| Title: | Discordance in Creatinine- and Cystatin C-Based eGFR and Clinical Outcomes |
| Journal: | JAMA: The Journal of the American Medical Association |
| Published: | 2 Dec 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41202182/ |
| DOI: | https://doi.org/10.1001/jama.2025.17578 |
| URL: | https://pmc.ncbi.nlm.nih.gov/articles/PMC12595547/ |
Publication 18782
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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.</p>
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.</p>
Data Sources: Participants in the Chronic Kidney Disease Prognosis Consortium (CKD-PC).</p>
Study Selection: Participants with concurrent cystatin C and creatinine measurements and clinical outcome measurement.</p>
Data Extraction and Synthesis: Between April 2024 and August 2025, data were synthesized using individual-level meta-analysis.</p>
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.</p>
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]).</p>
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.</p>
15 Keywords
- Aged
- Atherosclerosis
- Cardiovascular Diseases
- Creatinine
- Cystatin C
- Female
- Glomerular Filtration Rate
- Heart Failure
- Humans
- Kidney Failure, Chronic
- Male
- Middle Aged
- Prognosis
- Renal Insufficiency, Chronic
- Renal Replacement Therapy
93 Authors
- 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
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