Neutrophil Gelatinase-Associated Lipocalin and Cystatin C Are Sensitive Markers of Renal Injury in Patients With Multiple Myeloma

Neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C are sensitive markers that reflect renal injury and tubular-glomerular activation feedback response in newly diagnosed patients with multiple myeloma (MM). The high levels of NGAL in asymptomatic patients with MM and in patients with monoclonal gammopathy of undetermined significance may indicate the presence of subclinical renal damage early in the disease course. NGAL is an early marker that predicts the development of renal insufficiency in MM. Background: Renal impairment is a common complication of patients with multiple myeloma (MM). We aimed to evaluate the clinical significance of 2 newly discovered biomarkers of renal injury, cystatin C (CysC), a protein reflecting glomerular filtration rate, and neutrophil gelatinase associated lipocalin (NGAL), a protein reflecting tubular injuries. Patients and Methods: We studied 64 patients with newly diagnosed myeloma: 16 with asymptomatic (smoldering) MM and 48 with symptomatic myeloma; 8 patients with monoclonal gammopathy of undetermined significance (MGUS); and 20 healthy control subjects. Along with common blood and urine chemistry determinations, measurements of CysC, NGAL, beta 2-microglobulin, high-sensitivity C-reactive protein, and interleukin 6 were performed. Results: We found that only patients with symptomatic MM had increased levels of CysC compared to controls (P < .01); that serum NGAL levels were elevated in all patients compared to controls P < .001; that NGAL strongly correlated with both estimation of glomerular filtration rate (eGFR) (CysC) and eGFR (Modification of Diet in Renal Disease [MDRD] formula) (r = 0.616, P < .0001; and r = 0.371, P < .01, respectively); that CysC showed strong correlation with eGFR (r = 0.782, P < .001) and with the International Scoring System (ISS) (more pronounced in patients with ISS-3); and that receiver operating characteristic curve analysis showed that NGAL values of > 50.5 mu g/L have a 80.8% sensitivity and 86.4% specificity for eGFR < 60 mL/min (area under the curve = 0.764). Conclusion: These findings suggest that both NGAL and CysC are very sensitive markers that reflect renal impairment in newly diagnosed patients with MM. The high levels of NGAL in asymptomatic patients and in MGUS patients support the hypothesis of the presence of renal damage in these patients early in the course of their disease and may reveal NGAL to be an early marker that predicts the presence of renal impairment in MM. (C) 2016 Elsevier Inc. All rights reserved.