Makindo Medical Notes

Related Subjects: |Metabolic acidosis |Lactic acidosis |Acute Kidney Injury (AKI) / Acute Renal Failure |Renal/Kidney Physiology |Chronic Kidney Disease (CKD) |Anaemia in Chronic Kidney Disease |Analgesic Nephropathy |Medullary Sponge kidney |IgA Nephropathy (Berger's disease) |HIV associated nephropathy (HIVAN) |Balkan endemic nephropathy (BEN) |Adult Polycystic kidney disease |Focal Segmental Glomerulosclerosis (FSGS)

Focal Segmental Glomerulosclerosis (FSGS) represents a spectrum of clinicopathological syndromes with shared histological features on renal biopsy. "Focal" indicates that only some glomeruli are affected, while "Segmental" specifies that only a portion of each affected glomerulus is involved.

About

• Known as Focal and Segmental Glomerulosclerosis (FSGS), a leading cause of end-stage renal disease (ESRD) globally.
• Commonly causes proteinuria, ranging from nephrotic to subnephrotic levels.
• Increasing incidence worldwide, posing a significant public health concern due to its association with chronic kidney disease.

Aetiology

• FSGS encompasses multiple etiologies, often linked to podocyte injury and depletion, which impair glomerular filtration.
• Possible involvement of a plasma factor responsive to immunosuppressive therapy, suggesting an immune-mediated component.
• Can arise from genetic mutations, particularly in cases presenting in younger patients.
• Clinically resembles Minimal Change Disease (MCD) due to shared features like proteinuria and podocyte damage, despite minimal immune deposits.

Microscopy of Glomerulus from Renal Biopsy

Associations

• Nephropathies: Reflux nephropathy, analgesic nephropathy.
• Infections and Substances: HIV infection, intravenous heroin use.
• Other Conditions: Sickle cell disease, severe obesity.
• Post-Transplant: FSGS can recur after renal transplantation, often contributing to graft loss.

Clinical Presentation

• Primarily presents with nephrotic syndrome symptoms, including high-grade proteinuria, hypoalbuminemia, and edema.
• May be associated with:
  • Thrombosis: Increased risk due to nephrotic syndrome.
  • Haematuria: May be present in some cases.
  • Hypertension: Common in adults with FSGS.

Investigations

• Urine Dipstick: Detects blood and protein presence.
• 24-Hour Urine Collection: Quantifies proteinuria level for diagnosis and monitoring.
• Renal Function Tests (U&E): Elevated creatinine may indicate renal impairment.
• Renal Ultrasound (USS): Generally appears normal but helps exclude other renal pathologies.
• Renal Biopsy: Key diagnostic tool showing segmental sclerosis of glomerular capillaries and mesangial matrix expansion in affected glomeruli.

Management

• Immunosuppressive Therapy:
  • Steroids and Ciclosporin are commonly used, although response varies widely.
  • Relapse is frequent, and Ciclosporin can have nephrotoxic effects, requiring close monitoring.
• Supportive Therapy:
  • ACE inhibitors or ARBs to reduce proteinuria and manage hypertension.
  • Lifestyle modifications, including weight management, particularly in cases associated with obesity.
• Progression to Chronic Kidney Disease: Patients may progress to ESRD, necessitating renal replacement therapy such as dialysis or transplantation.

References

• Focal Segmental Glomerulosclerosis - Clinical Journal of the American Society of Nephrology