7/19/14 9:18 AMClinical Practice Guidelines : Nephrotic Syndrome

Page 1 of 4http://www.rch.org.au/clinicalguide/guideline_index/Nephrotic_Syndrome/

Nephrotic Syndrome

This guideline has been adapted for statewide use with the support of the Victorian Paediatric ClinicalNetwork

See also BSA & Steroid Dose Calculator(/uploadedFiles/Main/Content/genmed/clinical_resources/BSA_and_prednisolone_dose_calculator.xls)

BackgroundNephrotic syndrome is a clinical disorder characterised by heavy proteinuria, hypoalbuminaemia andoedema90% of children will have Idiopathic Nephrotic Syndrome, either minimal change disease (85%), or FocalSegmental Glomerulosclerosis (10-15%)

Idiopathic Nephrotic Syndrome (INS) – 90% of children(for which this guideline applies)Minimal change disease (MCD)Focal segmental glomerulosclerosis (FSGS)

Non-idiopathic Nephrotic Syndrome - rare (discuss with nephrology if features)Secondary

Systemic Lupus Erythematosis (SLE), Henoch Schonlein Purpura (HSP),Membranoproliferative Glomerulonephritis (MPGN)

Membranous nephropathyCongenital nephrotic syndrome

The key acute complications of nephrotic syndrome are hypovolemia, infection and thrombosisAlthough in 80-90% of cases INS will respond to initial steroid therapy (hence called ‘steroid-sensitivenephrotic syndrome’, SSNS), children with SSNS have an 80% chance of having one or more relapsesand approximately 50% of these children will have frequent relapses.

Thus, the first admission is an important opportunity to educate families about home monitoringand management (see ‘Family Education’, below), knowing that they will be likely to have one ormore relapses

AssessmentOedema is the primary presenting feature. History can also include weight gain, poor urine output,dizziness, or discomfort as a result of the oedema (including abdominal pain). Degree of oedema ranges from:

Mild (subtle peri-orbital region, scrotum or labia) Moderate with peripheral pitting oedema of the limbs and sacrum. Severe with gross limb oedema, ascites and pleural effusions.

In the child with oedema, confirm the diagnosis of nephrotic syndrome with Heavy proteinuria (dipstick 3-4+ or urine protein/creatinine ratio >0.2g/mmol)

Hypoalbuminaemia (<25g/L). Other causes of generalised oedema include liver disease or protein losing enteropathy (leadingto hypoalbuminaemia) or congestive cardiac failure.

Assess for features suggesting not INS Age <1y or >12y Systemic symptoms of fever, rash, joint pains (SLE). Persistent hypertension (can have mild hypertension first 1-2 days)

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Rule out any nephritic features (requiring entirely different management) Macroscopic haematuria (INS may have microscopic haematuria) Hypertension Raised serum creatinine (INS may have mild elevation with mod-severe volume depletion)

Assess for severity and complications of INS Intravascular volume depletion

Although patients are invariably oedematous, they can be concurrently intravascularvolume deplete Clinically

Dizziness, abdominal cramps Peripheral hypoperfusion (cold hands or feet, mottling, capillary refill time > 2seconds), tachycardia, oligoanuria, low urinary sodium, hypotension (late sign)

Severe/symptomatic oedema – potential skin breakdown/cellulitis, gross scrotal/vulval oedema,increased work of breathing from pleural effusion Infection (at increased risk in nephrotic state)

Cellulitis from gross oedema with skin compromise Spontaneous bacterial peritonitis – abdominal pain, fever, nausea/vomiting, reboundtenderness

Thrombosis (at increased risk in nephrotic state) Deep vein thrombosis, pulmonary embolus Renal vein thrombosis – macroscopic haematuria, palpable kidney, loin tenderness, raisedcreatinine, hypertension Cerebral vein thrombosis - headache, vomiting, impaired conscious state or focalneurology

Investigations:Urine

Dipstick (proteinuria)Microscopy (quantify any haematuria)Spot protein: creatinine ratio

For quantification of proteinuria with correction for urinary concentrationAlso useful if lack of response to steroids (compare initial result to later results for trend)

Sodium if required (to confirm intravascular volume depletion if clinically unclear. Less than10mmol/L consistent with volume depletion)

BloodFBCUECr, LFT (albumin)Immunology

C3 and 4 (low in SLE and MPGN)ANA (SLE)

Hep B if risk factors on history (secondary cause of membranous nephropathy)Varicella serology (so serostatus known while immunosuppressed in case of contact)

Management Admitting unit based on hospital policy. Paediatric nephrology consultation recommended if:

Age <12 months or >12 yearsPersistent hypertension +/- persistent microscopic hematuriaElevated creatinine despite correction of any hypovolemiaC3 or 4 below normal rangeUnclear if nephrotic versus mixed nephritic-nephrotic (e.g. macroscopic haematuria, intravascular fluidoverload with hypertension, renal impairment)Steroid resistance (Failure to achieve remission despite 4 weeks of prednisolone)

Treatment for INS1. Admit to hospital on first presentation.2. Manage the oedematous state

a. No added salt dietb. Daily weights, daily urine dipstickc. Strict fluid balance with close attention to volume status

Discuss with nephrology if severe, difficult to control oedema

d. Intravenous 20% albumin (with Frusemide) 1. There are 2 indications (see above for details)

a. Intravascular volume depletion

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b. Severe or symptomatic oedema

2. It should only be given in consultation with the treating consultant, and ideally in daytimehours (risk of hypertension and pulmonary oedema), unless severe oedema or depletion –very rarely indicated.

