Nephrotic Syndrome

Nephrotic Syndrome

Preschool children (2-5 years )

M>F

Definition

§ Proteinuria >40mg/m2/hr, 1g/m2/24hrs, protein creatinine ratio >200mg/mml. (adult3.5g/day)

§ Hypoalbuminaemia <25g/l

§ Oedema

§ Hypercholesterollemia (>5.5 mmol/l)

Terms used

v Remission: proteinuria <40mg/m2/hr>

v Relapse: protenuria >40mg/m2/hr or dipstix >2+ for 3 consecutive days

v Frequent Relapse: 2 or more relapse within 6 months of initial response or 4 or more relapse within 12 months period.

v Steroid dependence: 2 consecutive relapses when on alternative day steroid therapy or within 4 weeks of stopping the Rx

v Steroid sensitive: normalization of protenuria within 4 weeks of after start of standard initial therapy with daily oral prednisolone.

v Steroid resistance: failure to achieve remission inspite of 4 weeks of prednisolone 60mg/m2/day.

v Congenital NS: NS presenting within the first 3 months of life.

v Infantile NS: NS presenting between 3-12 months of life.

Causes

§ Primary Glomerular diseases

1. Minimal Change Nephropathy	Commonest dx in children Steroid sensitive Assoc with Allergy? Hodgkin disease. electron microscopy reveals effacement of the epithelial cell foot processes
2. Focal Segmental Glomerulosclerosis	Commoner dx in middle-aged & elderly
3. Membranous GN (associated with Renal vein thrombosis, cancer, SLE, Hep B)
4. Mesangioproliferative GN
5. Membranoproliferative GN

§ Secondary Glomerular diseases

1. Diabetic nephropathy

2. Autoimmune – SLE, henoch schonlein purpura

3. Post-infectous glomerulonephritis

4. Infections – Hepatitis, HIV, syphilis

5. Drugs – gold, NSAIDS, penicillamine

6. Amyloidosis

7. Hereditary nephritis – eg Alport’s

8. Toxins &Allergens – bee sting , food allergy

Pathophysiology

Massive proteinuria and hypoalbuminemia: increase in permeability of the glomerular capillary wall( in minimal change disease due to loss of negatively charged glycoproteins, In FSGS a plasma factor, perhaps produced by lymphocytes, may be responsible for the increase in capillary wall permeability)

Mechanism of edema : urinary protein loss leads to hypoalbuminemia, which causes a decrease in the plasma oncotic pressure and transudation of fluid from the intravascular compartment to the interstitial space. The reduction in intravascular volume decreases renal perfusion pressure, activating the renin-angiotensin-aldosterone system, which stimulates tubular reabsorption of sodium. The reduced intravascular volume also stimulates the release of ADH, which enhances the reabsorption of water in the collecting duct. Because of the decreased plasma oncotic pressure, fluid shifts into the interstitial space, exacerbating the edema.

Hyperlipidemia: Hypoalbuminemia stimulates generalized hepatic protein synthesis, including synthesis of lipoproteins.

Diminished lipid catabolism, as a result of reduced plasma levels of lipoprotein lipase, related to increased urinary losses of this enzyme.

Complications of Nephrotic Syndrome

1. Susceptibility to infections	§ UTI, peritonitis, septicaemia § Pneumococcal infections ,flare of TB Due to:- § Loss of IgG § Immunosuppression by steroids or immunosuppressants § Loss of factor B of the alternate complement activation pathway § edema/ascites acting as a potential “culture medium.” §
2. Thrombosis & embolism	§ DIVC, pulmonary embolism, renal vein thrombosis Hypercoagulability due to § ¯ plasma antithrombin III (urinary loss) § ­ plasma fibrinogen & clotting factors V & VIII § Haemoconcentration and stasis of blood flow
3. ¯ volaemia	§ Shock § Acute Tubular Necrosis / Acute renal failure
4. ­lipidaemia	§ ¯ apolipoprotein (urinary loss) § increased risk of CHD & atherosclerosis
5. ¯calcaemia	§ Urinary loss of Vit D binding proteins § Bone demineralization in the long term
6. Negative nitrogen balance	§ Due to Proteinuria, LOA & nausea
7. ESRF	§
8. Steroid toxicity	§

History

General condition	Anorexia, wt gain, lethargy, xanthomata, xanthelasma
Oedema	Periorbital, pedal, sacral, scrotal, ascites (abdominal distension,SOB)
Pleural effusion	SOB
Urinary	Oliguria, haematuria, concentrated urine
Others	Infections, HTN, abdominal pain, hepatomegaly Diarrhea(intestinal Odema)

