This document provides information on nephrotic syndrome, specifically defining it as a clinical syndrome characterized by heavy proteinuria, hypoproteinemia, edema, and hypercholesterolemia. It describes the epidemiology, classification, pathophysiology, clinical manifestations, investigations, diagnosis, management, and prognosis of nephrotic syndrome. The key points are that minimal change disease is the most common type, presenting with edema, ascites, weight gain, and respiratory distress in children aged 1-10 years. Investigations show proteinuria, hypoalbuminemia, and normal renal function. Management involves steroid therapy, addressing complications, and educating parents on infection prevention and immunization.

1. NEPHROTIC SYNDROMETHE SWOLLEN CHILD

2. DEFINITIONIt is a clinical syndrome of:1. Heavy proteinuria>1 g/m2/day2. Hypoproteinemia↓ serum albumin < 2.5 g/dL

3. Protein:Creatinine > 200mg/mmol3. Oedema4. Hypercholestrolnemia> 250 mg/dLEPIDEMIOLOGYWest Uncommon: 3 new cases per 100,000 child populationAsianHigher incidence: 16 new cases per 100,000 child populationMalaysia No available data, it is thought to have higher incidence than in the west

4. CLASSIFICATION

5. Minimal Change Disease most common (70-80%)

6. M:F = 2:1

7. < 7 years old

8. steroid-sensitive nephrotic syndrome

9. do not progress to renal failure

10. often precipitated by respiratory infections

11. Features:age between 1 and 10 years no macroscopic haematuria normal blood pressure normal complement levels normal renal function.

13. PATHOPHYSIOLOGYPrimary disorder:

14. Edema:- under fill theory: hypoalbuminemia- over fill theory:↑ tubular NaClreabsorption secondary to RAAS -> intravascular expansion -> fluid shift following pressure gradient Hypercholesterolemia - hypopratenemia -> hepatic lipoprotein synthesis -> ↑serum lipid (cholesterol, lipoprotein) -> lipid metabolism

15. COMPLICATIONInfectionSpontaneous bacterial peritonitis, cellulitis, bacteriemia (S.pneumoniae, E.coli)

16. Steroid and immunosuppressant toxicityHypovolaemiaabdominal pain and may feel faint, cold peripheries, poor pulse volume, hypotension, and haemoconcentration.

17. A low urinary sodium (<20mmol/L) and a high packed cell volume

18. Thromboembolism

19. hypercoagulable state due to urinary losses of antithrombin, thrombocytosis

20. exacerbated by steroid therapy

21. increased synthesis of clotting factors

22. increased blood viscosity from the raised haematocrit,

23. This is usually arterial and may affect the brain, limbs and splanchnic circulation

24. Hypercholesteroleamia

25. Acute renal failure (rare)CLINICAL MANIFESTATIONSudden onset of dependent pitting oedema - periorbital - scrotal or vulva - ankle or legWeight gainAscites - abdominal pain - malaiseDiarrhea (dt intestinal oedema)Respiratory distress (dtpulm. oedema)

27. HISTORY TAKINGFirst time or relapse???History of edema noted on awakening in the morning or sudden swelling??Distribution

28. Colour changes

29. Initiating factor? (bee sting)

30. Painful??Weight gain (edema)Respiratory distressBreathlessnessDiarrheaUrine: frothy Pass medical and drug history: recent illness, allergies, asthmaFamily history

31. PHYSICAL EXAMINATIONAssessment of hydration status identifies fluid imbalances (dehydration, overhydration)Blood pressure: hypertensionHenoch-Schönleinpurpura (purpura)Systemic lupus erythematosus (malar rash)Rales heard on lung auscultation suggest extravascular fluid from overload or hypoalbuminemiaPalpation and percussion of the abdomen may reveal ascites or massesLiver enlargement is present in several multisystem diseases (systemic lupus erythematosus, infections, polycystic disease) and in glomerulosclerosis

32. DIFFERENTIAL DIAGNOSISMain ddx:AnaphylaxisCellulitis (orbital,periorbital)AngioedemaNephrotic synd.Other causes of hypoalbuminaemiaTransient proteinuria

33. Postural orthostatic proteinuria

34. Glomerular abnormalitiesINVESTIGATIONSDiagnostic studies:Proteinuria +1> on 2/3 random urine sample (Dipstick)P:C (> 200mg/mmol) (early morning)Serum lipidC3 level ( sensitive n specific if other than MCD)Full blood count: HCT, WBCRenal profile: normal in MCDSerum albumin: <25g/dLUrinalysis and quantification for urinary protein excretionabundant hyaline cast

