Childhood nephrotic syndrome: Diagnosis and managementAshara Heshani Group 24KSMU 2015

OverviewNephrotic syndrome in childrenIntroduction, definitionClinical presentationInvestigationsReferral to a paediatric nephrologistManagementConclusions (Practice points)

IntroductionNephrotic syndrome (NS)Commonest glomerular disease affecting childrenFrequently encountered in general paediatricsCharacterised by Significant proteinuria (early morning urine protein to creatinine ratio > 200mg/mmol) leading to Hypoalbuminaemia (plasma albumin of < 25g/l)

IntroductionNS defined by the clinical triad of OedemaNephrotic range proteinuria and HypoalbuminaemiaTypically accompanied by Dyslipidaemia with elevated plasma cholesterol and triglycerides

IntroductionNS can be Congenital or acquiredCongenital disease May be due to a genetic mutation or secondary to a congenital infectionAcquired disease More common and is usually idiopathicCategorised according to the response to corticosteroid treatment as Either steroid sensitive or steroid resistant disease

IntroductionAcquired nephrotic syndrome Idiopathic (primary) or Secondary (table hereunder)

Clinical presentationHistoryTypically children present because of oedemaInitially in a peri-orbital distribution and many children are initially diagnosed with an allergic reactionthe lower limbs and genital area swollen later in the day as extracellular fluid accumulates and edema develops in the dependent areas.Often history of a preceding viral infectionThe duration of symptoms variable and a past history of atopic disease is present in 30-60% of childrenThe vaccination history and previous varicella infection should be notedAbout 3% of children will have an affected parent or sibling and If there is a family history the disease is likely to follow a very similar pattern

Clinical presentationHistoryOften upper respiratory tract infection and, with onset of oedema, children will be LethargicIrritable and have Poor appetite, and may have Diarrhoea and Abdominal pain

Clinical presentationExaminationDocumentHeightWeightBlood pressure, Capillary refill time, Heart rateEvidence of pleural effusions, ascites, peripheral, scrotal or sacral oedema.The assessment of intravascular volume is important sinceHypovolaemia is a common finding and is the leading cause of mortality and morbidity in these children

Clinical presentationExaminationDocument the following; height, weight, blood pressure, capillary refill time, heart rate, evidence of pleural effusions, ascites, peripheral, scrotal or sacral oedema.The assessment of intravascular volume is important since hypovolaemia is a common finding and is the leading cause of mortality and morbidity in these childrenThe following are recognised markers of hypovolaemia: capillary refill time >2 seconds, toe-core temperature gap >2C, hypotension, persistent tachycardia and abdominal pain. Since assessment of hypovolaemia can be difficult a urinary sodium can be useful with a urine Na

Clinical presentationDifferential diagnosesAt presentation it is important to consider the differential diagnosis of a child presenting with oedema. These include Acute nephritis (hypertension, oliguria, oedema) or Renal failure (abnormal plasma creatinine) and Non-renal causes of oedema such as Protein losing enteropathy, Severe cardiac failure,Chronic liver disease

NS: InvestigationsThe purpose of investigations in NS is (1) to confirm the clinical diagnosis; (2) to seek a possible cause; (3) to assess renal function; and (4) to identify biochemical disorders related to the nephrotic state

NS: InvestigationsChildren presenting with typical features of NS will require minimal investigations

NS: InvestigationsThe finding of heavy proteinuria (34+) on dipstick and oedema in a child usually means a diagnosis of NSProteinuria needs to be quantified as the protein: creatinine ratio or per litre of urineTwenty-four hour urine collections are impractical and unnecessary in most children with NS; instead proteinuria is usually measured on first morning spot voids

NS: InvestigationsSome relevant laboratory findings

NS: InvestigationsIndications for kidney biopsy

Referral to a paediatric nephrologistMost children with MCNS will respond to steroids and not require a renal biopsy at presentation\However, if any of the following features are present, there is the possibility of an alternative diagnosis (less likely to respond to steroid therapy)and children should be referred to a paediatric nephrologist:Age 12yrHypertensionRenal impairmentMacroscopic haematuriaDecreased C3 complementRash or arthropathyPrimary steroid resistance (failure to go into initial remission with 60mg/m2 steroids for 28 days)

Referral to a paediatric nephrologist

Referral to a paediatric nephrologistMicroscopic haematuria may be present in up to 25% of children with steroid-sensitive NS and should not be a contraindication to empirical steroid therapy

Some important clinical questionsEstimation of dry weight. Is the childs weight known prior to onset of NS? How much oedema has the child? 1 kg = 1 L? 3 kg = 3 L? Or more?Is the child euvolaemic or hypovolaemic? This simple question can be difficult to answer clinically. Methods of assessing circulating volume are listed in Table in next slide.

Some important clinical questions

Some important clinical questions3. Does this child need volume expansion?

