Prognostic value of morphologic and morphometric analyses in IgA nephropathy biopsies

Background: IgA nephropathy (IgAN) exhibits a variable course ranging from a benign condition to progressive renal failure with a high proportion of patients undergoing end-stage renal disease in the long term. It is unclear how to predict the risk of this progression. Mesangial C4d deposition has been found to be associated with a poor prognosis. Our aim was to search histological lesions with possible prognostic value in IgAN biopsies performed at the time of the diagnosis. Methods: Clinical and laboratory records of 44 patients undergoing renal biopsy were reviewed. IgAN was diagnosed in 32 patients and minimal change disease (MCD) in 12. C4d deposition, glomerular endothelial cell area, glomerular and interstitial macrophages were evaluated in all biopsies. Clinical and laboratory data were available in all IgAN patients at the time of diagnosis and in 21 patients at the end of follow-up (mean follow-up 48.09 ± 19.69 months). Results: All IgAN and MCD biopsies were C4d negative. The number of glomerular macrophages and the area of glomerular endothelial cells in IgAN were greater than in MCD (P < 0.001 and P < 0.0001, respectively), indicating glomerular inflammation associated with endothelial cell enlargement. Glomerular macrophages positively correlated with diffuse IgA and fibrinogen immunoreactivity (P < 0.02 and P < 0.002, respectively). Interstitial macrophages positively correlated with segmental glomerulosclerosis (P < 0.01) and tubular atrophy (P < 0.001), according to the Oxford classification. They correlated with hypertension (P < 0.03) and renal functional impairment both at the time of biopsy and at the end of follow-up. The receiver operating characteristic analysis curve and a cut-off value of ≥19.5 macrophages per high power field showed 75.0% sensitivity and 88.9% specificity in predicting worse clinical outcome. A Poisson generalized regression fit model showed that hypertension and tubular atrophy were the most significant factors in predicting a high number of interstitial macrophages. Conclusions: The number of interstitial macrophages correlated with hypertension, histological damage, functional impairment at the time of biopsy and worse outcome. A high number of interstitial macrophages in C4d negative biopsies may allow the identification of patients at increased risk of progression to renal failure.