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Updated: Jun 10 2024

Nephritic Syndrome

  • Snapshot
    • A 26-year-old man presents with hematuria, periorbital edema, and jaundice. He has a medical history of opioid use disorder with prior hospitalizations for heroin overdose. He is on methadone but is non-adherent. His blood pressure is 155/102 mmHg. Physical examination is significant for scleral icterus, hepatomegaly, and palpable purpura. Serology shows decreased C3 and C4 levels and elevated anti-hepatitis C antibodies. Urinalysis demostrates dysmorphic red blood cells and red blood cell casts. (Membranoproliferative glomerulonephritis)
  • Introduction
    • Clinical definition
      • renal disease secondary to an inflammatory process injuring the glomerulus
        • this results in damage involving the
          • basement membrane
          • capillary endothelium
          • mesangium
    • Presentation
      • symptoms
        • hypertension
        • hematuria
        • oliguria
        • headache
      • physical exam
        • edema
          • can be peripheral and/or periorbital
    • Diagnosis
      • studies
        • complete blood cell count
          • anemia may be noted
        • azotemia
        • complement levels
          • C3, C4, and CH50 should be obtained
        • urinalysis
          • dysmorphic red blood cells (RBCs)
            • suggests hematuria is of glomerular origin
          • RBC casts
          • subnephrotic range proteinuria (< 3.5 g/day)
            • if the nephritic syndrome is severe enough it can lead to nephrotic range proteinuria (> 3.5 g/day)
      • renal biopsy
        • may be necessary to arrive to a definitive diagnosis and to determine prognosis
      • Nephritic Syndrome
      • Type
      • Pathophysiology
      • Renal Biopsy
      • Diagnostic Studies and Treatment
      • Acute poststreptococcal glomerulonephritis
      • Glomerulonephritis secondary to nephritogenic strains of streptococcus
      • - type III hypersensitivity reaction
      • Light microscopy
      • - glomerular hypercellularity
      • e.g., polymorphonuclear leukocytes
      • Immunofluoresence
      • - diffuse granular pattern on glomerular capillary and mesangium
      • deposition of IgG, IgM, and C3
      • Electron microscopy
      • - electron-dense, glomerular subepithelial immune-complex deposits ("humps")
      • Streptococcus titers and serologies are positive
      • e.g., ASO levels
      •  ↓ serum C3 levels
      •  Typically self-resolves
      • Rapidly progressive glomerulonephritis
      • Goodpasture syndrome 
      • - type II hypersensitivity
      • - anti-GBM antibodies against α3-chain of collagen type IV 
      • - antibodies to the alveolar basement membrane result in hemoptysis and lung disease
      •  Pauci-immune processes
      • - granulomatosis with polyangiitis
      • - microscopic polyangiitis
      • Light microscopy and immunofluoresence
      • - crescent-shaped deposition of fibrin, C3b, glomerular parietal cells, monocytes, and macrophages
      • Granulomatosis with polyangiitis
      • - PR3-ANCA/c-ANCA
      •  Microscopic polyangiitis
      • - MPO-ANCA/p-ANCA
      • Corticosteroids and cyclophosphamide
      • IgA nephropathy (Berger disease)
      • IgA immune-complex deposition in glomerular mesangial cells that results in its proliferation
      • - patients present with hematuria and upper respiratory tract or gastrointenstinal infection
      • Light microscopy
      • - mesangial proliferation
      •  Immunofluoresence
      • - IgA immune-complex deposition in the mesangium
      • ACE inhibitor or ARB for proteinuria and hypertension
      • Alport syndrome
      • Collagen type IV mutation that results in an abnormal basement membrane
      • - more commonly an X-linked genetic disorder
      • characterized by:
      • renal involvement
      • ocular involvement
      • sensorineural hearing loss
      • Electron microscopy
      • - glomerular basement membrane lamellation
      • No curative treatment
      • Membranoproliferative glomerulonephritis (MPGN) 
      • Immune-complex and/or complement protein deposition in the mesangium and subendothelium of the capillaries
      • - this results in proliferation of the mesangium and remodeling of the capillary wall
      • - may be secondary to
      • hepatitis C virus
      • hepatitis B virus
      • C3 nephritic factor
      • MPGN type II
      •  Can also present as a nephrotic syndrome 
      • Light microscopy
      • - mesangial proliferation and thickening of the capillary wall
      •  Immunofluoresence
      • - "tram-track" appearance
      • ↓ serum C3 and C4 levels
      • - Treat underlying disease in secondary causes
      • e.g., control of hepatitis C virus infection
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