What is IgA Nephropathy
IgA nephropathy is the most common primary glomerulonephritis worldwide, characterized by mesangial dominant or co-dominant IgA deposits in the kidney, resulting from immune complexes containing galactose-deficient IgA1 that trigger progressive glomerular inflammation and can lead to end-stage kidney disease. 1, 2
Pathophysiology
The disease is driven by a specific immunologic cascade:
The hallmark is deposition of poorly O-glycosylated IgA1 (galactose-deficient IgA1) in the glomerular mesangium, which forms immune complexes with autoantibodies against these abnormal IgA1 molecules 3, 4
These immune complexes activate mesangial cells and trigger complement-mediated inflammation, leading to glomerular injury and progressive tubulointerstitial fibrosis 4, 5
Genetic susceptibility plays a significant role, with multiple risk loci identified in the major histocompatibility complex region, some of which are linked to mucosal immune defense against pathogens 6
Diagnostic Criteria
Kidney biopsy remains the gold-standard diagnostic test and is required for definitive diagnosis: 2, 3
Immunofluorescence microscopy must demonstrate mesangial dominant or co-dominant IgA deposits 1, 2
Electron microscopy typically reveals electron-dense deposits in the mesangium 1, 2
C3 complement is often present alongside IgA deposits, while C1q is less commonly found 1
Histological features using the MEST-C scoring system independently predict disease outcomes 3
Clinical Presentation and Prognosis
The disease affects individuals of all ages and accounts for 20-25% of prevalent kidney failure cases in most registries: 7
Patients with proteinuria >1 g/day, hypertension, and impaired renal function at diagnosis are at high risk for disease progression 1
The 15-year kidney survival rate from apparent disease onset typically exceeds 70%, though progression when it occurs is usually slow and indolent 8
Spontaneous remission of disease activity occurs in approximately 7% of patients 8
Hypertension develops in 50% of patients during the disease course 8
Disease Burden
IgA nephropathy represents a major global health challenge: 3, 6
It is the most prevalent form of primary glomerulonephritis reported worldwide 3, 4
In children, teenagers, and young adults, it is one of the most common causes of irreversible kidney damage 7
The disease carries a high lifetime risk of kidney failure, making it both a source of personal suffering and a major socioeconomic problem 7, 3