Origin and Scope of Injury
Glomerulonephritis (Glomerulonephritis) may develop as an independent pathology or as a consequence of other diseases. Based on origin, it is divided into:
- Primary: The kidneys are the sole or main target organ.
- Secondary: Glomerular injury occurs secondary to systemic diseases (immune — SLE, vascular — hypertension, metabolic — diabetes mellitus) or inherited disorders (Fabry disease).
To precisely describe the morphology, a classification based on the distribution of the process is used. If all glomeruli in the kidneys are involved, it is termed diffuse involvement; if only a portion are affected, it is focal. Regarding the extent of damage within an individual glomerulus, total (the entire glomerulus is involved) and segmental (only a portion of the capillary loops are affected) glomerulonephritis are distinguished.
Key Morphological Reactions
Tissue alterations in glomerulonephritis come down to three key types of reactions, which may be combined:
- Hypercellularity. Results from active proliferation of intrinsic glomerular cells (mesangial, endothelial, parietal epithelial) and infiltration by leukocytes (neutrophils, monocytes, lymphocytes).
- Basement Membrane Thickening. Well-visualized by light microscopy using the PAS (periodic acid–Schiff) reaction. The cause of thickening is the deposition of immune complex deposits (subepithelial, subendothelial, or intramembranous).
- Hyalinosis and Sclerosis. These represent the outcome of injury. Hyalinosis manifests as the accumulation of extracellular precipitated plasma proteins (eosinophilic masses). Sclerosis is characterized by thickening of the membrane combined with expansion of the mesangial matrix.
Additionally, deposits of fibrin, amyloid, lipids, and signs of intraglomerular thrombosis may be found within the glomeruli.
Pathogenesis: Mechanisms of Immune Injury
Most glomerulopathies are rooted in immune-mediated injury. The localization of immune complexes (ICs) plays a crucial role:
- Deposition of Circulating ICs. Complexes form in the systemic circulation and deposit in the glomeruli, vessel walls, and tubular basement membranes. Upon immunofluorescence microscopy, they yield a characteristic granular pattern.
- Formation of ICs in situ. Today, this mechanism is considered predominant. Antibodies bind directly within the glomerulus to stationary antigens (such as type IV collagen in the glomerular basement membrane — GBM) or to planted exogenous molecules. In this case, a linear pattern is observed along the GBM.
A special mention is Goodpasture syndrome (anti-GBM nephritis). In this rare pathology (accounting for less than 5% of cases), anti-GBM antibodies cross-react with the basement membranes of pulmonary alveoli, causing combined severe injury to both 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 undergoes lysis. 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 massive role in the progression of chronic forms. Furthermore, resident glomerular cells, particularly mesangial cells, are capable of sustaining inflammation on their own. Even without leukocyte participation, they secrete:
- Reactive oxygen species and nitric oxide (NO).
- Cytokines and growth factors.
- Eicosanoids and endothelin.
Inflammation frequently 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.
Clinicomorphological Forms
Based on the duration of the disease, glomerulonephritis is classified into:
- Acute: lasts up to 1 year.
- Rapidly progressive: leads to severe outcomes within up to 1.5 years.
- Chronic: persists for more than 1 year.
Clinically, the disease manifests as nephritic syndrome, nephrotic syndrome, or a combination of both.