Mesangioproliferative glomerulonephritis

Pathogenesis and Morphological Picture

Proliferative forms of glomerulonephritis are based on active inflammation, with glomerular hypercellularity acting as the main histological sign. It occurs due to the multiplication of intrinsic kidney cells and infiltration of the tissue by leukocytes (monocytes and neutrophils). In the mesangioproliferative variant, the proliferation of mesangial cells can be either focal or diffuse, accompanied by expansion of the mesangial matrix.

The disease has an immune complex nature. The pathological cascade develops as follows:

1. The glycosylation and polymerization processes of IgA molecules are impaired.
2. Due to the structural alteration, the synthesis of these molecules increases compensatorily.
3. Cells of the reticuloendothelial system fail to recognize and destroy the formed macromolecules.
4. Immune complexes circulate in the blood for a long time and ultimately deposit in the mesangium of renal glomeruli.

These deposits cause kidney cells to produce cytokines and growth factors, leading to the mesangial expansion visible under the microscope.

Classification and Clinical Variants

The pathology may develop as an independent nosology — a primary form known as Berger's disease. A secondary form also occurs, arising secondary to systemic vasculitis (Henoch-Schönlein purpura), autoimmune pathologies (systemic lupus erythematosus), viral hepatitis B and C, sarcoidosis, or inflammatory bowel diseases (Crohn's disease, ulcerative colitis).

The clinical picture is polymorphic, but most often fits the development of nephritic syndrome. Two typical patterns of the course are distinguished:

• Recurrent episodic macroscopic hematuria. It has a "synpharyngitic" nature: urine acquires a brownish hue synchronously with a respiratory infection or within the first 2–3 days. The episode may last from a few hours to a couple of days. Microscopic hematuria persists during the inter-recurrent period.
• Persistent microscopic hematuria. It may be completely isolated, but is often accompanied by elevated blood pressure and moderate proteinuria.

Diagnosis and management tactics

The key method for specific diagnostics is phase-contrast microscopy of the urinary sediment. It is this method that allows the detection of dysmorphic red blood cells — a reliable sign that the source of bleeding is located in the glomerular apparatus. A blood test reveals an increased concentration of IgA in 35–60% of patients, though this sign is not strictly mandatory.

The treatment strategy depends directly on the risk of progression to renal failure:

• Non-intervention tactics (active surveillance) are used in the presence of isolated hematuria only.
• Nephroprotective therapy is indicated for patients with a moderate risk: in the presence of hematuria combined with mild protein loss (proteinuria from 0.5 to 1 g/day), provided there is no arterial hypertension and normal glomerular filtration rate is preserved.
• Immunosuppressive therapy (a standard 6-month course of glucocorticoids) is prescribed only when protein loss reaches the nephrotic range.

To prevent exacerbations, the sanitation of chronic infection foci is mandatory, as they serve as the main triggers of relapses.

Differential diagnosis

First and foremost, differential diagnosis is performed with hereditary glomerulopathies.

• Thin basement membrane disease (familial benign hematuria). It is inherited in an autosomal dominant manner and manifests only as isolated hematuria. It has a favorable course. The main difference: electron microscopy reveals thinning of the glomerular basement membranes, while immune deposits in the renal tissue are completely absent.
• Alport syndrome. A genetic pathology with various inheritance patterns, based on a mutation in genes encoding the main membrane protein — type IV collagen. Unlike thin basement membrane disease, Alport syndrome progressively worsens and leads to end-stage renal disease. It manifests with hematuria (with or without proteinuria) and is accompanied by systemic manifestations: bilateral sensorineural hearing loss and eye lesions (corneal erosion, anterior lenticonus, macular flecks).

Class and exam questions

What else to study on this topic

• Mechanisms of immune complex formation and IgA glycosylation defects
• Morphological differences between membranoproliferative and mesangioproliferative variants of GN
• Principles of nephroprotective therapy and calculation of glomerular filtration rate
• Genetics of Alport syndrome and the molecular structure of type IV collagen
• Technique of phase-contrast microscopy for detecting dysmorphic red blood cells

Other topics in "Chapter 8. Kidney and Urinary Tract Diseases"

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