35. Haematuria (other thn MCD)

36. Na+ <10mmol/L in hypovolaemiaOther investigations complement levels: decrease suggest other thn MCD

37. Antistreptolysin O titre and throat swab

38. Hepatitis B antigenDEFINITION FOR DX & TX OF IDIOPATHIC NS REMISSION:Urinary protein excretion < 4 mg/m2/hour or urine dipstix nil/trace for 3 consecutive days. RELAPSE:Urinary protein excretion > 40 mg/m2/hour or urine dipstix ++ or more for 3 consecutive days. FREQUENT RELAPSES:Two or more relapses within 6 months of initial response or four or more relapses within any 12 month period. STEROID DEPENDENCE:Two consecutive relapses occurring during the period of steroid taper or within 14 days of its cessation.STEROID SENTITIVE:Normalization of proteinuria within 4 weeks after start of standard initial therapy with daily oral predinisolone STEROID RESISTANCE:Failure to achieve remission in spite of 4 weeks of standard prednisolone therapy.

39. MANAGEMENTSTEROID SENSITIVEPrednisolone regime for initial dx:60 mg/m2/day (max 80mg/day) for 4 weeks

40. 40 mg/m2/48 hr (max 60mg/dose) for further 4 weeks

41. Prednisolone regime for relapses:

42. 60 mg/m2/day (max 80mg/day) until remission

43. 40 mg/m2/48 hr for 4 weeksFrequent relapse or steroid dependent:Long term low dose prednisolone for 3-6 monthsSCHEMA OF TREATMENT OF IDIOPATHIC NEPHROTIC SYNDROME 1. Nephrotic Syndrome Initial Diagnosis Prednisolone 60 mg/m2/day (max 80/day) for 4 week Response No ResponsePrednisolone 40 mg/m2/48 hours for 4 weeks Renal Biopsy *Discontinue *Steroid taper at 25% monthly over 4 months 2. Relapse Prednisolone 60 mg/m2/day (max 80 mg/day) till remission, then 40 mg/m2/48 hours for 4 weeks and discontinue. 3. Frequent RelapsesReinduce as for (2) above, then taper and keep low dose alternate day prednisolone at 0.1 - 0.5 mg/kg/dose for 6 months. 4. Relapse on prednisolone As for (3) if not steroid toxic, consider cyclophosphamide (cumulative dose 168 mg/kg) if steroid toxic. 5. Relapses post cyclophosphamide As for (2) and (3) if not steroid toxic. If steroid toxic, refer paediatricnephrologist to consider a). second course cyclophosphamide or b). cyclosporine therapy.

44. STEROID RESISTANTSymptomatic therapy:

45. diuretic

46. blood pressure control : ACEi (captopril, enalapril), angiotensin II receptor antagonist

47. hyperlipidaemia

48. Immunosuppressive therapy:

49. Steroids

50. cyclophosphamide

51. Cyclosporin, tacrolimus, mycophenolatemofetil

52. Indications for renal biopsy

53. A renal biopsy is also NOT required prior to cytotoxictherapy

54. Steroid resistant nephroticsyndrome

55. Secondary NS

56. Congenital NS

57. Steroid toxicityStunting of growth

58. Cataracts

59. Striae

60. Severe cushingoid features

61. behavioural changes, a rounded face, central obesity and the tendency to bruise more easily, hirsutism

62. Osteoporosis

63. Proximal myopathy

64. Recurrent infection dt low immunity

65. MANAGEMENTMx of oedematous stateBed rest to be avoided as there is a tendency of hrpercoagulability

66. Dietary advice: no added salt, normal protein with adequate calories

67. Prophylactic antibiotics: oral penicillin particularly in during relapse with gross oedema

68. Hypovolaemia: infuse salt poor albumin or 5% albumin, plasma protein derivatives or human plasma

69. DiureticsMx complication:Infection: parenteral penicillin and a third generation cephalosporin (in primary peritonitis)

70. If exposed to chickenpox and measles varicella-zoster immunoglobulin (VZIG) should be given within 72 hours after exposure to chickenpox / single dose of intravenous immunoglobulin.

71. Thrombosis : Warfarin, low-dose aspirin, and dipyridamole all have been used to minimize the risk of clots. URINE ALBUMIN MONITORING It is advocated that monitoring of urine albumin excretion be done regularly either at home with urinary dipstix or at the nearest health centre.

