The relationship between nephropathy which is developped in newly diagnosed multiple myeloma patients and podocyturia and evaluation of it's response to treatment

SUMMARY The Relationship Between Nephropathy Which is Developped in Newly Diagnosed Multiple Myeloma Patients and Podocyturia and Evaluation of it's Response to Treatment Objective: Multiple myeloma is a malignant disease that results in the proliferation of a single plasma cell clone originating from post-germinal center B cells. The disease is frequently accompanied by renal dysfunction. Proteinuria; also may be observed in patients receiving multiple myeloma diagnosis, at the time of diagnosis or throughout the disease. Proteinuria may not be accompanied by renal dysfunction. The most common causes of renal damage are precipitation and reabsorbtion of light chains in tubules and metabolic disorders like hypercalcemia. The purpose of our study; to assess the presence of podocyturia with laboratory and clinical findings of the disease by measuring podocyte-specific proteins at the beginning and after treatment of patients with newly diagnosed multiple myeloma. Material and Methods: This study group consisted of 27 newly diagnosed multiple myeloma patients who were followed in our hematology and oncology clinics between April 2016 and July 2017. Seven patients in this group died before completing our study, so they could not be assessed at 6th month. In addition, 20 individuals who have no any disease and take medications were included for control group. With the informed consent of all participants, the study was approwed by the Ethics Review Board at Çukurova University Faculty of Medicine. Urines were collected by both control and study group as 24 hour or spot urine at first in the morning and RNA was isolated by using RNA isolation kit from urine. Then, cDNA was produced and PCR was processed. Podocytes were identified by PCR tagging nephrin, podocyn and VEGF-A and podocyte characteristic mRNA was detected. Results: Mean age was 59,63±10,21 and 34,75±12,07 in patients and controls, respectively. Proteinuria was found in 74% and renal failure in 33% of the cases. Median proteinuria was 45 mg in controls and 725 mg in patients (p<0,001). Proteinuria significantly decreased at the sixth month of therapy (p<0,002) while urine podocyte proteins increased not significantly after treatment as compared with the pretreatment levels; p values for nephrin, podosin and VEGF-A were 0,184, 0,629 and 0,794, respectively. Nephrin/creatinine, podosin/creatinine and VEGF-A/creatinine ratios were increased after treatment as compared with pretreatment levels (p:0,039, p<0,001, p<0,001 respectively). Nephrin/creatinine ratio was also found to be increased after treatment in cases with older than 65 years (p<0,046). All the podosit proteins were detected in controls and there were correlations between podosinuria and serum calcium and total protein and urine VEGF A and creatinine clearance. The most common finding was renal failure in cases dying before the completion of treatment (p<0,029). Conclusion: Proteinuria and renal failure were detected in 74% and 33% of the patients with newly diagnosed multiple myeloma. At the end of 6 months of treatment, proteinuria statistically significantly decreased while podosit proteins such as nephrin, podosin and VEGF-A increased. Renal failure and proteinuria were found more frequently in cases dying within 6 months. Proteinuria and renal failure improved with myeloma treatment. However podosit proteins increased after treatment and this may be related with drugs used in these cases or due to other factors. It can be said that podosit damage can not be determined by the measurement of urinary podosit specific proteins in early stage of multiple myeloma or myeloma associated light chains may be more important in tubular damaging effects in renal failure. Keywords: Multipl Myeloma, Podocyturia, Proteinuria