nephrotic syndrome.pptx

renal disease in children

1. NEPHROTIC SYNDROME Dr. Shami Pokhrel MD. Pediatrics

2. DEFINITION It is a clinical manifestation of glomerular disease Proteinuria >3.5g/24hr Urine protein: creatinine ratio >2

3. TRIAD Large urinary losses of protein causing hypoalbuminemia (< or equal to 2.5g/dl) Edema Hyperlipidemia (>200mg/dl)

4. EPIDEMIOLOGY Affects 1-3 per 100,000 children < 16 years of age 80% respond to corticosteroid therapy There is no differentiation between ethics while MCNS incidence is higher in males

5. ETIOLOGY Most of the nephrotic syndrome have a form of a primary or idiopathic nephrotic syndrome Idopathic cases can have various underlying pathology like minimal change disease (the most common), focal segmental glomerulosclerosis , membranoproliferative glomerulonephritis , C3 glomerulopathy and membranous nephropathy.

6. ETIOLOGY Nephrotic syndrome may also be secondary to systemic diseases such as SLE, HSP, malignancy (lymphoma and leukemia), and infections ( hepatitis, HIV, and malaria) A number of hereditary proteinuria syndromes are ca used by mutations in genes that encode critical protein components of the glomerular filtration apparatus

7. PATHOGENESIS Role of podocyte The underlying abnormality is an increased permeability of the glomerular capillary wall, which leads to massive proteinuria . The podocytes plays a crucial role in the development of proteinuria and progression of glomerulosclerosis

8. Foot processes are the extension of podocytes that terminate on the GBM. The foot processes of the podocytes interdigitate with those from adjacent podocytes and are connected by a slit called the slit diaphragm. The podocyte functions as structural support of the capillary loop.

9. Podocytes are the major component of the glomerular filtration barrier to proteins, and is involved in synthesis and repair of the GBM Slit diaphragm is one of the major impediments to proteins permeability across the glomerular capillary wall

10. Important component proteins of the slit diaphragm include nephrin , podocin , and alpha-actin4 Any injury to the podocyte or genetic mutations of genes producing podocyte proteins may cause nephrotic -range proteinuria

11. In idopathic , hereditary, and secondary forms of nephrotic syndrome, there are immune and non-immune insults to the podocyte that lead to foot process effacement of the podocyte A decrease in number of functional podocytes Altered slit diaphragm integrity

12. CLINICAL CONSEQUENCES Edema: the most common presenting symptom in children with nephrotic syndrome Underfill hypothesis Overfill hypothesis

13. Hyperlipidemia It is thought to be the result of increased synthesis as well as decreased catabolism of lipids There has been found to be an increase in cholesterol, triglycerides, low-density lipoprotein, and very low density lipoproteins. The high density lipoprotein level remains unchanged or is low

14. Increased susceptibility to infections Cellulitis Spontaneous bacterial peritonitis Bacteremia Reason is because of hypoglobulinemia , loss of C3, C5. Hence, they are at risk for infection with encapsulated bacteria like pneumococcus

15. Hypercoagulability Vascular stasis from hemoconcentration and intravascular volume depletion, increased platelet number and aggregability , and changes in coagulation factor levels. Increased hepatic production of fibrinogen along with urinary losses of antithrombotic factors such as antithrombin III and protein S.

16. MINIMAL CHANGE NEPHROTIC SYNDROME It accounts for 90% cases of nephrotic syndrome Renal biopsy does not show significant abnormalities on light microscopy Electron microscopy shows obliteration of epithelial cell foot processes, which is not specicfic Immunofluorescence studies do not show any deposits, except in a small proportion, where mesangial deposits of IgM may be present

17. CLINICAL FEATURES Typical presentation is an insidious onset of swelling starting first from peri -orbital edema progressing then to legs Edema is pitting edema Gradually edema may become generalized with ascites , hydrothorax and hydrocele As edema worsens urine output decreases

18. CLINICAL FEATURES Blood pressure is usually normal. Sustained elevation suggests the possibility of significant glomerular lesions Severe muscle wasting underlies the misleading relatively bloated and well-looking child Infections may be present at the onset and during relapses

19. LABORATORY FINDINGS Urine examination shows heavy protienuria (3+ or 4+) 24 hr urinary protein excretion A spot urinary protein: creatinine ratio>2 Gorss hematuria or persistent microscopic hematuria suggests the likelihood of significant glomerular lesions.

20. LABORATORY FINDINGS Blood levels of IgG are low and those of IgM elevated C3 level is normal Hypercholesterolemia Renal insufficiency

21. LABORATORY FINDINGS Hyaline and granular casts may be present Low serum albumin values (<2.5g/dl) Renal biopsy recommended in children with atypical presentation (age onset <1 yr or over 10yrs), persistent hematuria , low C3 level, hypertension or impaired renal function

22. Treatment Single daily dose of 60mg/m2/day or 2mg/kg/day of prednisolone for 4-6 weeks followed by alternate day of 40mg/m2/day or 1.5mg/kg/day for a period ranging from 8wk – 5 months, with tapering of dosage Side effects of the drug must be explained

