Discordance in creatinine- and cystatin C-based eGFR and clinical outcomes: a meta-analysis
QuestionDo individuals with a cystatin C-based estimated glomerular filtration rate (eGFRcys) value at least 30% lower than their creatinine-based estimated glomerular filtration rate (eGFRcr) have higher rates of mortality, cardiovascular events, and kidney failure compared with individuals whose e...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
November 7, 2025
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| In: |
The journal of the American Medical Association
Year: 2025, Volume: 334, Issue: 21, Pages: 1915-1926 |
| ISSN: | 1538-3598 |
| DOI: | 10.1001/jama.2025.17578 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1001/jama.2025.17578
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| Author Notes: | Michelle M. Estrella, MD, MHS; Shoshana H. Ballew, PhD; Yingying Sang, MSc; Morgan E. Grams, MD, PhD; Josef Coresh, MD, PhD; Aditya Surapaneni, PhD; Natalia Alencar de Pinho, PhD; Johan Ärnlöv, MD, PhD; Hermann Brenner, MD, MPH; Juan-Jesus Carrero, PharmD, PhD; Teresa K. Chen, MD, MHS; Debbie L. Cohen, MBBCH; Mary Cushman, MD, MSc; Ron T. Gansevoort, MD, PhD; Shih-Jen Hwang, PhD; Lesley A. Inker, MD, MS; Joachim H. Ix, MD, MAS; Keiko Kabasawa, MD, PhD, MPH; Tsuneo Konta, MD, PhD; Jennifer S. Lees, MBChB, PhD; Kevan R. Polkinghorne, MBChB, PhD; Michael G. Shlipak, MD, MPH; Robin W.M. Vernooij, MS; David C. Wheeler, MD; Ashok Kumar Yadav, PhD; Andrew S. Levey, MD; Kai-Uwe Eckardt, MD; for the Chronic Kidney Disease Prognosis Consortium Investigators and Collaborators |
| Summary: | QuestionDo individuals with a cystatin C-based estimated glomerular filtration rate (eGFRcys) value at least 30% lower than their creatinine-based estimated glomerular filtration rate (eGFRcr) have higher rates of mortality, cardiovascular events, and kidney failure compared with individuals whose eGFRcys is not at least 30% lower than their eGFRcr?FindingsIn this individual participant-level meta-analysis of 821 327 participants from 23 cohorts, an eGFRcys at least 30% lower than eGFRcr was associated with higher mortality, cardiovascular events, and kidney failure with replacement therapy, compared with individuals whose eGFRcys was not at least 30% lower than their eGFRcr.MeaningAn eGFRcys value at least 30% lower than eGFRcr was associated with higher rates of mortality, cardiovascular events, and kidney failure with replacement therapy. ImportanceEstimated 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.ObjectivesTo 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 SourcesParticipants in the Chronic Kidney Disease Prognosis Consortium (CKD-PC).Study SelectionParticipants with concurrent cystatin C and creatinine measurements and clinical outcome measurement.Data Extraction and SynthesisBetween April 2024 and August 2025, data were synthesized using individual-level meta-analysis.Main Outcomes and MeasuresThe 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.ResultsA 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 RelevanceIn 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. This meta-analysis evaluates the prevalence and characteristics of discordance between creatinine- and cystatin C-based estimated glomerular filtration rate as well as the association of discordance with adverse outcomes. |
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| Item Description: | Gesehen am 16.03.2026 |
| Physical Description: | Online Resource |
| ISSN: | 1538-3598 |
| DOI: | 10.1001/jama.2025.17578 |