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Management Of Nephrotic Syndrome

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Management Of Nephrotic Syndrome
Objectives
To briefly review the definition & etiology of nephroticsyndrome.
To understand the terminology pertaining to clinical course of nephroticsyndrome.
To understand the management of nephroticsyndrome:Specific management & Supportive care and management of complications
Management of congenital nephrotic syndrome

Published in: Health & Medicine
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Management Of Nephrotic Syndrome

  1. 1. MANAGEMENT OF NEPHROTIC SYNDROME Dr C. Naveen Kumar, 1st year Post Graduate Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  2. 2. Objectives • To briefly review the definition & etiology of nephrotic syndrome. • To understand the terminology pertaining to clinical course of nephrotic syndrome. • To understand the management of nephrotic syndrome:  Specific management  Supportive care and management of complications  Management of congenital nephrotic syndrome Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  3. 3. Definition Nephrotic syndrome, is a manifestation of glomerular disease (due to various etiologies) characterized by, Nephrotic range proteinuria • Early morning urine protein is 3+/4+ (on dipstick or boiling test) or • Spot protein/creatinine ratio >2 mg/mg, or • Urine albumin excretion >40 mg/m2 per hr (on a timed-sample) or • Urine protein excretion > 50 mg/kg/24 hr Hypoalbuminemia • Serum albumin < 2.5 g/dL Hyperlipidemia • Serum cholesterol >200 mg/dL Generalised Edema Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  4. 4. Etiology of nephrotic syndrome In 95% cases there is primary glomerular abnormality.Remaining are secondary to systemic disorder. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  5. 5. Specific Management Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  6. 6. Evaluation at onset • Essential investigations: Urinalysis: Proteinuria, red cells, casts; Spot urine protein creatinine ratio Blood levels of urea, creatinine, albumin, cholesterol Complete blood count Tuberculin test • If required: C3 and ASO titres (gross or persistent microscopic hematuria) Chest X-ray (positive tuberculin test, history ofTB contact) HIV, HBV, HCV serology in highrisk groups ANA (if features of SLE are present) Urine culture (if clinical features of UTI are present) USG abdomen (to ruleout anomalies in kidney) Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  7. 7. Indications for renal biopsy • At Onset (If cause other than minimal change nephrotic syndrome is suspected) • Age of onset <1 year. • Gross hematuria, persistent microscopic hematuria or low serum C3. • Sustained hypertension. • Renal failure not attributable to hypovolemia. • Suspected secondary causes of nephrotic syndrome. • After InitialTreatment • Proteinuria persisting despite 4-weeks of daily corticosteroid therapy – steroid resistance. • Before treatment with Cyclosporin A orTacrolimus. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  8. 8. Management of the initial episode • Appropriate therapy at the first episode is an important determinant of the long term course of the disease. • Prednisolone is the drug of choice. • It is given at a dose of 2 mg/kg per day (maximum 60 mg in single or divided doses) for 6 weeks, followed by 1.5 mg/kg (maximum 40 mg) as a single morning dose on alternate days for the next 6 weeks; therapy is then discontinued. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  9. 9. Following initial treatment with steroids for 12 weeks, the disease may take any of the following course: Remission Urine albumin nil or trace (or proteinuria <4 mg/m2/hr) for 3 consecutive early morning specimens. Relapse Urine albumin 3+ or 4+ (or proteinuria >40 mg/m2/hr) for 3 consecutive early morning specimens, having been in remission previously. Frequent relapses Two or more relapses in initial six months or more than three relapses in any twelve months. Infrequent relapses Three or less relapses a year. Steroid dependence Two consecutive relapses when on alternate day steroids or within 14 days of its discontinuation. Steroid resistance Failure to achieve remission despite therapy with daily prednisolone at a dose of 2 mg/kg per day for 4 weeks. