2 nephrotic-syndrom

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NEPHROTICSYNDROME


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DEFINITION

PROTEINURIANephrotic range

HYPOALBUMINEMIA

HYPERLIPIDEMIA

OEDEMA


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Nephrotic RangeProteinuria

24 hour urine..40mg/m2/hdifficult

First morning urine sampleprotein and

creatinine ratio.more than 2-3:1


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Causes of secondarynephrotic syndrome

Membranous nephropathy (MN)[3]

Hepatitis B

Sjogren's syndrome

Systemic lupus erythematosus (SLE)Diabetes mellitus

Sarcoidosis

Syphilis

Drugs

Malignancy (cancer)

Focal segmental glomerulosclerosis (FSGS)[3]

Hypertensive Nephrosclerosis

Human immunodeficiency virus (HIV)

Diabetes mellitus

Obesity

Kidney loss

Minimal change disease (MCD)[3]

DrugsMalignancy, especially Hodgkin's lymphoma

Primary nephrotic syndrome

Diagnosis of exclusion
http://en.wikipedia.org/wiki/Nephrotic_syndromehttp://en.wikipedia.org/wiki/Hepatitis_Bhttp://en.wikipedia.org/wiki/Sjogren's_syndromehttp://en.wikipedia.org/wiki/Systemic_lupus_erythematosushttp://en.wikipedia.org/wiki/Diabetes_mellitushttp://en.wikipedia.org/wiki/Sarcoidosishttp://en.wikipedia.org/wiki/Syphilishttp://en.wikipedia.org/wiki/Malignancyhttp://en.wikipedia.org/wiki/Nephrotic_syndromehttp://en.wikipedia.org/wiki/Human_immunodeficiency_virushttp://en.wikipedia.org/wiki/Obesityhttp://en.wikipedia.org/wiki/Nephrotic_syndromehttp://en.wikipedia.org/wiki/Hodgkin's_lymphomahttp://en.wikipedia.org/wiki/Hodgkin's_lymphomahttp://en.wikipedia.org/wiki/Nephrotic_syndromehttp://en.wikipedia.org/wiki/Nephrotic_syndromehttp://en.wikipedia.org/wiki/Nephrotic_syndromehttp://en.wikipedia.org/wiki/Obesityhttp://en.wikipedia.org/wiki/Human_immunodeficiency_virushttp://en.wikipedia.org/wiki/Nephrotic_syndromehttp://en.wikipedia.org/wiki/Nephrotic_syndromehttp://en.wikipedia.org/wiki/Nephrotic_syndromehttp://en.wikipedia.org/wiki/Malignancyhttp://en.wikipedia.org/wiki/Syphilishttp://en.wikipedia.org/wiki/Sarcoidosishttp://en.wikipedia.org/wiki/Diabetes_mellitushttp://en.wikipedia.org/wiki/Systemic_lupus_erythematosushttp://en.wikipedia.org/wiki/Sjogren's_syndromehttp://en.wikipedia.org/wiki/Hepatitis_Bhttp://en.wikipedia.org/wiki/Nephrotic_syndromehttp://en.wikipedia.org/wiki/Nephrotic_syndromehttp://en.wikipedia.org/wiki/Nephrotic_syndrome


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Primary nephrotic syndrome /idiopathic nephrotic syndrome

Steroid resistant INS(SRNS)

Steroid sensitive IN(SSNS)

response to steroids has a high correlation with histologicalsubtype and prognosis


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PATHOPHYSIOLOGY

PROTEINURIA /HYPOALBUMINIA

Immune pathogenesisDeregulation of T-cell

subsets.Circulating factorsCytokines/other molecules

Allergic response

Poison ivy, bee stings


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PODOCYTE BIOLOGY

Effacement of

podocytes is nowthought to be theprimary pathology.

-ve charge of thebasementmembrane isalso important.


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GENETICS.

NephrinTransmembrane proteinencoded by NPHS 1 onchromosome 19.(FINISHtype congenital NS.

PodicinEncoded by NPHS 2on chromosome 1.Autosomal recessive.

Mutations in -actinin-4,encoded by the geneACTN4on chromosome19 and TRPC6onchromosome 11, areassociated with

autosomal dominantforms of FSGS


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PATHOPHYSIOLOGYcontinued.


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Pathophysiology cont

Decreased plasma oncoticpressure may play a role in

increased hepatic lipoproteinsynthesis, as demonstratedby the reduction ofhyperlipidemia in patientswith INS receiving eitheralbumin or dextran infusions

Patients with nephroticsyndrome are at increasedrisk for thrombosis.

Abnormalities described inINS include increasedplatelet activation andaggregation; elevation infactors V, VII, VIII, and XIIIand fibrinogen; decreased

antithrombin III, proteins Cand S, and factors XI andXII; and increasedactivities of tissueplasminogen activator andplasminogen activator

inhibitor-1.

Decreased levels of Ig G andincreased losses of factor B.


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INVESTIGATIONS

ESTABLISH nephroticsyndrome

Nephrotic rangeproteinuria

Hypoalbuminemia

Hyperlipidemia

Primary orsecondarynephroticsyndromes

If Primary,Whetherin renalfailure?....