4. Does this child need diuretics or ACE inhibitors?

5. Does this child need antibiotic prophylaxis?

ComplicationsBefore the introduction of appropriate medical treatment as many as 30% of patients died from NS Complications of NS include:HypovolaemiaInfectionThrombosisWith careful modern management most children should expectNot to experience hypovolaemia, thrombosis or serious infection

ManagementAll children presenting with their first episode of NS should be admitted to hospital for Diagnostic assessmentNursing and medical management, and Parental educationWe will first cover General management and then the use of prednisolone or equivalent

ManagementRoutine nursing management includes:Semi-quantification of urine protein losses (dipsticking all urine specimens)Daily weighingPulse and blood pressure monitoringPrevention of infection and appropriate isolationCareful fluid balance with recording of oral/parenteral input and measurement of urine outputParental information, education, support and reassuranceMaintaining child mobility and morale

ManagementFluid balance, hypovolaemia and blood pressureA no added salt diet is appropriate measureIf hypovolaemia is present it should be promptly corrected with administration of 1020 ml/kg of 4.5% albuminDiuretics are used in some cases to help control the oedema until remission begins, e.g. frusemide at 2 mg/kg/24 hThe use of diuretics should be reviewed on a daily basis and the patients electrolytes should be checked regularly

ManagementFluid balance, hypovolaemia and blood pressureTwenty per cent albumin in combination with diuretics is used in centres to relieve severe symptomatic oedema: 0.51.0 g/kg of 20% albumin can be given slowly over 46 h and 0.51 mg/kg of frusemide given at the end or mid way through the infusionRapid administration should be avoided to prevent intravascular volume overloadTwenty per cent albumin should never be used to correct low serum albumin levels

ManagementFluid balance, hypovolaemia and blood pressureHypotension is a sign of severe hypovolaemia and should be quickly addressedHypertension may also occur in the acute phasePersistence of hypertension in the absence of hypovolaemia warrants referral to a paediatric nephrologist

Management of edema in patients with nephrotic syndrome

Patients requiring high-dose frusemide or addition of other diuretics should be under close supervision, preferably in a hospitalMonitoring of serum electrolytes is necessary in all patients receiving diureticsPatients showing hypokalemia require potassium supplements or coadministration of spironolactone. The medications are reduced stepwise once diuresis ensues. *Management of hypovolemia consists of rapid infusion of normal saline at a dose of 15-20 ml/kg over 20-30 min; this may be repeated if clinical features of hypovolemia persist. Infusion of 5% albumin (10-15 ml/kg) or 20% albumin (0.5-1 g/kg) may be used in subjects who do not respond despite two boluses of saline

ManagementInfectionStreptococcus pneumoniae and Gram-negative organisms are the commonest pathogens causing possible peritonitis, septicaemia and cellulitisProphylactic oral phenoxymethylpenicillin (12.5 mg/kg twice daily) administration is recommended while the child is oedematous and Any suspected infection should be promptly treated with broad-spectrum antibiotics while awaiting culture

Clinical features and management of infections

ManagementMobilizationBed rest may increase the risk of venous thrombosisEncouraged to mobilize as normal DietAs mentioned above, a no added salt diet is advisable in view of the salt and water overloadNo evidence for use of a high protein dietEncouraged to have a normal healthy diet

ManagementParent informationParents need a clear explanation of the diagnosis of NS, its implications for the future and the importance of compliance with medication.Side effects of medications must also be clearly explained.Families should be provided with written information

ManagementParent informationParents need to be taught how to do urinalysis for home testing.They should keep a clear record of daily urinalysis and medications givenIt is important that parents know to contact the appropriate medical staff in the case of a relapse, intercurrent illness or exposure to varicella infection (when nonimmune)

ManagementImmunizationLive vaccines should not be given to immunosuppressed childrenChildren with steroid-sensitive nephrotic syndrome are considered immunosuppressed if they have received daily steroids for greater than 1 week in the previous 3 monthsA live vaccine can however be given if the child is on a low dose alternate day regimen

ManagementCorticosteroid therapyThe International Study of Kidney Disease in Children (ISKDC) demonstrated that in MCNS the majority of children will respond to steroids with 95% of children going into complete remission following an 8 week course of high dose steroids

Definitions related to NS

Definitions related to NS

ManagementISKDC regimen of steroids gold standard for three decadesAn eight week course of oral steroids(prednisolone) starting at 60mg/m2 daily for 4 weeks followed by 40mg/m2 on alternate days for the next 4 weeks

Management

Management

Management

ManagementIn view of lack of consensus regarding the most appropriate therapy, the Expert Group accepts that the choice of initial treatment shall continue to depend on the preference of the physician and the cost of medicationsThere is a lack of consensus on the most appropriate first line therapy for children with SRNS, with many of the regimens extrapolated from studies in adults.

Management

ManagementThe wide range of options available for the pharmacotherapeutic management of NS and the lack of evidence about the comparative efficacy and safety of the different therapeutic strategies, make its positioning rather difficultTherefore each hospital needs to draw up protocols based not only on the small amount of evidence available, but also on the Authorized indications, availability of the drugs, clinical experience, associated costs, and patient preferences with regard to the duration of treatment, incidence and type of adverse effects

ManagementDevelopment of new randomized controlled trials should be encouraged and setting up national plans for the treatment of this pathology might be a good approach for this problem

ManagementThe vast majority of children with MCD will outgrow NS with normal kidney functionIn the interim, Paediatricians need appropriately to care for these children, support their parents, and ensure that NS does not metamorphose into the neurotic syndrome

Conclusions