| Severe lupus nephritis(LN)has complicated pathogenesis and heterogeneous pathology.It concludes focal segmental LN,diffused proliferative LN,and the two classes in combined with memberanous lesions.The classification and therapy of severe LN have developed for half an century,nevertheless,a lot of doubts and difficulties await resolved.The therapy of severe LN is always tough,especial Class ?+?.In comparison with Class ?,Class ?+? has an inferior response to immunosuppressants.Multi-target therapy(MT)is a pioneering work for the therapy of LN.It significantly increased the remission rate of Class ?+? LN,but the evaluation of efficacy and safety is limited to induction phase.Whether MT could be an efficious and safe maintenance regimen is unknown.The first part of this study will answer this question.It was confirmed that severe focal and segmental LN(WHO ?,>50%of glomeruli involved)manifested as "pauci-immune complex deposit",with a worse renal survival than diffused proliferative LN.Hence,2003 ISN/RPS classification proposed two subclasses of Class IV,ie.diffused segmental(Class ?-S)and diffuse glomerular(Class ?-G),according to the involved area of glomerular capillary loop.Subsequent studies about comparison of Class ?-S and ?-G didn't validate the different prognosis between them.For more clear and accurate acknowledge of the subclasses of Class IV LN,we herein compare the diffused homogeneous segmental and diffused glomeruar LN,to evaluate whether they are different in nature.Part 1.Multi-target Therapy as Continuous Induction and Maintenance Treatment for Class ?+? Lupus NephritisObjective:To further evaluate the long-term efficacy and safety of multi-target therapy(MT)as continuous induction and maintenance therapy for Class ?+? LN.Methods:Eighty patients with biopsy-proved Class ?+? LN were included in this study.They were randomly assigned to MT group(MT inducing remission followed by MT maintenance,n=40)and IVCY-AZA group(IVCY inducing remission followed by AZA maintenance,n=40),both in combination with prednisolone.The total duration of observation was 24 months.Primary end point was complete remission,and secondary end point included partial remission,renal relapse,and adverse effects.Results:Thirty-six patients in MT group and 24 patients in IVCY-AZA group responded favorably(complete or partial remission)to induction treatment(P<0.01).In multi-target group,the complete-remission rate at 6 mo(45%vs 12.5%,P<0.01)and 24 mo(80%vs 47.5%,P<0.01)were significantly higher than those in IVCY-AZA group.Rate of renal relapse and renal relapse-free survival were similar between the two groups(8.3%vs 4.8%,P>0.05).Infections were noted in more than 20%of patients in both groups(P>0.05).Alopecia,nausea and vomiting were more common during IVCY induction(P<0.05),conversely,new onset hypertension occurred only in patients with MT induction(P<0.05).During maintenance,there were 11.1%and 28.6%patients of leucopenia episode(P>0.05).Conclusions:MT therapy was an effective induction-maintenance treatment for patients with Class ?+? LN,with higher response rate and favorable tolerability.Part 2.Comparison of Clinicopathologic Characteristics and Prognosis between Diffused Segmental and Glomerular Lupus NephritisObjective:Previous comparisons between Class ?-S and ?-G lupus nephritis(LN)were controversial.The study aimed to determine whether homogenous segmental and glomerular lesions are different in clinicopathological features and outcome.Methods:Thirty-one patients with biopsy-proven difused segmental LN(Class ?-S group)and 89 with diffused glomerular LN(Class ?-G group)were identified and retrospectively analyzed.Class ?-S was defined as ?50%of glomeruli manifesting segmental endothelium proliferation or fibrinoid necrosis,with or without crescents.Class ?-G was defined as ?50%of the glomeruli manifested as mesangial endothelial proliferation involving the whole glomerular,without fibrinoid necrosis or crescent.Results:(1)Class ?-S had significantly higher complement C3(0.515 vs 0.351,P<0.01)and C4(0.124 vs 0.061,P<0.01)than ?-G The proportion of low complement C4 in ?-S group was significantly lower than ?-G group(38.7%vs 84.7%,P<0.01)?(2)Wire loop and hyaline thrombi were significantly rare in ?-S group than ?-G group(0%vs 42.7%,3.2%vs 34.8%;P<0.01).Subendothelial deposit was rare in ?-S group than in ?-G group(P<0.01).(3)The media follow-up time of ?-S and ?-G group was 64,57months,respectively.Cumulative complete-remission rate within 6 months by intravenous cyclophosphamide(IVCY)was significantly lower in ?-S than in ?-G group(22.2%vs 56.2%,P=0.048).MMF seemed to be more effective than IVCY in ?-S patients with a 6-month complete-remission rate of 46.2%,but statistical significance was not obtained.The 10-year survival without renal function deterioration in ?-S group was significantly inferior than that of ?-G(61%vs 96%,P=0.049).Conclusions:.Compared to Class ?-G LN,Class ?-S has a significantly lower complement consumption,a "panic-immune complex deposit" pathology and a worse prognosis.MMF may increase the efficacy of ?-S,and it needs further prospective investigation. |
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