3. 20% albumin 5ml/kg (1g/kg) over 4-6hrs IV.1. Give frusemide 1mg/kg (max 40mg) mid infusion2. If giving for severe/symptomatic oedema, repeat frusemide 1mg/kg (max 40mg) at

end of infusion, unless already has had brisk diuresis or signs of peripheralhypoperfusion

3. Larger doses of frusemide are sometimes given if poor response

3. Prophylaxis against complicationsOral penicillin V (phenoxymethylpenicillin) at a prophylactic dose 125mg/dose 12 hrly if under 5years, or 250mg/dose 12hrly if over 5 years. Phenoxymethylpenicillin is to continue until oedemasubsides.

i. If the child is profoundly ill or appears to have sepsis use IV Ceftriaxone 50mg/kg/dose 24 hrly (max 2g)

Ranitidine 2-4mg/kg/dose 12 hrly (max 150mg per dose) or a proton pump inhibitor asprophylaxis for prednisolone induced gastritis

4. Prednisolone: to induce remission, followed by a slow wean to reduce risk of relapse. Consult withpaediatric nephrology if remission not achieved after 4 weeks of prednisolone. BSA & Steroid Dose Calculator(/uploadedFiles/Main/Content/genmed/clinical_resources/BSA_and_prednisolone_dose_calculator.xls)

60 mg/m2 per day as a single dose (max 60 mg/day) for 4 weeks. Then:40 mg/m2 alternate day (max 40mg) for 4 weeks.20 mg/m2 per alternate day for 4 weeks.15 mg/m2 per alternate day for 4 weeks.10 mg/m2 per alternate day for 4 weeks.5 mg/ m2 per alternate day for 4 weeks.

5. Family Educationa. The family should be taught to test urine protein each morning

a. These can be documented in the booklets produced by the nephrology department, whichalso contain information on INS. Printable forms for documentation are available here:NEPH DEPT BOOKLET (PDF)DIARY FOR ENTERING PROTEIN LEVEL(/uploadedFiles/Main/Content/clinicalguide/Proteinuria record.docx)

b. After remission, the urine protein should still be checked and documented daily (for at least 1-2years), in order to identify a relapse (defined as 3+ or 4+ protein for 3 consecutive days), atwhich point the family should contact their treating clinician

a. This allows for re-institution of prednisolone prior to the onset of oedema, thus avoidingthe associated consequences (admission, risk of sepsis, thrombosis).

b. Weight should also be checked daily while nephrotic (as a sign of fluid accumulation).

c. It is important to convey that, though their child will likely respond to therapy, they will likely haverelapses (80% chance)

d. The most common relapse trigger is intercurrent infection. In patients on weaning or maintenancealternate day prednisolone, the risk of relapse can be reduced by temporarily increasing the dosefrom alternate to every day for 3-5 days.

Treatment of relapsesA relapse is defined as proteinuria 3+ or 4+ for 3 consecutive days, and should prompt re-introductionof full dose prednisolone:

Prednisolone 60 mg/m2 per day until urine protein is 0, trace or + for 3 consecutive days.Then weaning regimen:

40 mg/m2 alternate day for 2 weeks.20 mg/m2 alternate day for 2 weeks.15 mg/m2 alternate day for 2 weeks.10 mg/m2 alternate day for 2 weeks.5 mg/m2 alternate day for 2 weeks.

The total time of weaning regimen can be shortened if the patient relapses infrequently (2 – 3 relapses inany 12 month period) and responds to treatment quicklyIf oedema recurs, penicillin prophylaxis should also be restarted.

Additional issues with relapsing or steroid dependant diseaseIncreased infection

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Children with relapsing or persistent nephrotic syndrome qualify for the additional boosterPrevenar (pneumococcal conjugate vaccine), and the Pneumovax (23-valent pneumococcalpolysaccharide vaccine), timing as per schedule.

Vitamin D deficiency (loss in urine)HyperlipidaemiaHypothyroidism (loss in urine)Bone density and eye examination for cataracts should be monitored in patients on prolongedmaintenance steroid therapy.

Consider if >12m continuous therapy

Ongoing reasons for referral to nephrology

Frequent relapses (2 or more in first 6 months or 4 or more in any 12 month period)Steroid dependant (relapses while taking steroids – or within 2 weeks of cessation)Steroid toxicity prompting consideration of alternative agent.

For advice and inter-hospital (including ICU level) transfers ring the Sick Child Hotline: (03) 9345 7007

Parent information sheet: Nephrotic Syndrome booklet(/uploadedFiles/Main/Content/clinicalguide/130561 SCOTT Nephotic Syndrome booklet A5_LR.pdf)

Information Specific to RCH – Including who to consult for inpatients.Specimen collection and results

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Last updated 16 April 2014.