Cystatin C versus Creatinine: Which is the Superior Biomarker in Kidney Transplant Recipients?

Although widely used, serum creatinine–based formulas for estimating GFR have multiple pitfalls related to the production and secretion of creatinine. Serum cystatin C, a low molecular weight protein made in nucleated cells, has been proposed as a superior biomarker for estimating GFR. Recent standardization of cystatin C measurements have made it possible to study cystatin Cbased GFR formulas in various settings. In an article published in February 2013 issue of the American Journal of Kidney Diseases, the Masson et al compare GFR estimating equations created by the CKD-EPI group using standardized cystatin C, serum creatinine, and a combination of creatinine and cystatin C in the kidney transplant population. Authors Drs. Ingrid Masson (IM) and Christophe Mariat (CM) discuss this study with Dr. Vinay Nair (eAJKD), eAJKD Advisory Board member.

eAJKD: Please summarize your study.

IM&CM: Our study evaluated the performance of the new GFR CKD-EPI estimating equation based on cystatin C, as compared to the traditional equation based on serum creatinine. The originality of our study was to focus specifically in the kidney transplant population.

eAJKD: In your study, it is suggested that cystatin C may be a superior biomarker for GFR than serum creatinine. If so, why did the equation that performed the best include both cystatin C and creatinine?

IM&CM: This is something that has been found in the general non-transplant population as well. It may have to do with less bias when you combine the two biomarkers, serum creatinine and serum cystatin C. In the kidney transplant population, we observed the equation based solely on serum cystatin C performed better than serum creatinine–based equations. This is something that was not found in the general population. We believe cystatin C may be an even better GFR marker in transplant patient than in the general population.

eAJKD: In transplant patients, did cystatin C performed better than you expected?

IM&CM: Yes. And we think that this is probably related to the fact that serum creatinine is probably even worse in the transplant than in the general population.

eAJKD: Did you look at any particular characteristics within the population that lead to GFR formulas based on cystatin C to perform especially well or poor? For example, you had patients both on corticosteroids and those not on corticosteroids.

IM&CM: We looked at this specific sub-population. It makes sense because we know steroids influence serum cystatin C in some situations independent of GFR variation.

However, in conventional immunosuppressive regimens used in kidney transplantation, corticosteroid dose is pretty low. You don’t have much difference in test performance between the groups because the patients that are on corticosteroids are typically on very low doses.

We looked at other sub-populations according to BMI, gender, and level of proteinuria. We did not observe significant differences in these categories. We may have lacked statistical power to detect a difference because even though we described cystatin C in a large kidney transplant population, when it comes to looking at sub-populations, the groups become rather small in size.

eAJKD: Cystatin C production may also vary with markers of inflammation. Do you believe these formulas will continue to be valid in instances of AKI? Have they been studied in inflammatory disorders such as transplant rejection, polyomavirus nephropathy, or pyelonephritis?

IM&CM: We do have some data about cystatin C and AKI in critically ill patients in the intensive care unit, where GFR was measured using iohexol clearance.

We found that cystatin C was better correlated with measured GFR than creatinine. Even in a situation when you have some degree of inflammation, we think cystatin C is still better than creatinine in estimating GFR.

In our study population, as maybe you have seen, we tried to evaluate whether the level of CRP was associated with serum cystatin C concentration independent of the GFR. We were unable to find a strong association.

eAJKD: In the future, do you believe we will move from creatinine-based to cystatin C–based formulas for estimating GFR in transplant patients?

IM&CM: We think it’s difficult. You have to consider various situations. When it comes to managing patient in daily practice, it will be difficult to implement cystatin C worldwide because of the cost of cystatin C measurement.

In clinical research, evaluating new therapeutic strategies and new drugs to improve graft function, cystatin C might be better. We think in that specific situation, it would make sense to select cystatin Cbased GFR estimating equations than creatinine-based equations, because when selecting cystatin C, you are in the position to better evaluate the impact of the drug on kidney function.

At this point, we still have a problem with time and economic considerations. Worldwide implementation of serum cystatin C is still premature.

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