Classification and relation to other diseases
IgA nephropathy is part of the large group of mesangioproliferative glomerulonephritides. It is important to understand that this is not an independent nosological entity, but rather a collective term grouping diseases with a common morphological pattern. In addition to Berger's disease, this group includes primary prolonged acute glomerulonephritis, the mesangial form of systemic lupus erythematosus (SLE), infective endocarditis, rheumatoid arthritis, hepatitis A, IgM nephropathy, and a number of other pathologies.
Berger's disease typically presents as an isolated renal lesion. However, it shares many features with Henoch-Schönlein purpura (a systemic vasculitis more common in children). In addition, secondary forms of the disease can develop against the background of liver and bowel disorders.
Pathogenesis: how the disease develops
Under normal conditions, immunoglobulin A is the main protective protein of mucosal secretions. It is present in low amounts in blood serum and is represented primarily by monomers. Polymeric forms are rapidly catabolized in the liver in a healthy body.
In IgA nephropathy, this physiological balance is disrupted:
- The serum level of polymeric IgA₁ increases sharply (while the level of IgA₂ remains unchanged).
- In some patients, circulating immune complexes (CICs) containing this abnormal IgA₁ are formed.
- These complexes are captured and deposited in the mesangium of the renal glomeruli.
- The complement system is activated via the alternative pathway. This is indicated by the presence of the C₃ fraction and properdin in the glomeruli with a complete absence of C₁q and C₄ components.
The underlying etiology is believed to be a congenital or acquired anomaly of immune regulation. In response to environmental factors (viruses, bacteria, dietary proteins) entering through the respiratory or gastrointestinal tract, the mucous membranes begin to overproduce IgA.
Morphological picture and diagnostics
To make an accurate diagnosis, light microscopy alone is insufficient — on biopsy samples, it only allows for suspicion of the pathology. The gold standard for verification is immunohistochemistry or immunofluorescence.
- Light microscopy: the main feature is the expansion of the mesangial zone due to proliferation of mesangial cells. Changes can be diffuse (classic mesangioproliferative glomerulonephritis) or segmental (focal proliferative glomerulonephritis, where only a part of the glomeruli is involved, with foci of necrosis and fibrin deposition). Crescentic glomerulonephritis is much less common. Over time, scarring of focal lesions can lead to focal sclerosis.
- Immunofluorescence microscopy: characteristic staining is detected in the mesangial matrix, indicating massive IgA deposits. These are frequently accompanied by the C₃ complement fraction and properdin, and small amounts of IgG or IgM may occasionally be present. Other complement components are usually absent.
- Electron microscopy: at high magnification (e.g., ×18,000), dark electron-dense deposits corresponding to immune complex aggregates are visualized in the mesangium.
Clinical manifestations and prognosis
The leading clinical symptom of Berger's disease is recurrent gross hematuria or microscopic hematuria (presence of blood in the urine). Proteinuria is usually mild. Nephrotic syndrome is possible but not mandatory.
In most cases, the disease has a relatively stable course, but in rare situations it can progress to a severe complication — rapidly progressive glomerulonephritis (RPGN).
Briefly: answers to topical questions
Which specific liver and bowel diseases are associated with the secondary form of IgA nephropathy?
The secondary form of IgA nephropathy is associated with the following specific liver and bowel diseases:
- Liver diseases — chronic viral hepatitis B and C, as well as liver cirrhosis.
- Bowel diseases — inflammatory bowel diseases, which include ulcerative colitis and Crohn's disease.
What criteria are included in the Oxford classification of IgA nephropathy (MEST-C)?
The Oxford classification (MEST-C) includes five histological evaluation criteria for a renal biopsy:
- Mesangial hypercellularity (M) — M0: present in <50% of glomeruli; M1: present in ≥50% of glomeruli.
- Endocapillary hypercellularity (E) — E0: absent; E1: present.
- Segmental glomerulosclerosis or adhesion (S) — S0: absent; S1: present.
- Tubular atrophy and interstitial fibrosis (T) — T0: 0–25%; T1: 26–50%; T2: >50% of the cortical area.
- Cellular or fibrocellular crescents (C) — C0: absent; C1: present in <25% of glomeruli; C2: present in ≥25% of glomeruli.
To remember the pathogenesis of Berger's disease, use the rule of three «A»s: Abnormal immunity causes overproduction of IgA, which activates complement via the Alternative pathway.
Class and exam questions
Can IgA nephropathy be diagnosed using light microscopy alone?
No, light microscopy only allows for the identification of a mesangial proliferative pattern and suspicion of the disease. Final verification strictly requires immunofluorescence or immunohistochemistry confirming the presence of IgA deposits.
Through which pathway is complement activated in Berger's disease, and how is it proven?
Complement is activated via the alternative pathway. Proof of this is the detection of component C₃ and properdin in the glomeruli with the complete absence of classical pathway components — C₁q and C₄.
Which systemic vasculitis is closely associated with IgA nephropathy?
The disease shares pathogenetic mechanisms with Henoch-Schönlein purpura (hemorrhagic vasculitis), in which IgA deposits can be found both in the kidneys and extrarenally.
What else to study on this topic
- Focal proliferative and necrotizing glomerulonephritis: histological variants
- Henoch-Schönlein purpura as a systemic counterpart of Berger's disease
- Mesangioproliferative glomerulonephritis: differential diagnosis within the group
- Rapidly progressive glomerulonephritis (RPGN) as an outcome of glomerular diseases
- Secondary forms of IgA nephropathy in liver and bowel pathologies
Master the entire topic in the "Pathological Anatomy" course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "IgA nephropathy" and 4,414 other subject pages
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 153 video lessons on the subject
Other topics in the section "Diseases of the Kidneys and Urinary Tract"
Free video lessons: pathological anatomyShort lessons with study notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.