Define nephrotic syndrome. Describe its pathophysiology, causes, morphology and complications.

Definition

Pathophysiology

Injury to the glomerular filtration barrier, chiefly the podocyte → Increased permeability to protein → heavy proteinuria → Urinary loss exceeds hepatic synthesis → hypoalbuminaemia → Reduced plasma oncotic pressure → fluid moves into the interstitium → Reduced effective circulating volume → renin–angiotensin–aldosterone activation → sodium and water retention → oedema, characteristically periorbital first and then generalised → The liver increases lipoprotein synthesis in response to low oncotic pressure → hyperlipidaemia; lipid appears in the urine as oval fat bodies and "maltese cross" forms under polarised light

Causes

Morphology of the Primary Causes

Complications

Secondary Causes Worth Knowing

Selective and Non-selective Proteinuria

• Selectivity predicts steroid responsiveness, and was used clinically before biopsy became routine; the underlying logic still explains why minimal change disease behaves so differently from the rest

Applied Aspects

• In a child with typical nephrotic syndrome, biopsy is not performed first — minimal change disease is so likely that corticosteroids are given empirically, and over 90% respond within four weeks. Biopsy is reserved for steroid resistance, or for atypical features such as haematuria, hypertension, impaired function or age under 1 or over 10
• Minimal change disease responds beautifully to steroids but relapses often; it does not progress to renal failure
• Focal segmental glomerulosclerosis often does not respond, and progresses to end-stage disease; it may recur in a transplanted kidney, which suggests a circulating permeability factor
• Membranous nephropathy in an adult over 50 requires a search for an underlying malignancy — carcinoma of lung, colon or breast — and for hepatitis B, SLE and drugs. Anti-PLA2R antibody identifies the primary form
• Membranous nephropathy follows the "rule of thirds" — about a third remit spontaneously, a third persist with stable function, and a third progress
• Treatment common to all — salt restriction, diuretics, ACE inhibitors or ARBs to reduce proteinuria, statins, and anticoagulation where albumin is very low; plus pneumococcal vaccination in children
• Diurese cautiously — the intravascular volume may be low despite gross oedema, and aggressive diuresis precipitates acute kidney injury and thrombosis
• Sudden loin pain with haematuria and deteriorating function in a nephrotic patient suggests renal vein thrombosis, and requires urgent imaging
• Amyloidosis should be considered in an older patient with nephrotic syndrome, especially with chronic infection, rheumatoid arthritis or myeloma; Congo red staining with apple-green birefringence confirms it
• HIV-associated nephropathy is a collapsing variant of focal segmental glomerulosclerosis with heavy proteinuria and rapid progression, and responds to antiretroviral therapy
• In Indian practice, always consider infection-related causes — hepatitis B and C, malaria (especially quartan malaria in children), filariasis, leprosy and syphilis all cause nephrotic syndrome and are treatable
• Steroid-dependent and frequently relapsing children need steroid-sparing agents — levamisole, cyclophosphamide or calcineurin inhibitors — to avoid growth suppression and cataract