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Snapshot
  • A 6-year-old boy is brought to the emergency department by his mother due to swelling around his eyes and legs. The mother reports that the patient recently recovered from an upper respiratory tract infection. Physical exam is significant for periorbital and lower extremity edema. Laboratory testing is significant for hypoalbuminemia and normal complement levels. Urinalysis demonstrates 4+ protein. A presumptive diagnosis of minimal change disease is made and the patient is started on steroid therapy.
Introduction
  • Clinical definition
    • a type of kidney disease that results in proteinuria, peripheral edema, hyperlipidemia, and hypoalbuminemia
  • Epidemiology
    • incidence
      • annually there are 3 cases per 100,000 adults
  • Etiology
    • primary glomerular disease
      • focal segmental glomerulosclerosis
      • membranous nephropathy
      • minimal change disease
    • secondary causes
      • diabetic nephropathy
      • systemic lupus erythematosus
      • amyloidosis
  • Pathogenesis
    • the glomerulus becomes permeable to large molecules (e.g., albumin)
      • this loss of albumin (proteinuria) results in hypoalbuminemia and edema
      • associated with a hypercoagulable state
        • pathophysiology unclear but may be due to loss of antithrombin and plasminogen proteins
      • increased lipid synthesis secondary to proteinuria
        • this in turn results in hypercholesterolemia and hyperlipidemia
  • Associated conditions
    • chronic kidney disease
  • Prognosis
    • depends on the underlying cause
      • e.g., patients with minimal change disease typically respond well to steroid therapy
Presentation
  • Symptoms
    • edema
      • periorbital, lower extremity, and genital edema
    • frothy urine
    • ascites
    • weight gain
    • fatigue
    • shortness of breath
  • Physical exam
    • hypertension
    • edema
    • leukonychia
      • suggestive of a low albumin state and presents as white streaking on the fingernails
Studies
  • Labs
    • hypoalbuminemia (serum albumin of < 2.5 g/dL)
    • hyperlipidemia
  • Urine studies
    • rule out transient / orthostatic proteinuria if no symptoms or signs are present other than proteinuria
    • proteinuria > 3-3.5 g/day 
      • or > 300-350 mg/mmol on spot urine protein to creatinine ratio
    • fatty casts with "maltese cross" sign

Nephrotic Syndrome
Type
Pathophysiology
Renal Biopsy
Treatment and Notes
Focal segmental glomerulosclerosis
  • Podocyte injury or decreased glomerular filtration barrier integrity
  • Light microscopy 
    • segmental scarring
  • Treat underlying etiology in secondary causes
  • Steroid therapy
  • Can be secondary to 
    • HIV
    • sickle cell disease
    • heroin abuse
    • interferon treatment
Minimal change disease 
  • Unclear but may be due to an immune-related mechanism 
  • Light microscopy
    • normal appearing
  • Electron microscopy
    • effacement of the foot processes  
  • Steroid therapy
  • Most common in children
  • May follow recent infection, immunizations, or may be idiopathic
  • Can be associated with Hodgkin lymphoma
Membranous nephropathy
  • Antibody-immune complex deposition
    • IgG antibodies target podocyte antigens
      • or antigens in close proximity to the podocytes
  • Complement-mediated podocyte injury
  • Light microscopy
    • glomerular basement membrane thickening
  • Immunofluoresence
    • immune complex deposition leading to granular appearance
  • Electron microscopy
    • "spike and dome" 
    • subepithelial deposits
  • Immunosuppressive therapy in primary cases
    • steroids and cyclophosphamide
  • Most common cause of primary nephrotic syndrome in Caucasian adults
  • Primary causes
    • antibodies targeting phospholipase A2 receptors
  • Secondary causes
    • medications
    • systemic lupus erythematosus
    • nonsteroidal anti-inflammatory drugs
    • gold
    • penicillamine
    • hepatitis B and C infection
Amyloidosis
  • Amyloid deposits in the mesangium
  • Electron microscopy 
    • apple-green birefringence on Congo red stain under polarized light
  • Treatment involves addressing the plasma cell dyscrasia
Diabetic glomerulonephropathy
  • Glomerular hyperperfusion and hyperfiltration result in albumin leaking
    • under these conditions the glomerulus responds via
      • glomerular basement membrane thickening
        • due to non-enzymetic glycosylation
      • hypertrophy
      • sclerosing
      • podocyte injury
  • Light microscopy 
    • expansion of the mesangium
    • Kimmelstiel-Wilson lesions
  • Angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs)
  • Adequately controlling diabetes
 
 

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