Podocytopathies

Abstract

Podocytopathies are glomerular diseases caused by initial podocyte injury or dysfunction that lead to proteinuria and often nephrotic syndrome. The term encompasses characteristic histological patterns, most commonly focal segmental glomerulosclerosis, minimal changes, membranous nephropathy, diffuse mesangial sclerosis and collapsing glomerulopathy. However, proteinuria of glomerular origin is frequently managed without biopsy; importantly, when the protein loss is mostly albumin, it is a direct readout of podocyte injury and a strong predictor of cardiovascular events, kidney failure and reduced survival. Patients present with oedema and volume disturbances and are at risk of thromboembolism, serious infections and progressive kidney dysfunction. Aetiologically, podocytopathies arise from autoimmune, genetic, mechanical (hyperfiltration), infectious, toxic or monoclonal mechanisms, which may coexist and vary by age; this unifying, mechanism-based view bridges the historically divergent paediatric (response-based) and adult (histology-based) classifications. Diagnosis integrates clinical features with emerging serology for podocyte-directed autoantibodies, targeted genetic testing and kidney biopsy when required. Diagnostic workup has to delineate the causes of podocyte dysfunction. Management combines supportive care with aetiology-guided therapy aimed at minimizing steroid exposure and preventing relapses. Current advances in the field and their effects on diagnostic and therapeutic algorithms open the path towards personalized use of traditional treatments and newly available drugs, which should improve outcomes and quality of life for patients with podocytopathies.