A 63-year-old male who had proteinuria for three years presented at our department for aggravating anemia and impaired renal function. Before he came to our hospital, he had already received a renal biopsy which revealed an MPGN-like glomerular injury. He also had monoclonal IgGkappa on serum IFE. He had received a 1-year course of immunosuppressive therapy combined with prednisone (15 mg daily) and tacrolimus (1.5 mg twice daily) due to nephrotic syndrome (UTP 5.48 g/d, Alb 30.4 g/L, eGFR 95.372 ml/min/1.7 m2). After immunosuppressive therapy, his nephrotic syndrome achieved complete remission, but his anemia and impaired renal function persisted. His vital signs were normal when referred to our hospital. His past medical history included hypertension and dyslipidemia. The laboratory findings indicated relieved proteinuria but persistent hypoproteinaemia and impaired renal function (UTP 0.88 g/d, Alb 28.6 g/L, eGFR 61.022 ml/min/1.7 m2). The hematological evaluation revealed moderate anemia (Hgb 89 g/L). He had no microscopic haematuria, hypercalcemia, or myocardial injury. He had normal IgG and IgA serum levels with a lower serum level of IgM (0.39 g/L) and a deficient C4 serum level (<0.07 g/L) with a relatively low C3 level (0.67 g/L). Complement factor H, anti-CFH antibody, and ADAMTs13 activity were normal. He had monoclonal IgGkappa+kappa on serum IFE, and monoclonal kappa on urine IFE. The serum free kappa/lambda ratio was 43.7 (kappa 1580.0 mg/L, lambda 36.1 mg/L). He also had cryoglobulinemia, which was monoclonal IgG and kappa, but without correlative clinical symptoms. The bone marrow aspiration revealed 4% plasma cells with 2.5% naive plasma cells, while the bone marrow biopsy did not reveal evidence of plasmacytoma. A repeated renal biopsy was conducted. Light microscopy showed moderate diffuse mesangial cell proliferation and an increase in the mesangial matrix that contained nodular lesions and a thickening and double contour of the GBM. The tubulointerstitium exhibited multifocal lymphocyte and monocyte infiltration, fibrosis, and moderate tubular atrophy. No microthrombus was observed. Congo red staining was negative. Immunofluorescence results were strongly positive for kappa light-chain deposition along the glomerular capillary wall, mesangial region, and segmental TBM. Electron microscopy revealed electron-dense deposits on the inner side of the GBM, mesangial area, and endolysosome of renal tubular epithelial cells, which were prominent kappa under immunoelectron microscopy (Figures 3A-D). Given his outstanding anemia, the diagnosis of multiple myeloma was suspected but unproven. Therefore, he was temporally diagnosed with monoclonal gammopathy of renal significance. A combination of BCD therapy was administered (bortezomib 2 mg, once weekly, cyclophosphamide 200 mg, once weekly, and dexamethasone 20 mg, once weekly). After six cycles of BCD therapy, the status of anemia was not improved. However, proteinuria was exacerbated (UTP 3.04 g/d), and edema relapsed. He received repeated serum-free light chain tests and exhibited hematological progression (kappa/lambda ratio 168.1, kappa 1697.5 mg/L, lambda 10.1 mg/L,). His repeated bone marrow smear revealed 4.5% plasma cells, but plasmacytoma was observed in bone marrow biopsy. A diagnosis of MM was determined. He was referred to the haematologic department. The treatment was changed to Rd therapy (lenalidomide, 25 mg daily, days 1 through 21 of each 28-day cycle, and dexamethasone, 20 mg once weekly). However, the patient was intolerant to lenalidomide, presenting with severe skin rash. Thus, the lenalidomide dosage was decreased to 12.5 mg daily. After four courses of Rd therapy, his free light chain ratio showed improvement (kappa 1185 mg/L, lambda 42.4 mg/L, kappa/lambda ratio 27.9), but his nephrotic syndrome and anemia both aggregated (UTP 9.07 g/d, Alb 23.1 g/L, and Hgb 49 g/L) with relatively preserved renal function (eGFR 59.911 ml/min/1.73 m2) (Figure 4). Then, he received treatment in another hospital, and the follow-up was conducted by telephone. He received IRd therapy (ixazomib, lenalidomide, dexamethasone) for an additional 5 months without a clear hematological or renal response, and the free kappa value once reached ~5,000 mg/L. Thereafter, antiCD38 monoclonal antibody therapy was administered. His nephrotic syndrome achieved partial remission with stable eGFR, and free light-chain kappa decreased to ~700 mg/L after 17 cycles of CD38 monoclonal antibody therapy. ASCT was considered as a further treatment option.