Nephrotic syndromeNephrotic syndrome is a clinical complexcharecterized by a number of renal and extrarenalfeatures :1- protien urea of > 3.5 gram /24 hr.2- hypoalbominaemia (usually <30 gm/L ).3- oedema .4- hyperlipidemia , hyperlipiduria .5- hypercoagulability .
The key point for nephrotic syndrom is proteinuria (>3.5 gm/24 hr ) . The proteinuria result from altered permiability of the glumerular filtration barrier for protein (namely the GBM & podocytes ) The other components & metabolic complications of nephrotic syndrome are all secondary to protein loss in urine .
Consequences & Complications of NS :1- edemaNS. Cause Hypoalbominaemia , & this results in decrease intravascular oncotic pressure, leading to leakage of extracellular fluid from the blood to the interstitium .The oedema accumulate predominantely in the lower limbs in adults. Extending to the genitalia & lower abdomen as it becomes more sever .In the morning the upper limbs & face may be more affected .In children : ascitis occurs early & the oedema is often seen in the face .
2-Hyperlipidemia– It is due to the increased hepatic lipoprotein synthesis that is triggered by reduced oncotic pressure .– LDL & cholestrol are increase in majority of patiens .– VLDL & triglyceride are increase in patients with sever disease .– Hyperlipidemia may accelerate atherosclerosis & progression of renal disease .
3-hypercoagulability It is multifactorial in origin & caused by : 1-Increased urinary loss of antithrombin 3 . 2-Altered level &lor activity of protein C & S . 3-Hyperfibrinogenemia (due to increased hepatic synthesis ) .4-Impaired fibrinolysis .5-Increased platelet aggregability .The patient may develop peripheral arterial or venous thrombosis , renal vein thrombosis or pulmonary embolism .Venous thrombosis is common & some time fatal.
4-Increased susceptability to Infection It is due to the low level of IgG ( due to the urinary loss of IgG ) . Usually susceptable to infection by Pneumococci .
5-Other metabolic complications of nephrotic syndromeA- Protien malnutrition .B- Iron resistance hypochromic microcytic anaemia due to transferrin loss.C-Hypocalcaemia & secondary hyperparathyroidism as a consequence of Vitamine D deficiency due to the increased urinary excreation of cholecalciferol – binding protein .D- Depressed thyroxine level . due to the loss of thyroxine – binding globulin .
Causes of nephrotic syndrome(types)A- Nephrotic range proteinuria(NS.) with bland urine sidement (non-inflammatory) (Pure nephrotic ) 1- Primary glomerular disease : - minimal change NS. - membranous glomerulopathy. - focal glomerulosclerosis .2- Secondary glomerular disease : - diabetic nephropathy . - amyloidosis .
Management of nephrotic syndromeManagement of NS. Has 4 elements :1- Establish the cause .2- Treat the cause (if possible ) .3- Measures to control proteinuria & treatment of complications.4- Prevent complications.
Renal biopsyRenal biopsy in adults with NS. Is a valuable tool for establishing definitive diagnosis , guiding therapy & estimating prognosis .Renal biopsy is not required in the majority of children with NS. As most cases are due to minimal change disease &respond to emperic treatment with glucocorticoid .In NS. Renal biopsy is indicated in : 1- adult patient . 2-children not respond to steroid .
Lines of management of NSA- Treatment of proteinuria: non specific measure that may reduce proteinuria is Angiotensin-converting enzyme inhibitors like lisinopril . ACE-inhibitors reduce proteinuria & slow the rate of progression of renal failure by lowering intraglomerular pressure & preventing the development of hemodynamically mediated focal segmental glomerulosclerosis . ACE-inhibitors are renoprotective in diabetic nephropathy.
B-Treatment of complications of NS1-Oedema-Moderate salt restriction ( 1-2 g/day)-Diuretics : usually we use loop diuretic (frusemide) . But in sever NS & sever oedema combination of diuretics can be used acting on different parts of the nephron (frusemide , thiazide , amiloride )We should not remove > 1 Kg. of the oedema per day , as more aggressive diuretics may precipitate intravascular volume depletion & pre-renal azotemia .
If the patient have sever hypoalbuminaemia , the oedema may be resistant to diuretics & may need to give IV albumine by infusion.Giving albumine in NS. Is some times harmful , because the more albumine you give the more will be loss in the urine & this may cause more glomerular damage .
2-HypercholestrolemiaTreated by lipid lowering drugs ( statin group ) to prevent accelerated atherosclerosis & slow the decline in GFR.
3- ThromboembolismAnticoagulation is indicated for patients with NS. developed DVT , arterial thrombosis or pulmonary embolism. Also anticoagulation indicated routinly in all patients with chronic or sever NS.There may be a resistance to heparin because of antithrombine III deficiency .
4-InfectionRisk of infection can be reduced by immunization ( particularly pneumococci).
5- Vit. D deficiencyVitamin D supplementation is advisable in patients with clinical or biochemical evidence of vit. D deficiency .
C-Steroid & other immunosupressant drugsIn adults : renal biopsy should be done before giving steroid & other immunosupressant drugs ( as cyclophosphamide ). giving steroid & other immunosupressant drugs depend on the result of renal biopsyIn children : we can start steroid without renal biops because most cases are minimal change type which have a good response to steroid . renal biopsy is indicated if the child with NS. have no response to steroid.