A Multi-center Application And Evaluation Of The Oxford Classification Of IgA Nephropathy In Chinese Patients

Part I:Long-term renal survival and related risk factors in patients with IgA nephropathy:Results from a cohort of1155cases in a Chinese adult populationBackground We sought to identify the long-term renal survival rate and related risk factors of progression to renal failure in Chinese adult patients with IgA nephropathy(IgAN) and to quantify the effects of proteinuria during the follow-up on outcome in patients with IgAN.Methods Patients with biopsy-proven primary IgAN in the Nanjing Glomerulonephritis Registry were studied. Renal survival and the relationships between clinical parameters and renal outcomes were assessed.Results1155patients were enrolled in this study. The10,15, and20-year cumulative renal survival rates, calculated by Kaplan-Meier method, were83%,74%and64%respectively. At the time of biopsy, proteinuria>1.0g/d (HR3.2, P<0.001), eGFR<60 ml/min per1.73m2(HR2.6, P<0.001), hypertension (HR1.9, P<0.001), hypoproteinemia (HR2.0, P<0.001), and hyperuricemia (HR2.1, P<0.001) were the independent risk factors. Multivariate COX analysis showed the time-average proteinuria(TA-P) during follow-up was the most important risk factor of renal failure. Patients with TA-P>1.0g/d were associated with a9.4-fold risk than patients with TA-P<1.0g/d (P<0.001), and46.5-fold risk than those with TA-P<0.5g/d (P<0.001). Moreover, patients who achieved TA-P<0.5g/d benefit much more than those with TA-P between0.5and1.0g/d (HR13.1, P<0.001).Conclusions36%of Chinese adult patients with IgAN have progressed to End Stage of Renal Disease (ESRD) within20years. Five clinical features--higher proteinuria, hypertension, impaired renal function, hypoproteinemia and hyperuricemia are independent predictors of an unfavorable renal outcome. The basic goal of antiproteinuric therapy for Chinese patients is to lower proteinuria less than1.0g/d, and the optimal goal is to lower proteinuria to less than0.5g/day. Part II:A Multi-center Application and Evaluation of the Oxford Classification of IgA Nephropathy in Chinese adult patientsBackground:The Oxford classification of IgA nephropathy (IgAN) provides a histopathological grading system that is associated with kidney disease outcomes, independent of clinical features. However, the application of the Oxford IgAN classification should be evaluated in larger cohorts and in different ethnic groups. Methods:Retrospective study. A total of1026adults with IgAN from18renal centers in China were enrolled in this study. The inclusion criteria and statistical analysis were similar to the Oxford study. Predictors:Histologic findings of mesangial hypercellularity score, endocapillary proliferation, segmental sclerosis or adhesion, crescents, necrosis, tubular atrophy/interstitial fibrosis. Clinical features of blood pressure, estimated glomerular filtration rate (eGFR), proteinuria, and treatment modalities. Outcomes:Time to a50%reduction in renal function or ESRD (the combined event); the rate of renal function decline (slope of eGFR); proteinuria during follow-up.Results:The Chinese cohort had a lower proportion of patients with mesangial hypercellularity (43%) and endocapillary proliferation (11%), a higher proportions of segmental sclerosis or adhesion (83%), and necrosis (15%), and a similar proportion with crescents (48%) and tubular atrophy/interstitial fibrosis (moderate, T1,24%; severe, T2,3.3%) compared with the Oxford cohort. During a median follow-up period of53months (interquartile range36-67months), the mean (SD) rate of eGFR decline was-1.5±10.4ml/min/1.73m2per year, the mean urine protein excretion was0.7g/d (interquartile range0.45-1.2g/d), and15.5%of patients (159cases) reached the combined event. Our study showed that patients with mesangial hypercellularity>0.5were associated with a2.0-fold (95%CI1.5-2.8, P<0.001) risk of the combined event than those patient with mesangial hypercellularity<0.5, patients with tubular atrophy/interstitial fibrosis of25-50%were associated with a3.7-fold (95%CI2.6-5.1, P<0.001) risk of the combined event than those patient with tubular atrophy/interstitial fibrosis<25%, and patients with tubular atrophy/interstitial fibrosis>50%were associated with a15.1-fold (95%CI9.5-24.2, P<0.001) risk of the combined event than those patient with tubular atrophy/interstitial fibrosis<25%. However, endocapillary proliferation, glomerular crescents and necrosis showed no significant prognostic value in the Chinese cohort.Conclusions:We confirmed the associations of mesangial hypercellularity and tubular atrophy/interstitial fibrosis with kidney disease outcomes. Part III:Validation of the Oxford Classification of IgA Nephropathy for Pediatric Patients from ChinaBackground:The Oxford classification of IgA nephropathy (IgAN) provides a useful tool for prediction of renal prognosis. However, the application of this classification in children with IgAN needs validation in different patient populations.Methods. A total of218children with IgAN from7renal centers in China were enrolled. The inclusion criteria was similar to the original Oxford study.Results. There were98patients (45%) with mesangial proliferation (M1),51patients (23%) with endocapillary proliferation (E1),136patients (62%) with segmental sclerosis/adhesion lesion (S1),13patients (6%) with moderate tubulointerstitial fibrosis (T126-50%of cortex scarred), and only2patients (1%) with severe tubulointerstitial fibrosis (T2,>50%of cortex scarred). During a median follow-up duration of56months,24children (12.4%) developed ESRD or50%decline in renal function. We found that tubular atrophy/interstitial fibrosis (HR4.3, P<0.001) was the most powerful lesion for predicting renal prognosis, while associations between some pathological lesions (mesangial hypercellularity, segmental sclerosis or adhesion) and renal outcome were inconsistent in different models. Moreover, endocapillary proliferation, crescents, and necrosis were not associated with renal prognosis.Conclusions. We confirmed tubular atrophy/interstitial fibrosis was the only feature independently associated with renal outcomes in Chinese children with IgAN.