Superiority of serum cystatin-C over creatinine in prediction of long-term prognosis at discharge from ICU

Abstract

Objective: Renal outcomes after critical illness are seldom assessed, despite strong correlation between chronic kidney disease (CKD) and survival. Outside hospital, renal dysfunction is more strongly associated with mortality when assessed by serum cystatin-c than by creatinine. The relationship between creatinine and longer-term mortality might be particularly weak in survivors of critical illness. Design: Retrospective observational cohort study Patients: In 3077 adult intensive care unit (ICU) survivors we compared ICU- discharge cystatin-c and creatinine and their association with one year mortality. Exclusions: death within 72h of ICU-discharge, ICU stay <24h, end-stage renal disease. Interventions: None Measurements and main results: During ICU admission serum cystatin-c and creatinine diverged so that by ICU discharge, almost twice as many patients had glomerular filtration rate (GFR) <60ml/min/1.73m2 when estimated from cystatin-c (eGFR-Cys-c) compared to creatinine (eGFR-Cr), 44% vs. 26%. In 743 patients without AKI, where ICU-discharge renal function should reflect ongoing baseline, discharge eGFR-Cr consistently over-estimated follow-up eGFR-Cr, while ICU- discharge eGFR-Cys-c well-matched follow-up CKD status. By one year 535 (17.4%) had died. In survival analysis adjusted for age, sex and comorbidity, cystatin- c was near-linearly associated with increased mortality, hazard ratio (HR)=1.78 (95% CI: 1.46-2.18), 75th versus 25th centile. Conversely, creatinine demonstrated a J- shaped relationship with mortality, so that in the majority of patients there was no significant association with survival, HR=1.03 (0.87-1.2), 75th vs. 25th centile. After adjustment for both creatinine and cystatin-c levels, higher discharge creatinine was then associated with lower long-term mortality. Conclusions: In contrast to creatinine, cystatin-c consistently associated with long- term mortality, identifying patients at both high and low risk, and better correlated with follow-up renal function. Conversely, lower creatinine relative to cystatin-c appeared to confer adverse prognosis, confounding creatinine interpretation in isolation. Cystatin-c warrants further investigation as a more meaningful measure of renal function after critical illness.