Nephrotic Syndrome

Nephrotic Syndrome is a manifestation of glomerular disease characterized by increased permeability of the glomerular filtration barrier to plasma proteins. The diagnostic triad consists of: 1. Proteinuria (Albumin:Creatinine Ratio >220 mg/mmol or protein >3.5 g/24h). 2. Hypoalbuminaemia (<30 g/L). 3. Oedema (typically peripheral, can be periorbital). Common causes include Minimal Change Disease (most common in children), Membranous Nephropathy (most common in adults), and Focal Segmental Glomerulosclerosis (FSGS). Secondary causes include Diabetes mellitus (most common cause overall in the UK), systemic lupus erythematosus (SLE), and amyloidosis. The loss of protein leads strictly to a fall in oncotic pressure, resulting in fluid shifting to the interstitium and compensatory renal salt and water retention. Furthermore, the liver increases protein synthesis, leading to hyperlipidaemia. Patients are at high risk of venous thromboembolism (VTE) due to the loss of Antithrombin III and increased fibrinogen, and are prone to infections due to the loss of immunoglobulins. Management involves high-dose steroids (especially for Minimal Change), ACE inhibitors for proteinuria, and anticoagulation in high-risk cases.

The glomerular filtration barrier consists of the fenestrated endothelium, the glomerular basement membrane (GBM), and the podocytes (epithelial cells). In nephrotic syndrome, this barrier—specifically the podocytes and their slit diaphragms—is damaged. In Minimal Change Disease, electron microscopy shows 'effacement' of podocyte foot processes, but light microscopy is normal. In Membranous Nephropathy, there is thickening of the GBM due to immune complex deposition (often anti-PLA2R antibodies). In FSGS, some (focal) glomeruli show partial (segmental) scarring. The physiological result is massive proteinuria. The 'Underfill' hypothesis suggests low oncotic pressure leads to fluid loss into tissues, reducing effective circulating volume and activating RAAS. The 'Overfill' hypothesis suggests a primary renal defect in sodium excretion causes fluid retention regardless of oncotic pressure.

The hallmark is pitting oedema, often starting in the ankles but progressing to the thighs, scrotum/labia, and abdomen (ascites). Periorbital oedema is common in children, often mistaken for allergy. Breathlessness may indicate pleural effusions or pulmonary embolism. Patients may notice 'frothy' urine (due to protein). Complications are significant: 1. Thromboembolism: Loss of Antithrombin III and Protein C/S leads to an hypercoagulable state. 2. Infection: Loss of IgG and complement factors increases susceptibility to encapsulated organisms (e.g., S. pneumoniae). 3. Cardiovascular: Hyperlipidaemia and fluid overload increase risk. 4. AKI: Can occur due to profound hypovolaemia (pre-renal) or renal vein thrombosis.

Bedside: Urinalysis (3+ protein); BP measurement. Bloods: U&Es (check GFR), Albumin (low), LFTs, Lipid profile (cholesterol high), FBC, CRP. Screen for secondary causes: HbA1c, ANA, C3/C4, Hepatitis B/C, HIV, and PLA2R antibodies. Urine: ACR or 24-hour urinary protein collection. Imaging: Renal ultrasound. Gold Standard: Renal Biopsy (essential in adults; not usually done in children first-line as 90% have Minimal Change).

Conservative: Salt restriction (<2g/day) and fluid restriction if hyponatraemic. Medical: 1. Oedema: Loop diuretics (e.g., Furosemide), often requiring high doses. 2. Proteinuria: ACE inhibitors or ARBs to reduce intraglomerular pressure. 3. Thromboembolism: Prophylactic LMWH or Warfarin, especially if albumin <20 g/L. 4. Lipids: Statins. 5. Disease-specific: High-dose Prednisolone for Minimal Change; Cyclophosphamide or Rituximab for Membranous/FSGS. Vaccinations (Pneumococcal) are vital due to infection risk.