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  10. 10. Treatment of relapse • Relapse is defined as urine albumin 3+ or 4+ (or proteinuria >40 mg/m2/hr) for 3 consecutive early morning specimens, having been in remission previously. • An URTI or some other infection usually precipitates a relapse. • Appropriate therapy of an infection before starting therapy might result in spontaneous remission. • Prednisolone is administered at a dose of 2 mg/kg/day (single or divided doses) until urine protein is trace or nil for three consecutive days. • Subsequently, Prednisolone is given in a single morning dose of 1.5 mg/kg on alternate days for 4 weeks, and then discontinued. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  11. 11. Infrequent Relapsers • An infrequent relapser is defined as initial responder with three or less relapses a year. • They are managed using standard prednisolone regimen for each relapse. • Such children are at a low risk for developing steroid toxicity. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  12. 12. Management of Frequent Relapsers and Steroid Dependence • Frequent relapse is defined asTwo or more relapses in initial six months or more than three relapses in any twelve months. • Steroid dependence is defined as occurrence two consecutive relapses when on alternate day steroids or within 14 days of its discontinuation. • Following treatment of a relapse, prednisolone is gradually tapered to maintain the patient in remission on alternate day dose of 0.5-0.7 mg/kg. • A close monitoring of growth and blood pressure, and evaluation for features of steroid toxicity (cushingoid features – obesity, hirsutism, striae, hypertension, impaired glucose tolerance, posterior subcapsular opacities, emotional problems & growth retardation) is essential. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  13. 13. Management of Frequent Relapsers and Steroid Dependence contd. • If prednisolone threshold to maintain remission less than 0.5-0.7mg/kg on alternate day and there is no steroid toxicity, it is continued for 9-18 months.And then breakthrough relapses are treated with standard therapy of relapse. • If prednisolone threshold to maintain remission greater than 0.5-0.7mg/kg on alternate day and there is steroid toxicity, addition of following immunomodulators is suggested. • Levamisole • Cyclophosphamide • Calcineurin inhibitors: Cyclosporin (CsA), Tacrolimus • Mycophenolate mofetil (MMF) Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  14. 14. Levamisole • Immunostimulant drug. • Dose & duration: 2-2.5 mg/kg on alternate days for 12- 24 months • Concomitant steroid therapy: Prednisolone dose is gradually tapered to 0.25-0.5 mg/kg over a period of 8 months. Occasionally, it might be possible to discontinue Prednisolone. • Side effects: Neutropenia, flu-like symptoms, liver toxicity, convulsions and skin rash. • Monitoring:The leukocyte count should be monitored every 3-4 months. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  15. 15. Cyclophosphamide • Immunosuppressive drug. • Dose & duration: 2-2.5 mg/kg/day for 12 weeks. Should be started following remission of proteinuria. • Concomitant steroid therapy: Prednisolone dose is gradually tapered to 1 mg/kg over a period of 6 months and then stopped. • Side effects: Hemorrhagic cystitis, alopecia, nausea and vomiting, gonadal toxicity. • Monitoring:Total leukocyte counts are monitored every 2 weeks;temporarily discontinued if the count falls below 4000/mm3. • Use of more than one course (12 weeks) should preferably be avoided in view of gonadal toxicity.Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  16. 16. Calcineurin inhibitor : Cyclosporin (CsA) • Immunosuppressive agent. • Dose & duration: 4-5 mg/kg daily for 12-24 months. • Concomitant steroid therapy: Prednisolone is gradually tapered to 0.25-0.5 mg/kg over 8 or more months. Occassionally it can be discontinued. • Side effects: Hypertension, gum hypertrophy, hirsutism, nephrotoxicity, hypercholesterolemia and elevated transaminases. • Monitoring: Plasma CsA levels should be kept between 80-120 ng/mL. • Serum creatinine is monitored every 2-3 months. • Lipid profile is checked annually. • A repeat kidney biopsy, to examine for histological evidence of nephrotoxicity, should be done if duration of treatment is extended beyond 2 years. