IgA nephropathy (IgAN), also known as Berger disease, is the most common form of primary glomerulonephritis worldwide.
It is a chronic immune-mediated kidney disorder characterised by the deposition of immunoglobulin A (IgA) in the glomeruli, leading to inflammation and progressive kidney damage in some patients.
Whilst many individuals experience a benign course, others develop progressive chronic kidney disease (CKD) or end-stage kidney disease (ESKD).
Advances in understanding the disease’s immunopathogenesis have led to improved risk stratification and targeted therapies.
Causes
IgA nephropathy is caused by a multistep immune dysregulation process, often described by the “four-hit hypothesis.”
Pathophysiology of IgA Nephropathy
- Overproduction of galactose-deficient IgA1 (Gd-IgA1)
- Formation of autoantibodies against Gd-IgA1
- Circulating immune complex formation
- Deposition of immune complexes in the glomerular mesangium, triggering inflammation
Genetic and Environmental Factors
- Strong genetic predisposition, especially in East Asian and European populations
- Mucosal immune activation, particularly from:
- Upper respiratory infections
- Gastrointestinal infections
- Dysregulation of gut-associated lymphoid tissue (GALT)
IgA nephropathy is almost always a primary kidney disease, distinct from IgA vasculitis (Henoch–Schönlein purpura), although the two share overlapping mechanisms.
Symptoms
Symptoms of IgA nephropathy are highly variable and may be intermittent or absent in early disease.
Common Clinical Features
- Haematuria, often visible (tea- or cola-colored urine) following infections
- Microscopic haematuria on routine urinalysis
- Proteinuria, ranging from mild to nephrotic range
- Fatigue
- Hypertension
Less Common Symptoms
- Peripheral oedema
- Flank discomfort during episodes of gross hematuria
- Declining kidney function in advanced disease
Many patients are diagnosed incidentally after abnormal urine tests.
Diagnosis
Diagnosis of IgA nephropathy requires careful clinical evaluation and, in most cases, kidney biopsy.
Laboratory Tests
- Persistent microscopic haematuria
- Variable proteinuria
- Elevated serum creatinine in progressive disease
- Normal complement levels (helps distinguish from other glomerulonephritides)
Kidney Biopsy
- Gold standard for diagnosis
- Demonstrates mesangial IgA deposition on immunofluorescence
- Histologic findings are graded using the Oxford MEST-C score, which provides prognostic information
Risk Stratification
- Degree of proteinuria
- Glomerular filtration rate (GFR)
- Blood pressure
- Histological (biopsy) features
- Use of validated IgAN risk prediction tools
Treatment
Treatment focuses on slowing disease progression, reducing proteinuria, and minimizing immune-mediated injury.
Supportive (Optimised Conservative) Therapy
Foundation of treatment for all patients:
- Renin–angiotensin–aldosterone system (RAAS) blockade (ACE inhibitors or ARBs)
- Strict blood pressure control
- Sodium restriction
- Weight management and lifestyle optimization
- SGLT2 inhibitors (increasingly used to slow CKD progression)
Immunosuppressive and Targeted Therapies
Considered in high-risk patients with persistent proteinuria despite optimized supportive care:
- Corticosteroids (selected patients only, due to infection risk)
- Targeted-release budesonide (acting on gut mucosal immunity)
- Emerging biological therapies targeting B cells and complement pathways
Treatment decisions are individualised based on risk–benefit assessment.
Complications
Potential complications of IgA nephropathy include:
- Chronic kidney disease
- End-stage renal failure (ESRF)
- Persistent hypertension
- Cardiovascular disease associated with CKD
- Recurrent episodes of gross hematuria
- Rarely, acute kidney injury (AKI) during severe flares
IgA nephropathy may recur after kidney transplantation, though graft survival is usually preserved.
Outlook (Prognosis)
The prognosis of IgA nephropathy varies widely.
- Approximately 20–40% of patients progress to ESRD within 20–30 years
- Favourable prognostic factors include:
- Low-grade proteinuria
- Preserved eGFR
- Good blood pressure control
- Poor prognostic indicators:
- Persistent proteinuria >1 g/day
- High blood pressure (BP; hypertension)
- Declining kidney function
- High-risk biopsy features (MEST-C score)
Early diagnosis, aggressive supportive care, and emerging disease-specific therapies have significantly improved long-term outcomes.
