Improved Prediction of Kidney Disease by Estimating Renal Function: Use in Multiple Myeloma Patients Treated with Standard Versus High-Dose Chemotherapy Followed by Autologous Peripheral Blood Stem Cell Transplantation.
Authors: Kleber Martina , Ngo Truc , Ihorst Gabriele , Koch Bernd , Engelhardt Monika 
Published: October 2019

Abstract
Multiple myeloma (MM) is characterized by the expansion of clonal plasma cells, leading to bone disease, marrow insufficiency and renal impairment (RI). However, the influence of milder degrees of RI and chronic kidney disease (CKD) is less well defined which seems of importance especially in MM patients (pts). We have previously reported in 167 cancer pts that estimating the glomerular filtration rate (eGFR) as compared to serum creatinine (crea) or cystatin levels best defines certain risk groups: with decreased eGFR, pts demonstrated to be older, had a higher body mass index and various other risk factors, indicating that eGFR determines early stages of renal impairment (RI) and prognostically adverse risk groups (Blood2005;106:2250). In order to analyze the frequency and particularly mild RI in a homogenous pt group, we determined renal function in 131 MM pts receiving standard (Std; n=69) or high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (hd CTx; n=62). We determined the disease-stage, sex, age, performance status (Karnofsky index=KI) and number of concurrent diagnoses (CD). Moreover, serum crea and eGFR (estimated by the four-component “Modification of Diet in Renal Disease” (MDRD) equation: NEJM2006;354:2473) were assessed. We defined CKD according to the guidelines of the National Kidney Foundation/Kidney Disease Outcome Quality Initiative. Despite a median of only 3 CD (range; 0–9) and an almost normal KI (median: 90%; range; 40–100) of all pts, the median age in the Std vs. hd CTx group was significantly higher with 65 vs. 54 years (p<0.001, Wilcoxon 2sample test), respectively. More advanced disease, as defined as pt number with stage II/III disease by Durie and Salmon (D&S) were lower in the Std vs.hd CTx group (86 vs. 95.1%, respectively), but pts with D&S stage B disease were higher in the Std group with 20% vs. 8% in the hd CTx group. This led us to hypothesis, that due to advanced age and more stage B disease in the Std group, RI was more frequent in this pt group. Of note, the median serum crea levels were comparable with 0.9 in the Std vs. 0.7mg/dl in the hd CTx group. Nevertheless, substantial differences between Std. vs. hd CTx pts were detected with analysis of the pt percentages with an elevated crea (>1.1mg/dl) [39% vs. 13%], eGFR<60ml/min/1.73m2 [37% vs. 9.7%], number of CD≥3 [46% vs. 69%] and KI≥90% [48% vs. 68%] (p<0.05), leading to decreased odds ratios (OR) in the hd CTx group of 0.1 (95%CI 0.1–0.3) for age ≥60y, 0.2 (CI 0.1–0.6) for crea>1.1 and 0.2 (CI 0.1–0.5) for eGFR<60, and increased OR for KI≥90 of 2.3 (CI 1.1–4.7) and CD≥3 of 2.7 (CI 1.3–5.6) as compared to the Std group. Differences in RI with active vs. non-active MM disease for all pts and within Std and hd CTx pts were insignificant. These results highlight the importance of reliably detecting early RI in cancer pts and its potential clinical consequences. eGFR may prove a valuable marker to subgroup MM pts and important for their assessment. Future longitudinal analyses with inclusion of disease outcome will determine whether eGFR, compared to other measurements of renal dysfunction, can be used as a useful prognostic marker in MM.