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  17. 17. Calcineurin inhibitor :Tacrolimus • Immunosuppressive agent. • Dose & duration: 0.1-0.2 mg/kg daily for 12-24 months. • Concomitant steroid therapy: Prednisolone is gradually tapered to 0.25-0.5 mg/kg over 8 or more months. Occassionally it can be discontinued. • Side effects: Hyperglycemia, diarrhea and rarely neurotoxicity (headache, seizures). • Preferred especially in adolescents, because of lack of cosmetic side effects (Gum hypertrophy & hirsutism). • Monitoring: Serum creatinine and glucose every 2-3 months. • A repeat kidney biopsy, to examine for histological evidence of nephrotoxicity, should be done if duration of treatment is extended beyond 2 years. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  18. 18. Mycophenolate mofetil (MMF) • Immunosuppressive agent. • Dose & duration: 800-1200 mg/m2/day for 12-24 months. • Concomitant steroid therapy: Prednisolone is gradually tapered over 12-24 months. Recent trials supported its use as a steroid sparing agent. • Side effects: Gastrointestinal discomfort, diarrhea and leukopenia. • Monitoring: Leukocyte counts every 1-2 months; Withheld if count falls below 4000/mm3 Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  19. 19. Choice of immunomodulator: • First choice is Levamisole or Cyclophosphamide. • Cycloposphamide is preferred in patients showing poor compliance or difficult follow- up, where 12 weeks therapy is beneficial. • Relapses occurring during immunomodulator therapy must be treated with regular Prednisolone relapse regimen. • If there are two or more relapses over 6 months while on treatment with any of them, its replacement with an alternative medication should be considered. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  20. 20. Management of patients with steroid sensitive nephrotic syndrome Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  21. 21. Steroid resistant nephrotic syndrome • Failure to achieve remission despite therapy with daily prednisolone at a dose of 2 mg/kg per day for 4 weeks is called steroid resistance. • Incidence approximately 10-20%. • Initial resistance: Lack of remission at the first episode. • Late resistance: Steroid sensitive initially, but show steroid resistance during subsequent relapse. • All chidren with steroid resistant nephrotic syndrome should under go renal biopsy. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  22. 22. SRNS - renal biopsy rationale • Most patients with steroid sensitive nephrotic syndrome (90%) show minimal change nephrotic syndrome on renal histology. • 30-40% of SRNS patients show minimal change nephrotic syndrome,30-40% show FSGS. • 20% patients with SRNS show membranoproliferative glomerulonephritis, membranous nephropathy, IgA nephropathy and amyloidosis.These conditions differ in their evaluation and treatment. • The response to therapy is determined by renal histology; patients with minimal change nephrotic syndrome show satisfactory response to therapy, while presence of FSGS or chronic tubulointerstitial changes is associated with unsatisfactory outcomes. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  23. 23. Treatment regimens for SRNS There is lack of consensus regarding the most appropriate regimen, the choice of initial treatment depends on the preference of the physician. Duration of therapy is for 2-3 years. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  24. 24. SRNS - Management • All patients with SRNS should receive treatment with angiotensin converting enzyme inhibitors (e.g., Enalapril, Ramipril). • These agents should be avoided if the estimated GFR is <30 ml/minute/1.73 m2. • Angiotensin receptor blockers (e.g., Losartan,Valsartan) may be used in patients intolerant to ACE inhibitors, or as add-on therapy to achieve better antihypertensive and antiproteinuric effect. • Dyslipidemia should be managed by HMG CoA reductase inhibitors (e.g.Atrovastatin 10-20 mg daily).Target LDL level is <130 mg/dL. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  25. 25. Supportive care & Management of complications Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  26. 