Cystatin C Levels May Accurately Stratify Risk of Cardiovascular Disease in Patients With Chronic Kidney Disease


The estimation of glomerular filtration rate based on cystatin C could provide a more robust prediction of cardiovascular disease and mortality in patients.

For patients tested for chronic kidney disease (CKD), estimations of glomerular filtration rate based on cystatin C (eGFRcys) were found 4 times more effective than testing levels of estimated glomerular filtration rate based on serum creatinine (eGFRcr).

“Use of eGFRcys better discriminated CVD and mortality risk than eGFRcr,” the study authors wrote in an article published by JAMA Network Open. “The eGFRcys appears to be more sensitive and specific for CVD and mortality risks in mild CKD.”

CVD and mortality risks were 2-times greater in older patients with an eGFRcys that was less than 60 mL/min/1.73 m2. Additionally, when eGFRcys was greater than/equal to 60 mL/min/1.73 m2, the 10-year probability of CVD or death was found low.

CKD is tested by finding the glomerular filtration rate (GFR), and multiple tests have determined that the threshold for CKD diagnosis is 60 mL/min/1.73 m2.

The guidelines for Kidney Disease Improving Global Outcomes do not recommend diagnosing CKD using the eGFRcr test alone because it measures GFR using creatinine. This test could lead to inaccuracies because older patients generally have less muscle mass, and creatinine is not quickly produced in a low muscle mass environment.

In previous studies, eGFRcys was found to be a risk stratification for kidney failure, death, and to improve risk prediction of CVD and death.

Researchers wanted to evaluate whether testing concordance between eGFRcr, eGFRcys, or performing tests (eGFRcr-cys) could improve detecting high-risk CKD. In the study, 428,402 participants sampled from the UK Biobank were stratified by age and tested for cystatin C levels, creatinine levels, or both.

“Our findings suggest that in the absence of eGFRcys testing, eGFRcr underestimates the broader risks of CVD and death associated with mild CKD,” the study authors wrote in the report. “Our findings have important implications for CKD guideline development.”

The data further showed that eGFRcys improved Net Reclassification Index (NRI) by 0.7%. The NRI was implemented to examine eGFRcys and its ability to assess CVD risk factors over a 10-year timeframe. If the NRI was greater than 7.5%, the CKD patient could be eligible (or considered) to take a moderate- or high-intensity statin to reduce CVD risk.

Researchers defined CKD using baseline measurements of creatine, cystatin C, and albuminuria, which is considered a study limitation. Additionally, the findings may not be generalized to individuals older than 73 years of age or people in other racial groups. Finally, patients did not have measured GFR levels, which suggests risk may not solely relate to kidney function, according to the study.

“Measuring cystatin C levels allows the flexibility to report the combined equation (eGFRcr-cys), which reduces bias associated with non-GFR determinants of creatinine and cystatin C levels,” the study authors wrote in the report.


Lees, Jennifer, Rutherford, Elaine, Stevens, Kathryn, et al. Assessment of Cystatin C Level for Risk Stratification in Adults With Chronic Kidney Disease. JAMA Netw Open. 2022;5(10):e2238300. doi:10.1001/jamanetworkopen.2022.38300

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