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Nephrotic Syndrome

Definition - This is characterized by
  1. Albuminuria
  2. Hypoalbuminemia
  3. Edema
  4. HyperlipidemiaQ,
  5. lipiduria.
Important Points

RBC cast is not a feature of nephrotic syndrome. It is a feature of nephritic syndrome.


Nephrotic Syndrome and Other Hypoalbuminemia States (Ref. Hari. 18th ed., pg - 292, 2345)
  1. The primary alteration in this disorder is a diminished colloid oncotic pressure due to losses of large quantities of protein into the urine. 
  2. Due to reduced colloid osmotic pressure, the NaCl and H2O that are retained cannot be retained within the vascular compartment, and total and effective arterial blood volumes decline. 
  3. This process initiates the activation of the RAA system. Impaired renal function contributes further to the formation of edema.
Most other proteins are decreased in Nephrotic Syndrome. 
Proteins decreased Consequence
1. Albumin Oedema due to Hypoalbuminemia
2. Transferrin Fe resistant microcytic anemia
3. Cholecalciferol binding protein Low total serum calcium
4. Thyroxine binding globulin Decreased total thyroxin
5. AT III Increase thrombus formation

Extra Edge Nephrotic syndrome is characteristically associated with increased fibrinogen levels (Hyper fibrinogenemia). (LQ 2012)


Causes -
  1. Systemic causes (25%)
    1. Diabetes mellitus (most common cause), SLE, Amyloidosis
    2. Drugs: Gold, penicillamineQ, probenecidQ, street heroin, captoprilQ, NSAIDsQ
    3. Infections: Bacterial endocarditisQ, hepatitis BQ, shunt infections, syphilis, malariaQ
    4. Malignancy: Hodgkin’s and other lymphomasQ, leukemia, carcinoma of breast and GI tractQ
    5. Allergic reactions
Important Points

DM is the most common cause of nephrotic syndrome in adult.

  1. Glomerular disease (75%)
    1. Minimal change disease (90% in children and 15% in adults)
    2. Membranous (40% in adults)
    3. Focal glomerulosclerosis
    4. Membranoproliferative GN
Clinical Features-
  1. Patient usually presents with insidious onset of generalized edema, without a decrease in urine output. 
  2. Patient may complain of passing frothy urine due to presence of protein.
  3. Nephrotic syndrome is associated with = ↑LDL, ↑Tg, ↓HDL
  4. Patient of nephrotic syndrome can develop spontaneous peripheral arterial or venous thrombosis. 
Specially Renal vein thrombosis due to
  1. Increase Fibrinogen
  2. Increase Lipoproteins
  3. Reduced antithrombin III.

Extra Edge Nephrotic syndrome due to diabetic mellitus, minimal change disease and focal segmental sclerosis are rarely associated with renal vein thrombosis


Table: Conditions associated with Renal Vein Thrombosis (Ref. Hari. 18th ed., pg - 2382)
  1. Trauma
  2. Extrinsic compression (lymph nodes, aortic aneurysm, tumor)
  3. Invasion by renal cell carcinoma
  4. Dehydration (infants)
  5. Nephrotic syndrome specially membranous GN (Ref. Hari. 18th ed., pg - 2382) (LQ 2012)
  6. Pregnancy or oral contraceptives

Extra Edge
CT Angiography is the most sensitive test for renal vein thrombosis. (Ref. Hari. 18th ed., pg - 2382)



Nephrotic Syndrome: Common Renal pathologies causing Renal Vein Thrombosis
  1. Membranous Glomerulonephritis (strongest association) (LQ 2012) (Ref. Hari. 18th ed., pg - 2382)
  2. Membranoproliferative Glomerulonephritis
  3. Amyloidosis
  4. Lupus Nephritis
Treatment of nephrotic syndrome
  1. Bed rest
  2. If GFR > 60 ml/min, no dietary restriction required. If GFR < 60 ml/min dietary protein restriction of 0.8 gm/kg/d
  3. Diuretics relieve oedema. Overzealous use of diuretics should be avoided as the patients are often intravascularly depleted and may precipitate prerenal failure.
  1. Venous thrombosis and pulmonary embolism (urinary loss of antithrombin III, low plasma volume, increased Fibrinogen)
  2. Infections (pneumococcal peritonitis)
  3. Hypercholesterolemia (atherosclerosis, xanthomata) (FAQ) 'The lipid profile in Nephrotic syndrome is characterized by elevations in total plasma cholesterol, VLDL and LDL and often (increases in later stages) triglyceride & reduced HDL.
  4. Hypovolemia and renal failure
  5. Loss of specific binding proteins, e.g. transferrin, thyroid – binding globulin.

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