Avaliação de biomarcadores em pacientes com podocitopatias pediátricas

Abstract

Introduction: Minimal Change Disease (MCD) and Focal and Segmental Glomerulosclerosis (FSGS) are podocytopathies, one of the main groups of glomerulopathies in childhood. It is controversial whether they are distinct glomerular lesions or diverse manifestations within the same spectrum of diseases, since they may present a similar clinical course and may have varying outcomes ranging from remission to therapeutic failure. CD80, uPAR and some podocyte slit diaphragm proteins may be altered in glomerulus of patients with FSGS and MCD and may function as podocytopathy biomarkers and / or prognostic markers in renal biopsies. Objective: To evaluate the diagnostic potential of CD80, uPAR, nephrin and podocin for MCD and FSGS in renal pediatric biopsies and to detect the potential of uPAR as prognostic marker. Methods: Renal biopsies of 50 children with age ranging from two to 18 years old, with diagnosis of MCD (29) and FSGS (21) were selected. Control group consisted of 15 renal fragments from pediatric autopsies, with no change in renal function. In situ expressions of WT1, Nephrin, Podocin, CD80 and uPAR were evaluated by immunoperoxidase technique. ROC curve was used to analyze biomarkers diagnostic performance. Clinical outcome and drug therapy of 22 children, six years after diagnosis, were also evaluated. Biomarkers were evaluated regarding clinical outcome. Results: Patients with MCD and FSGS had decreased expression of WT1 and nephrin on renal biopsies comparing to control group (p≤0,0001, F = 19.35 and p <0.0001; H = 21.54). Patients with FSGS showed less nephrin and podocin than control cases (p <0.0359; H = 6.655) and there was a positive and significant correlation between nephrin and podocin (p = 0.0026, rS = 0.6502). There was no difference between groups regarding CD80 expression (p = 0.1895; H = 3.327). FSGS cases expressed more uPAR than control and MCD cases (p = 0.0019; H = 12.57). Podocin presented sensitivity of 73.3% and specificity of 86.7% (p = 0.006) and uPAR had sensitivity of 78.9% and specificity of 73.3% (p = 0.004) in FSGS biopsies. Most patients presented some degree of remission of initial condition after treatment (64%). UPAR expression at the time of diagnosis was significantly higher among patients who evolved with therapeutic resistance than those who evolved with remission (p = 0.04; t = 0.2524). Conclusion: Podocin and uPAR are good markers for FSGS. Higher uPAR expression in cases of podocytopathies is a predictor of therapeutic resistance. These findings suggest that podocin and uPAR can be routinely used as biomarkers in renal biopsies from cases of podocytopathies in which the lesion (sclerosis) is not sampled and that uPAR may assist in determining prognosis