IgA nephropathy (Berger’s disease) is a renal disease characterized by IgA deposition in the mesangium, causing glomerular inflammation (glomerulonephritis (GN)).
- Most common cause of primary GN in developed countries
- Often presents in the second to third decades of life
- Seen more commonly among Caucasians and East Asians
- Both sexes affected equally among East Asians; approximately 2:1 male-to-female predominance among Caucasians
- Unknown in most cases
- Often preceded by an upper respiratory or GI infection
- Exercise can be a trigger (worsens hematuria in patients with IgA nephropathy).
- Can be associated with conditions such as:
- Celiac disease
- HIV infection
- Minimal change disease
- Membranous nephropathy
- Granulomatosis with polyangiitis
- Preceding mucosal infection → impaired regulation of synthesis and metabolism of IgA (abnormal O-galactosylation of the hinge region of primarily polymeric IgA1)
- Poorly galactosylated IgA1 increases recognition by circulating antibodies → immune complexes → mesangial deposition of immune complexes → type III hypersensitivity reaction → mesangial inflammation and GN
IgA nephropathy presents with recurrent gross hematuria or asymptomatic microscopic hematuria as the most common manifestations.
- Up to 50% of cases
- Usually presents with recurring episodes of:
- Gross hematuria accompanied by upper respiratory infection (synpharyngitic hematuria)
- Flank pain
- Low grade fever
- Up to 40% of cases
- Presents with asymptomatic, microscopic hematuria
- Occasionally accompanies mild proteinuria
- Less than 10% of cases
- Patients can present with:
- Nephrotic syndrome: kidney excretes > 3.5 g/day of protein
- Acute, rapidly progressive GN:
- Renal insufficiency
- Malignant hypertension:
- Extremely high BP (typically > 180/120 mm Hg) with acute end-organ damage
- Rare presentation
- Disease was not detected early enough as patient did not have typical hematuria.
The diagnosis is usually based on the clinical presentation and suspicion arising from a preceding infectious event.
- Urinalysis (findings consistent with nephritic syndrome):
- RBC casts, occasional dysmorphic RBCs
- May have mild to moderate proteinuria
- Other laboratory results:
- Normal complement levels
- May have increased creatinine
- Increased serum IgA concentration (in 30%–50% of patients) but without correlation with disease activity
- Renal biopsy provides the definitive diagnosis.
- Because of the benign course of GN, the invasive test of renal biopsy is indicated only in severe or progressive disease:
- Persistent urine protein excretion > 500 mg/day
- Increased serum creatinine
- New-onset hypertension or significant elevation in BP over baseline
- Biopsy results:
- Light microscopy → mesangial hypercellularity
- Electron microscopy → electron-dense deposits in the mesangium
- Immunofluorescence microscopy → mesangial deposits of IgA
Management and Prognosis
- For patients with hematuria, normal renal function, and minimal proteinuria:
- No active treatment
- Monitoring of kidney function (including proteinuria) and BP
- For patients with proteinuria > 500 mg/day and/or hypertension:
- Goal: proteinuria < 500 mg/day and BP < 130/80 mm Hg
- ACE inhibitors or angiotensin-receptor blockers (ARBs) decrease disease progression.
- Statin therapy decreases cardiovascular risk (but has no effect on renal progression).
- Other options, such as fish oil treatment and tonsillectomy, have conflicting results.
- For severe, active, or progressive disease:
- Increasing serum creatinine
- Persistent proteinuria (> 1 g/day) despite ACE inhibitor or ARB intake
- Biopsy findings of active disease
- Therapy: glucocorticoids
- For rapidly progressive disease: Consider combination therapy using glucocorticoids + cyclophosphamide, then azathioprine.
- In up to 50% of patients, slow progression to end-stage renal failure noted over 20–25 years.
- In others, complete remission or persistent low grade hematuria but preserved renal function
- Predictors of progressive renal disease:
- Elevated serum creatinine
- Persistent proteinuria for more than 6 months (> 1 g/day)
The following conditions are among the differential diagnoses for IgA nephropathy.
- Henoch–Schönlein purpura (HSP) or IgA vasculitis: another IgA-mediated GN that can be triggered by an upper respiratory or GI infection: HSP usually occurs in children < 10 years old. Patients present with palpable purpura on the buttocks and lower extremities, abdominal pain, and arthralgias. HSP disease is identical in histology to IgA nephropathy.
- Alport syndrome (hereditary nephritis): also presents with isolated hematuria: Alport syndrome is a commonly X-linked inherited disease resulting in defective type IV collagen; this disorder is associated with sensorineural hearing loss and ocular abnormalities. Patients often present during infancy with episodic gross hematuria. Renal biopsy reveals splitting of the glomerular basement membrane.
- Thin basement membrane nephropathy: can also present with isolated hematuria as well as gross hematuria with flank pain: This hereditary disease is characterized by mutations of type IV collagen. Renal biopsy reveals diffuse thinning of the glomerular basement membrane.
- Membranoproliferative GN: a pattern of glomerular disease detected on biopsy that can be seen in association with hepatitis B and C infections: Hematuria is the most common presentation, but nephrotic syndrome and abnormal renal function are also seen. Renal biopsy shows hypercellularity with thickening and splitting of the glomerular basement membrane.
- Poststreptococcal GN: a self-limited type of GN that occurs in children: Poststreptococcal GN is an immune-complex–mediated condition that is often preceded by group A beta-hemolytic streptococcal pharyngitis or skin infections. Laboratory results show decreased complement levels, elevated antistreptolysin-O and anti-DNase B levels. Renal biopsy reveals granular glomerular basement membrane on immunofluorescence microscopy and subepithelial humps on electron microscopy.
- Cattran DC, Appel GB. Treatment and prognosis of IgA nephropathy. UpToDate. Retrieved February 10, 2021, from https://www.uptodate.com/contents/treatment-and-prognosis-of-iga-nephropathy
- Chueng CK, Barratt J. Clinical presentation and diagnosis of IgA nephropathy. UpToDate. Retrieved February 10, 2021, from https://www.uptodate.com/contents/clinical-presentation-and-diagnosis-of-iga-nephropathy
- Cheung CK, Barratt J. Pathogenesis of IgA nephropathy. UpToDate. Retrieved February 10, 2021, from https://www.uptodate.com/contents/pathogenesis-of-iga-nephropathy
- Lewis JB, Neilson EG. Glomerular Diseases. In: Jameson J, et al. (Eds.). Harrison’s Principles of Internal Medicine, 20th ed. McGraw-Hill.