Nefropatia por IgA primária: relação entre dados clínicos e parâmetros morfológicos, papel dos subtipos de glomeruloesclerose segmentar e das alterações ultraestruturais podocitárias

Abstract

Introduction: IgA nephropathy (IgAN) is the most common primary glomerulonephritis, has a broad range of histological and clinical manifestations. This study aims to assess sensitivity, specificity and accuracy of clinical data at the time of biopsy in predicting Oxford classification parameters and investigate if subtypes of segmental sclerosis (FSGS), podocyte injury, foot process effacement (FPE) and evidences of cell death influence clinical presentation. Material and methods: Transversal study with 103 IgAN patients. Renal samples underwent light microscopy, immunofluorescence, immunohistochemistry for WT1 and transmission electron microscopy (TEM). Oxford classification was updated and FSGS lesions were subclassified. ROC curves, univariate and multivariate logistic regression were used. WT1-labeled cells in glomerular loops were counted as podocytes and glomerular area was measured to get podocyte density (PD). The length (μm) of the loop divided the number of slit diaphragms (SD), resulting in density of SD/μm. The perimeter of the loop covered by FPE or denuded areas were divided by total perimeter, resulting in Effacement Index (EI). Results: In Oxford classification, the majority of patients had M0, E0, S1, T2 and C0. Hypertension increases the chance of M1 in 2.54x (p=0.02). For each unit of increased creatinine, 2.6x more chances of E1 (p=0.001). S1 is predicted by proteinuria with 75% sensitivity and 90.9% specificity (p < 0.0001). For each unit of increase in GFR, there is a reduction of 6% in the chance of T2 in relation to T0 (p=0.0001). If hypertension, there is 5x more chances of T2 than T0 (p=0.01). For each unit of increase in creatinine, there are 2.8x more chances of C (p=0.003). Creatinine also showed 75.8% sensitivity and 75% specificity for prediction of C (p=0.002). Inversely, for each unit of GFR, the chance of C is reduced by 4% (p=0.007). Proteinuria was the only clinical parameter with significative difference, between S0 and S1 groups (p < 0.0001). FSGS subtypes related to proteinuria were cellular (p=0.03) and peri-hilar (p=0.02). PD was lower in cases with nephrotic proteinuria (p= 0.03; r=-0.22). Detached podocytes were found in all groups of podocyte death, with significantly lower proportion in cases with autophagy (p=0.03). In most cases with detached podocytes, there were podocyte death, specially autophagy and necrosis. No apoptotic podocyte was found. Pseudocysts were not correlated with podocyte detachment (p=0.49). Cases with autophagy, had significantly lower frequency of hematuria (p=0.03). SD density and EI did not correlate with clinical or morphological data. Conclusion: Oxford classification parameters corresponded to some clinical data, making it possible to predict, in the future, morphological data from clinical parameters. FSGS lesions not specifically related to podocytopathies may also influence clinical parameters. Proteinuria correlated with PD and not with FPE, which reinforces the theory that this FP change is an adaptive mechanism. Detached podocytes were related to podocyte injury and not with pseudocysts, which reinforces the hypothesis that in IgAN, podocyte loss is related to cell injury and not just mechanical factors. Autophagy seems to be a protection mechanism with a smaller proportion of detached podocytes and fewer cases with hematuria. These characteristics may add to severity assessment in diagnostic routine.