The Validation Of The Predictive Value Of The Oxford Classification And The Classification Study About Risk Factors In IgA Nephropathy

Background and ObjectiveAlthough certain clinical parameters are gaining attentions for their predictive values of prognosis as risk factors of IgA nephropathy, no consensus has been reached, which limits the related clinical investigation. None of the pathological classifications of IgA nephropathy developed has been widely recognized over the last nearly30years until the development of the Oxford classification, which demonstrated many improvements in pathological reproducibility, and identified4pathological features with a value independent of the clinical parameters in predicting the outcome of IgA nephropathy. This study aimed to develop a classification of the risk factors based on the validation of the Oxford classification and the analysis of the risk factors.MethodsA total of533adult patients in the Peking Union Medical College Hospital were enrolled in this retrospective study. All the patients were diagnosed primary IgA nephropathy based on renal biopsy with more than eight glomeruli per biopsy section and have been followed up for at least12months. Some clinical parameters, such as the levels of proteinuria, blood pressure, serum creatinine and others were recorded. Two pathologists reviewed the slides referring to the definition of the Oxford classification and the extracapillary glomerular activity index (ExGAI) was scored based on previous report. The end-stage renal disease, doubling creatinine and50%reduction in renal function were defined as the composite end points to evaluate the predictive value of the clinical or pathological lesions in predicting renal outcome in different subgroups. Cox regression was performed to identify the risk factors associated with clinical outcomes. A classification of risk factors was established to predict prognosis.Results 1. The validation of the Oxford Classification in different subgroups of this study indicated that only tubular atrophy and interstitial fibrosis (T) were independent predictive factors of combined end points in IgA nephropathy. Mesangial hypercellularity,and segmental glomerulosclerosis or adhesion could predict prognosis only in the patients with insufficient renal function. The renal function, proteinuria levels and as well as MAP at the time of biopsy were associated with tubular atrophy/interstitial fibrosis. Mesangial score was associated with proteinuria levels at the time of biopsy.2. Multivariate analysis showed that CKD stage, tubular atrophy/interstitial fibrosis and ExGAI were independent predictive factors of the combined end points. Their risk ratios were2.70(95%CI:1.48-4.93,P=0.001),2.76(95%CI:1.52-4.99,P=0.001) and2.94(95%CI:1.21-7.14,P=0.018), respectively. A classification was established based on the sum of the value of the three risk factors. The definitions are as follows:1as low risk group,2or3as moderate risk group and4or more as high risk group. In the low risk group, none has (0/211) developed the combined end points.3.1%(7/223)of the moderate risk group, and20.2%(20/99) of the high risk group have developed the combined end points. The risk ratio using the classification to predict prognosis is9.63(95%CI:4.44-20.88, P<0.001). In the low risk group, the cumulative renal survival over20years was100%. In the moderate risk group, the cumulative renal survival over5,10,15years was98%,73%and57%, respectively. In the high risk group, the cumulative renal survival over3,5,10years was80%,69%and49%, respectively. Analysis in the subgroups demonstrated that the classification could predict renal outcomes of IgA nephropathy.3. In this study group, the time average proteinuria of25.7%of the patients were more than1g/24hours and time average MAP during only6.6%of the patients were over107mmHg during the follow-up, which suggested that the proteinuria and blood pressure were well controlled in most patients in this study group. The proportions of patients who had received corticosteroids, immunosuppressant and RAS blockade were65%,70%,94%, respectively. The radical treatment maybe delay the decline of renal function which affect the validation of Oxford classification and the foundation of the classification of the risk factorsConclusionTubular atrophy and interstitial fibrosis of the Oxford classification were independent predictive factors of combined end points in Chinese patients with IgA nephropathy. CKD stage, tubular atrophy and interstitial fibrosis, as well as extracapillary glomerular activity index were three independent risk factors of renal combined end points. The classification based on the three risk factors may facilitate predicting prognosis. The study results come from the group whose proteinuria and blood pressure were well controlled during follow-up.