Stratifying risk for progression in IgA nephropathy: how to predict the future?

INTRODUCTION  IgA nephropathy (IgAN) is characterized by a highly heterogeneous clinical course, which results in controversies regarding the assessment of individual prognosis and establishing the optimal treatment approach. OBJECTIVES  The aim of the present study was to define risk factors for IgAN progression. We evaluated histopathological features derived from the Oxford classification of IgAN and additional, non‑Oxford biopsy findings, as well as baseline and follow‑up clinical data. PATIENTS AND METHODS  We conducted a single‑center retrospective study on 52 patients with biopsy‑proven IgAN. The endpoint was an increase in serum creatinine levels of 50% from baseline. RESULTS  Eight subjects (12%) reached the endpoint. Poor renal outcome was independently related to time‑average proteinuria (TA‑P) exceeding 2.0 g/d (P = 0.047), estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.73 m2 (P = 0.01), history of tonsillectomy (P = 0.01), and crescent lesions in renal biopsy (P = 0.03). High global sclerosis index (GSI) (P = 0.009), TA‑P (P = 0.03), and the presence of microscopic hematuria (P = 0.03) were independent predictors of a more rapid rate of renal function loss, assessed by the velocity of eGFR decline. Of the variables included in the Oxford classification, only interstitial fibrosis and tubular atrophy proved to have prognostic value, as revealed by a univariate, but not multivariate Cox regression analysis. CONCLUSIONS  The extent of proteinuria during follow‑up and impaired renal function at the time of diagnosis remain the most significant clinical prognostic factors in IgAN. We also report additional, non‑Oxford histopathological features that can be used for risk stratification in IgAN, including the GSI and the presence of crescents.