a discordance between cystatin C-based eGFR (eGFRcys) and creatinine-based eGFR (eGFRcr), identify characteristics associated with greater discordance, and evaluate associations of discordance with adverse outcomes. Data Sources: Participants in the Chronic Kidney Disease Prognosis Consortium (CKD-PC). Study Selection: Participants with concurrent cystatin C and creatinine measurements and clinical outcome measurement. Data Extraction and Synthesis: Between April 2024 and August 2025, data were synthesized using individual-level meta-analysis. Main Outcomes and Measures: The primary independent measurement was a large negative eGFR difference (eGFRdiff), defined as an eGFRcys that was at least 30% lower than eGFRcr. Secondary (dependent) outcomes included all-cause and cardiovascular mortality, atherosclerotic cardiovascular disease, heart failure, and kidney failure with replacement therapy. Results: A total of 821327 individuals from 23 outpatient cohorts (mean [SD] age, 59 [12] years; 48% female; 13.5% with diabetes; 40% with hypertension) and 39639 individuals from 2 inpatient cohorts (mean [SD] age, 67 [16] years; 31% female; 30% with diabetes; 72% with hypertension) were included. Among outpatient participants, 11% had a large negative eGFRdiff (range, 3%-50%). Among inpatients, 35% had a large negative eGFRdiff. Among outpatient participants, at a mean (SD) follow-up of 11 (4) years, a large negative eGFRdiff, compared with an eGFRdiff between -30% and 30%, was associated with higher rates of all-cause mortality (28.4 vs 16.8 per 1000 person-years [PY]; hazard ratio [HR], 1.69 [95% CI, 1.57-1.82]), cardiovascular mortality (6.1 vs 3.8 per 1000 PY; HR, 1.61 [95% CI, 1.48-1.76]), atherosclerotic cardiovascular disease (13.3 vs 9.8 per 1000 PY; HR, 1.35 [95% CI, 1.27-1.44]), heart failure (13.2 vs 8.6 per 1000 PY; HR, 1.54 [95% CI, 1.40-1.68]), and kidney failure with replacement therapy (2.7 vs 2.1 per 1000 PY; HR, 1.29 [95% CI, 1.13-1.47]). Conclusions and Relevance: In the CKD-PC, 11% of outpatient participants and 35% of hospitalized patients had an eGFRcys that was at least 30% lower than their eGFRcr. In the outpatient setting, presence of eGFRcys at least 30% lower than eGFRcr was associated with significantly higher rates of all-cause mortality, cardiovascular events, and kidney failure.

Authors with CRIS profile

Involved external institutions

University of California San Francisco (UCSF) United States (USA) (US) New York University (NYU) United States (USA) (US) Research Center in Epidemiology and Population Health / Centre de recherche en Epidémiologie et Santé des Populations (CESP) France (FR) Dalarna University / Högskolan Dalarna Sweden (SE) Ruprecht-Karls-Universität Heidelberg Germany (DE) Karolinska Institute Sweden (SE) Tufts Medical Center United States (USA) (US) Yamagata University (YU) Japan (JP) University of Glasgow United Kingdom (GB) University of Pennsylvania (UPenn) United States (USA) (US) University of Vermont United States (USA) (US) University Medical Center Groningen (UMCG) / Universitair Medisch Centrum Groningen Netherlands (NL) Framingham Heart Study United States (USA) (US) University College London (UCL) United Kingdom (GB) Postgraduate Institute of Medical Education and Research (PGIMER) / स्नातकोत्तर चिकित्सा शिक्षा एवं अनुसंधान संस्थान चण्डीगढ़ India (IN) VA San Diego Healthcare System United States (USA) (US) Niigata University / 新潟大学 Japan (JP) Monash University Australia (AU) University Medical Centre Utrecht (UMC Utrecht) Netherlands (NL)

How to cite

APA:

Estrella, M.M., Ballew, S.H., Sang, Y., Grams, M.E., Coresh, J., Surapaneni, A.,... Eckardt, K.-U. (2025). Discordance in Creatinine- and Cystatin C-Based eGFR and Clinical Outcomes: A Meta-Analysis. Journal of the American Medical Association. https://doi.org/10.1001/jama.2025.17578

MLA:

Estrella, Michelle M., et al. "Discordance in Creatinine- and Cystatin C-Based eGFR and Clinical Outcomes: A Meta-Analysis." Journal of the American Medical Association (2025).

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