ABSTRACT
(1) Background: Soluble urokinase-type plasminogen activator receptor (suPAR) has been implicated in the pathogenesis of kidney disease in different disease settings. The aim of this study was to investigate a possible link between suPAR circulating levels and renal impairment (RI) in newly diagnosed patients with symptomatic multiple myeloma (NDMM) before and after frontline therapy with bortezomib-based regimens. (2) Methods: We studied 47 NDMM patients (57% males, median age 69.5 years) before the administration of anti-myeloma treatment and at best response to bortezomib-based therapy. suPAR was measured in the serum of all patients and of 24 healthy matched controls, using an immuno-enzymatic assay (ViroGates, Denmark). (3) Results: suPAR levels were elevated in NDMM patients at diagnosis compared to healthy individuals (p < 0.001). suPAR levels strongly correlated with disease stage (p-ANOVA < 0.001). suPAR levels both at diagnosis and at best response negatively correlated with estimated glomerular filtration rate (eGFR) values (p < 0.001). Interestingly, no significance changes in suPAR levels were observed at best response compared to baseline values (p = 0.31) among 18 responding patients with baseline eGFR < 50 mL/min/1.73 m2. (4) Conclusions: SuPAR levels reflect renal function in NDMM patients treated with bortezomib-based induction. Responders may have elevated circulating suPAR levels, possibly reflecting persistent kidney damage, despite their renal response.
ABSTRACT
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, ß2-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 µg/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.
