Glomerulopathies

Origin and scale of damage

Glomerulonephritis (Glomerulonephritis) can develop as an independent pathology or be a consequence of other diseases. By origin, it is divided into:

• Primary: the kidneys are the sole or main target organ.
• Secondary: glomerular damage occurs against the background of systemic diseases (immune — SLE, vascular — arterial hypertension, metabolic — diabetes mellitus) or hereditary pathologies (Fabry disease).

To accurately describe morphology, the classification by process distribution is used. If all glomeruli in the kidneys are involved, it is called a diffuse lesion; if only a part, a focal lesion. Regarding the extent of damage within the glomerulus itself, total (the entire glomerulus is involved) and segmental (only a part of the capillary loops is affected) glomerulonephritis are distinguished.

Main morphological reactions

Tissue changes in glomerulonephritis come down to three key types of reactions, which can be combined:

1. Hypercellularity. It arises due to active proliferation of resident glomerular cells (mesangial, endothelial, parietal) and infiltration of tissue by leukocytes (neutrophils, monocytes, lymphocytes).
2. Thickening of the basement membrane. It is well visualized under a light microscope using the PAS reaction. The cause of thickening is the deposition of immune complex deposits (subepithelial, subendothelial, or within the membrane itself).
3. Hyalinosis and sclerosis. These are the outcomes of injury. Hyalinosis manifests as the accumulation of extracellular precipitated plasma proteins (eosinophilic masses). Sclerosis represents thickening of the membrane combined with proliferation of the mesangial matrix.

Additionally, deposits of fibrin, amyloid, lipids, as well as signs of intraglomerular thrombosis, may be detected in the glomeruli.

Pathogenesis: mechanisms of immune injury

Immune injury underlies the majority of glomerulopathies. A key role is played by the localization of immune complexes (ICs):

• Deposition of circulating ICs. Complexes form in the systemic circulation and deposit in the glomeruli, vessel walls, and tubular basement membrane. Upon immunofluorescence microscopy, they yield a characteristic granular fluorescence.
• Formation of ICs in situ. Today, this mechanism is considered leading. Antibodies bind directly within the glomerulus to stationary antigens (e.g., type IV collagen in the glomerular basement membrane — GBM) or to molecules planted from outside. In this case, linear fluorescence along the GBM is observed.

Goodpasture syndrome (anti-GBM nephritis) stands out separately. In this rare pathology (less than 5% of cases), antibodies to the GBM cross-react with the basement membranes of pulmonary alveoli, causing combined severe damage to the kidneys and lungs with the development of rapidly progressive renal failure.

Acute inflammation and cellular mechanisms

Acute glomerular injury is accompanied by cellular swelling, neutrophil infiltration, and necrosis (with karyorrhexis and nuclear pyknosis). Fibrinoid necrosis develops — destroyed cells are replaced by fibrin, and the matrix is lysed. The process is triggered by a cascade of mediators: complement components, coagulation factors, proteases, and cytokines.

Cellular immunity (sensitized T-lymphocytes and macrophages) plays a huge role in the progression of chronic forms. At the same time, resident glomerular cells, especially mesangial ones, are capable of sustaining inflammation themselves. Even without the participation of leukocytes, they secrete:

• Reactive oxygen species and nitric oxide (NO).
• Cytokines and growth factors.
• Eicosanoids and endothelin.

Inflammation often extends to the renal interstitium. The appearance of an interstitial infiltrate is associated with delayed-type hypersensitivity (DTH) reactions or the action of cross-reacting antibodies.

Clinical and morphological forms

According to the duration of the course, glomerulonephritis is classified into:

• Acute: lasts up to 1 year.
• Rapidly progressive: leads to severe consequences within up to 1.5 years.
• Chronic: lasts over 1 year.

Clinically, the disease manifests with the development of nephritic syndrome, nephrotic syndrome, or a combination thereof.

Class and exam questions

What else to study on this topic

• Morphological differences between nephritic and nephrotic syndromes
• Mechanisms of fibrinoid necrosis development in renal glomeruli
• The role of delayed-type hypersensitivity in interstitial injury
• Specific renal changes in systemic lupus erythematosus (SLE) and diabetes mellitus

Other topics in the section "Diseases of the Kidneys and Urinary Tract"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.