Pathologic Predictors of Renal Outcome and Therapeutic Efficacy in IgA Nephropathy

Abstract

SummaryBackground and objectives The Oxford classification of IgA nephropathy (IgAN) may aid in predicting prognosis and providing therapeutic strategy but must be validated in different ancestry.Design, setting, participants, & measurements A total of 410 patients with IgAN, enrolled from one of the largest renal centers in China, were evaluated for the predictive value of the Oxford classification to prognosis defined as end stage renal disease. A total of 294 of these patients were prospectively treated with renin-angiotensin system blockade and immunosuppressants sequentially and were evaluated separately to assess the predictive value to therapeutic efficacy (defined as time-averaged proteinuria Ͻ1 g/d). Three pathologists reviewed specimens independently according to the Oxford classification and were blinded to clinical data.Results Segmental glomerulosclerosis and tubular atrophy and interstitial fibrosis were independent predictive factors of end stage renal disease. Patients who had Ͼ25% of glomeruli with endocapillary hypercellularity showed higher proteinuria, lower estimated GFR, and higher mean BP than patients with less endocapillary hypercellularity. Immunosuppressive therapy showed a protective effect to prognosis of endocapillary hypercellularity in patients with endoncapillary hypercellularity could benefit from immunosuppressive therapy. Mesangial hypercellularity and tubular atrophy and interstitial fibrosis were independent factors of inefficiency of renin-angiotensin system blockade alone. Crescents were not significant in predicting prognosis or in therapeutic efficacy. ConclusionsThe Oxford classification may aid in predicting prognosis and providing a therapeutic strategy in Chinese patients with IgAN.

Development and Validation of a Prediction Rule Using the Oxford Classification in IgA Nephropathy

“…These inconsistencies may be due to insufficient statistical power resulting from the small sample sizes of the studies. Like most previous studies, the present study failed to reveal a significant association of E with renal prognosis (15,18,36). Therefore, the variables included in our prediction rule would seem to be reasonable for application to research or clinical studies.…”

“…In this study, M, S, and T were independently associated with renal outcome. T has been established as a significant prognostic factor associated with renal outcome in other studies, whereas the effects of M and S on renal prognosis have been inconsistent among studies (11,15,16,36). Some reports showed that M or S were not both selected as risk factors for future ESRD in multivariate analysis (15,16,36).…”

Clinical and pathological analysis of IgA nephropathy with chronic renal failure

“…[12][13][14] An elegant study showed that segmental glomerulosclerosis and tubular atrophy and interstitial fibrosis were independent predictive factors of end stage renal disease but not mesangial cell proliferation. 15 So, we further speculate that during the progression of IgAN, mesangial cell proliferation is probably the initiating factor, while injury of podocyte and tubular cell are the key elements. IgAN is characterized by mesangial deposition of IgA immune complexes, with or without IgG and C3.…”

A Multicenter Study of the Predictive Value of Crescents in IgA Nephropathy

“…The original Oxford study 1 and several subsequent validation studies [3][4][5][6]15 with similar entry criteria, excluding patients with eGFR,30 ml/min per 1.73 m 2 at the time of biopsy and/or rapid progression to ESRD, did not find crescents to be an independent predictor of poor renal outcomes in patients with IgA nephropathy. However, some other studies with less restrictive entry criteria 7-10 did find a significant association between crescents and a composite outcome including either ESRD or doubling of SCr/$50% reduction in eGFR (in one instance, also including death).…”

“…Endocapillary hypercellularity (E), although not predictive of poor outcome in the Oxford cohort, was associated with a significantly reduced rate of eGFR decline in patients treated with immunosuppressive therapy compared with those who were not. The Oxford Classification is, thus, composed of scores for M, E, S, and T. However, the presence or absence of cellular/fibrocellular crescents was not a significant predictor of these outcomes in the original Oxford cohort 1 or a number of validation studies [3][4][5][6] with similar entry criteria, which excluded patients with eGFR of ,30 ml/min per 1.73 m 2 at the time of biopsy and/or progression to ESRD within 12 months of the biopsy.…”