Renalfunctions.


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Investigations

Urea creatinine and

electrolytes

CBC

Testing for hep B and C

Complement system

ANA,Anti doublestranded DNAantibodies.

Imaging;U/S abdomenand chest.

X ray chest.Genetic testing.

Renal biopsy


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INTERPRETATIONS

Anemia , raised ureacreatinine,acidosis,hyperkalemia,hyperphosphatemia,indicateChronic renal disease.

Hyponatremia may be due tohyperlipidemia and due towater

retention(pseudohyponatremia.

Raised Hb andhaemetocrat indicateshaemodilution.reducedintravascular volume.Platelet is raised.

Check liverenzymes..forHepatitis B and C.anddo screening forviruses.

MANAGEMENT OF NEPHROTIC SYNDROME


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MANAGEMENT OF NEPHROTIC SYNDROME

A trialof corticosteroids isthe first step intreatment ofidiopathic nephrotic

syndrome (INS) inwhich kidneybiopsy is not initiallyindicated.

patients aged 1-8years with normalkidney function

Normal kidneyfunctions

No macroscopicgross haemeturia

No symptoms ofsystemic disease.

Normal complement

levels

Negative viral screen

No family hisory.


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IMPORTANT DEFINITIONS

RESPONSE; protein free urine on 3 consecutive days within 7days.

RELAPSE; protein +ve urine on 3 consecutive days withinone week with edema.

FREQUENT RELAPSING NS; steroid sensitive nephroticsyndrome with 2 or more relapses in 6 months or more than3 in one year.

STEROID DEPENDANT; responder who relapses whilesteroid is being tapered or within 14 days of stopping steroid

treatment.


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INITIAL NON RESONDER; no response during initial 8weeks of therapy.

LATE NON RESPONDER; an initial steroidresponder who fails to respond to 4 week treatmentin relapse.


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SSNS steroid sensitive nephrotic syndrome

Corticosteroids

INDUCTION THERAPY

Exclude active infectionsand other contraindicationsto steroids

Oral prednisilone60mg/m2/dayeither singleor divided doses for 4weeks.

6 weeks therapy provesbetter .

MAINTAINANCE THERAPY

Oral prednisilone at40mg/m2/day singlemorning dose at alternate

Days for 4-6 weeks.

Longer duration ofmaintenance therapyresults in fewer relapses.


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Relapse therapy

For infrequent relapsessteroid therapy may beresumed at60mg/m2/day untilproteinuria resolves..

Then switch to40mg/m2/day foralternate days for 4weeks.

Other therapy

Pneumococcal vaccines toall the patients.

Diuretic therapy forsymptomatic edema. withfurosamide 2mg/kg/day.

Anasarca with lowintravascular volume,albumin infusion, slow1mg/kg/day can beconsidered.


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HOME MONITORING

Home monitoring of urine

protein and fluid status isimportant.

Parents should be trained tomonitor first morning urine bydipstick.

Record of daily weight,urineprotein and steroid doseshould be kept in log book.

Any increase in urine protein or

daily weight should be reportedas early as possible.


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TREATING FREQUENT RELAPSERS AND SDNS

ALKYLATING AGENTS

CyclophospamideChlorambucilNitrogen mustard

CALCINEURINEINHIBITORS

CyclosporinTacrolimus

LEVAMISOLE MYCOPHENOLATEMOFETIL


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DOSING AND REGIMENS

Cyclophosphamide (22.5 mg/kg daily) is given orally for 8-12 weeks.

Steroids are usually overlapped with initiation of CYPthen tapered

Patients must have weekly CBC counts to monitor forleukopenia.

Patients must also maintain adequate hydration and takeCYP in the morning (not at bedtime) to limit the risk of

hemorrhagic cystitis


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CYCLOSPORIN

CSA can be used in those children who fail to respond to, orsubsequently relapse after, treatment with CYP, or for children whosefamilies object to use of CYP

Initial doses of CSA are started at 56 mg/kg daily divided every

12 hours, adjusted for trough concentrations of 50125 ng/mL

Low-dose steroids are continued for a variable length of time

Kidney function and drug levels must be carefully

monitored due to the risk of CSA inducednephrotoxicity.

Deterrence/Prevention


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Deterrence/Prevention

Yearly influenza vaccination is recommended to prevent seriousillness in the immunocompromised patient, as well as to prevent thispossible trigger of relapse.

Pneumococcal vaccination should be administered to all patientswith INS to reduce the risk of pneumococcal infection. Vaccinationshould be repeated every 5 years while the patient continues tohave relapses.

Routine childhood vaccines with live virus strains arecontraindicated in patients taking steroids and until off steroidtreatment for a minimum of 1 month.

Because of the high risk of varicella infection in the immunocompromisedpatient, in the nonimmune patient, post exposure prophylaxis with

varicella-zoster immune globulin is recommended. Patient with varicella-zoster infection should be treated with acyclovir and carefully monitored

Routine, nonlive viral vaccines should be administeredaccording to their recommended schedules

2 nephrotic-syndrom

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