Date post: | 15-Mar-2018 |
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Dr. Muhammad Sajjad SabirMBBS, DCH, MCPS, FCPS
Assistant Professor of Paediatrics
Manifestation of glomerular disease, characterized by nephrotic range proteinuria and a triad of clinical findings associated with large urinary losses of protein : hypoalbuminaemia , edema and hyperlipidemia
EdemaHeavy proteinuria > 40mg/m2/hrHypoalbuminemia <2.5g/dlHyperlipidema >250mg/dl
15 times more common in children than adults
2 – 7 cases per 100,000 children per year (Global)
Incidence South Asia 16/100,000 children
Most common= 1.5-6 year
boys : girls--- 2:1 ratio
Defined as protein excretion of > 40 mg/m2/hr First morning protein : creatinine ratio of > 2-3 : 1
- Nelson Textbook of Paediatrics, Vol 2, 19th Edition, page 1801
Idiopathic or Primary GeneticSecondary
Minimal Change disease ( >80 % ) Mesangial proliferation Focal segmental Glomerulosclerosis Membranous Nephropathy Membranoproliferative glomerulonephritis
- Nelson Textbook of Paediatrics, Vol 2, 19th Edition, page 1804
Finnish type Congenital Nephrotic SyndromeFocal Segmental GlomerulosclerosisDiffuse Mesangial SclerosisDenys-Drash Syndrome
- Nelson Textbook of Paediatrics, Vol 2, 19th edition, page 1802, table 521-1
Congenital Oligomeganephronia
Infectious Hepatitis (B,C) , HIV-1, Malaria, Syphilis, Toxoplasmosis
Inflammatory Glomerulonephritis
Immunological Castleman Disease, Kimura Disease, Bee sting, Food allergens
Neoplastic Lymphoma, Leukemia
Traumatic ( Drug induced ) Penicillamine, Gold, NSAIDS, Pamidronate, Mercury, Lithium
Permeability of glom.cap.memb. Proteinuria
Intravascular vol
ADH Renal perfusionpressure
WaterReabsorptnInCollectingducts
Actv. reininAng. ald. sys
Tubular reabsorp.Of Na
Hypoalbuminemia
Hepatic protein synthesis Plasma oncoticpressure
Hyperlipidemia Transudation of fluidfrom intravascularcomp. To interstialspace
Edema
Preceding flu-like illnessGeneral health (anorexia, weight gain ,lethargy)Edema Urinary symptoms(hematuria, oliguria) Infection, diarrhea, abd. painDrug intakePast history
Edema Mild to start with – peri orbital puffiness, lower
extremities Progression to generalized edema, ascites, pleural
effusion, genital edemaDecreased urine output Anorexia, Irritability, Abdominal pain and diarrhoea Absence of Hypertension Gross hematuria Vital & BP Height & weight for age Anemia
- Nelson Textbook of Paediatrics, Vol 2, 19th Edition, page 1802
Clinical Features-Examination
CLINICAL FEATURES Minimal Change Nephrotic Syndrome
Focal Segmental Glomerulosclerosis
Membranous Nephropathy
Age ( yr ) 2 - 6 2 - 10 40 - 50
Sex ( M : F ) 2 : 1 1.3 : 1 2 : 1
Nephrotic Syndrome
100 % 90 % 80 %
Asymptomatic proteinuria
0 10 % 20 %
Hematuria 10 – 20 % 60 – 80 % 60 %
Hypertension 10 % 20 % early infrequent
Rate of progression to renal failure
Non progressive
10 yrs 50 % in 10 – 20 yrs
Associated Conditions
Usually none None Renal vein thrombosis, SLE, Hepatitis B
Periorbital puffiness
Protein losing enteropathy Hepatic failure Heart failure Acute/Chronic Glomerulonephritis Protein Malnutrition• < 1 year old• Family history of nephrotic Syndrome• Hypertension• Pulmonary edema• Gross hematuria• Extrarenal findings
• < 1 year old• Family history of nephrotic Syndrome• Hypertension• Pulmonary edema• Gross hematuria• Extrarenal findings
URINE ANALYSIS PROTEINURIA: 3+ Or 4+ MICROSCOPIC HEMATURIA: 20% PUS CELLS: underlying UTI CELLULAR CASTS: not in minimal
change disease 24HRS URINARY PROTEIN
EXCRETION: Children : >40mg/m2/hr
URINARY spot PROTEIN : CREATININE > 2.0 (Spot UPC ratio > 2.0)
trace /nil (10-20mg/dl) + (30mg/dl) ++ (100mg/dl)+++(300mg/dl)++++(1000-2000mg/dl)
SERUM:S. CREATININE: NormalS. CHOLESTROL: ElevatedS. ALBUMIN: <2.5g/dlC3 & C4: NormalTOTAL CALCIUM: Decreased
VITRAL SEROLOGY: HBV associated with membranous nephritis
BLOOD COUNTS: Hb, TLC & DLC Normal ESR raised
X-RAY CHEST: R/O pulmonary TB R/O pleural effusion
MANTOUX TEST: R/O TB before starting steroids
RENAL BIOPSY ANA: R/O SLE
• Age below 12 months• Gross or persistent microscopic hematuria• Low blood C3• Hypertension• Impaired renal Function• Failure of steroid therapy
Indications for Renal biopsyIndications for Renal biopsy
Other forms of glomerulonephritis including post streptococcal glomerulonephritis
Pyelonephritis Obstructive Uropathies Hemolytic Uremic Syndrome Fever, Exercise, Orthostatic protein urea Renal Failure Congestive cardiac failure Liver failure
Management
DIETARY ADVICE: A balanced diet adequate in proteins and
calories is recommended foods high in sodium avoided High protein diet Edema no added salt
Treatment of infections Parent Education Can attend school Can participate in physical activities as tolerated
If significant edema Diuretics + Aldosterone antagonist ( Fursemide, spironolactone ) Salt restriction DIURETICS INDICATIONS: Severe symptomatic edema Steroid toxicity or steroid contraindicated
Q.Best diuretic in Nephrotic Syndrome?