26. Dietary management • A balanced diet, adequate in protein (1.5-2 g/kg) and calories is recommended. • Patients with persistent proteinuria should receive 2- 2.5 g/kg of protein daily. • Not more than 30% calories should be derived from fat. • Treatment with corticosteroids stimulates appetite, so adequate physical activity is to be ensured to prevent excessive weight gain. • Patients on prolonged (>3 months) treatment with steroids should receive daily supplements of oral calcium (250-500 mg/day) and vitamin D (125-250 IU/day). Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  27. 27. Dietary management contd. • Salt restriction is not necessary in most patients with steroid sensitive nephrotic syndrome • Reduction of salt intake (1-2 g per day) is advised for those with persistent edema. Salt should not be added to salads and fruits, and snacks containing high salt avoided. • Fluid restriction is needed in addition to Sodium restriction in children with persistent edema. • Severe edema: Intake of fluid restricted to insensible water loss • Moderate edema: Fluid intake = Insensible water loss (400 mL/m2/day) + Previous day's urine output • Mild edema: Fluid is minimally restricted Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  28. 28. Edema – Underfill hypothesis Heavy proteinuria Hypoalbuminemia Decreased plasma oncotic pressure Transudation of fluid from intravascular to interstitial space Decreased circulating blood volume (Underfill) Activation of Renin-Angiotensin System Elevated Aldosterone, ElevatedVasopressin Sodium and water retention Edema Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  29. 29. Edema – Overfill hypothesis Heavy proteinuria Proteolytic enzymes enter tubular lumen Activation of Epithelial Sodium Channels (ENaC) Increased blood volume (Overfill) Edema Hypoalbuminemia Low plasma oncotic pressure Intrinsic resistance of kidney to ANP (Atrial Natriuretic Peptide) Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  30. 30. • Prednisolone therapy usually results in diuresis with in 5-10 days. • Diuretics shouldn’t be given to patients with diarrhea, vomiting or hypovolemia. . • Gradual reduction of edema over one week is preferred. • Spironolactone added for patients requiring Furosemide dose >3mg/kg/day or used >1 week. • Monitor weight, urine output, BP, heart rate & serum electrolytes of patients who are on IV diuretic therapy. • In case of refractory ascites interfering with respiration, paracentesis should be done.Patients receiving Albumin should be observed for respiratory distress (pulmonary edema), hypertension and congestive heart failure. Edema – Management Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  31. 31. Hypovolemia • May occur during severe disease relapse, following diuretic administration particularly in children with poor oral intake, diarrhea and vomiting. • Symptoms: Dizziness, lethargy, abdominal pain and leg cramps. • Signs: Dry mucous membrane, orthostatic hypotension,raised hematocrit, elevated blood urea, uric acid, tachycardia, feeble pulses, cold extremities, slow capillary refill, low FENa & high urinary Potassium. • Treatment: Rapid infusion of normal saline (10-20 mL/kg) over 20-30 minutes. Repeat another bolus if features of hypovolemia persist. If no response with two blouses,Albumin infusion (5% Albumin at 10-15 mL/kg or 20% Albumin at 0.5-1 g/kg) is given. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  32. 32. Infections Children with nephrotic syndrome are prone to develop infections because of: • Low IgG levels • ImpairedT-lymphocyte function • Edema fluid acting as potential culture medium • Impaired tissue perfusion due to edema • Low factor B (C3 pro-activator) & Factor D levels - decreased bacterial opsonization • Immunosuppressive therapy • Skin breaks due to stretching of edematous skin, are easy portal of entry for organisms.  ESR, leukocyte count are poor markers of infection in nephrotic syndrome. CRP, pro-calcitonin can be helpful instead. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  33. 