TY - JOUR
T1 - Discordance in Creatinine- and Cystatin C-Based eGFR and Clinical Outcomes
T2 - A Meta-Analysis
AU - Estrella, Michelle M.
AU - Ballew, Shoshana H.
AU - Sang, Yingying
AU - Grams, Morgan E.
AU - Coresh, Josef
AU - Surapaneni, Aditya
AU - Alencar De Pinho, Natalia
AU - Ärnlöv, Johan
AU - Brenner, Hermann
AU - Carrero, Juan Jesus
AU - Chen, Teresa K.
AU - Cohen, Debbie L.
AU - Cushman, Mary
AU - Gansevoort, Ron T.
AU - Hwang, Shih Jen
AU - Inker, Lesley A.
AU - Ix, Joachim H.
AU - Kabasawa, Keiko
AU - Konta, Tsuneo
AU - Lees, Jennifer S.
AU - Polkinghorne, Kevan R.
AU - Shlipak, Michael G.
AU - Vernooij, Robin W.M.
AU - Wheeler, David C.
AU - Yadav, Ashok Kumar
AU - Levey, Andrew S.
AU - Eckardt, Kai Uwe
N1 - Publisher Copyright:
© 2025 American Medical Association.
PY - 2025/12/2
Y1 - 2025/12/2
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105021447828
U2 - 10.1001/jama.2025.17578
DO - 10.1001/jama.2025.17578
M3 - Article
C2 - 41202182
AN - SCOPUS:105021447828
SN - 0098-7484
VL - 334
SP - 1915
EP - 1926
JO - JAMA
JF - JAMA
IS - 21
ER -