Berger’s Disease typically presents in younger males with recurrent macroscopic haematuria coinciding with upper respiratory tract infections, and exhibits mesangial deposition of IgA on immunofluorescence.
Description
Berger’s Disease, or IgA nephropathy, is a common cause of glomerulonephritis worldwide, characterised by the deposition of IgA in the mesangium of glomeruli. It primarily affects younger males, often presenting with recurrent macroscopic haematuria during or after upper respiratory tract infections.
Pathogenesis
Berger’s disease is primarily caused by abnormal glycosylation of IgA1, leading to formation of immune complexes that deposit in the mesangium of glomeruli, inciting inflammation and damage. This process eventually leads to mesangial proliferation and matrix expansion, potentially culminating in glomerulosclerosis and tubulointerstitial fibrosis.
Subtypes
The condition is generally seen as a single entity, without distinct subtypes.
Epidemiology, Risk Factors & Associations
- Most common form of glomerulonephritis worldwide (20-40% of all primary glomerular diseases)
- Higher prevalence in Asians and Caucasians, lower in Africans and African Americans
- Males affected more than females (2:1 ratio)
- Commonly presents in second to fourth decades of life
Clinical Features
- Often presents with recurrent episodes of macroscopic haematuria, typically coinciding with upper respiratory tract infections
- Microscopic haematuria and proteinuria may also be present
- Hypertension and renal insufficiency can occur in more advanced disease
Complications
- Risk of progression to chronic kidney disease or end-stage renal disease over a period of decades (up to 30-40% in 20-30 years)
- No risk of malignant transformation
Pathological Features
Histopathology
- Macroscopic: Normal-sized kidneys in early stages, potentially shrunken in chronic disease
- Microscopic: Mesangial proliferation, with varying degrees of glomerulosclerosis and tubulointerstitial fibrosis in advanced disease
Serology
- Increased serum IgA levels in about 50% of patients
Biochemistry
- Varying degrees of renal insufficiency in advanced disease, with elevated serum creatinine
Radiological Features
General Features
- Typically, kidneys appear normal in early stages
- Signs of chronic kidney disease may be seen in later stages, such as decreased size and increased echogenicity
US
- B-mode: Normal kidney size and echotexture in early disease, potential decrease in size and increased echogenicity in chronic disease
- Colour: No specific findings
Grading and Staging
Berger’s disease is classified according to the Oxford Classification which considers mesangial hypercellularity (M), endocapillary proliferation (E), segmental glomerulosclerosis (S), tubular atrophy/interstitial fibrosis (T), and presence of crescents (C).
Diagnosis
Diagnosis is typically made through renal biopsy demonstrating mesangial deposition of IgA on immunofluorescence, along with typical light microscopy findings.
Differential Diagnosis
- Thin Basement Membrane Disease: Presents with recurrent macroscopic haematuria, but characteristically demonstrates thinning of glomerular basement membranes on electron microscopy
- Alport Syndrome: X-linked disorder also presenting with recurrent haematuria, but additionally features hearing loss and ocular abnormalities. Histopathology reveals characteristic glomerular basement membrane abnormalities.
- Post-infectious Glomerulonephritis: Presents following infection, but typically shows granular deposition of IgG and C3 in a “starry sky” pattern on immunofluorescence.
Management
Management primarily involves control of blood pressure (often with ACE inhibitors or ARBs) and immunosuppressive therapy in severe disease or rapidly progressive forms. Patients with progressive renal dysfunction may require renal replacement therapy. Regular follow-up with nephrology is recommended.