Histopathologic features aid in predicting risk for progression of IgA nephropathy

Abstract

Background and objectives: IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. Accurately identifying patients who are at risk for progressive disease is challenging. The extent to which histopathologic features improves prognostication is uncertain.

Design, setting, participants, & measurements: We studied a retrospective cohort with biopsy-proven IgAN in Calgary, Canada. Renal biopsies were reviewed by a nephropathologist with histopathologic data abstracted using a standardized form. The primary outcome was the composite of doubling of serum creatinine, ESRD, or death. Spline models defined significant levels of interstitial fibrosis, glomerulosclerosis, hypertension, proteinuria, and creatinine. The prognostic significances of clinical and histopathologic parameters were determined using Cox proportional hazards models.

Results: Data from 146 cases were available for analysis with a median follow-up of 5.8 years. Greater than 25% interstitial fibrosis, >40% glomerular sclerosis, and a systolic BP >150 mmHg were risk thresholds. In univariable analyses, baseline creatinine, proteinuria, systolic BP, glomerular sclerosis, interstitial fibrosis, and crescentic disease were predictors of the primary outcome. In multivariable models adjusted for clinical characteristics, interstitial fibrosis (hazard ratio [HR]2.7; 95% confidence interval [CI] 1.2 to 6.0), glomerular sclerosis (HR 2.6; 95% CI 1.2 to 4.5), and crescents (HR 2.4; 95% CI 1.2 to 5.1) remained independent predictors of the primary outcome and significantly improved model fit compared with clinical characteristics alone.

Conclusions: Baseline histopathologic parameters are independent predictors of adverse outcomes in IgAN even after taking into consideration clinical characteristics. Relatively small degrees of interstitial fibrosis confer an increased risk for progressive IgAN.

Figure 1.

Spline model of the proportion of interstitial fibrosis used to predict the hazard of the composite end point of time to doubling of creatinine, ESRD, or death. An inflection at approximately 25% fibrosis demonstrates increased risk above this level.

Figure 2.

Spline model of the proportion of glomeruli with sclerosis used to predict the hazard of the primary composite end point. An inflection at approximately 40% fibrosis demonstrates a large increased level of risk.