Original Investigation GFR Estimation Using Standardized Cystatin C in Kidney Transplant Recipients Ingrid Masson, MD, 1,2 Nicolas Maillard, MD, 1,2 Ivan Tack, MD, PhD, 3 Lise Thibaudin, MD, 2,4 Laurence Dubourg, MD, 5 Pierre Delanaye, MD, PhD, 6 Etienne Cavalier, MD, PhD, 7 Christine Bonneau, MD, 8 Nassim Kamar, MD, PhD, 9,10,11 Emmanuel Morelon, MD, PhD, 12 Olivier Moranne, MD, PhD, 13 Eric Alamartine, MD, PhD, 1,2 and Christophe Mariat, MD, PhD 1,2 Background: The utility of serum cystatin C (SCysC) as a filtration marker in kidney transplantation is uncertain. We took advantage of the recent validation of a reference calibrator for SCysC and of newly developed CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations (2012) expressed for use with standardized SCysC level to reassess the performance of SCysC as a filtration marker in kidney transplant recipients. Study Design: Study of diagnostic test accuracy. Setting & Participants: 670 kidney transplant recipients from 3 centers undergoing glomerular filtration rate (GFR) measurements from December 2006 to November 2012. Index Test: Estimated GFR (eGFR) using the 2012 SCysC-based and serum creatinine (SCr)/SCysC- based CKD-EPI equations (eGFR cys and eGFR cr-cys , respectively) and the 2009 SCr-based CKD-EPI equation (eGFR cr ), with SCysC and SCr measured at a single laboratory between April 2011 and June 2011. Reference Test: Measured GFR (mGFR) using urinary clearance of inulin. Results: Bias (the difference between mGFR and eGFR) was significantly smaller for eGFR cys and eGFR cr-cys versus eGFR cr (-2.82 and -0.54 vs +4.4 mL/min/1.73 m 2 , respectively; P  0.001). Precision (standard deviation of the mean bias) also was better for eGFR cys and eGFR cr-cys versus eGFR cr (12 and 11 vs 13 mL/min/1.73 m 2 [P  0.001 for both comparisons]). Accuracy (percentage of GFR estimates within 30% of mGFR) was greater for eGFR cys and eGFR cr-cys versus eGFR cr (81% and 86% vs 75%, respectively [P = 0.004 and P  0.001]). Net reclassification index with respect to mGFR of 30 mL/min/1.73 m 2 for eGFR cr-cys and eGFR cys versus eGFR cr was 18.8% [95% CI, 8.6%-28.9%] and 22.5% [95% CI, 10.2%-34.9%]. Limitations: Patients were exclusively of European descent; association with transplant outcome was not evaluated. Conclusions: Our data validate the use of both the newly developed SCysC-based and SCr/SCysC-based CKD-EPI equations (2012) in kidney transplant recipients. Both equations perform better than the SCr-based CKD-EPI equation (2009). Am J Kidney Dis. 61(2):279-284. © 2013 by the National Kidney Foundation, Inc. INDEX WORDS: Glomerular filtration rate; inulin; renal transplantation; cystatin C. S erum creatinine (SCr)-based glomerular filtration rate (GFR) estimates by their nature are bound to be suboptimal in many situations. 1-3 The primary limitations of creatinine as an endogenous filtration marker are its direct dependency on muscle (and thereby on several variables linked to muscular mass) and the process of tubular secretion that, along with glomerular filtration, substantially contributes to its clearance. 4 Serum cystatin C (SCysC), as an alternative GFR biomarker, has the potential to circumvent many of the shortcomings of SCr and as such is being evaluated as part of several GFR-estimating equations. 5,6 However, until recently, thorough evaluation of SCysC has been From the 1 Service de Néphrologie Dialyse Transplantation rénale, CHU Hopital Nord; 2 Université de Saint-Etienne PRES Université de Lyon, Saint-Etienne; 3 Service des explorations fonc- tionnelles physiologiques, CHU Toulouse Rangeuil, Toulouse; 4 Laboratoire d’explorations fonctionnelles rénales, CHU Hopital Nord, Saint-Etienne; 5 Explorations fonctionnelles rénale et mé- tabolique, CHU Edouard Herriot, Lyon, France; 6 Service de dialyse and 7 Service de Biochimie, CHU Sart Tilman, Liège, Belgium; 8 Service de Biochimie, CHU Hopital Nord, Saint- Etienne; 9 Service de Néphrologie Dialyse Transplantation d’organes, CHU Toulouse Rangeuil; 10 INSERM U1043, IFR– BMT, CHU Purpan; 11 Université Paul Sabatier Toulouse; 12 Ser- vice de Transplantation rénale, CHU Edouard Herriot, Lyon; and 13 Service de Néphrologie Dialyse Transplantation rénale et départe- ment d’épidémiologie, CHU Nice, Nice, France. Received January 26, 2012. Accepted in revised form September 27, 2012. Originally published online November 12, 2012. Address correspondence to Christophe Mariat, Service de Néphrologie, Dialyse et Transplantation Rénale, Hôpital Nord, C-H-U de Saint-Etienne, 42055 Saint-Etienne, France. E-mail: christophe.mariat@univ-st-etienne.fr © 2013 by the National Kidney Foundation, Inc. 0272-6386/$36.00 http://dx.doi.org/10.1053/j.ajkd.2012.09.010 Am J Kidney Dis. 2013;61(2):279-284 279