关键词: 肾病, 利妥昔单克隆抗体, 继发性肾小球肾炎, 挽救治疗, 预后, 感染, 药物毒性

Abstract: Background　Rituximab（RTX） has been used to treat glomerular diseases for nearly 20 years.Although there have been accumulated results from evidence-based studies of RTX for primary and secondary nephropathy，there is no research on RTX salvage therapy for severe renal insufficiency.Objective　To study the efficacy and safety of RTX salvage therapy in patients with secondary refractory nephropathy.Methods　Total 48 adult inpatients with refractory nephropathy，who received RTX treatment in Peking University International Hospital from 2018 to 2019，were enrolled in this retrospective study.They were divided into primary nephropathy （PN） group and secondary nephropathy （SN） group according to renal biopsy diagnosis of primary disease.Those in SN group were further divided into SN with non-salvage therapy group （SN-NST subgroup，Scr<300 μmol/L） and SN with salvage therapy group （SN-ST subgroup，Scr≥300 μmol/L） according to the Scr level before RTX treatment.General information （including gender，age，weight，height，body surface area and primary diagnosis），and laboratory tests results before and after using RTX，such as 24-hour urine protein （Upro），white blood cell （WBC） count，red blood cell （RBC） count，platelet （PLT） count，serum albumin （Alb），Scr，and CD4+ cell count as well as calculated CD4+ cell count/WBC ratio were collected.The serious adverse events during RTX treatment 〔including serious infection （treated either by 7 or more days of systemic antibiotic therapy or by more than one antibiotic agents），renal replacement therapy，multiple organ dysfunction syndrome，and death〕，were recorded.3-month renal outcome after the final RTX therapy（namely，whether requiring maintenance hemdialysis） was also recorded.Results　There were 19 （39.6%） patients in PN group，14 （29.2%）in SN-NST subgroup，and 15 （31.2%）in SN-ST subgroup.The mean age of SN-ST subgroup was less than that of PN group and SN-NST subgroup （P<0.05）.PN group showed higher mean baseline levels of 24 hUpro，RBC and PLT，and lower mean Alb than both subgroups SN-NST and SN-ST before using RTX（P<0.05）.SN-ST subgroup had higher mean level of Scr and less mean CD4+ cell count than PN group and SN-NST subgroup before using RTX（P<0.05）.The following several parameters were found with significant pre- and post-RTX treatment differences（P<0.05）：24 hUpro decreased in PN group and SN-NST subgroup，WBC count decreased in subgroups SN-ST and SN-NST，RBC count increased in SN-ST subgroup，PLT count decreased in PN group but increased in SN-ST subgroup，and Alb level increased in PN group and SN-NST subgroup.Post-RTX treatment intergroup comparison found that the mean level of Scr in SN-ST subgroup was higher than that of PN group and SN-NST subgroup （P<0.05）.The accumulated doses of RTX for PN group and SN-NST and SN-ST subgroups were （437±322）mg?month-1?（m2）-1，（503±344）mg?month-1?（m2）-1，and （331±312）mg?month-1?（m2）-1，respectively，showing no significant differences（F=1.048，P=0.359）.SN-ST subgroup had higher rates of serious infection and renal replacement therapy during RTX treatment as well as higher rate of maintenance hemodialysis 3 months after RTX treatment than PN group（P<0.05）.Moreover，compared to SN-NST subgroup，SN-ST subgroup had higher rates of renal replacement therapy during RTX treatment and maintenance hemodialysis 3 months after RTX treatment than PN-NST subgroup（P<0.05）.Conclusion　In those with Scr≥300 μmol/L，rather than improving the remission of nephropathy effectively and safely，RTX therapy may significantly increase the risks of serious infections and renal failure，so it should not be used as salvage therapy in them.

Key words: Nephrosis, Rituximab, Secondary glomerulonephritis, Salvage therapy, Prognosis, Infection, Drug toxicity