Predicting Treatment Response And Long-term Renal Outcome In Crescentic ANCA-associated Glomerulonephritis

Background:The morphological features of Anti-neutrophil cytoplasmic antibodies associated glomerulonephritis(AAGN)are segmental necrosis with crescents and "pauci-immune" deposition in glomeruli.The AAGN are now divided into four histological classes:Focal,crescentic,mixed,and sclerotic.In crescentic AAGN,more than 50%glomeruli show cellular crescents.The patients with AAGN usually present rapidly progressive renal failure and require intensive immunosuppressive treatment and even plasma exchange.But the clinical manifestations and histological features are heterogeneity because of different ratio of crescents,normal glomeruli,glomerulosclerosis and tubulointerstitial lesion.The treatment response and renal survival are much different,renal function will not recover even after the intensive immunosuppressive therapies,such as MP pulse therapy,Ⅳ-CTX,plasma exchange.Meanwhile,intensive immunosuppressive therapies have high incidence of infection,which is the leading cause of death in AAGN patients.Therefore,treatment choices should be fully evaluated,and it is very important to evaluate the benefit and risks prior to make treatment decision.However,few researches have been made in patients with crescentic AAGN to predict the treatment response and long-term renal survival.Objective:In this study,we analyze the factors which may predict treatment response and long-term renal outcome in Chinese patients with crescents AAGN.Methodology:60 cases with renal biopsy proven crescentic AAGN were included in the study(male 25,female 30,median age 54 years(IQR),mean SCr 5.0±2.9mg/dl).According to whether the renal replacement therapy(RRT)was needed on admission,the patients were divided two groups,the RRT group(n=30)and non-RRT group(n=30).The treatment response was defined as good response(GR)and non-response(NR),according to the renal function after 3 months induction treatment.The GR was defined as the patients get rid of RRT in RRT group and the SCr decreased by 25%in non-RRT group or more,otherwise,the treatment was defined as NR.Histological lesions included the ratio of normal glomeruli,total cellular crescents,circumferential crescents,circumferential/total crescents,sclerotic glomeruli.Tubulointerstitial lesions were scored semiquantitatively as mild(1’),moderate(2’)and severe(3’).Multivariate Cox regression analysis was applied to evaluate clinical and histologic features predicting treatment response and long-term renal outcome in crescentic AAGN.Results:Age,BVAS score and SCr level were much higher in RRT Group than that in non-RRT Group.The percentage of circumferential crescents/total crescents in RRT Group was higher than that in non-RRT Group,but without statistical differences.Total cellular crescents and the ratio of sclerotic glomeruli showed no differences between the two groups.At three months induction treatment,four patients died(3 in RRT group,1 in non-RRT group),40 patients showed GR(16 in RRT group,24 in non-RRT group),16 patients were NR(11 in RRT group,5 in non-RRT group).According to multivariate Cox regression analysis,the percentage of circumferential crescents/total crescents was the main factor affecting the treatment response in RRT group(HR=17.24(CI 1.16～255.63),p=0.038),with the percentage≥50%being the high risk to be NR(HR=22.2(CI 2.17～200),p=0.002).In the non-RRT Group,the ratio of normal glomeruli in GR patients was significantly higher than that in NR patients.When the ratio of normal glomeruli was higher than 7%,the treatment response was more likely to be GR(HR=13.3(CI 1.7～107.4),p=0.006).During a median follow-up of 19 months(6～58 months),6 patients(10%)dead and 18(30%)patients developed to ESRD.The 5 year patient and renal survival were 87.4%and 56.0%,respectively.Multivariate Cox analysis showed that the need of RRT and nephrotic range of proteinuria were the independent risk factors for long-term renal survival.Conclusion:For patients with crescentic AAGN,the extend of circumferential crescents and normal glomeruli were the key factors predicting the treatment response in RRT and non-RRT groups,respectively.While the the need of RRT and proteinuria were the main factors affected long-term renal survival.Our results indicate that renal histology is required prior to the treatment decisions.