Nephritic Syndrome

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 microscopyglomerular hypercellularity e.g., polymorphonuclear leukocytes Immunofluorescencediffuse granular pattern on glomerular capillary walls and mesangiumdeposition of IgG, IgM, and C3 Electron microscopy electron-dense, glomerular subepithelial immune-complex deposits (“humps”)	Streptococcus titers and serologies are positive↓ serum C3 levelsTypically self-resolves
Rapidly progressive glomerulonephritis	Goodpasture syndrome type II hypersensitivityanti-GBM antibodies against α3-chain of collagen type IV antibodies to the alveolar basement membrane result in hemoptysis and lung disease Pauci-immune processesgranulomatosis with polyangiitismicroscopic polyangiitis	Light microscopy and immunofluorescencecrescent-shaped deposition of fibrin, C3b, glomerular parietal cells, monocytes, and macrophages	Granulomatosis with polyangiitisPR3-ANCA/c-ANCA positive Microscopic polyangiitisMPO-ANCA/p-ANCACorticosteroids 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 microscopymesangial proliferationImmunofluorescenceIgA 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 membranemore commonly an X-linked dominant disorder characterized byrenal involvementocular involvementsensorineural hearing loss	Electron microscopyglomerular 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 capillariesthis results in proliferation of the mesangium and remodeling of the capillary wallmay be secondary tohepatitis C virushepatitis B virusC3 nephritic factorMPGN type II	Light microscopymesangial proliferation and thickening of the capillary wallImmunofluorescence”tram-track” appearance	↓ serum C3 and C4 levelsTreat underlying disease in secondary causese.g., control of hepatitis C virus infection
Diffuse proliferative glomerulonephritis (DPGN)	> 50% of glomeruli (thus diffuse) demonstrates an inflammatory process on histologyCommon in patients with systemic inflammatory diseases (e.g., systemic lupus erythematosus)can be secondary to membranoproliferative glomerulonephritis	Light microscopycapillary “wire-looping”Electron microscopyimmune complex deposition affecting thesubendothelial regionmaybe intramembranousImmunofluorescencegranular appearance	Can lead to death in patients with systemic lupus erythematosusAggressively treat with steroids

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