Objective ·To investigate the effect of plasma exchange combined with classical chemotherapy on renal function in patients with multiple myeloma (MM). Methods ·A retrospective analysis was conducted on data from patients newly diagnosed with MM in the Department of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, between October 2021 and September 2023. Sixty-eight MM patients admitted from October 2021 to September 2022 served as the control group, and 41 patients admitted from October 2022 to September 2023 comprised the experimental group. The control group received classical chemotherapy for MM [PAD (bortezomib+adriamycin+dexamethasone) or PCD (bortezomib+cyclophosphamide+dexamethasone)], and the experimental group underwent plasma exchange before classic chemotherapy. The frequency of plasma exchange was determined according to the clearance rate of M-protein in patients, with the criterion being a reduction of more than 40% in plasma M-protein levels after exchange, and the total number of exchanges ranged from 1 to 3 sessions. After 2 chemotherapy courses, the free light chain difference (dFLC), serum creatinine (Scr), and other renal function indexes were compared between the two groups. Results ·Compared with the control group, the experimental group showed no statistically significant difference in dFLC levels. The Scr level decreased [67.00 (54.00, 75.00) μmol/L vs 77.50 (63.00, 94.00) μmol/L, P=0.011], and the estimated glomerular filtration rate (eGFR) increased [97.80 (92.80, 101.30) mL/(min·1.73 m²) vs 85.80 (61.35, 95.35) mL/(min·1.73 m²), P<0.001] after treatment. Before treatment, the numbers of patients with MM-related severe renal injury [eGFR<50 mL/(min·1.73 m²)] were 41 in the control group and 28 in the experimental group. After treatment, 8 patients (19.51%) in the control group achieved complete renal response [eGFR≥60 mL/(min·1.73 m²)], while 12 patients (42.86%) in the experimental group achieved the same, with the difference being statistically significant (P=0.036). After two courses of treatment, the overall response rates (ORR) of the control group and the experimental group were 76.47% and 92.68%, respectively, and the difference in overall therapeutic efficacy was statistically significant (P=0.031). Conclusion ·Plasma exchange combined with classical chemotherapy can significantly reduce the Scr levels and increase eGFR in MM patients within a short period, ameliorating the MM-related renal impairment to some extent and improving clinical treatment outcomes.