33. Infections contd. Spontaneous bacterial peritonitis: • Streptococcus pneumoniae is the most common cause. Streptococcus pyogenes, gram negative organisms (E.coli, Hemophilus) are the other causative organisms. • Presentation:Abdominal pain, nausea, vomiting, fever, diarrhea, tenderness & rigidity. • Other causes of abdominal pain in nephrotic syndrome: splanchnic ischemia due to hypovolemia & gastritis due to steroid intake. • Diagnosis: Examination of ascitic fluid (hazy/turbid), presence of leukocytes (>75-100/mm3) with >50% neutrophils & culture. • Treatment: IV Ampicillin and Aminoglycoside or monotherapy with IV Ceftriaxone for 7-10 days. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  34. 34. Infections contd. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  35. 35. Infections contd. Tuberculosis: • Mantoux test is to be done before starting steroid therapy. • Those with Mantoux positive but show no evidence of TB, should receive INH prophylaxis (10 mg/kg/day) for 6 months. • Those showing evidence of active tuberculosis should receive standard anti-tubercular therapy. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  36. 36. Infections contd. Varicella: • Varicella may be a severe illness in patients with nephrotic syndrome receiving corticosteroids or other immunosuppressive drugs. • Susceptible patients (unimmunized / no history ofVaricella), who are exposed to a case of chickenpox should therefore receive a single dose of Varicella Zoster Immunoglobulin (VZIG) or 400 mg/kg Intravenous Immunoglobulin (IVIG) within 96 hr of exposure. • Patients who develop varicella should receive intravenous acyclovir (1500 mg/m2/day in 3 doses) or oral acyclovir (80 mg/kg/day in 4 doses) for 7-10 days. • The dose of prednisolone should be tapered to 0.5 mg/kg/day or lower during the infection. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  37. 37. Stress doses of corticosteroids • Children who have received high doses of corticosteroids (>1mg/kg daily) for more than 2 weeks in the past year are at risk of HPA (hypothalamo- pitutary-adrenal) axis suppression. • Such children, during the periods of stress (infection, surgery & anesthesia) should be given, IV hydrocortisone at 2-4 mg/kg/day, followed by Oral Prednisolone 0.3-1 mg/kg/day – for the duration of stress and then tapered rapidly. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  38. 38. Immunization • Patients receiving prednisolone at a dose of 2 mg/kg/day or greater, or total 20 mg/day or greater for more than 14 days are considered immunocompromised. • Such patients should not receive live attenuated vaccines; inactivated or killed vaccines are safe. • Live vaccines can be administered once the child is off immunosuppressive medications for at least 4 weeks. • Administration of some vaccines, e.g., Hepatitis B, Measles-Mumps-Rubella or Meningococcal vaccines may rarely precipitate a relapse. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  39. 39. Immunization contd. PneumococcalVaccines: • Children below 2 yr of age 2-4 doses of the heptavalent conjugate pneumococcal vaccine • Previously unimmunized children between 2-5 yr A priming dose of the conjugate vaccine should be followed 8 weeks later, by the 23- valent polysaccharide vaccine. • Children older than 5 yr Only a single dose of the polysaccharide vaccine. Revaccination after 5 yr is considered for children (<10-yr-old) with active nephrotic syndrome. Varicella vaccine: Patients in remission and not on immunosuppressive therapy should receive the varicella vaccine.  12 months and 12 yr of age – Single dose  13 yr or older – 2 doses separated by an interval of at least 4 weeks Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  40. 40. Thromboembolism • Incidence 2-5%. More common in steroid resistant nephrotic syndrome than steroid sensitive nephrotic syndrome. • Venous thrombosis more common than arterial thrombosis. • Predisposing factors:Urinary loss of Anti-Thrombin III, protein C, protein S; elevated Fibrinogen levels; volume depletion caused by diuretic therapy or diarrhea; immobilization. • Renal vein thrombosis:Oligoanuria, hematuria, flank pain • Saggittal sinus & cortical vein thrombosis: Convulsions, vomiting, altered sensorium and neurologic deficits. • Femoral vein thrombosis, mesenteric vein thrombosis & deep vein thrombosis leading to pulmonary embolism can occur. • Diagnosis:USG, Doppler studies and MRI. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  41. 