72. EDUCATIONEducation:Parents and school teachers should be provided with information regarding the disease which includes: Advice and precaution of infectionDanger of sudden steroid withdrawal (adrenal crisis)Immunisation:While the child is on corticosteroid treatment and within 6 weeks after its cessation, only killed vaccines may be safely be administered to the child. Live vaccines can be administered 6 weeks after cessation of corticosteroid therapy

73. PROGNOSIS

74. Acute nephritic syndromeNUR AMIRA BINTI MOHD ASRI

75. CASE SCENARIO A 7 year old Malay boy was admitted 3 days ago with the chief complaints of facial puffiness and passing smokey and frothy urine for 1 week. The facial puffiness initially started off as periorbitaloedema which then progressed to involve the entire face within a week. Urinary output was also decreased. He also complaint of fever for one week which was of low grade, intermittent with no chills and rigor. There is also presence of an erythematous itchy skin lesion on his right elbow which was first noticed 2 weeks back. There is no history of sore throat, flu, blood transfusion, nausea, and vomiting, rashes, dyspnoea and chest pain. General examinations revealed pallor, high blood pressure of 139/96 mmHg, and an erythmatous scaly circular skin lesion on his right elbow. Urine biochemistry revealed protein 3+, RBC 4+. Blood urea was raised to 500 umol/L.

76. NEPHRITIC SYNDROMEIt is a clinical complex, usually acute onset, characterized by:oedemaeg facial puffinessMicroscopic/macroscopic haematuria (tea-coloured urine)hypertensionOligouria (decreased urine output)Azotemia/uremia (excess urea in urine)

77. The lesions that cause nephritic syndrome have in common proliferation of cells within in glomeruli, accompanied by a leukocytic infiltration.This inflammatory reaction injures the capillary walls, permitting escape of RBC into the urine(hematuria) , and induced hemodynamics changes that lead to a reduction in GFR which are manifested clinically by oligouria, reciprocal fluid retention and azotemiaHypertension is the result of the fluid retention by kidney secretion of renin.

78. NEPHROTIC SYNDROMEGLOMERULONEPHRITISAcute poststreptococcal GNlgA nephropathyNEPHRITIC SYNDROMEHenoch-schönleinpurpuraSLE

79. POSTSTREPTOCOCCAL AGNThe commonest cause of nephritic syndromeUsually followed a nephritogenic streptococcal pharyngitis or impetigo with a strain of group A beta-hemolytic streptococciImmune-mediated inflammationOccurs most frequently in children 2 to 12 years oldBoys are frequently affectedThis is diagnosed by evidence of a recent streptococcal infection (culture of the organism, raised ASOT) and low complement C3 levels, that return to normal after 6-8 weeksLong term prognosis is good

80. Epidemiology of post acute strep GN121 of the 124 nephritis patients had poststreptococcal infection. (Department of paediatrics, HUSM, July 1987-June 1988)Globally-incidence has decreased in the past 3 decadesMost commonly-sporadicDespite that,epidemic cases in some poor and rural communities

81. pathogenesis

82. Streptococcal infectionImmune complex formation +deposited in GBMComplement system activatedLow serum complementImmune injuriesCellular proliferationGBM fractureCapillary lumen narrowedhematuriaproteinuriaGlomerular blood flow decreased oligouria GFR lowDistal sodium reabsorptionRetention of water and sodiumEdema and hypertensionBlood volume increased

83. HENOCH-SCHöNLEIN PURPURAIt is a systemic syndrome involving the skin (purpuric rash), gastrointestinal tract (abdominal pain, joints (athritis), and kidneyUsually occurs between the ages of 3-10 years olds

84. Twice as common in boys

85. peaks during winter months

86. Is often preceded by an upper respiratory infection

87. Unknown cause however it is postulated that genetic predisposition and antigen exposure increase circulating lgA levels.

88. By immunofluorescence and electron microscopy the findings may be similar to those of IgAN

89. The combination of

90. Skin rashes(symmetrical distributed over the buttocks,extensor surface of arms and legs and the ankles.

91. Athralgia (knees and ankles)

92. Periarticularoedema

93. Colicky abdominal pain, GI petechiae,hematemesis, melaena, intussusception

94. GlomerulonephritisSystemic lupus erythematosus (SLE)Is an autoimmune disease that presents mainly in adolescent girls and young women(5% in childhood girl, rare in children younger than 9 yo, equal gender distribution in children)Multisystem disorder of unknown etiology characterized by the production of large amounts of circulating antibodies due to loss of T lymphocytes control on B lymphocytes which leads to autoantibody productionPresence of multiple antibodies including antibodies to double-stranded DNA .

