Multiple myeloma (MM) frequently causes renal impairment (RI), and clinical therapy becomes more challenging if renal function deteriorates or renal failure results. Therefore, in order to evaluate their prognostic potential in predicting renal impairment risk in MM patients, we investigated the expression levels of miR- 17 - 5p and miR- 125a- 5p as well as STAT3 and CD69 proteins as probable shared target genes in MM adult patients with and without RI. This study included 60 controls and 120 MM patients. By using RT-qPCR, the expression levels of miR- 17 - 5p and miR- 125a- 5p in the sera of MM patients and controls were evaluated. Also, the expression levels of CD69 and STAT- 3 were examined using ELISA and flowcytometry techniques, respectively. When MM patients were compared to controls and MM patients with RI to MM patients without RI, the expression levels of miR- 17 - 5p and miR- 125a- 5p were reduced, but CD69 and STAT- 3 were elevated. Results obtained from ROC curve showed that they were good prognostic biomarkers could predict renal impairment in MM patients, with AUC 0.754, 0.936, 1 & 0.991; respectively for miR- 17 - 5p, miR- 125a- 5p, STAT- 3 and CD69, 60%, 93.3%, 100% & 96.7% sensitivity and 73.3%, 86.7%, 100% & 90% specificity; respectively for miR- 17 - 5p, miR- 125a- 5p, STAT- 3 and CD69. While for Kaplan-Meier survival, our results indicated that patients with lower expression levels of miR- 17 - 5p and miR- 125a- 5p, but higher STAT- 3 and CD69 concentration, had a poorer prognosis and possessing a shorter OS. The integrated approach reveals miR- 17 - 5p, miR- 125a- 5p, CD69, and STAT- 3 as reliable prognostic biomarkers for predicting renal impairment in MM patients.