What are the primary types of glomerular syndromes?

Primary Types of Glomerular Syndromes

The primary types of glomerular syndromes include IgA nephropathy, membranous nephropathy, minimal change disease, focal segmental glomerulosclerosis, infection-related glomerulonephritis, ANCA-associated vasculitis, lupus nephritis, anti-GBM antibody glomerulonephritis, and complement-mediated glomerular diseases. 1

Classification of Glomerular Syndromes

Primary Glomerular Diseases

• IgA Nephropathy (IgAN) and IgA Vasculitis (IgAV): Characterized by mesangial IgA deposits, often presenting with hematuria and variable proteinuria 1
• Membranous Nephropathy: An autoimmune disease with antibodies targeting podocyte antigens, typically presenting with nephrotic syndrome 1
• Minimal Change Disease (MCD): Characterized by normal-appearing glomeruli on light microscopy but podocyte foot process effacement on electron microscopy, commonly causing nephrotic syndrome 1
• Focal Segmental Glomerulosclerosis (FSGS): Features segmental sclerosis affecting some but not all glomeruli, can be primary (mediated by circulating factors) or secondary 1
• Membranoproliferative Glomerulonephritis (MPGN): Now reclassified as "Immunoglobulin- and complement-mediated glomerular diseases with an MPGN pattern of injury" 1
• C3 Glomerulopathy: Characterized by dominant C3 deposits with minimal or no immunoglobulin deposits, including dense deposit disease and C3 GN 1

Immune-Complex Mediated Glomerulonephritis

• Lupus Nephritis: Glomerular involvement in systemic lupus erythematosus, classified according to ISN/RPS criteria 1
• Infection-Related Glomerulonephritis: Associated with bacterial, viral, or parasitic infections 1
• IgA-Dominant Infection-Related GN: Often associated with Staphylococcus aureus infections 1

Pauci-immune Glomerulonephritis

• ANCA-Associated Vasculitis: Including microscopic polyangiitis, granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis 1
• Anti-GBM Antibody GN (Goodpasture's Syndrome): Characterized by linear IgG deposits along the glomerular basement membrane, often with pulmonary involvement 1, 2

Complement-Mediated Glomerular Diseases

• C3 Glomerulopathy: Including dense deposit disease and C3 GN, associated with dysregulation of the alternative complement pathway 1
• Atypical Hemolytic Uremic Syndrome: Complement-mediated thrombotic microangiopathy 1

Clinical Presentation Patterns

• Nephrotic Syndrome: Characterized by heavy proteinuria (>3.5g/day), hypoalbuminemia, edema, and hyperlipidemia; common in membranous nephropathy, minimal change disease, and FSGS 3, 4
• Nephritic Syndrome: Features hematuria, proteinuria, hypertension, and reduced GFR; common in IgA nephropathy, infection-related GN, and lupus nephritis 5
• Rapidly Progressive Glomerulonephritis (RPGN): Characterized by rapid decline in kidney function over days to weeks; typical of ANCA vasculitis, anti-GBM disease, and severe lupus nephritis 2, 6
• Asymptomatic Urinary Abnormalities: Microscopic hematuria and/or non-nephrotic proteinuria; often seen in early IgA nephropathy 4, 7
• Chronic Glomerulonephritis: Gradual progression to end-stage kidney disease; can occur in any untreated or treatment-resistant glomerular disease 6, 7

Diagnostic Approach

• Kidney Biopsy: Essential for definitive diagnosis, providing information on:
  • Pattern of injury (mesangial proliferative, membranoproliferative, necrotizing/crescentic, focal segmental sclerosis) 1
  • Immunofluorescence findings (IgA, IgG, C3, etc.) 1
  • Electron microscopy findings (location and characteristics of deposits) 1
• Serological Testing: Anti-GBM antibodies, ANCA, anti-nuclear antibodies, complement levels, and specific autoantibodies (e.g., anti-PLA2R in membranous nephropathy) 1, 2

Prognostic Considerations

• Patients with IgAN and FSGS generally have faster eGFR decline and higher rates of kidney replacement therapy compared to other common causes of CKD 6
• Membranous nephropathy and minimal change disease typically have slower eGFR decline and better renal outcomes 6
• The presence of crescents, severe interstitial fibrosis and tubular atrophy, and high-grade proteinuria are associated with worse outcomes across most glomerular diseases 1

Treatment Principles

• Treatment approaches vary by specific glomerular disease but often include:
  • Supportive care (blood pressure control, proteinuria reduction with RAAS blockade) 1
  • Disease-specific immunosuppressive therapy 1
  • Management of complications (edema, hyperlipidemia, thrombotic risk) 1
• Treatment decisions should be guided by disease severity, risk of progression, and patient-specific factors 1