Renal expression of advanced oxidative protein products predicts progression of renal fibrosis in patients with IgA nephropathy

Abstract

Predicting the risk of disease progression in IgA nephropathy (IgAN) remains a challenge. This study was conducted to test the hypothesis that renal accumulation of advanced oxidized protein products (AOPPs) is an early predictor for renal progression in IgAN. This was a single-center prospective cohort study. One hundred IgAN patients with eGFR>80 ml/min/1.73 m2 were enrolled. Seventy-seven patients were followed for a mean of 4.2 years, and 30 patients received repeat renal biopsy at a mean of 42 months after diagnosis. The outcomes were the progression of renal fibrosis and rapid progression of CKD (>5 ml/min/1.73 m2/year) during follow-up. Immunoreactivity of AOPPs was detected predominantly in tubular epithelial cells and co-localized with expression of TGF-β1 and angiotensin II. Renal staining score of AOPPs at diagnosis was associated with the level of tissue cellular inflammation. Accumulation of AOPPs, particularly in interstitial-infiltrating cells, was negatively correlated with changes of eGFR during follow-up; those with expression scores greater than the median at diagnosis had significantly higher incidences of rapid decline of eGFR compared with those with the score less than or equal to the median. For patients who received repeat renal biopsy, renal AOPP levels greater than the median at diagnosis were associated with increase in renal fibrosis index at repeat biopsy. After multivariate adjustment, renal AOPP expression was an independent predictor for progression of renal fibrosis and rapid decline of eGFR. Taken together, these results demonstrate that renal AOPPs might be a predictor, detectable at the time of diagnosis, for renal progression in patients with early stage IgAN. © 2014 UPSAC, Inc.