Berger's disease

Berger and Hinglais first described IgA nephropathy (IgAN) in 1968, and since then, it has been named Berger disease (1):

• IgAN is typically characterized by prominent immunofluorescent mesangial IgA deposits detected by immunofluorescence microscopy

IgA nephropathy (IgAN) is a chronic kidney disease involving deposition of IgA-containing immune complexes in the glomerulus, causing glomerular inflammation and scarring (2)

• is the most common immune-mediated glomerular disease worldwide (2)
• immune-mediated damage to the basement membrane results in haematuria, proteinuria, and renal insufficiency (3)
• pathologically, a spectrum of glomerular lesions may be seen, with mesangial proliferation and prominent IgA deposition being the most commonly observed change (1,2,3)

The disease commonly manifests in children and young adults, with a peak incidence in the second and third decades of life (3).

IgA nephropathy is less common in black people than in Asian or white populations (1).

The disease has a 2:1 male predominance in White populations (2).

Incidence is highest in East Asia (2).

Clinical presentation:

• most patients have some or all elements of the nephritic syndrome (ie, nonvisible haematuria, proteinuria, and impaired kidney function), but 10% to 30% have episodes of visible haematuria, often concomitantly with an upper respiratory or gastrointestinal infection (ie, synpharyngitic haematuria) (2)
  • less than 10% of patients with IgAN present with more rapid loss of kidney function due to severe glomerular inflammation or tubular toxicity from haematuria, and less than 5% of patients present with the nephrotic syndrome.
• IgAN may present with different grades of hematuria (mild, moderate, or severe haematuria) (1)
  • gross hematuria occurs around the same time as the infection or within the first 2 to 3 days, lasting typically for less than three days and usually manifesting with loin discomfort in about 30% of patients
    • the loin pain is primarily due to the sudden enlargement of the kidney, leading to stretching of the renal capsule
  • gross haematuria predominantly affects children and youth and is usually a self-limiting symptom
• clinically, most patients with IgAN have unimpressive physical findings at the time of initial clinical presentation
• note that some patients may acquire hypertension early in the disease

Histology

• reveals a focal proliferative glomerulonephritis with IgA, and in some cases IgG, C3 and properdin deposits in the mesangium

Diagnosis of primary IgAN

• based on presence of IgA-dominant immune deposits in the glomerular mesangium after excluding (2):
  • other causes of this histologic appearance, ie, IgA vasculitis, IgA-dominant infection-related glomerulonephritis, and
  • secondary IgAN from diseases such as cirrhosis, inflammatory bowel disease, celiac disease, infection (eg, viral hepatitis), and autoimmune diseases (eg, axial spondyloarthritis)
    • is essential to differentiate primary from secondary IgAN, as secondary forms typically do not require treatment with immunosuppressive agents; instead, the focus is on addressing the underlying cause (3)

Management principles (3):

• induction of remission and prevention of complications by addressing proteinuria, estimated glomerular filtration rate (GFR), blood pressure, and histological findings
• treatment strategies aim to mitigate immune reactions, reduce IgA deposition, and slow renal damage progression

End-stage Renal Disease (ESRD)

• occurs in around 15 to 20% of IgAN patients within ten years and in over a third (30%–40%) of patients during 20 years of follow-up (1)
  • IgAN was previously known as a rare and benign cause of recurrent haematuria

Notes:

• IgA nephropathy-like kidney injury has been related to autoimmune diseases such as (1):
  • Henoch-Schönlein purpura, chronic hepatitis, systemic lupus erythematosus, dermatitis herpetiformis, and ankylosing spondylitis. IgA glomerular mesangial deposits are frequently detected in histological analyses in all these conditions
• despite the finding that IgAN is often preceded by an infectious disease, which triggers a dysregulated immune response, it is noteworthy that IgAN itself is not of an infectious aetiology (3):
  • there is no evidence to suggest that specific infectious agents cause IgAN

Reference:

1. Habas E, Ali E, Farfar K, Errayes M, Alfitori J, Habas E, Ghazouani H, Akbar R, Khan F, Al Dab A, Elzouki AN. IgA nephropathy pathogenesis and therapy: Review & updates. Medicine (Baltimore). 2022 Dec 2;101(48):e31219.
2. Stoneman S, Teh JW, O’Shaughnessy MM. IgA Nephropathy in Adults: A Review. JAMA. Published online January 26, 2026.
3. Rout P, Afzal M. IgA Nephropathy (Berger Disease) [Updated 2024 Apr 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-.