Nephrotic Syndrome

This condition lies on a spectrum of glomerular disease (glomerulonephritis).

– It encompasses non-inflammatory damage to the glomerular capillary wall due to a podocyte pathology –> gives abnormal function or podocyte injury/death

– It increases permeability to plasma proteins, giving albumin loss in the urine.

Symptoms:

These are caused by loss of protein in urine (>3g/24h)

– Hypoalbuminemia (<30g/dL) – oedema in ankles, periorbital and scrotal areas

– Hypercoaguble state – due to loss of antithrombin III, gives ­risk of thrombosis e.g. renal vein thrombosis

– Hyperlipidaemia –increase in protein synthesis in the liver results in increase in cholesterol synthesis

Management:

The definitive treatment is by correcting the underlying cause

– 1st Reduce oedema by fluid and salt restriction + diuretics   – 2nd Protect renal function with ACEi/ARB

 

There are many specific conditions which give rise to nephrotic syndrome, which have specific treatments:

Minimal Change disease

This is the most common form seen in children

– T cells release cytokines affecting podocyte function which allows the loss of albumin

– However, this does not cause renal failure and glomeruli appear normal

– Gives nephrotic syndrome with proteinuria, but not raised blood pressure

Cause:

Idiopathic (90%), but seen in Infectious mononucleosis + Hodgkin’s lymphoma

Diagnosis:

Renal biopsy –> electron microscope shows effacement of foot processes

Management:

1st line is Steroid treatment (Prednisolone) – very effective.

2nd line = Immunosuppression e.g cyclophosphamide

Focal segmental glomerulosclerosis (FSGS)

– This is the most common form in adults

– There is damage to podocytes –> effacement of foot processes

– Poor response to steroids and progresses to chronic renal failure

Cause:

Usually idiopathic, but can occur after HIV and Sickle cell disease

Diagnosis:

Renal biopsy –> shows focal sclerosis (scarring of glomerulus in parts)

Management:

ACE-inhibitors and BP control to slow progression + Steroids for underlying disease

Membranous nephropathy

– This is more common in adults than children

– Here there is immune complex deposition in glomerulus basement membrane, causing thickening and damage

Cause:

Usually idiopathic and associated with anti-phospholipase A2 receptor antibodies

– Secondary to infections (Hep B and C)

– Cancers + Autoimmune disease (SLE, Rheumatoid)

Diagnosis:

Renal biopsy –> thickened basement membrane with spike and dome appearance

– Blood test shows anti-phospholipase A2 receptor antibodies

Management:

ACE-inhibitor and blood pressure control to slow progression

– Immunosuppression with steroids + Chlorambucil

Membranoproliferative glomerulonephritis

This is a type of nephrotic syndrome which is not very steroid responsive and leads to gradual renal failure. In 2 main types:

i) Immune complex:

This is the most common due to infections (Hepatitis C) or cryoglobinaemia

– These conditions lead to the formation of immune complexes which get deposited in the kidney

– This causes immune deposits in glomerulus giving a classic a tram-track appearance

ii) C3b glomerulopathy:

This occurs due to genetic defect in alternative complement pathway

– It leads to overactivation of the alternative complement pathway giving inflammation

– C3b antibody (an antibody against C3bBb) is found which lowers serum complement levels, meaning immune complexes cannot be cleared, so get deposited in the kidney

Diagnosis:

Renal biopsy –> shows proliferative inflammation + immune complex deposition

Management:

ACE-inhibitors and BP control to slow progression + Steroids for underlying disease

Diabetes mellitus

Diabetes can lead to nephrotic syndrome as glucose in the blood gives non-enzymatic glycosylation of basement membrane

– First gives microalbuminuria –> later progresses onto nephrotic syndrome

– Gives enlarged kidneys (all conditions above reduce size of kidneys)

– Diabetics get yearly urinary albumin:creatinine ratio screening to monitor damage

Management:

ACE inhibitors slow progression of hyperfiltration-induced damage

– Manage diabetes with weight-loss + medications e.g. metformin