41. Thromboembolism contd. • Management: Correction of dehydration, IV Heparin or SC LMWH initially followed by oral-anti coagulants on the long term. • Prevention:Avoid prolonged bed rest, maintenance of hydration, avoid injudicious use of diuretics • Prophylactic anti-coagulant therapy such as low dose aspirin is not routinely recommended in nephrotic syndrome. • Prophylactic anti-coagulant therapy can be given in the setting of: • Previous history of thromboembolism • An underlying hypercoagulation disorder other than nephrotic syndrome • Presence of a central venous catheter Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  42. 42. Thromboembolism contd. • Management: Correction of dehydration, IV Heparin or SC LMWH initially followed by oral-anti coagulants on the long term. • Prevention:Avoid prolonged bed rest, maintenance of hydration, avoid injudicious use of diuretics • Prophylactic anti-coagulant therapy such as low dose aspirin is not routinely recommended in nephrotic syndrome. • Prophylactic anti-coagulant therapy can be given in the setting of: • Previous history of thromboembolism • An underlying hypercoagulation disorder other than nephrotic syndrome • Presence of a central venous catheter Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  43. 43. Hyperlipidemia • Hyperlipidemia in nephrotic syndrome is characterized by elevated LDL, IDL,VLDL and Lipoprotein (a). HDL levels are reduced or unchanged. LDL/HDL ratio is increased. • Mechanism: Hypoalbuminemia upregulates HMG-CoA reductase and downregulates lipoprotein lipase,VLDL receptor and hepatic triglyceride lipase. • In steroid sensitive nephrotic syndrome, hyperlipidemia is associated with relapse and lipid levels fall once remission is achieved. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  44. 44. Hyperlipidemia contd. • Patients with steroid resistant nephrotic syndrome with frequent relapses and persistent proteinuria tend to have continued dyslipidemia and require drug therapy. • Management: Dietary fat should be restricted to <30% of calories. Saturated fat should be <10% of total calorie intake. Dietary cholesterol intake should be <300 mg/day. When dietary modification is not effective, HMG-CoA reductase inhibitors (Atrovastatin) can be used. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  45. 45. Hypertension • Hypertension may be present at the onset or may appear late due to steroid toxicity. • Goal is to maintain blood pressure to <90th percentile of normal. • Management: Low salt diet, exercise, weight reduction. ACE inhibitors and Angiotensin Receptor Blockers are the first line agents as they also reduce proteinuria. Calcium channel blockers and β2 agonists can also be used. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  46. 46. Education of parent • Parents should be provided information about the course, complications & outcome of the disease. • Urine examination with dipstick or by boiling method at home. Daily during relapse or during periods of infection. Once or twice a week during remission. • Maintain a dairy containing information about proteinuria, medications & infections. • Ensure that the child participates in all activities and sports during periods of remission. No restrictions are imposed. • As infections constitute significant proportion of morbidity, need for appropriate immunization should be stressed. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  47. 47. CONGENITAL NEPHROTIC SYNDROME Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  48. 48. Onset with in 3 months of life Congenital nephrotic syndrome Onset after 3 months of life but before 1 year of life Infantile nephrotic syndrome Onset after 1 year of life Childhood nephrotic syndrome Most common varieties of congenital nephrotic syndrome are: • Finnish type due to Nephrin gene (NPHS1) mutation & • Diffuse mesangial sclerosis due to Wilms tumor suppressor 1 (WT1) gene mutation. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  49. 49. PRIMARY CONGENITAL NEPHROTIC SYNDROME SECONDARY CONGENITAL NEPHROTIC SYNDROME MALFORMATIONS & SYNDROMES • Nephrin (NPHS1) gene mutation - Finnish type • Podocin (NPHS2) gene mutation • Phospholipase C Epsilon- 1 (PLCE 1 - NPHS3) gene mutation • Infections (Congenital Syphilis,Toxoplasmosis, Rubella, CMV, Hepatitis B, HIV & Malaria) • SLE • Neonatal antibodies against neutral endopeptidase • WT1 gene mutation: Denys-Drash syndrome, Fraiser syndrome,WAGR or isolated nephrotic syndrome • Laminin Beta 2 (LAM-β2) mutation: Pierson syndrome or isolated nephrotic syndrome • LMX1β gene mutation: Nail-Patella Syndrome • Galloway Mowat syndrome Etiology of congenital nephrotic syndrome Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  50. 