Comparison of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD) Study Equations and A Formula Based on Cystatin-C and Serum Creatinine for the Estimation of Glomerular Filtration Rate in Patients with Multiple Myeloma; Is It Time to Change From MDRD to CKD-EPI Equation?
Authors: Dimopoulos Meletios Athanasios , Kastritis Efstathios , Katodritou Eirini , Pouli Anastasia , Michalis Eurydiki , Christoulas Dimitrios , Gkotzamanidou Maria , Papassotiriou Ioannis , Zervas Konstantinos , Terpos Evangelos 
Published: October 2019

Abstract
Abstract 5091
Renal impairment (RI) is a frequent complication in multiple myeloma (MM). The IMWG has recommended the use of the MDRD formula for the estimation of glomerular filtration rate (GFR) in MM patients with stabilized serum creatinine (sCr) and the classification of these patients in the 5 stages of RI, according to the KDIGO classification (Dimopoulos et al, JCO 2010;28:4976–84). Because MDRD equation has limitations, especially in the normal or near-normal GFR range, other prediction equations based on serum cystatin-C (cys-C), a very sensitive GFR surrogate marker, have been suggested for use in patients with CKD. Furthermore, the CKD-EPI has proposed a new formula for the estimation of GFR, which is based on age, race and sCr, and it seems to be more accurate than the MDRD equation in the estimation of GFR in CKD and in kidney transplant patients (Levey et al, Ann Intern Med 2009;150:604–12). The aim of this study was to evaluate the renal function of newly diagnosed patients with symptomatic MM using the MDRD, the CKD-EPI equations and an equation based on Cys-C/age/sCr (Stevens et al, Am J Kidney Dis 2008;51:395–406) and explore their prognostic value on survival.
We studied 204 newly-diagnosed, previously untreated, symptomatic MM patients. The median age was 69 years (range: 36–94 years); 62% of patients were >65 years of age, 57% were males and 16% had sCr ≥2 mg/dl. Serum Cys-C was measured using a latex particle-enhanced nephelometric immunoassay (Dade Behring, Liederbach, Germany). Serum Cys-C was increased in MM patients compared to 52 age- and gender-matched controls [median: 1.07 mg/l vs. 0.72 mg/l, p<0.0001]. The median values for eGFR calculated by the MDRD, the Cys-C/age/sCr and the CKD-EPI equations were 63.95 ml/min/1.73m2, 68.08 ml/min/1.73m2 and 56.5 ml/min/1.73 m2, respectively (p<0.01 for all comparisons between equations).
Patients were divided in the 5 CKD stages of KDIGO classification, according to eGFR (stage 1: eGFR >90 ml/min/1.73 m2; stage 2: 60–89 ml/min/1.73m2; stage 3: 30–59 ml/min/1.73 m2; stage 4: 15–29 ml/min/1.73 m2; stage 5: <15 ml/min/1.73 m2 or on dialysis). For each studied equation, the number of patients with RI stage 3–5 (i.e. eGFR <60 ml/min/1.732) was 43% for MDRD vs. 42% for Cys-C/age/sCr vs. 53% for CKD-EPI (p<0.001; see also the table). Concordance for CKD stage allocation for the three equations of estimating eGFR was 68% for MDRD vs. CKD-EPI, 68% for MDRD vs. Cys-C/age/creatinine and 61% for CKD-EPI vs. Cys-C/age/sCr (see also the table). A significant correlation was found between ISS stage and MDRD, Cys/age/creatinine and CKD-EPI calculated eGFR (p<0.001 for all).
The median survival for all patients was 49 months. Overall survival was significantly shorter for patients with CKD stage 3, 4 or 5, calculated by the different studied equations, compared to those with CKD stage 1 or 2 (p<0.01 for all equations). Thus, we pooled patients with CKD stages 1 and 2 and CKD stages 3–5 for survival analysis. By using the eGFR of 60 ml/min/1.73 m2 as a cut-off, patients with eGFR <60 ml/min/1.73 m2, assessed by each of the 3 studied equations, had a significantly shorter median overall survival: 24 months vs. 98 months (χ2=9.8, p=0.002) for MDRD equation, 27 months vs. 98 months (χ2=12.8, p<0.001) for Cys-C/age/sCr equation and 38 months vs. not reached (χ2=13.3, p<0.001) for CKD-EPI equation.
When we adjusted for ISS stage, the allocation to RI of stage 3–5, using the CKD-EPI equation, was significantly associated with survival (p=0.041); this was not observed for the allocation to stage 3–5 RI using the other formulas (p=0.357 for MDRD equation and p=0.235 for Cys-C/age/sCr equation).
Our data suggest that CKD-EPI equation for the estimation of GFR detects more MM patients with stage 3–5 RI than MDRD or Cys-C/age/sCr equations. Furthermore, CKD-EPI was the only equation that could predict for overall survival adjusted for ISS stage. The confirmation of these data may lead to the broader use of CKD-EPI formula for the evaluation of RI in patients with MM, as it has been suggested for patients with several renal disorders.Table.Evaluation of Renal Function Stage by Different EquationsCKD stageMDRD equationEquation based on Cys-C/age/sCrCKD-EPI equationp-value147 (23%)51 (25%)30 (15%)270 (34%)68 (33%)66 (32%)Friedman-test354 (26%)54 (26%)68 (33%)p<0.001422 (11%)23 (11%)23 (11)511 (5%)8 (4%)17 (8%)

Disclosures:
No relevant conflicts of interest to declare.