IgA nephropathy, also known as Berger disease or IgA/IgG Mesangial Nephropathy, is a glomerular disease with IgA-dominant or codominant (with IgG or IgM) mesangial immunoglobin deposits. Although IgA nephropathy is a primary renal disease, it is closely related to Schoenlein-Henoch purpura probably as a spectrum of a single disease the former being limited to the kidney and the latter occurring with a nonthrombopenic leukocytoclastic vasculitic purpura in association with arthalgias, and abdominal pain in addition to mesangial IgA deposits.

Epidemiology

• The most common form of primary glomerular disease in the world although varies in geographic distribution: 10% in North America (more common in Native Americans less common in African Americans), 20% in Europe/Australia, 40% in Asia.
• Clinically silent disease is seen in 5% of population at autopsy; clinically apparent disease has a prevalence of 25-50/100,000; comprising 10-20% of the ESRD population.
• Age range is between 10 and 50y. with 80% of patients being between 16 - 35y.. Male preponderance of 2:1

• Clinical presentation is extremely varied; most consistent features are gross hematuria 40%, asymptomatic hematuria 40%, nephrotic syndrome 10%, renal failure 10%.
• All patients have microscopic hematuria and at least low level proteinemia
• Hematuria often quickly follows or is concurrent with a non-specific virus like illness, infection or tonsillitis; thus known as synpharyngitic nephritis (as opposed to PSGN)
• Hematuria is often associated with mild constitutional symptoms: malaise, myalgia, back pain, dysuria, low grade fever (often misdiagnosed as UTI)
• Blood Pressure is usually normal; but in more advanced disease may have mild to severe hypertension
• Associated diseases include: liver disease (alcoholic), ankylosing spondylitis, psoriasis, Reiter's, uveitis, IBD, celiac sprue, dermatitis herpetiformis, HIV, MF/Sezary, adenocarcinomas, toxoplasmosis, sicca, bronchiolitis, idiopathic pneumonitis

Laboratory Findings

• Urinalysis: gross or microscopic hematuria with dysmorphic red cells; gross hematuria lasts from 2-6 days. RBC casts are seen 50% of the time. 50% of patients have only a single episode of hematuria. Proteinuria is usually mild (1-2g/d)
• Renal function is usually normal at diagnosis; but GFR may decline slowly
• Serum IgA is increased in 50%
• Complement (C3, C4) are normal or elevated
• Increased IgA-fibronectin aggregates
• Decreased plasma omega-3 fatty acid concentrations
• Cryoglobulins, ANA, RF, ANCA are usually negative, or not thought to be pathogenic
• Dermal biopsies often show IgA and C3 deposits in the vasculature

Pathology

• IgA nephropathy can only be diagnosed by kidney biopsy
• Light Microscopy: expansion of mesangium seen in all glomeruli of all lobules, but a focal increase in mesangial cellularity thus a focal mesangioproliferative glomerulonephritis. Also may see focal and segmental or global sclerosis or crescent formation.
• Electron Microscopy: fine granular electron dense deposits in mesangium of all lobules of all glomeruli.
• Immunofluorescence: By definition IgA is the predominant (or co-dominant with IgG +/- C3) immunoglobulin and is localized to mesangium and found in all biopsy specimens.

• Unknown: ?genetic (HLA), ? mucosal vs. marrow source of IgA1, ? Antigen

Course and Therapy

• Most patients have recurrent episodes of gross or microscopic hematuria
• Spontaneous complete remissions occur in <4% of adult patients after 4 years of disease
• Development of CRF is poorly predictable; 20-30% of Europeans will have progressive renal insufficiency after 20 years. Poor prognostic factors are: male sex, older age at onset, decreased GFR at diagnosis, persistent nephrotic range proteinuria, and moderate hypertension. Persistent microscopic hematuria with proteinuria is associated with the worst prognosis. On pathology, diffuse crescents or FSGS or fibrosis suggest poor prognosis.
• 1-2% of patients will enter ESRD each year after diagnosis.
• Overall 10-year renal survival is 80%

For the majority of patients no specific therapy is required. There is no consensus on treatment.

 Generally Recommended:

• Glucocorticoids: if >1g/d of proteinuria and if GFR >70mL/min if started early may be of benefit. Steroid are of clear benefit if patient has nephrotic syndrome with mild lesions.
• Omega-3 fatty acids (fish oil): if >1g/d proteinuria has been shown to decrease renal decline and progression to ESRD
• ACE-Inhibitors: of probable benefit in hypertensive patients
• Dipyridamole and low-dose warfarin may slow progression in high risk patients (?)
• Antigen elimination (gluten-free) diets improve protein excretion (?)
• If course is rapidly progressive may try plasmapheresis, cytotoxic drugs with anti coagulant / anti-thrombotic drugs (?)
• Tonsillectomy my reduce frequency of hematuric episodes (but may peri-operatively induce ARF)

Generally NOT recommended: Cyclosporin, Phenytoin (reduces IgA), Anti-biotics

 References:
1. Glassock, Cohen, Adler "Primary Glomerular Diseases" pp1414- 1421 The Kidney, Brenner and Rector, 4th ed.
2. Harper, Savage. "Treatment of IgA Nephropathy" Lancet 353(9156) pp860-862.
3. Jennette, Falk "Diag. & Mgmt of Glomerular Dis." McofNA 81(3) May 97 pp667-669.
4. Nolin, Courteau "Mgmt of IgA neph. Evidence based rec." KI 70:s56-62 Jun 1999.