Podocyte Injury in Cases with Newly Diagnosed Multiple Myeloma

Abstract

Renal impairment is a frequent complication of multiple myeloma (MM). Our aim was to assess the expression of podocyte-associated nephrin, podocin, and vascular endothelial growth factor (VEGF) A and their relation to renal function, proteinuria, and clinical outcome in patients with newly diagnosed multiple myeloma. This study included 27 patients with newly diagnosed MM and 20 healthy volunteers as control. Patients were evaluated for clinical and laboratory parameters, renal function, proteinuria, and podocyturia at the time of diagnosis and at six months. Seven patients died before completing of treatment (within the first 6 months). Proteinuria was measured in daily urine samples. First-morning spot urine RNA was isolated, cDNA was produced, and polymerase chain reaction (PCR) was processed. Podocytes were identified by PCR tagging nephrin, podocin, and VEGF-A. The mean ages were 59.63 ± 10.21 and 34.75 ± 12.07 for patients and controls, respectively. After six months proteinuria decreased from 885.45 ± 2033.12 mg/day to 398.55 ± 811.34 mg/day (P = 0.002). Comparing to baseline urinary nephrin/creatinine, podocin/creatinine, VEGF-A/creatinine were significantly increased (P = 0.039, P = 0.001, P = 0.001 respectively) while renal function and proteinuria were improved in patients. In controls urinary protein and nephrin/creatinine were lower than that of patients (P = 0.001, P = 0.044). The presence of renal failure at the initial diagnosis was the most important for death (P <0.029). Proteinuria and renal dysfunction were found in 74% and 33%, in patients with newly diagnosed MM, respectively. The presence of podocyte injury at the beginning and also increase after therapy while improvement of proteinuria and renal failure, suggests that podocyte injury can be seen in MM and is affected with treatment. This is the first report about podocyte injury in MM.