Nephritic Syndrome - Renal - Medbullets Step 1

Snapshot

A 14-year-old boy presents with hematuria, problems with vision, and deafness. Approximately 2 weeks prior to symptom development, he recovered from a viral upper respiratory tract infection. Family history is significant for deafness and early initiation of lisinopril in his father. His temperature is 99°F (37.2°C), blood pressure is 140/90 mmHg, pulse is 75/min, and respirations are 18/min. Physical examination is signifcant for anterior lenticonus and sensorineural hearing loss. Urinalysis demonstrates dysmorphic red blood cells and red blood cell casts. (Alport syndrome)

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 Immunofluorescence diffuse granular pattern on glomerular capillary walls and mesangium deposition of IgG, IgM, and C3 Electron microscopy electron-dense, glomerular subepithelial immune-complex deposits ("humps")	Streptococcus titers and serologies are positive ↓ 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 immunofluorescence crescent-shaped deposition of fibrin, C3b, glomerular parietal cells, monocytes, and macrophages	Granulomatosis with polyangiitis PR3-ANCA/c-ANCA positive Microscopic polyangiitis MPO-ANCA/p-ANCA Corticosteroids and cyclophosphamide
IgA nephropathy (Berger's disease)	IgA immune-complex deposition in glomerular mesangial cells that results in its proliferation patients present with hematuria and upper respiratory tract or gastrointestinal infection	Light microscopy mesangial proliferation Immunofluorescence 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 dominant disorder characterized by renal involvement ocular involvement sensorineural hearing loss	Electron microscopy glomerular basement membrane lamellation "basket weave" appearance	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	Light microscopy mesangial proliferation and thickening of the capillary wall Immunofluorescence "tram-track" appearance	↓ serum C3 and C4 levels Treat underlying disease in secondary causes e.g., control of hepatitis C virus infection
Diffuse proliferative glomerulonephritis (DPGN)	> 50% of glomeruli (thus diffuse) demonstrates an inflammatory process on histology Common in patients with systemic inflammatory diseases (e.g., systemic lupus erythematosus) can be secondary to membranoproliferative glomerulonephritis	Light microscopy capillary "wire-looping" Electron microscopy immune complex deposition affecting the subendothelial region maybe intramembranous Immunofluorescence granular appearance	Can lead to death in patients with systemic lupus erythematosus Aggressively treat with steroids