Disease areas:
  • heart and blood vessels
  • reproductive and urinary health
Last updated:
Author(s):
Michelle M. Estrella, Shoshana H. Ballew, Yingying Sang, Morgan E. Grams, Josef Coresh, Aditya Surapaneni, Natalia Alencar de Pinho, Johan Ärnlöv, Hermann Brenner, Juan-Jesus Carrero, Teresa K. Chen, Debbie L. Cohen, Mary Cushman, Ron T. Gansevoort, Shih-Jen Hwang, Lesley A. Inker, Joachim H. Ix, Keiko Kabasawa, Tsuneo Konta, Jennifer S. Lees, Kevan R. Polkinghorne, Michael G. Shlipak, Robin W. M. Vernooij, David C. Wheeler, Ashok Kumar Yadav, Andrew S. Levey, Kai-Uwe Eckardt, Teresa K Chen, Yingying Sang, Morgan E Grams, Josef Coresh, Steven Chadban, Kevan Polkinghorne, Nisha Bansal, Joachim H Ix, Michael G Shlipak, Marie Metzger, Benedicte Stengel, Martin Landray, John N Townend, Jonathan Emberson, Chi-yuan Hsu, Wei Yang, Amanda Anderson, Hermann Brenner, Dietrich Rothenbacher, Ben Schöttker, Hannah Stocker, Daniel Levy, Martin Larson, Anna Kottgen, Peggy Sekula, Ulla T Schultheiss, Markus P Schneider, Vivek Kumar, Manisha Sahay, Narayan Prasad, Robin WM Vernooij, Andrew S Levey, Lesley A Inker, Mark Sarnak, Orlando M Gutierrez, Mary Cushman, Stephan JL Bakker, Lyanne M Kieneker, Marco van Londen, Katharine Cheung, Titi Ilori, Edouard L Fu, Anne-Laure Faucon, Aurora Caldinelli, Antoine Creon, Tsuneo Konta, Kazunobu Ichikawa, Satoru Nagase, Masafumi Watanabe, Jennifer S Lees, Patrick B Mark, Anders Larsson, Vilmantas Giedraitis, Keiko Kabasawa, Yumi Ito, Junta Tanaka, Ichiei Narita, Michelle Estrella, Shoshana H Ballew, Juan-Jesus Carrero, Ron T Gansevoort, Kunihiro Matsushita, Dorothea Nitsch, Angela Yee-Moon Wang, Carina M Flaherty, Aditya Surapaneni
Publish date:
2 December 2025
Journal:
JAMA: The Journal of the American Medical Association
PubMed ID:
41202182
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 821 327 individuals from 23 outpatient cohorts (mean [SD] age, 59 [12] years; 48% female; 13.5% with diabetes; 40% with hypertension) and 39 639 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.