nephrotic syndrome

NEPHROTIC SYNDROME

Soumya Ranjan ParidaBasic B.Sc. Nursing 4th year

Sum Nursing College

Nephrotic syndrome

Nephrotic syndrome is 15 times more common in childre than adults.

Incidence – 2-3 / 1lac children /yr

It is characterized by –

- Heavy proteinuria ( > 3.5gm/day or 40mg/m²/hr ),

- Hypoalbuminemia (< 2.5gm/dl ),

- Edema ,

- Hyperlipidemia.

Hematuria , hypertension and impaired renal function are occasionally associated.

Nephrotic SyndromeEtiology –• 90% Idiopathic nephrotic syndrome - Minimal change disease ( 85%), - Mesangial proliferation (5%) , - Focal segmental glorulosclerosis (10%)• 10% Secondary nephrotic syndrome - Membranuous nephropathy - Membranoproliferative GN

Pathophysiology –• T cell dysfunction• Altration of cytokines• Loss of negative charged glycoproteins

Pathophysiology

Heavy proteinuria

Hypoalbuminemia

Reduced plasma oncotic pressure

Extravasation of intravascular fluid

hypovolemia

Aldosterone Antidiuretic hormone

Distal Na & water reabsorption

Edema

Hyperlipidemia –

• Increased hepatic protein synthesis

• Decreased lipoprotein lipase activity

• LDL and VLDL are increased

• HDL may increase, normal or decrease

• Cholesterol and triglyceride are increased

Pathophysiology

Idiopathic Nephrotic SyndromePathology – • Minimal change disease ( 85% ) Minimal increase in mesangium and matrix IFMC – normal EMC – Effacement of epithelial cell foot processes Steriod sensitive – 90%• Mesangial proliferative ( 5% ) LMC - Diffuse increase in mesangium and matrix. IFMC – Mesangial IgM and IgA staining. EMC - Mesangium cell and matrix increased. Effacement of epithelial cell foot processes Steriod sensitive – 50%• Focal segmental glomerulosclerosis ( 10% ) LMC – mesangial proliferation and segmental scarring IFMC – IgM and C3 staing in the area of scarring

Clinical features –

• Sex – M:F 2 : 1

• Age – 2 – 6 yrs

Common –

• Periorbital edema

• Generalized edema

• Oliguria

• Irritability

• Abdominal pain

• Diarrhoea

Uncommon –

• Hypertension

• Gross hematuria

Idiopathic Nephrotic Syndrome

Diagnosis –

Urine examination –

• Proteinuria

• Hematuria

• 24 hour urinary protein

• Spot urine - protein mg% / creatinine mg %

Blood investigations –

• Sreum creatinine

• Total protein

• Serum albumin

• Serum cholesterol and triglyceride level

• C3-C4 levels – N

• IgG- low, IgM - increased

Idiopathic Nephrotic Syndrome

• Glomerular Proteinuria – Selective – LMW & albumin Nonselective – HMW IgG Selectivity = IgG / Transferrin ratio 1gm – 30 gm / day Hematuria , hypertension ,renal insufficiency• Tubular proteinuria – <1gm / day Low molecular proteinuria Little or no albumin • Transient proteinuria• Orthostatic proteinuria.R/o infections – Urine r/m , Urine c/s, Hb ,CBC, ESR , MT test Chest x- ray , USG abdomen.

Idiopathic Nephrotic Syndrome

Treatment

1st episode mild to moderate edema – • Out patient management• Sodium intake restricted initially

• Oral diuretics judiciously.

Severe edema –

• Hospitalized• Fluid restrction• IV diuretics

• 25% human albumin – 0.5gm/kg/12hour

Renal biopsy – • Hematuria, hypertension• Renal insufficiency• Hypocomplementemia

• Age beyond 1-8 yrs

• RBC casts

Prednisone - 60 mg/m²/day divided into 2-3 doses for at least 4wksAfter 4-6 wks - 40 mg/m²/day EOD single morning dose after mealsAfter 3 months – gradually tapered and stopped• Steroid responsive – Urine protein negative, trace or 1+ for 3 consecutive days• Steroid resistant – Urinary protein 2+ or more after 8 wks of therapy.• Steroid dependent – Relapse while on EOD therapy or within 28 days of stopping of steroids.• Relapse – Reappearance of proteinuria 3+ or 4+ and edema.• Infrequent relapse – 3 or less in a year.• Frequent relapse – 4 or more in a year

Treatment

Frequent relapses or steroid dependent – • Prednisolone alternate day – - 0.3 – 0.7 mg/kg: - Duration – 9-12 months• Levamisole – - 2-2.5mg/kg and prednisolone 1.5 mg/kg on alternate days. - Duration: 1 – 2yrs. - Prednisolone dose tapered and discontinued• Cyclophosphamide – - 2 mg/kg daily and prednisolone 1.5 mg/kg alternate days. - Duration : 12 wks• Cyclosporine – - 5 mg/kg daily and prednisolone 1-1.5 mg/kg alternate days. - Duration : 1-3 yrs. - Prednisolone dose tapered

Treatment

Complications

• Edema

• Infection –

- Urinary loss of Ig, properdin factor B

- Defective cell mediated immunity

- Malnutrition , edema, ascitis

- Spontaneous bacerial peritonitis ( Strept. Peumoniae, E.coli )

- Vaccination – pneumococcal, varicella, Infuenza.

• Thrombotic complications –

- Increased prothrombotic factors ( Fibrinogen, thrombocytosis,

hemoconcentration, relative immobilization.

- Decreased fibrinolytic factors ( urinary loss of AT3, protein C, S.

• Acute renal failure

• Steroid toxicity

Secondary Nephrotic Syndrome

• Glomerular diseases –

Membranous GN, MPGN, Lupus & HSP nephritis.

• Infection –

Malaria, Schistosomiasis, HBV, HCV, Filariasis, Leprosy, HIV.

• Malignancy –

Lung and GIT carcinoma, Hodgkins lymphoma

• Druga –

- Membranous GN – Penicillamine, captropil ,gold, NSAIDS,

mercury .

- Minimal change disease – Probencid, ethosuximide,

methimazole, lithium.

- MPGN – Procainamide, chlorpropamide, phenytoin,

trimethadion, paramethadione

• < 3 months

• Finnish type, AR

• Mutation in NPHS1 gene, ch 19, Nephrin

• Pathology –

Dilatation of proximal tubules, mesangial hypercellularity,

glomerular sclerosis

• Clinical features –

Massive proteinuria, large placenta, marked edema,

prematurity, RDS, seperation of cranial sutures

• Treatment -

ACE inhibitors, indomethacin, unilateral nephrectomy

• Denys-Drash syndrome –

Diffuse mesangial sclerosis, Male pseudohermaphroditism,,

Wimls tumor. Mutation in WT1 chromosome

Congenital Nephrotic Syndrome

THANKS