Large cystatin C-based eGFR and creatinine-based eGFR Discrepancy Linked to Higher Mortality and Kidney Risk: JAMA
Researchers have found in a new study that an eGFRcys value that is 30% or more lower than eGFRcr was associated with increased mortality, more cardiovascular events, and a higher risk of kidney failure requiring replacement therapy. The study was published in JAMA by Michelle M. and colleagues.
This investigation employed an individual-level meta-analysis of global cohorts to quantify the prevalence of large negative eGFR differences, where eGFRcys is at least 30% lower than eGFRcr. It assessed the adverse outcomes associated with them. Data were synthesized between April 2024 and August 2025 from 23 outpatient cohorts (n = 821,327) and 2 inpatient cohorts (n = 39,639). Participants were included only when they had concurrent cystatin C and creatinine measurements along with clinical outcome data. The major measurement was the presence of large negative eGFRdiff, while the secondary outcomes included all-cause mortality, cardiovascular mortality, atherosclerotic cardiovascular disease, heart failure, and kidney failure requiring replacement therapy. Hazard ratios (HRs) were computed by comparing individuals with large negative eGFRdiff to persons with eGFR differences between −30% and 30%.
Among the outpatient participants, the mean ± SD age was 59 ± 12 years, 48% were women, with 13.5% having diabetes and 40% having hypertension. Among the inpatient participants, the mean ± SD age was 67 ± 16 years, 31% were women, with 30% having diabetes and 72% having hypertension. This wide representation made sure that the results generalized across both stable clinical populations and hospitalized people with higher burdens of comorbidities.
Results
A large negative eGFRdiff was present in 11% of outpatient participants (range 3%–50% across cohorts) and 35% of inpatients, indicating that discordance was common and more frequent among hospitalized individuals.
During a mean (SD) outpatient follow-up of 11 (4) years, participants with large negative eGFRdiff exhibited substantially higher adverse event rates.
All-cause mortality occurred at 28.4 vs 16.8 per 1000 person-years (PY) (HR 1.69, 95% CI 1.57–1.82).
Cardiovascular mortality was 6.1 vs 3.8 per 1000 PY (HR 1.61, 95% CI 1.48–1.76).
Atherosclerotic cardiovascular disease occurred at 13.3 vs 9.8 per 1000 PY (HR 1.35, 95% CI 1.27–1.44).
Heart failure events were 13.2 vs 8.6 per 1000 PY (HR 1.54, 95% CI 1.40–1.68).
Kidney failure requiring replacement therapy occurred at 2.7 vs 2.1 per 1000 PY (HR 1.29, 95% CI 1.13–1.47).
These associations collectively demonstrate that cystatin C-based eGFR provides important prognostic information not captured by creatinine alone when discordance is present.
This large CKD-PC analysis reported that 11% of outpatient and 35% of inpatient individuals had cystatin C-based eGFR values at least 30% lower than creatinine-based eGFR, and this discordance was strongly associated with higher mortality, cardiovascular events, and kidney failure. These findings emphasize the clinical prognostic value of identifying eGFR discordance and underscore the importance of cystatin C testing when precision in kidney function assessment is required.
Reference:
Estrella MM, Ballew SH, Sang Y, et al. Discordance in Creatinine- and Cystatin C–Based eGFR and Clinical Outcomes: A Meta-Analysis. JAMA. 2025;334(21):1915–1926. doi:10.1001/jama.2025.17578