23. Approximately 80-90% of children respond to steroid therapy Response : attainment of remission within the initial 4 wk of corticosteroid therapy Remission : consists of urine protein:creatinine ratio of <0.2 or <1+ protein on urine dipstick for 3 consecutive days. The vast majority of children who respond to prednisone therapy do so within the first 5 wk of treatment

24. Management The child should receive a high protein diet No extra salt is given Associated infection treated Tuberbulosis is ruled out Judicious use of diuretics Rapid fluid loss should not be attempted

25. Management Edema : severe symptomatic edema needs hospitalization such as pleural effusions, ascites , or severe genital edema Diuretics may be used but with extreme caution as patient may be in intravascular volume depletion although he or she may look edematous

26. MANAGEMENT 25% albumin may be infused followed by furosemide (1-2mg/kg/dose) whenever patient has severe edema with evidence of intravascular volume depletion eg ., hemoconcentration , hypotension, tachycardia. Such therapy mandates monitoring of blood pressure, volume status, renal function, electrolyte homeostasis. Rapid infusion of albumin may lead to volume overload, with hypertension, heart failure, and pulmonary edema

27. MANAGEMENET Dyslipidemia : It should be managed with low-fat diet. Dietary fat intake should be limited to <30% of calories with saturated fat intake <10% calories. Dietary cholesterol intake should be <300mg/day. There are insufficient data to suggest the use of HMG- CoA reductase inhibitors in children with dyslipidemia

28. MANAGEMENET Infections: Families of child with nephrotic syndrome must be counseled regarding the signs and symptoms of infections such as cellulitis , peritonitis, and bacteremia . Suspicion of infection should prompt to send blood cultures before starting empiric antibiotic therapy that covers mainly pneumococcal and gram negative organisms

29. Thromboembolism : children with clinical signs of thromboembolism should be evaluated by appropriate imaging studie s to confirm the presence of a clot Heparin, low-molecular-weight heparin, and warfarin are therapeutic options

30. Obesity and growth: steroids may increase BMI in children who are overweight when therapy is initiated, and these children are more likely to remain overweight. Anticipatory dietary counseling is recommended. Growth may be affected in children who require long-term steroid therapy. Steriod -sparing strategies may improve linear growth in children who require prolonged courses of steroids

31. Relapse of nephrotic syndrome: it is defined as the urine protein : creatinine ratio of >2 or > or equal to 3+ protein on urine dipstick testing for 3 consecutive days. Relapses are treated in a manner similar to initial episode, except that daily prednisone courses are shortened. Daily high-dose prednisone is given until the child had achieved remission, and the regimen is then switched to alternate-day therapy.

32. Steroid resistance: failure to achieve remission after 8 wks of corticosteroid therapy. These children need renal biopsy, evaluation of kidney function and quantitation of urine protein in addition to urine dipstick testing. Cause of steroid resistant NS is usually caused by FSGN (80%), MCNS, or membranoproliferative glomerulonephritis .

33. ALTERNATIVE THERAPIES Candidates are steroid-dependent patients frequent relapsers , and steroid-resistant patients. Candidates who have severe corticosteroid toxicity

34. ALTERNATIVE THERAPIES Cylcophosphamide Calcineurin inhibitors ( cyclosporin or tacrolimus ) Mycophenolate Levamisole Rituximab Angiotensin -converting enzyme inhibitors and angiotensin II receptor blockers may be helpful in adjunct therapy to reduce proteinuria in steroid-resistant patients

35. IMMUNIZATION IN NS Full pneumococcal vaccine and influenza vaccine annually to the patient and their household contacts Defer vaccination with live vaccines until the prednisone dose is below either 1mg/kg daily or 2mg/kg on alternate day Live vaccine is contraindicated in those receiving corticosteroid-sparing agents

36. IMMUNIZATION IN NS Following close contact with varicella infection children under immunosuppresive drugs must be given varicella -zoster immunoglobulin Immuninze healthy household contacts with live vaccines to minimize the risk of transfer of infection to patients but avoid direct exposure of the child to gastrointestinal or respiratory secretions of vaccinated contacts for 3-6 wk after vaccination

37. Secondary nephrotic syndrome NS can occur as a secondary feature of many forms of glomerular disease Secondary nephrotic syndrome should be suspected in patient >8 yrs and those with hypertension, hematuria , renal dysfunction, extrarenal symptoms or depressed serum complement levels Malaria and schistosomiasis are the leading cause of NS in areas where these diseases are endemic

38. Secondary nephrotic syndrome Lymphomas Drugs ( penicillamine , captopril , gold, NSAIDS, mercury compounds can resemble membranous glomerulopathy ), MCNS ( probenecid , ethosuximide , methimazole , chlorpropamide , phenytoin , trimethadone , paramethadone ).

39. Congenital nephrotic syndrome NS has a poor prognosis when it occurs in the first year of life Manifest at birth or within first 3 months of age Can be primary or secondary to number of etiologies such as in utero infections (cytomegalovirus, toxoplasmosis, syphilis, hepatitis B and C, HIV), infantile systemic lupus erythematosus , or mercury exposure

40. Congenital nephrotic syndrome Infants with primary NS are typically born with an enlarged placenta (>25% of infants weight). Prenatal diagnosis can be made by the presence of elevated maternal and amniotic alpha-fetoprotein levels