1- nephrotic syndrome

• Nephrotic syndrome


  Triad of proteinuria (>3.5g/day), hypoalbuminemia (albumin <30g/L), and edema
• Nephrotic syndrome


  • May also have hyperlipidemia, abnormalities in coagulation, reduced renal function, and immunological disorders
• Pathophysiology of nephrotic syndrome

  1. Structural & functional abnormalities of the glomerular basement membrane à massively increased filtration of macromolecules à heavy proteinuria à hypoalbuminemia

  2. Renal sodium retention in the collecting tubules & increase in capillary permeability à edema

  3. Increased hepatic lipoprotein synthesis & impaired catabolism à hypercholesterolemia & hypertriglyceridemia

  4. Loss of antithrombin in urine & increased fibrinogen synthesis à hypercoagulability
• Clinical features of nephrotic syndrome

  • Pitting edema – may be periorbital, peripheral (limbs), dependent areas (sacral, scrotal), ascites, or anasarca
  • Frothy urine (proteinuria)
  • Signs of dyslipidemia – ex: eruptive xanthomata, xanthelasma
• Complications of nephrotic syndrome


  • Recurrent infections (including spontaneous peritonitis, septic arthritis, sepsis) due to loss of Igs in urine and immunosuppressive therapy (especially susceptible to infections by capsulated organisms)
  • Hyperlipidemia à accelerated atherosclerosis
  • Hypovolemia à acute kidney injury
  • Hypercoagulability: venous or arterial thrombosis – ex: DVT, renal vein thrombosis, MI
• Investigations for nephrotic syndrome


  • Urinalysis: 3+ or 4+ protein on dipstick
  • Urine sediment examination: casts indicate renal parenchymal disease
  • Urinary protein measurement: 24-hour urine collection or single spot urine albumin-to-creatinine ratio
  • Serum albumin: low
  • Serologic studies for infection and immune abnormalities: ANA, anti-DNA, ANCA, anti-GBM, HBV, HCV, HIV, cryoglobulins, etc.
  • Renal ultrasonography: size and echogenicity
  • Renal biopsy: usually not required in children. Adult nephrotic syndrome of unknown origin may require a renal biopsy for diagnosis
  • Low complement levels
• General management of nephrotic syndrome

  1. Lower intraglomerular pressure by administering an ACEI or ARB to decrease proteinuria

  2. Dietary sodium restriction (to 2 g or 80 mmol of sodium per day) to reduce edema (but no protein restriction)

  3. Loop diuretics (furosemide) are also used to reduce edema. IV route may be used if oral is not effective.

  4. Statins for the lipid abnormalities induced by the nephrotic syndrome

  5. Avoid prolonged rest +/- prophylactic anticoagulation to prevent VTE. If thrombosis occurs, it is typically treated with heparin followed by warfarin for as long as the patient remains nephrotic.

  6. Prompt treatment of infections and vaccinations (pneumococcal, influenza, and varicella)

  7. Treat underlying cause (infections, malignancy, systemic disease, drugs)

  8. Some primary causes respond to specific therapies
• Causes of nephrotic syndrome

  • Primary Nephrotic Syndrome
  • Minimal change disease
  • Focal segmental glomerulosclerosis
  • Membranous nephropathy
  • Membranoproliferative glomerulonephritis*
  • Secondary Nephrotic Syndrome
  • Amyloidosis
  • Diabetic nephropathy
  • SLE*
  • Cryoglobulinemia*
  • Henoch-Schoenlein purpura*
• Minimal change disease


  • Most common cause of nephrotic syndrome in children
  • Never progresses to chronic kidney disease
  • In adults (20%) it can be idiopathic or in association with drugs (NSAIDs) or paraneoplastic (Hodgkin's lymphoma)
  • Usually no need for kidney biopsy
  • Light microscopy and immunofluorescence are normal
  • Electron microscopy shows diffuse effacement of the epithelial podocyte foot processes (characteristic)
  • Treatment of choice: corticosteroids (prednisone)
• Focal segmental glomerulosclerosis


  • May be primary/idiopathic or secondary to vesicoureteric reflux, IgA nephropathy, Alport's syndrome, vasculitis, sickle-cell disease, or heroin use
  • May be associated with AIDs and IV drug use
  • HIV is associated with the collapsing subtype (poor prognosis)
  • Can cause impaired renal function (50%) leading to hypertension & hematuria
  • Light microscopy: not all glomeruli are affected, and the glomerulus affected shows segmental sclerosis/damage in some areas of the glomerulus
  • Electron microscopy and immunofluorescence: IgM deposits
  • Resistance to steroids is common (70%)
  • Cyclophosphamide or ciclosporin are considered if steroid resistant
  • May become chronic and progress to renal impairment/failure
• Membranous nephropathy


  • Most common cause of primary nephrotic syndrome in adults. (20-30%)
  • May be idiopathic or secondary to malignancy, hepatitis B, malaria, syphilis, drugs (gold, penicillamine, NSAIDS) and autoimmunity (thyroid, SLE)
  • Light microscopy shows basement membrane thickening, and spikes are seen with silver stain
  • Immunofluorescence and electron microscopy show granular subepithelial deposits of IgG & C3. (spike and dome appearance)
  • Treatment involves treating the underlying cause. All should be on ACEIs.
  • Corticosteroids with cyclophosphamide/chlorambucil are used if renal function deteriorates
  • May become chronic and progress to renal impairment/failure
  • May be linked to renal vein thrombosis
  • Good prognostic factors: female, young, asymptomatic, modest proteinuria
• Membranoproliferative glomerulonephritis


  • Also known as mesangiocapillary glomerulonephritis
  • Uncommon cause of chronic nephritis primarily in children and young adults
  • Can have a nephritic component
  • Type I: associated with cryoglobinemia & Hep C
  • Type II: associated with partial lipodystrophy
  • May be idiopathic or secondary to chronic infection (abscesses, infective endocarditis, infected VP shunt), cryoglobulinemia, or hepatitis C
  • Characterized by interstitial and mesangial expansion, subendothelial immune deposits, and mesangial interposition into the capillary wall, giving rise to a double-contour or tram-track appearance on light microscopy
  • Not responsive to steroids. Most patients develop renal failure over several years
• DM and HTN are the most common causes of nephrotic syndrome overall