Other things to note in Long case

Past History to note Initial diagnosis – date, symptoms, investigations, aetiology identified, Rx No. of episodes / year – precipitants, usual Rx No. of hospitalizations Cxs & Mx

Management Diet Medication & compliance Management problems Present Rx for current admission Previous drugs used Drug side effects Home urine testing and nephrotic diary F/U

Physical Examination

General	Odematous Cushingoid appearance Respiratory distress BP,Pulse Urine:colour/frothy Rashes Pedal odema Joint swelling (pain)	Cushing Features Growth retardation Central obesity Moon faces Acne/seborrhea Hirsutism Cataract Oral candidiasis Buffalo hump Supra clavicular fat pad Stria(shoulders, abdomen, thigh) Proximal myopathy Blood glucose high Hypertension
Abdominal	Distension Shifting dullness and fluid thrill Scrotal odema
Respiratory	Pleural effusion Infection (TB, pneumonia) Look for BCG scar

DDx of the child with marked edema :

• acute or chronic glomerulonephritis
• protein-losing enteropathy
• hepatic failure
• congestive heart failure
• protein malnutrition.

Investigations

Urine	Inspection	Frothy urine, straw coloured / heamturia.
	Urine Dipstix	2+
	24Hours urinary protein	>1g/m2 >3.5g
	UFEME C/S Urine Albumin creatinine ratio (>200mg/mmol)	Microscopic hematuria RBC Casts (AGN),Lipid casts (NS) Proteins, pus cells (infection) Albumin:creatinine ration - > 200mg/mmol Na Concentration - <20mmol/l>
Blood	FBC	Hemoconcentration, TWBC for infections
	Serum Albumin level	<25g/l
	Lipid profile	Asses for hyperlipidemia
	Renal profile	Urea and cretinine and electrolytes
	Others	§ Serum C3 & C4 – in MCGN & SLE § AutoAbs – ANA, ANCA, anti-dsDNA, anti-GBM § ASOT – in post-strep. GN § Hep B serology – associated with membranous nephritits Hep C serology – associated with MCGN
Imaging	CXR	If plural effusion
	KUB Ultrasound	Check the renal paranchyma
Throat swab If URTI		For microscopy, C/S. For post-strep GN
Renal Biopsy Indications :		Steroid resistant NS Atypical features suggesting renal disease persistent HTN Macroscopic hematuria Persistently low serum compliments C3 level Persistent microscopic heamturia Reduce compliment levels If very young, congenital type(<1>

Management

Non pharmacological

Nephrotic chart	Daily urine dipstix BP I/O chart Body weight
Restriction of fluid	500+ insensible loss+previous urine output 1000mls/day
Diet	Restrict salt Normal diet Normal protein 4g/kg/day If urea and creatinine high- low protein
General advice	Counsel with parents on high probability of relapse And monitoring of urine dipstix early morning If on steroids to be caution in ot getting exposed to chicken pox or measles if exposed treated like immunocompromised.( varicella should receive varicella zoster immune globulin (VZIG) within 72?hr of exposure) Pneumococcal vaccination during remission(Influenza vaccine should be given on a yearly basis)

Pharmacological

Prednisolone	Initial diagnosis 60mg/m2/day for 4 weeks 40mg/m2/EOD for 4 weeks Tapper down 25%every month for next 4 months Relapse 6omg/m2/day until remission followed by 40 mg for 4 weeks only Frequent Relapse 6omg/m2/day until remission followed by 40 mg for 4 weeks only Tapper prednisolone dose every 2 weeks and keep on as low dose EOD for 6 months
Steroid dependant NS with signs of steroid toxicity Cyclophosphamide therapy 2-3mg/kg/day for 8-12 weeks Monitor FBC and urine analysis 2 weekly Side effects of cycloposphamide Leucopenia, alopecia, hemorrhagic cystitis, gonadal toxicity If relapse occur after cyclopphosphamide therapy other drugs like cyclosporine and levamisole can be tried.
Penicillin prophylaxis	Penicillin v 125 mg BD (1-5 years ) Penicillin v 250mg BD (6-12 years ) During initial diagnosis and during relapses
Asses the hemodynamic status Human Albumin In gross odematous state	Human Albumin 0.5-1g/kg together with IV frusemide 1-2mg/kg to produce diuresis
Diuretics
Management of steroid resistant nephrotic syndrome	Control odema :restrict dietary sodium, diuretics To reduce proteinuria: ACE I, ARBS Hypertension: ACEI, ARBS Monitor BP and renal profile 1-2 weeks after initiation of ACEI, or ARBS Nutrition Evaluate Ca and Po4 metabolism

Management in Adults

General measures

Restrictt salt in take

Monitor U&E, BP, fluid balance and weight regularly

Diuretics : frusemide 80-250mg/24hrs