Nephrotic syndrome definition, pathopahysiology and management.pptx

nephrotic syndrome its definition
pathophysiology
diagnosis
indication of renal biopsy
treatment

1. Nephrotic syndrome - Bivek Kumar Yadav -1 st year pediatric resident -LMCTH

2. introduction Nephrotic syndrome is the clinical manifestation of glomerular disease associated with heavy proteinuria. Nephrotic range proteinuria is defined as proteinuria >3.5 g/24hr or >40mg/m2/ hr Urine protein:creatinine ratio >2 Triad of clinical findings associated with nephrotic syndrome are: Hypoalbuminemia (<=2.5 g/dl) Edema Hyperlipidemia (cholesterol >200mg/dl)

3. Epidemiology Nephrotic syndrome affects 1-3 per 100,000 children < 16 years of age Occurs in all ages most prevalent in children 2-6 years Boys > girls: Ratio 2:1 Higher in underdeveloped countries ( South east A sia and Africa) Fortunately 80% of children responds to corticosteroid therapy

4. Classification and ETIOLOGY Most children (90%) with nephrotic syndrome have a form of primary or idiopathic nephrotic syndrome Glomerular lesions associated with nephrotic syndrome include: Minimal change disease (most common) Focal segmental glomerulosclerosis MPGN C3 glomerulopathy Membranous nephropathy

5. Nephrotic syndrome may also be secondary to systemic diseases: Systemic lupus erythematosus- SLE Henoch schonlein purpura Malignancy ( lymphoma and leukemia) Infections ( hepatitis, HIV, malaria) A number of hereditary proteinuria syndromes are caused by mutations in genes that encodes critical protein of the glomerular filtration apparatus

6. Other causes include: Drugs ( captopril, penicillamine , gold, NSAIDS, lithium, rifampicin, sulfasalazine) Allergic disorders ( Bee sting, snake venom, food allergens, serum sickness) Glomerular hyperfiltration ( Oliogomeganephronia , Morbid obesity)

7. pathogenesis Role of the PODOCYTES: Plays a crucial role in the development of proteinuria and the progression of glomerulosclerosis Podocyte is a highly differentiated epithelial cell located on the outside of the glomerular loop Foot processes are extensions of the podocyte that terminate on the glomerular basement membrane Foot processes of a podocyte interdigitate with those from adjacent podocytes and are connected by a slit called the slit diaphragm

8. Continue…… Slit diaphragm are not simple passive filters; they consists of numerous proteins that contribute to complex signaling pathways and play an important role in podocyte function Important components proteins of the slit diaphragm include: Nephrin Podocin CD2AP Alpha actin 4

9. Continue…. Podocyte injury or genetic mutations of genes producing podocyte proteins may cause nephrotic range proteinuria Proportion of patient with genetic mutations of podocyte genes decreased by age: 66% in patient with congenital nephrotic syndrome to 15-16% in school age patient and adolescents Role of immune system: MCNS may occur after viral infections and allergen challenges MCNS has also been found to occur in children with Hodgkin lymphoma and T-cell lymphoma That immunosuppression occurs with corticosteroid and cyclosporine provides indirect additional evidence that immune system contributes to the overall pathogenesis of nephrotic syndrome

10. Clinical features The initial episodes of idiopathic nephrotic as well subsequent relapses may follow minor infections and uncommonly reactions to insects to insects bite, beestings or poison ivy Edema Ascites Pleural effusion Genital edema Anorexia, irritability, abdominal pain and diarrhea are common Absence of hypertension and hematuria

11. Continue…. The differential diagnosis of the child with marked edema includes: Protein-losing enteropathy Hepatic failure Heart failure Acute or chronic glomerulonephritis Protein energy malnutrition

12. diagnosis Urinalysis: The urinalysis reveals 3+ or 4+ proteinuria and microscopic hematuria is present in 20% children Spot urine protein:creatinine ratio: Which should be >2 BUN-Blood Urea Nitrogen: Elevated in 15-30% cases Serum creatinine: Usually normal but may be elevated

13. Continue…. Serum albumin: Level is <2.5 g/dl Serum cholesterol and triglycerides: Elevated >200 mg/dl Evaluation to rule out secondary forms of nephrotic syndrome: Serum complement c3 level and antistreptolysin O Normal Antinuclear antibody- ANA DS-DNA

14. Continue…. Hepatitis B and C HIV in high risk population Chest X-ray Urine culture Renal Biopsy

15. Indications of renal biopsy Atypical features at the onset: Age <1 year or >12 years Gross or persistent microscopic hematuria Low blood c3 levels Hypertension or impaired renal functions Patients who continue to show nephrotic range proteinuria despite appropriate steroid therapy Frequent relapses

16. Case definitions Response : Attainment of remission within initial 4 weeks of steroid therapy Remission : Urine albumin nil or trace (proteinuria <4mg/m2/ hr ) for 3 consecutive early morning specimen Relapse : Urine albumin 3+ or 4+ ( proteinuria >40mg/m2/ hr ) for 3 consecutive early morning specimen , having been in remission previously Frequent relapses : Two or more relapses in initial six months or four or more relapses in any 12 months Steroid dependence : Two consecutive relapses when on alternate day steroid or within 14 days of its discontinuation Steroid resistance : Absence of remission despite therapy with daily prednisolone at a dose of 60 mg/m2/day for 4 weeks and alternate day for next 4 weeks

17. management Management of initial episodes: Prednisolone as a single dose of 60 mg/m2/day or 2mg/kg day to max. 60mg daily for 4-6 weeks followed by alternate day prednisolone at 40 mg/m2/gay or 1.5 mg/kg/day for a period ranging from 8 weeks to 5 months with tapering doses. Prolonged steroid treatment with tapering schedule for 2-5 months is advocated for decreasing the incidence of relapse based on recent multicenter trials. The kidney disease improving global outcomes (KIDGO) recommends at least 12 week of steroid treatment 80-90% children respond to steroid therapy

18. High protein diet Salt restriction to the amount in usual cooking with no extra salt given (<1,500mg/day) Any associated infections in treated Diuretics are administered , only if edema is significant. Should be used cautiously and overzealous fluid loss is avoided Frusemide 1-4 mg/ kgday in 2 divided doses alone or with an aldosterone antagonist spironolactone 2-3 mg/kg/day in 2 divided doses Parent education

19. Dyslipidemia : low fat diet <30% of calorie Dietary cholesterol intake of <300 mg/day Thromboembolism: Obesity and Growth: steroid therapy may increase BMI who are overweight when therapy is initiated and likely to remain overweight. Growth may be affected . Steroid sparing strategies may improve linear growth

20. Management of relapses: prednisolone at 60 mg/m2/day until protein is negative/trace for 3 consecutive days, then on alternate days at 40 mg/m2/day for 4 weeks. Duration 5-6 weeks

21. Frequent relapses and steroid dependence

22. Steroid resistant nephrotic syndrome

23. Immunization in children with NS P neumococcal vaccination with 13-valent conjugant vaccine and 23-valent polysaccharide vaccine Influenza vaccine annually to the child and household contacts Live vaccine are contraindicated in children receiving steroid- sparing agents such as cyclophosphamide or cyclosporine Varicella –zoster immune globulin Vaccination is advised once the patient is off steroid for 4 weeks.

24. references Nelsons textbook of pediatrics O.P. GHAI