Abstract
Introduction: Glomerular diseases comprise a wide spectrum of histopathological appearances within a clinically defined diagnosis of nephrotic syndrome (NS). Many of glomerular diseases are the result of genetic mutations encoding podocytic markers.
Objective: Our aim in this study was to offer a framework that integrates renal morphology with podocytopathies to facilitate management strategies and prognostic information.
Materials and Methods: Descriptive study of 50 cases of NS along with 50 controls wherein a combination of histopathological examination, morphometric studies, immunohistochemistry, direct and indirect immunofluorescence (IFF) were employed for evaluation of podocyte markers (podocin and nephrin) in renal biopsies. The clinical and demographic profile, management received and follow up was recorded for each patient and correlated with renal biopsy.
Results: All control renal tissues (n=50) exhibited linear glomerular basement membrane (GBM) staining. To maintain homogeneity we analyzed patients of minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), mesangial hypercellularity and diffuse mesangial sclerosis (DMS) and we grouped them as ‘podocytopathies’ (n = 38). All cases (n = 38) exhibited evidence of podocyte injury as evident by change of linear GBM positivity to granular pattern or complete absence of podocin (07/38, 14%)) or nephrin (3/38, 7.8%). No histopathological variable predicted clinical response (P = 0.260). The integrated diagnosis formulated by incorporating glomerular morphology and podocyte molecular phenotype strongly correlated with steroid resistance and outcome. (χ2 = 26.437, P < 0.001and χ2 = 25.73, P < 0.001).
Conclusion: Evaluating podocytopathies in a more systematic manner by incorporating podocyte markers in the work up will facilitate more planned approach to diagnosis and management.