Lower Cystatin C based eGFR Compared to creatinine based eGFR Linked to Worse Outcomes: JAMA

A new study published in the Journal American Medical Association showed that patients with an Cystatin C based estimated glomerular filtration rates (eGFR) value at least 30% lower than their creatinine based eGFR showed significantly higher risks of mortality, cardiovascular events, and kidney failure requiring replacement therapy.

A clinically relevant indicator of renal and cardiovascular health is the discrepancy between eGFR calculated from serum creatinine and cystatin C. Although these indicators assess renal function, they represent distinct physiological pathways: cystatin C is regulated by inflammation and metabolic condition, whereas creatinine is influenced by muscle mass and nutrition.

Higher risks of death, cardiovascular events, and renal failure are frequently seen in those with lower cystatin C-based eGFR when compared to creatinine-based estimations. Thus, this study assessed the frequency of a discordance between cystatin C-based eGFR (eGFRcys) and creatinine-based eGFR (eGFRcr), identify traits linked to higher discordance, and assess correlations of discordance with unfavorable outcomes.

The Chronic Kidney Disease Prognosis Consortium (CKD-PC) participants provided the data. participants with simultaneous assessments of creatinine, cystatin C, and clinical outcomes. Individual-level meta-analysis was used to synthesize data between April 2024 and August 2025. A high negative eGFR difference (eGFRdiff), which is defined as an eGFRcys that was at least 30% lower than eGFRcr, was the main independent measurement. Heart failure, renal failure with replacement treatment, atherosclerotic cardiovascular disease, and all-cause and cardiovascular death were secondary (dependent) outcomes.

The study included 821,327 individuals from 23 outpatient cohorts (mean [SD] age, 59 [12] years; 48% female; 40% with hypertension, 13.5% with diabetes;) and 39,639 from 2 inpatient cohorts (mean [SD] age, 67 [16] years; 31% female; 30% with diabetes; 72% with hypertension). A significant negative eGFR difference (3%-50%) was seen in 11% of outpatients and 35% of inpatients.

Outpatients with a large negative eGFRdiff had higher rates of all-cause mortality (28.4 vs 16.8 per 1000 PY; 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]), and atherosclerotic cardiovascular disease .

Overall, in the CKD-PC, 11% of outpatients and 35% of inpatient patients had an eGFRcys that was at least 30% lower than their eGFR. In the outpatient environment, having eGFRcys at least 30% lower than eGFRcr was linked to considerably increased risks of all-cause mortality, kidney failure and cardiovascular events.

Source:

Estrella, M. M., Ballew, S. H., Sang, Y., Grams, M. E., Coresh, J., Surapaneni, A., Alencar de Pinho, N., Ärnlöv, J., Brenner, H., Carrero, J.-J., Chen, T. K., Cohen, D. L., Cushman, M., Gansevoort, R. T., Hwang, S.-J., Inker, L. A., Ix, J. H., Kabasawa, K., Konta, T., … Chronic Kidney Disease Prognosis Consortium Investigators and Collaborators. (2025). Discordance in creatinine- and cystatin C-based eGFR and clinical outcomes: A meta-analysis: A meta-analysis. JAMA: The Journal of the American Medical Association. https://doi.org/10.1001/jama.2025.17578