Definition and Classification Variants
The core feature of Focal Segmental Glomerulosclerosis (Glomerulosclerosis focalis segmentalis) is the selective injury of renal glomeruli. The term "focal" means that only some glomeruli are involved, while "segmental" indicates that damage is restricted to specific regions of the vascular tuft within those glomeruli.
In clinical practice, several main forms of the disease are distinguished:
- Idiopathic FSGS: A primary pathology diagnosed in a subset of patients with nephrotic syndrome.
- Adaptive FSGS: Develops secondary to other primary kidney diseases, such as membranous nephropathy or Alport syndrome.
- FSGS due to reduced renal mass: Observed in reflux nephropathy or analgesic nephropathy.
- Secondary FSGS: Caused by systemic factors and infections, including HIV or heroin use.
Pathogenesis and Mechanisms of Development
The underlying mechanism involves severe injury to podocytes—visceral epithelial cells. The idiopathic form is closely linked to minimal change disease and is viewed by some as a potential continuation of podocyte foot process disease.
- The key event is the detachment of podocytes from the glomerular basement membrane (GBM).
- Exposure of the basement membrane leads to a sharp increase in permeability and the deposition of plasma proteins in areas of capillary collapse.
- The process is accompanied by fibrin accumulation and a mesangial cell response, leading to hyalinosis and sclerosis.
- The recurrence of proteinuria following kidney transplantation suggests the circulation of a specific systemic permeability factor.
Morphological Findings and Microscopy
Initial changes frequently affect juxtamedullary glomeruli, originating near the vascular pole.
- Light microscopy: Early stages may appear normal or show mesangial widening and capillary loop collapse. Later, synechiae (adhesions) form with Bowman's capsule.
- Electron microscopy: Reveals diffuse effacement of podocyte foot processes in non-sclerotic areas and their focal detachment.
- Immunohistochemistry: Deposits of IgM and the C3 complement component are found within sclerotic zones.
- Progression: Over time, global glomerular sclerosis, tubular atrophy, and interstitial fibrosis develop.
Histological Variants
Within the classical presentation, several morphological variants of injury are distinguished:
- Cellular variant: Characterized by prominent endocapillary hypercellularity.
- Tip lesion: Damage is localized at the tubular outlet (the transition to the proximal tubule).
- Collapsing glomerulopathy: Distinguished by severe collapse of the glomerular tuft and rapid progression to chronic kidney disease.