Nephrotic Syndrome is defined by heavy proteinuria, hypoalbuminaemia, oedema, and hyperlipidaemia, and is typically associated with increased renal cortical echogenicity.
Description
Nephrotic syndrome is a renal disorder characterised by the excretion of an excessive amount of protein in the urine, leading to low levels of protein in the blood (hypoalbuminaemia), generalised body swelling (oedema), and high levels of cholesterol in the blood (hyperlipidaemia). It is one of the common causes of significant renal disease in both paediatric and adult populations.
Pathogenesis
The primary abnormality in nephrotic syndrome is increased permeability of the glomerular filtration barrier, allowing for excessive filtration of proteins into the urinary space. The exact cause varies by the subtype of nephrotic syndrome but often involves damage to the podocytes, the cells that help form the glomerular filtration barrier. Loss of proteins in the urine, particularly albumin, leads to decreased oncotic pressure in the blood, which drives fluid into the interstitial spaces, resulting in oedema.
Subtypes
Primary (idiopathic)
- Minimal Change Disease (most common in children)
- Focal Segmental Glomerulosclerosis (FSGS, increasingly common in adults)
- Membranous Nephropathy (common in adults).
Secondary
- Diabetes mellitus, systemic lupus erythematosus, or amyloidosis.
Epidemiology, Risk Factors & Associations
- Most common cause of nephrotic syndrome in children is Minimal Change Disease (MCD, ~80%)
- Most common cause in adults is FSGS and Membranous Nephropathy
- Secondary causes include Diabetes Mellitus (most common secondary cause), systemic lupus erythematosus, and infections such as Hepatitis B and C
- Associations with certain drugs, malignancies, and genetic mutations have been identified
Clinical Features
- Presents with oedema, often periorbital or in lower extremities
- Fatigue, loss of appetite, and frothy urine
- Ascites and pleural effusion in severe cases
Complications
- Acute kidney injury
- Chronic kidney disease and eventual end-stage renal disease
- Increased risk of infection due to loss of immunoglobulins in urine
- Increased risk of thrombosis due to loss of antithrombin III in urine and increased synthesis of clotting factors
Pathological Features
Histopathology
- Macroscopic: Kidneys are usually normal-sized, possibly slightly enlarged
- Microscopic: Dependent on subtype. MCD shows normal glomeruli, FSGS shows segmental sclerosis, Membranous Nephropathy shows thickened glomerular basement membrane
Serology
- Significant proteinuria (>3.5g/day), hypoalbuminaemia, and hyperlipidaemia
Biochemistry
- Elevated cholesterol and triglycerides
Radiological Features
General Features
- Kidneys are typically normal in size, but may be slightly enlarged
- Increased echogenicity of the renal cortex on ultrasound is common
US
- B-mode: Increased renal cortical echogenicity, normal to increased size
- Colour: Not typically useful
Grading and Staging
- Not typically graded or staged, though severity can be assessed based on clinical features and proteinuria levels
Diagnosis
- Diagnosis is made based on clinical features and lab findings of heavy proteinuria, hypoalbuminaemia, and hyperlipidaemia
- Renal biopsy may be needed for definitive diagnosis and to identify subtype
Differential Diagnosis
- Acute and chronic renal failure
- Nephritic syndrome
- Congestive heart failure
- Liver disease
Management
- Management typically involves a Nephrologist. Main goals are to reduce proteinuria, manage oedema, and manage hyperlipidaemia
- Specific management strategies depend on the underlying cause and may include corticosteroids, other immunosuppressants, and ACE inhibitors or ARBs
- Diuretics are used to manage oedema