NEPHROTIC SYNDROME

The nephrotic syndrome consists of the following features:

• Heavy proteinuria (>3g/day)

• Hypoalbuminemia

• Edema

• Hyperlipidemia

• Hypercoagulability

PATHOGENESIS

Proteinuria

Injury to the capillary wall of the glomeruli results in increased permeability to the plasma proteins, allowing the protein to escape from the plasma into the glomerular filtrate, resulting in proteinuria.

Hypoalbuminaemia

Proteinuria results in decreased serum albumin resulting in hypoalbuminemia. Urinary loss of 3-5 g of protein daily is required to produce hypoalbuminemia in adults.

Generalized oedema

The cause of oedema is salt and water retention due to renal disease. Hypoalbuminaemia may be the contributing factor in oedema formation because it results in decreased colloid osmotic pressure which in turn, allows fluid to escape from vessels and to produce generalized oedema.

Hyperlipidemia

Hypoalbuminemia triggers the increased synthesis of all forms of plasma proteins including lipoproteins resulting in hyperlipidemia.

Hypercoagulability

It may result from:

• Increased urinary loss of antithrombin III.

• Altered levels and/or activity of protein C and protein S.

• Hyperfibrinogenemia. Due to increased hepatic synthesis.

• Impaired fibrinolysis.

• Increased tendency of platelet aggregation.

ETIOLOGY OF NEPHROTIC SYNDROME

Pure nephrotic syndrome

Primary glomerular disease

• Minimal change nephropathy

• Focal segmental glomerulosclerosis

° Membranous Glomerulonephritis (most common cause in adults > 40 years of age).

Secondary glomerulonephritis as  associated with systemic disease 

• Diabetic nephropathy

• Amyloidosis

• Drugs: penicillamine, gold, mercury, cadmium

• Allergic reaction: allergy to poison ivy, pollens, bcc stings, and cow milk.

Mixed nephrotic/nephritic syndrome

Primary glomerular disease

Membranoproliferative glomerulonephritis

Secondary glomerulonephritis associated with systemic disease.

9 Membranoprolifterative glomerulonephritis.

SLE

HSP

CLINICAL FEATURES

Oedema

• Peripheral oedema involving upper limbs & mostly lower limbs. In children, it may be more obvious on the face (periorbital oedema) & abdomen (ascites).

• Intense oedema of scrotum or vulva may occur,

” There may be bilateral hydrothorax.

• Edema of the intestine causes anorexia, diarrhoea, and vomiting.

Malnutrition

Malnutrition may be due to proteinuria, frequent infections & muscle wasting.

Features of the underlying cause such as

Features of the cause of nephritic syndrome may be present e.g. butterfly rash in SLE and neuropathy or retinopathy in diabetes mellitus.

Hypercoagulability

Hypcrcoagubility manifests as peripheral arterial or
venous thrombosis, renal vein thrombosis and
pulmonary embolism.

Infections

There is an increased susceptibility to infection due to urinary loss of IgG antibodies.

INVESTIGATIONS

1 . Urine D/R – proteinuria

2. 24 hours urinary proteins: usually more than 3g/day.

3. Serum albumin – less than 3g/dl and total serum protein < 6 mg/dl.

4. Low-density lipoprotein (LDL) is elevated but HDL is usually normal.

5. Raised ESR due to increased serum fibrinogen

6 . Blood sugar for diabetes & antinuclear factor
for SLE,

7. Hepatitis B serology, serum complements.

8. Renal biopsy: confirms the diagnosis.

COMPLICATIONS

• Protein malnutrition

• Hypercoagulability – due to the rise in many clotting factors.

• Impaired resistance to infection (due to low body immunoglobulins as a result of hypoproteinaemia)

• Sepsis, blood loss, and hypovolemia may lead to acute oliguric renal failure.

MANAGEMENT

Diet

• Low salt diet.

• Moderate protein restriction (0.5-0. 6 g/kg/d) because increased protein intake may have an adverse effect on renal function in some diseases.

Diuretics

• Frusemide

Hypercholesterolemia

HMG-CoA reductase inhibitors are preferred for the treatment of hypercholesterolemia such as atorvastatin.

Hypercoagulability

Patients with serum albumin of less than 2g/dl can become hypercoagulable. Anticoagulation therapy is required when there is evidence of thrombosis.

• Maintain blood pressure & fluid volume

Specific therapy

Specific therapy such as prednisolone and depends on the cause of the nephrotic syndrome. It is not discussed here as it is a specialist domain