ROLE OF INTRAVENOUS ALBUMIN
INDICATIONS: Signs of hypovolemia Sever oedema
DOSAGE & ADMINISTRATION: I/V salt poor 25% albumin infusion 0.5-1 gm/kg/doze over 6-12 hrs followed
by Frusemide 1-2 mg/kg/dose (I/V)
CORTICOSTEROID THERAPY: DOSAGE & ADMINISTRATION:(after a -ve PPD test)
Prednisolone 60mg/m2 /day (max 80mg) single daily dose {or 2-3 dd} for 6 wks consecutively
After the initial 6-wk course, prednisone dose tapered to 40 mg/m2/day given every other day as a single daily dose for at least 4 wk.
Alternate-day dose then slowly tapered→discontinued over next 1-2 mo
REPONSE TO STEROID:80-90% of children respond within 3 wk
10% respond by first week 70% by second week 85% by third week 92% by forth week
Response means clinical remission, diuresis, and urine trace or negative for protein for 3 consecutive days
Who respond to prednisone therapy do so within the first 5 wk of treatment.
STEROID DEPENDENT: Patients who relapse while on alternate-day steroid therapy or within 28 days of completing a successful course of prednisone therapy
FREQUENT RELAPSERS: Patients who respond well to prednisone therapy but relapse ≥4 times in a 12-mo period
INFREQUENT RELAPSERS :3 or less relapses per yr
STEROID RESISTANT: Fail to respond to corticosteroid therapy within 8 wks
Children who continue to have proteinuria (2+ or greater) Diagnostic renal biopsy should be performed
Relapses should be treated with 60 mg/m2/day (80 mg daily max) in a single am dose until the child enters remission (urine trace or negative for protein for 3 consecutive days)
The prednisone dose is then changed to alternate-day dosing as noted with initial therapy, and gradually tapered over 4-8 wk.
Ghai Essential Paediatrics,8th edition, page 479
ALTERNATIVE THERAPY: INDICATIONS: steroid dependent frequent relapsers steroid responsive unwanted effects of steroids
Alternate Day prednisoloneSteroid sparing agents
Levamisole ( 2 – 2.5 mg/kg ) Cyclophosphamide ( 2 – 2.5 mg/kg/day) Mycophenolate Mofetil ( 20 – 25 mg/kg/day ) Cyclosporin ( 4 – 5 mg/kg/day ) Tacrolimus (0.1 – 0.2 mg/kg/day ) Rituximab ( 375mg/m2 IV once a week )
Ghai Essential Paediatrics,8th edition, page 479, 480
INFECTIONS: SBP Pneumonia Cellulitis UTI disseminated varicella
THROMBOEMBOLISM: Renal vein thrombosis pulmonary embolism saggital sinus thrombosis
OTHERS: Acute renal failure Hypertension Malnutrition Flare up of tuberculosis Steroid & drug related
toxicity
Blood CPUrine REGrowth parametersGeneral examination Blood PressureEye examination RFTsSerum electrolytesBSR
Serum calcium X-Ray wristX-Ray spineChest X-Ray PT/APTT
Steroid Responsive NS : Good prognosis ( MCNS )
Steroid Resistant NS : Poor prognosis ( FSGS )
Mortality rate 1-2 %
- Nelson Textbook of Paediatrics, Vol 2, 19th Edition, page 1806
Infants who develop nephrotic syndrome within first 3 months of life
ETIOLOGY: Finish type congenital nephrotic syndrome Congenital infections HIV/HBV Diffused mesengial sclerosis Drash syndrome Minimal change disease Focal segmental glomerulosclerosis
TREATMENT: ACE inhibitors + Indomethacin + unilateral neprectomy B/L nephrectomy → chronic dialysis & kidney transplant no role of steroid or immunosuppressive agents
PROGNOSIS: Poor Progressive renal failure Death by 5 yrs age if untreated