Pathological consequences of glomerular proteinuria:

Pathological consequences of glomerular proteinuria:

Hypoalbuminaemia: 

Hypoalbuminemia found in nephrotic syndrome is due to urinary loss exceeding hepatic synthesis. Also due to increased loss in urine, the absorbed albumin is catabolized in renal tubule cells (PCT) where much of filtered albumin is reabsorbed. Also loss of fixed anionic charge may extend to endothelium of all capillaries leading to generalized increase in capillary permeability to albumin in addition to increased glomerular filtration.

Oedema and salt and water retention: 

Oedema occurs due to hypoalbuminaemia which decreases oncotic pressure and sieving of fluid for intravascular space. The resulting hypovolaemia stimulate the renin-aldosterone system and vasopressin release, leading to sodium and water retention.

Abnormalities of other plasma proteins: 

Patients with nephrotic syndrome have changes in the concentrations of circulating clotting factors which increases the risk of thrombus formation. Urinary loss of natural anticoagulant antithrombin III is probably involved together with increased plasma concentration of fibrinogen and factors V, VII, VIII and IX. Urinary loss of vitamin D and vitamin D-binding globulin may lead to vitamin D deficiency with low plasma ionized calcium, secondary hyperparathyroidism and renal osteodystrophy. Patients with NS also loose Igs and complement components with attendant increased risk of infections like pleurisy, pneumococcal pneumonia and peritonitis.

Hyperlipidaemia: 

Patients with NS has increased cholesterol and Tg which correlate inversely with serum concentration of albumin. VLDL and LDL are increased, partly due to reduced clearance and partly to increased hepatic synthesis, while HDL is reduced may be due to increased urinary loss. VLDL and LDL are apoB containing lipoproteins which are atherogenic that results in glomerular and interstitial renal disease. 

The activities of LCAT and lipoprotein lipases are reduced in NS which could reduce HDL production. Hepatic synthesis of VLDL and LDL is stimulated by reduction in plasma colloidal osmotic pressure, since treatment with albumin or dextran infusions reduces hepatic lipoprotein synthesis. Nephrotic hyperlipidemia is accompanied by an increased risk of cardiovascular complications and is usually treated aggressively with statins.

Massive proteinuria – Nephrotic syndrome >3.5g/day, usually no hematuria, hypoalbuminemia, hyperlipidemia, edema, hypo or normotensive, GFR normal or increased.

Moderate proteinuria – Nephritic syndrome (acute nephritis), acute renal failure.

Asymptomatic proteinuria (or transient) – Proteinuria <1g/day, no other abnormalities, probably orthostatic, proteinuria >2g/day possible early glomerulonephritis

Persistent low level proteinuria/microabluminuria – Associated with early diabetic nephropathy, tubulointerstitial disease, early CVD, hypertension.