来那度胺联合地塞米松治疗伴单克隆免疫球蛋白沉积的增生性肾小球肾炎

目的评估来那度胺(lenalidomide)联合地塞米松(dexamethasone)方案(LD方案)治疗伴单克隆免疫球蛋白(Ig)沉积的增生性肾小球肾炎(proliferative glomerulonephritis with monoclonal Ig deposits,PGNMID)的疗效及安全性。方法回顾性分析2010年1月至2019年10月于东部战区总医院采用LD方案治疗的PGNMID患者的临床病理资料。结果于东部战区总医院行肾活检并接受LD方案治疗≥3个月的患者共6例。随访6~19个月,肾脏缓解3例,缓解率为50%(3/6)。所有患者肾脏病理光镜:膜增生性肾小球肾炎。免疫荧光:单一κ型IgG3沉积于系膜区和血管袢。在服用LD方案前,6例患者的中位尿蛋白量7.76(1.27,14.57)g/24 h,中位血肌酐118.5(70.7,289.1)μmol/L,中位血白蛋白34.5(22.4,37.5)g/L。5例血清游离κ、λ轻链浓度升高,但血清游离轻链比值均正常。2例血补体C3下降。6例行骨髓流式细胞学检查,2例单克隆浆细胞升高,所占比例分别为0.7%和0.5%。1例患者血M蛋白阳性,为κ型IgG3。末次随访时,6例患者的中位尿蛋白量3.33(0.33,11.23)g/24 h,中位血肌酐108.7(80.4,160.9)μmol/L,中位血白蛋白35.9(24.5,45.6)g/L。5例血清游离轻链浓度升高患者中,4例浓度较服药前下降。2例补体C3下降的患者升高至正常浓度,另2例患者补体C3略有下降。随访期间,1例患者的血M蛋白阳性未见转阴。所有患者血清游离轻链比值均正常。不良反应有贫血、中性粒细胞减少、四肢麻木感和上呼吸道感染。结论本文首次报道LD方案用于治疗PGNMID可能有效,但需进一步关注来那度胺的血液系统不良反应。

Lenalidomide plus dexamethasone for proliferative glomerulonephritis with monoclonal immunoglobulin deposits

Objective To evaluate the efficacy and safety of lenalidomide plus dexamethasone (LD) in patients with proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID). Methods The clinicopathological data of PGNMID patients who were treated with LD protocol from January 2010 to October 2019 were retrospectively analyzed. Results All of 6 patients received LD treatment for≥3 months after renal biopsy in Jinling Hospital. During the follow-up period of 6 to 19 months, 3 patients achieved renal remission, and the renal remission rate was 50%(3/6). Light microscopy showed membranoproliferative glomerulonephritis and immunofluorescence showed single kappa type IgG3 was deposited in the mesangial region and the vascular loop. Before taking LD scheme, the median urinary protein were 7.76(1.27, 14.57) g/24 h, the median serum creatinine was 118.5(70.7, 289.1) μmol/L, and the median albumin was 34.5(22.4, 37.5) g/L. The concentration of serum free kappa and lambda light chain was increased in 5 patients, but the serum free light chain ratio was normal. Hypocomplementemia was detected in two cases. Six patients underwent bone marrow flow cytometry, and 2 patients had elevated monoclonal plasma cells, accounting for 0.7% and 0.5%, respectively. Immunofixation electrophoresis suggested that 1 patient had positive serum M protein for kappa type IgG3. At the last follow-up, median urine protein was 3.33(0.33, 11.23) g/24 h, median serum creatinine was 108.7(80.4, 160.9) μmol/L, and median albumin was 35.9(24.5, 45.6) g/L. The concentration of serum free light chain in 4 patients from 5 patients with elevated serum free light chain was lower than that before taking the drug. Decreased level of serum complement in two cases returned to normal after treatment. The M spike did not turn negative during the follow-up in one patient. Adverse events included anemia, neutropenia, limb numbness and upper respiratory tract infection. Conclusion This study reports for the first time that LD protocol may be effective in treating PGNMID, but more attention should be paid to the hematological adverse events of lenalidomide.