Combined Association of Creatinine, Albuminuria, and Cystatin C with All-Cause Mortality and Cardiovascular and Kidney Outcomes

Background Estimated GFR by serum creatinine (eGFR(creatinine)) is a pivotal measure of kidney function in clinical practice but can be affected by several non-GFR determinants, resulting in misclassification. Combining multiple kidney markers to predict risk is an area of substantial interest. Design, setting, participants, & measurements This study followed 9489 adults from visit 4 (1996-1998) of the Atherosclerosis Risk in Communities Study for a median of 11.2 years, and assessed joint association of eGFR(creatinine), eGFR(cystatin), and urinary albumin/creatinine ratio (ACR) with mortality, coronary heart disease, heart failure, AKI, and ESRD using Cox proportional hazards models. The predictive ability of ACR and eGFR(cystatin) beyond eGFR(creatinine) was also investigated. Results Lower eGFR(creatinine) and eGFR(cystatin) as well as elevated ACR were independently associated with risk for all outcomes. eGFR(creatinine) <60 was not associated with risk of mortality, coronary heart disease, or heart failure if eGFR(cystatin) >= 60 with ACR <30 mg/g compared with those with all three markers above CKD cutoffs (i.e., eGFR(cystatin) >= 60 eGFR(creatinine) >= 60 and ACR<30), whereas risk association with kidney outcomes remained: Hazard ratio (95% confidence interval), 0.96 (0.66, 1.39) for mortality, 0.85 (0.55, 1.31) for coronary heart disease, 0.99 (0.60, 1.63) for heart failure, 1.61 (0.92, 2.82) for AKI, and 3.53 (1.06, 11.68) for ESRD. Adding ACR to the fully adjusted model with eGFR(creatinine) or adding eGFR(cystatin) to both eGFR(creatinine) and ACR improved risk classification for all outcomes (P <= 0.01). Conclusions eGFR(cystatin) can be a useful confirmatory marker in those with eGFR(creatinine) <60 and whose ACR is <30 mg/g. This approach improves risk classification, and provides reassurance to a large group of individuals with eGFR(creatinine) <60. Clin J Am Soc Nephrol 8: 434-442, 2013. doi: 10.2215/CJN.04960512