Cystatin C beats creatinine at predicting complications of kidney disease

Testing for cystatin C, a protease inhibitor made by most cells and a biomarker of renal function, more accurately identifies chronic kidney disease (CKD) patients who are at high risk for complications than creatinine testing does, according to a new study.

The study included more than 11,000 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS). Patients were assessed for chronic kidney disease (defined as estimated glomerular filtration rate [GFR] <60 mL/min per 1.73 m²) using creatinine testing and cystatin C testing. The researchers used CKD-EPI equations to estimate GFR based on the biomarkers. In the MESA study, 9% of participants had CKD based on the creatinine test, 2% had it based on cystatin C and 4% had it according to both measures. In the other study, the percentages were 12%, 4% and 13% respectively. The results were published by the Journal of the American Society of Nephrology on Dec. 16.

The study also assessed the risk of death, cardiovascular events, heart failure and end-stage renal disease among the patients found to have CKD. In the MESA group, patients diagnosed by creatinine had no higher mortality risk than those without CKD (hazard ratio, 0.80; 95% CI, 0.50 to 1.26), while patients who were diagnosed by cystatin C had a significantly increased risk of death (hazard ratio, 3.23; 95% CI, 1.84 to 5.67). Those who tested positive on both had an increased risk with a hazard ratio of 1.93 (95% CI, 1.27 to 2.92). Trends were similar in the CHS study and for the other outcomes tracked by the study.

Recent efforts to improve detection of CKD have promoted the use of creatinine testing, the study authors noted. Given that this study found that patients whose creatinine indicated CKD had no greater risk than average, creatinine-based equations may be leading patients to receive unnecessary nephrology referrals, testing and treatments, the authors said. Cystatin C testing would offer greater specificity and therefore may be useful as either a confirmatory test for patients who've been identified with possible CKD by creatinine testing or, in high-risk groups, as a screening test.

The two tests could also be combined with albuminuria testing, the authors suggested. Future research should evaluate the cost-effectiveness of such a triple screening process. Cystatin C testing—which is becoming more readily available in U.S. labs, the authors noted—could be used in a stepwise system to identify CKD patients who are higher risk for complications. The end result could be more specific screening and less unneeded care, the authors concluded.