50. Clinical features • Proteinuria starts in-utero • Born premature with large placenta (Weight of placenta >25% of birth weight of the baby) • Edema soon after birth, abdominal distension, umbilical hernia, wide cranial sutures and fontanelle • Failure to thrive, delayed development, hypothyroidism, repeated infections, spontaneous vascular thrombosis • Prone for both hypotension and hypertension • Galloway Mowat syndrome: Hiatal hernia, microcephaly, psychomotor retardation, hypotonia and seizures. • Pierson syndrome: Microcoria • Denys Drash syndrome:Ambiguous genitalia Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  51. 51. Investigations • Nephrotic range proteinuria • Low serum albumin • ElevatedTSH • Dyslipidemia (Elevated triglycerides, elevated LDL cholesterol & low HDL cholesterol) • Deranged renal function is seen beyond infancy • Typical features are seen in renal biopsy done at 3-8 months of age • USG findings depend on the age. (Kidney size is normal and corticomedullary differentiation is intact till 2 months of age) • TORCH serology to detect congenital infections Prenatal Diagnosis: • Prenatal genetic testing by amniocentesis or chorionic villous biopsy to detect mutations • Elevated AFP in amniotic fluid Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  52. 52. Management • Goals:To provide good nutrition, control edema, prevent thrombosis, prevent infection and allow the child to reach weight (9Kg) suitable for renal transplantation. • Immunosupression has no role in the management of congenital nephrotic syndrome.There may be response to appropriate antimicrobial therapy for congenital syphilis and toxoplasmosis. • Nutritional support: • Calories 130 kc/kg/day • Proteins 4 g/kg/day • Vitamin D2 400 IU/day • Vitamin E 2.5 - 3.0 mg/day • Magesium 40-60 mg/day in the absence of renal failure • Calcium 500 mg/day for <6 months 750 mg/day for 6-12 months 1000 mg/day for >12 months Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  53. 53. Management contd. • Aggressive control of edema: By usage of loop and thiazide diuretics.Albumin infusion (3 to 4 g/kg/day) with Furosemide 0.5 mg/kg/day may be needed for refractory edema. • Thyroxine supplements:Thyroxine (6.25-12.5 μg/day) adjusted toTSH levels to control clinical or subclinical hypothyroidism • Reduction of proteinuria: o ACE inhibitors: Captopril 3-4 mg/kg/day or Enalapril 0.2- 0.5 mg/kg/day o Indomethacin: 1-2 mg/kg/day o Unilateral nephrectomy o Bilateral nephrectomy with continuous peritoneal dialysis Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  54. 54. Management contd. • Anticoagulant therapy: Low dose Aspirin or Dipyridamole and Warfarin to keep PartialThromboplastin Time (PTT) at 20% to 30% of normal. • Control of infections: Prophylactic use of antibiotics is not required but even minor infections need to be treated promptly. • Renal transplantation: Done once the child reaches 9 Kg of weight. Recurrence in transplanted kidney may respond to Steroids, Cyclophosphamide, Plasma Exchange or Rituximab (Anti- CD20). Prognosis: Patient survival after 5 years is >90%. Graft survival after 5 years is >80%. Due to the risk of chronic allograft nephropathy, second transplantation is inevitable when these patients become young adults. Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  55. 55. References: • NelsonTextbook of Pediatrics – 19th edition • IAPTextbook of Pediatrics – 5th Edition • Indian Society of Pediatric Nephrology - Guidelines on the management of steroid sensitive nephrotic syndrome 2008 • Indian Society of Pediatric Nephrology - Guidelines on the management of steroid resistant nephrotic syndrome 2009 • Principles and Practice of Pediatric Nephrology by M. Vijaykumar, B.R. Nammalwar – 2nd Edition • Pediatric Nephrology – R.N. Srivastava & Arvind Bagga – 5th Edition Dr Naveen Kumar Cheri S.V. Medical College, Tirupati
  56. 56. Thank you Dr Naveen Kumar Cheri S.V. Medical College, Tirupati

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