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Cystatin C May Trump Creatinine in Determining CKD Risk

Larry Hand
Sep 09, 2013

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Cystatin C alone, or in combination with, creatinine may be a better predictor for death or renal disease than creatinine alone, researchers report in an article published in the September 5 issue of the New England Journal of Medicine. Use of cystatin C may also help physicians better identify patients with chronic kidney disease (CKD) who need intense monitoring or treatment, according to the study results.

The study follows the development of an international cystatin C reference standard for use in various laboratories and publication by the Chronic Kidney Disease Epidemiology Collaboration of improved equations to determine an estimated glomerular filtration rate (eGFR).

Michael G. Shlipak, MD, MPH, and colleagues in the Chronic Kidney Disease Prognosis Consortium, Baltimore, Maryland, conducted a meta-analysis of 11 general population studies involving 90,750 participants and 5 studies involving 2960 participants with CKD. All participants were 18 years old or older, with a mean age of 60 years for the general population and 55 years for the CKD studies.

To calculate the rates of death from all causes, death from heart disease, and rate of end-stage renal disease, the researchers used Cox proportional hazard models with eGFR splines, adjusting for age, sex, race (black vs nonblack), smoking, history of heart disease, presence or absence of diabetes, body mass index, systolic blood pressure, and levels of total cholesterol and albuminuria. They also used the recently published equations.

They first reclassified patients originally classified by creatinine-based eGFR according to cystatin C-based eGFR and compared the 2 eGFR values. They then compared the creatinine equation with a cystatin C–creatinine combination equation.

Among the general population, the estimated risk for death increased across all categories for study participants whose creatinine-based eGFR values translated into lower eGFR values when reclassified based on cystatin C data. For instance, 44% of participants overall fell into the category of 60 to 89 mL/minute per 1.73 m2 of body surface area based on creatinine data. With the cystatin-based eGFR, 14% of these participants were reclassified to an eGFR lower than 60 mL/minute per 1.73 m2; their relative increase risk for death rose 57% compared with reference points (hazard ratio, 1.57; 95% confidence interval, 1.39 - 1.78).

Conversely, for creatinine-based eGFRs that were reclassified into higher eGFR values based on cystatin C data, the researchers found a reduced risk for death across all categories. For instance, when the creatinine-based eGFRs of 30 to 44 and 45 to 59 mL/minute per 1.73 m2 translated to 60 mL/minute per 1.73 m2 or higher, relative risk for death dropped by 34% compared with reference points, the researchers write.

The researchers also found similar results for risk for death from heart disease and risk for end-stage renal disease. They write that the differences may be a result of creatinine's susceptibility to being affected by reduced muscle mass, diet, and physical activity.

"The net reclassification improvement with the measurement of cystatin C, as compared with creatinine, was 0.23 (95% confidence interval [CI], 0.18 to 0.28) for death and 0.10 (95% CI, 0.00 to 0.21) for end-stage renal disease," the authors write. Limitations of this meta-analysis include various methods of measurement used in the studies and a possible lack of generalizability to all ethnic groups.

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"Knowing which patient with chronic kidney disease is at risk for end-stage kidney disease or death could tell us who needs intensive monitoring or intervention," write Julie R. Ingelfinger, MD, from the Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada, and Philip A. Marsden, MD, from the University of Toronto, in an accompanying editorial.

The editorialists note that an important distinction between the current study and previous ones is that in the past, studies usually included more elderly patients with chronic diseases, which make the creatinine eGFR less reliable.

"[T]he study by Shlipak et al. effectively shows that the cystatin C–based eGFR offers the best means of predicting rates of death and end-stage renal disease across diverse populations," the authors write.

This research was supported directly by the National Kidney Foundation and indirectly by Abbott and Amgen. One author reports receiving grant support from Gilead and Pharmalink, another reports serving on a steering committee for Novartis, another reports receiving consulting fees and grant support from Amgen and consulting fees from Merck, and another reports receiving grant support from Amgen. The other authors have disclosed no relevant financial relationships.

N Engl J Med. 2013;369:932-943, 974-975. Article abstract, Editorial extract

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Cite this article: Cystatin C May Trump Creatinine in Determining CKD Risk. Medscape. Sep 09, 2013.

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