IgA nephropathy
IgA nephropathy is the most common primary glomerular disease worldwide, caused by galactose-deficient IgA1 immune complexes depositing in the mesangium, presenting classically with synpharyngitic gross hematuria in young adults and confirmed by kidney biopsy showing dominant mesangial IgA deposits. First-line therapy is renin-angiotensin system blockade, since roughly 40% of patients progress to end-stage kidney disease within 15 years despite treatment.
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What this article covers
- Overview
IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide, caused by mesangial deposition of immune complexes containing galactose-deficient IgA1.
- Epidemiology
Diagnosed in up to 10% of all kidney biopsies performed in the United States and approximately one third of all kidney biopsies in Asian countries, where IgAN is the leading cause of ESKD.
- Risk factors
Male sex, with a 2:1 male-to-female ratio in diagnosed cases.
- Pathophysiology
A defect in IgA1-producing cells leads to hypogalactosylation of the hinge region of IgA1, producing elevated blood levels of galactose-deficient IgA1 (Gd-IgA1), the initiating molecular abnormality.
- Clinical features
Synpharyngitic gross hematuria, hematuria occurring during or immediately following an upper respiratory infection, is the classic and most recognizable presentation in younger patients; it usually…
- Differential diagnosis
Poststreptococcal (infection-related) glomerulonephritis: hematuria follows streptococcal infection by 1 to 3 weeks (a latent period) rather than occurring concurrently with the infection as in…
- Diagnosis
The diagnosis can only be confirmed by kidney biopsy showing dominant mesangial immune deposits of IgA, typically with C3 and occasionally IgG or IgM on immunofluorescence, though it may be suspected…
- Management
First, start renin-angiotensin system blockade in every patient with proteinuria or hypertension, the established first-line antiproteinuric therapy for IgAN, continued indefinitely with periodic…
- Complications
Progression to CKD or ESKD, occurring in the majority of patients who do not follow the benign phenotype, with up to 40% reaching ESKD within 15 years of diagnosis.
- Prognosis
Approximately one third of patients have a benign long-term course, with continued microscopic hematuria but little to no proteinuria and no evidence of kidney dysfunction.
- Prevention
There is no primary prevention for IgAN, since the underlying immune defect (Gd-IgA1 production) is not modifiable; prevention efforts focus on early detection and slowing progression once diagnosed.
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