Clinicopathological Features And Renal Prognosis Of IgA Vasculitis With Nephritis In Chinese Adult Patients

IgA vasculitis(IgAV),formerly Henoch-Schonlein purpura(HSP),is a systemic small-vessel vasculitis mediated by immune deposits.IgAV is characterized clinically by a nonthrombocytopenic purpuric rash,nondeforming arthritis,gastrointestinal involvement,and nephritis.IgAV affects people of all ages,but most cases occur in children.IgAV with nephritis(IgAVN)occurs in approximately 30-40%of children,whereas the incidence of renal involvement in adults ranges from 45 to 85%of cases.IgAVN has increasingly been identified as the major cause of mortality in IgAV patients.And some patients may progress to end-stage renal disease(ESRD).Considerably fewer reports have investigated IgAVN in adults than those in children,especially in Chinese population.Most sample sizes are relatively small and the follow-up time is not sufficient to predict renal prognosis accurately.As a result,we retrospectively analyzed adult IgAVN patients in our center.The aim of our study was to analyze the clinicopathological features of IgAVN in a Chinese adult patient cohort.Long-term renal survival and prognostic factors were also evaluated in order to develop an ideal therapeutic goal.The pathological classification of IgAVN in children is carried out according to the International Study of Kidney Disease in Children(ISKDC)pathology grade,which is based mainly on the degree of crescents.Histological classification is not consensual in adults with IgAVN.In this study,we explored the significance of histological crescent formation in IgAVN patients.IgAVN and IgA nephropathy(IgAN)are considered to be different clinical presentations of the same disease.This study also compared clinical and pathological indexes between adult IgAN and IgAVN patients.In addition,the application of the Oxford classification of IgAN in this adult IgAVN cohort was evaluated to find a more suitable pathological classification.Part 1.Clinicopathological features and renal prognosis of IgA vasculitis with nephritis:a cohort in Chinese adult patientsObjective:To investigate the clinicopathological characteristics of IgAVN in Chinese adult patients and analyze renal outcome and prognostic risk factors of progression to ESRD.Methods:Adult patients who had biopsy-proven IgAVN in our center between 2003 and 2013 were studied.Their clinicopathological data,renal prognosis and related risk factors were assessed.Results:A total of 698 patients were studied,including 363 men(52.0%)and 335 women(48.0%).Most patients had hematuria(85.8%)and/or proteinuria(82.1%).The incidence of nephrotic syndrome and renal insufficiency were 9.9%and 7.3%,respectively.21.1%of the patients suffered from hypertension at biopsy.Glomerular sclerosis,crescents and glomerulus-Bowman's capsule adhesion were the frequent lesions on renal biopsy.During a median follow-up of 54.0 months,32 patients(4.6%)progressed to ESRD.The 5-and 10-year cumulative renal survival rates from ESRD were 96.4%and 88.6%,respectively.Baseline urinary protein>1.0 g/d,renal insufficiency,glomerular sclerosis>10%and tubular atrophy/interstitial fibrosis were independent predictors of renal outcomes.Both the time-average mean arterial pressure(TA-MAP)and time-average proteinuria(TA-P)during follow-up also influenced the renal prognosis.Patients with TA-P>1.0 g/d were associated with 59-fold higher risk of ESRD than those with TA-P?1.0 g/d.And patients with TA-P<0.4 g/d had the lowest rates of ESRD or a 50%decline in renal function.Conclusions:Identifying of clinical and histological prognostic factors may permit the prediction of renal outcomes.The basic goal of therapy for Chinese adult IgAVN patients may be to lower proteinuria to<1.0 g/d and the optimal goal is to lower proteinuria in the normal range.In addition,controlled hypertension can also help to achieve an ideal renal outcome.Part 2.Significance of histological crescent formation in adult IgA vasculitis with nephritis patientsObjective:To explore the significance of histological crescent formation in adult patients with IgAVN.Methods:Adult patients with biopsy-proven IgAVN in our center were enrolled and divided into three groups as follows:control(no crescents,n =257),group 1(crescents<25%,n =381)and group 2(crescents ? 25%,n =60).The clinicopathological features,treatment and renal outcomes were compared among the three groups.Correlations between clinical,laboratory parameters and crescents were also analyzed.Results:There were no significant differences in gender and age at biopsy among the three groups.Groups with more crescents had shorter renal durations and higher prevalence of macroscopic hematuria,proteinuria and nephrotic syndrome.The presence of renal insufficiency at biopsy was similar,whereas laboratory findings indicated that patients in group 2 had higher levels of serum creatinine and blood urea nitrogen than the control and group 1,Histologically,the incidence of glomeruli-Bowman's capsule adhesion and capillary necrosis were proportional to the degree of crescent formation.Patients with more crescents received more positive immunosuppressive therapies.During follow-up,the levels of proteinuria and hematuria were in remission after treatment.The remission rate of proteinuria was higher in control than other groups.There was a significant difference in renal survival from ESRD or a 50%decline in renal function among the three groups(Log rank,P =0.030).However,no association between crescents and renal outcomes was found after adjusting baseline urinary protein,estimated glomerular filtration rate(eGFR),glomerular sclerosis,tubular atrophy/interstitial fibrosis and immunosuppressive treatment.Conclusions:Adult IgAVN patients with more crescents had more severe renal manifestations,more positive immunosuppressive therapies and less remission rates in proteinuria.The proportions of crescents were not associated with higher risks for renal survival.A more suitable pathological classification standard is needed to predict renal prognosis.Part 3.Application of the Oxford classification of IgA Nephropathy in adult IgA vasculitis with nephritis patientsObjective:To evaluate the Oxford classification of IgAN in a cohort of adult IgAVN patients.Methods:Adult patients with biopsy-proven IgAVN in our center were reviewed.Clinical features,pathology findings and renal outcomes of this cohort were compared with one adult IgAN cohort.Associations between pathologic lesions and clinical presentation were also analyzed.Results:Compared with the adult IgAN cohort,the baseline clinical indicators were better in IgAVN patients.There was more application of immunosuppressive agents in IgAVN patients.In terms of the Oxford classification of IgAN,the IgAVN cohort had a higher proportion with endocapillary proliferation(E)and cellular/fibrocellular crescents(C)and necrotizing lesions,lower proportion of patients with mesangial hypercellularity(M),segmental sclerosis(S)and tubular atrophy/interstitial fibrosis(T).The severities of M and T lesions in adult IgAVN patients were significantly correlated with baseline blood pressure,proteinuria and eGFR.There was more application of immunosuppressive agents in IgAVN patients with renal E,C and necrotizing lesions.The univariate Cox regression showed that the lesions of E,S and necrotizing lesions were not associated with renal prognosis.After adjusting for initial clinical data,no association between C lesion and renal outcomes was found.The M and T lesions predicted poor renal survival.After adjusting for follow-up data,only renal T lesion was the independent risk factor of renal outcome from ESRD.Conclusions:The renal T lesion in the Oxford classification of IgAN is an important independent risk factor affecting renal prognosis.The lesions of E,C and necrosis are related to the treatment of immunosuppressive agents.Our findings suggest that the Oxford classification of IgAN can be used in helping guide the therapy and predicting long-term outcomes of Chinese adult IgAVN patients.