95. Criteria for diagnosis of SLEsignsMalar rash (butterfly rash)PhotosensitivityOral and nasopharyngeal ulcersPleuritis and pericarditisNon erosive arthritis ( more than 2 joints with effusion and tenderness.Investigation dataProtenuria(>500mg/24 hrs) or RBC cellular cast in urinePositive anti-dsDNAEvidence of presence of antiphospholipid antibodies

97. lgA NEPHROPATHYAffects children and young adultsBegins as an episode of gross hematuria that occurs within 1 or 2 days of a nonspecific upper respiratory tract infection.Is one the most common causes of recurrent microscopic or gross hematuria and is the most common glomerular disease revealed by renal biopsyThe pathology hallmark is the deposition of lgA in the mesangiumPrognosis is good in children immunofluorescence with anti-IgA antibodies deposited in the mesangium

98. Familial nephritisThe commonest familial nephritis is Alport’s syndromeX-linked recessive disorderIs associated with nerve deafness and ocular defectThe mother may have hematuriaCan progress to end-stage renal failure by early adult life in males.

99. Basic workup of a child with hematuriaHistory-age,gender,sosioeconomicstatus,familyhistory,drug historyPhysical examination-height,weight,bloodpressure,funduscopy,presence or absence of abdominal mass,skinappearance,genitalia,edema,complete physical examination.Laboratory-urinalysis (includingmicroscopic examination and RBC morphology), urine culture, complete blood count (including platelets), serum electrolytes, creatinine,calcium, serum complement, random urine for total protein, creatinine, renal imaging studies.Nelson p758

100. Dalliana Adia Bte Abd Latif2008402292

103. HistoryAntedencenthx of streptococcal throat of skin infection- post-streptococcal GN

104. Ask about symptoms of swelling-facial, perioral,pedal edema, or ascites

105. Symptom of pulmonary edema/ CHF (egdyspnoea with exertion, orthopnoea, SOB)

106. Gross hematuria (eg dark, rust, coke, tea coloured)

107. Family hx, other family member with nephritis or renal failure- Alport syndromeThe general terms GN and nephritis are not specific enough to be very useful for treatment or prognosis!!!

108. Epistaxis, headache, encephalopathy- severe hypertensionOligouriaNonspecific symptoms eg malaise, fever, anorexia, weaknessFor tubulointestinal nephritis- try to obtain a history of a known etiology (eg bacterial, viral, drug related, metabolic, other)TIN, usually hx of polyuria than oliguria

109. InvestigationLaboratoryFBC- anemia, leucocytosisUrinalysis and culture- hematuria, proteinuria, RBCs cast,other cellular masts, pyuria?Bacteriological an serology- Anti streptolysin-O titer (>200IU/mL), Anti-DNAse B, throat swab/skin swab, lupus serology, serum IgAMeasure complement level- C3RFT- blood urea, serum creatinine, electrolytes, BUN

110. Acute poststreptococcal GGN- low C3, positive ASOT and anti DNAase BTIN- hematuria, eosinophilia, sterile pyuria, low grade proteinuria, eosinophiluria, urinary WBc casts

111. ImagingRenal ultrasonography- usually to exclude other causes of hypertension and hematuria but usually not conducted in real cut nephritic sydrome

112. Histologylight microscopy: lymphocytes, PMN leukocytesImmunofluoroscene- IgG, IgA, IgM, or complementElectron- deposit in mesangial, subendothelial, or subepithelial

113. Post-streptococcal nephritisUrinalysis ASOTLow complement C3 levels- return to normal after 3-4 weeks

114. ManagementTreat the primary pathology- immunosuppressive med eg steroids or cyclophosphamide in lupusSupportive care- Fluid and electrolyte balance, diuretics, Ca channel blocker, ACEi, monitor rapid deterioration in renal functionDiet- fluid restriction, sodium, potassium restriction, Ca supplementDialysis

115. ComplicationComplication of severe hypertension (e.g. cerebral haemorrhage, seizure, enchepalopathy,stroke, end organ damage)Complication of renal failure (e.g. hyperkalemia, fluid overload, electrolyte abnormality, uremic symtoms, anemia, abnormal bone mineralization, sexual dysfunction, poor growth, anorexia)Complication of primary disease (eg SLE)

116. Nephrotic and nephritic

118. Have a good fortune ahead!!! 