Immunoglobulin A Nephropathy in Children

Abstract

IgA nephropathy (IgAN), defined by dominant immunoglobulin A glomerular deposits, is the commonest glomerular disease in children presenting with microscopic hematuria. Its prevalence varies from 10% to 40% accounting for renal biopsy criteria and screening school programs. The pathogenetic events include mucosal production of galactose deficient IgA1, IgG autoimmune response, circulation and deposition of macromolecular IgA1 followed by complement activation, glomerular inflammation, and damage. The characteristic pathology feature is mesangial enlargement, with hypercellularity and matrix expansion. Renal pathology lesions are scored according to the Oxford Classification (mesangial hypercellularity M; endocapillary hypercellularity E; segmental glomerulosclerosis S; tubular atrophy/interstitial fibrosis T, crescents C) providing the MEST-C score. The most characteristic presentation is macroscopic hematuria associated with upper respiratory tract infections, sometimes with overt nephritic syndrome. Most children have microscopic hematuria with or without asymptomatic proteinuria, while a few have nephrotic onset. The outcome is generally favorable within the pediatric age, and up to 9% develop renal failure by 15 years. However, mild cases of IgAN in children might be missed and manifest irreversible damage only decades later. Hypertension, persistent heavy proteinuria, and reduced glomerular filtration rate at presentation and the MEST-C score provide prognostication indications. Not all children with IgAN need treatment as spontaneous remission may occur in mild cases. In children developing proteinuria angiotensin system, inhibitors are the first approach, while corticosteroids are an option for children with worsening proteinuria despite treatment or in cases with clinical and pathology features indicating active and potentially progressive IgAN.