Nephrotic Syndrome

BASICS

DESCRIPTION

  • A constellation of clinical and laboratory features defined by the presence of massive proteinuria (>3.5 g/1.73 m2/24 hr), hypoalbuminemia (<2.5 g/dL), and peripheral edema, with hypercoagulability and susceptibility to infection
  • In children nephrotic proteinuria is defined as >40 mg/m2/hr
  • It can be due to intrinsic renal disease or caused by congenital infections, diabetes mellitus, systemic lupus erythematosus, neoplasia or certain drug use (1),(2).

EPIDEMIOLOGY

  • Diabetic nephropathy
  • Minimal change disease (MCD)
    • Most common cause of nephrotic syndrome in children aged <10 years (90%)
    • Idiopathic condition in adults associated with NSAID use or Hodgkin lymphoma
  • Amyloidosis: 4–17% of idiopathic nephrotic syndrome—two renal types primary (AL) and secondary (AA)
  • Lupus nephropathy (LN): Adult women are affected about 10 times more often than men.
  • Focal segmental glomerulosclerosis (FSGS)
    • 35% of nephrotic syndrome in adults, most common primary nephrotic syndrome in African Americans
    • Has both primary (idiopathic) and secondary forms (associated with HIV, morbid obesity, reflux nephropathy, previous glomerular injury)
  • Membranous nephropathy
    • Most common cause of primary nephrotic syndrome in adults (40%)
    • Most often primary (idiopathic) but can be secondary associated with malignancy, hepatitis B, autoimmune diseases, thyroiditis, and certain drugs including NSAIDs, penicillamine, gold and captopril
  • Membranoproliferative glomerulonephritis (MGN)
    • May present in the setting of a systemic viral or rheumatic illness

Incidence

  • Worldwide, children have an incidence of 1.15 to 16.9 per 100,000 children, with lower incidence in Europe and North America, and higher in Southeast Asia and East Asia (1).
  • Approximately 3 cases per 100,000 per year in adults. There is increased incidence and development of severe disease in African American and Hispanic population.

ETIOLOGY AND PATHOPHYSIOLOGY

  • Primary renal disease (e.g., MCD, FSGS, MGN, IgA nephropathy)
  • Secondary renal disease (e.g., diabetic nephropathy, amyloidosis, and paraproteinemias)
  • Increased glomerular permeability to protein macromolecules, especially albumin
  • Edema results primarily from renal salt retention, with arterial underfilling from decreased plasma oncotic pressure playing an additional role.
  • The hypercoagulable state is likely due to loss of antithrombin III in urine.

Genetics

Mutations in genes regulating podocyte proteins identified in families with inherited nephrotic syndrome.

RISK FACTORS

  • Children
    • Often idiopathic, with kidney biopsy showing MCD
    • Family history of nephrotic syndrome may be associated with genetic mutations.
    • Viral infections, including HIV, hepatitis B, cytomegalovirus, and parvovirus B19
    • Sickle cell disease (2)
  • Adults
    • Drug addiction (e.g., heroin [FSGS])
    • Hepatitis B and C, HIV, CMV, Parvovirus B1, toxoplasmosis, other infections
    • Immunosuppression
    • Nephrotoxic drugs (lithium, bisphosphonates, interferon therapy, gold, bucillamine, and penicillamine)
    • Vesicoureteral reflux (FSGS)
    • Cancer (usually MGN, may be MCD)
    • Chronic analgesic use/abuse (NSAIDs)
    • Preeclampsia
    • Diabetes mellitus

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