Challenges Facing the Management of Idiopathic SteroidResistant Nephrotic Syndrome in Children

B Julius M.B. Ch.B (UCT)*

R. Bhimma M.B.Ch.B. (Natal); DCH (SA), FCP (Paeds) (SA), M.Med (Natal),M.D.(Natal), ISN Fellowship (Toronto, Canada), Certificate in PaediatricNephrology (SA)#

E. Naicker M.B.Ch.B. (Wits); DCH (SA); FCP (Paeds), Certificate inPaediatric Nephrology (SA)$

* Registrar in the Department of Paediatrics and Child Health

# Associate Professor of Paediatrics and Child Health, PrincipalPaediatrician and Paediatric Nephrologist at Inkosi Albert LuthuliCentral Hospital

$ Lecturer, Senior Specialist and Paediatric Nephrologist at InkosiAlbert Luthuli Central Hospital

Department of Paediatrics and Child Health

Paediatric Nephrology Unit

Inkosi Albert Luthuli Central Hospital and Nelson R Mandela School ofMedicine

University of KwaZulu-Natal

Durban

South Africa

Correspondence: R Bhimma

Department of Paediatrics and Child Health

Nelson R Mandela School of Medicine

University of KwaZulu-Natal

4013

Tel (Office): 031 260 4351

Fax.: 086 549 5481

E-mail: bhimma@ukzn.ac.za

Need an abstract please. Dear BhimmaHas this article been published elsewhere. If so please obtainpermission to republish in our journal. We will acknowledge them ifpermission is granted

A two and half 2½year old black male presented to the Inkosi AlbertLuthuli Central Hospital paediatric renal unit in June 2009 for primarysteroid resistant nephrotic syndrome (SRNS). On presentation hiskidney function was normal; he was normocomplementaemic, with normalblood pressure and no other significant findings on clinicalexamination. He was initially seen at a peripheral hospital when he wasjust over a year old and diagnosed with NS for which he was commenced onsteroids. Following frequent relapses he subsequently failed steroidtreatment and was diagnosed as having SRNS.

Ultrasound scan done at the Inkosi Albert Luthuli Central Hospitalshowed normal size kidneys, the right measuring 7.7cm and left 8cm inlenghtlength. Both kidneys were isoechoic with poor cortico-medullarydifferentiation. There were no focal lesions, no hydronephrosis, and noperinephric collections. Percutaneous kidney biopsy confirmed focalsegmental glomerulosclerosis (FSGS) with interstitial nephritis. He wassubsequently commenced on pulse methylprednisolone infusions, low doseoral steroids, angiotensin converting enzyme antagonists as well asvitamins ?which ones and folic acid supplements. Albumin withdDiuretics with albumin infusion were used for control of his oedemawhen necessary.

He unfortunately failed to respond to treatment and in April 2010 he wascommenced on tacrolimus but following 6 months of treatment, there wasno response. His kidney function deteriorated and in view of this, histacrolimus and angiotensin converting enzyme antagonist treatment wasstopped. During this hospitalisation he also developed a drip-siteabscesses of his right wrist and left ankle requiring incision anddrainage and a prolonged course of antibiotics.

In view of his deteriorating kidney function and failure to respond tocalcineurin inhibitor therapy (tacrolimus), hHe underwent a repeatkidney biopsy that showed a maximum of nine glomeruli, three glomerulidemonstrating global sclerosis; one glomerulus demonstrating segmentalsclerosis and an increase in mesangial cellularity. There were nobasement membrane spikes or double contours and no hypertensive vascularalterations. The overall glomerular features were compatible with FSGSwith an acute on chronic glomerulonephritis.

Based on the findings of deteriorating kidney function determined bycalculating the estimated glomerular filtration rate (Figure 1), andacute on chronic glomerulonephritis on kidney biopsy, he was commencedon mycophenolate mofetil in combination with low dose oral steroids.Following 8 months of treatment he had worsening kidney function anddeveloped severe anaemia with congestive cardiac failure. In view ofhis poor response to treatment as evidenced by his persistenthypoalbuminaemia (Figure 2) and his severe anaemia, mycophenolatemofetil was stopped. He was subsequently commenced on five doses of pulse methylprednisolonegiven on alternate days and intravenous cyclophosphamide given monthlyfor six months. Despite treatment he remains severely proteinuric, withdeteriorating kidney function that has progressed to Stage IV chronickidney disease with his last estimated glomerular filtration rate being20mls/m2/min (Figure 1). Presently he is being managed conservativelywith chronic anti-renal failure therapy and he will be worked up forrenal replacement therapy.

What therapeutic responses do we have left-? Renal transplant and if notwhat forms of palliative care would you recommend?

IntroductionSteroid resistance nephrotic syndrome (SRNS) is aone of the mostdifficult and challenging diseases to treat in children as to date thereare not sufficient and randomised controlled trials to guide treatment.Patients show a variable response to immunosuppression, adverse effectsof prolonged therapy, and an increased risk of progression to end-stagekidney disease.

Children are classified as having SRNS if they fail to achieve completeremission after 6 weeks of steroid treatment (2mg/kg/day or 60mg/m²perday). During the treatment period the child must be free of infections(e.g. respiratory tract infections, urinary tract infections,peritonitis, cellulitis etc.) as this may result in persistentproteinuria How is this ensured? . SR is classified as follows: initialresistance if there is lack of remission at the first episode of NS orlate resistance if there is an initial response to steroid but thepatient shows SR during a subsequent relapse .

About 10 to 20 percent of children will failure to respond to initialsteroid treatment . Children diagnosed with SRNS (initial or late)should undergo a kidney biopsy before instituting specific treatment.The majority of these patients with idiopathic NS will have focalsegmental glomerulosclerosis (FSGS). The presence of chronictubulotubulo-interstitial changes on histopathology is associated with aworse prognosis. The diagnosis of other histological forms of NS e.g.membranoproliferative glomerulonephritis and membranous nephropathy isimportant, since these patients are managed differently .

About 20% of patients with SRNS will progress to end-stage kidneydisease. Treatment in these patients is aimed at complete resolution ofproteinuria which reduces the complications associated with NS, andresults in preservation of kidney function. Unfortunately to date thereare no therapeutic regimes that consistently meet these aims as isclearly demonstrated in the case above.

Genetics of Steroid Resistant Nephrotic Syndrome

Children with genetics forms of SNRS are usually unresponsive toimmunosuppressive therapy. Single gene defects that affect glomerularpodocyte differentiation and function are responsible for a quarter to a

third of all paediatric cases of SRNS in many parts of the world .Unfortunately there is a paucity of data from Africa. These childrenhave accelerated progression to end-stage kidney disease but rarelydevelop recurrence of disease in the transplanted kidney .

Homozygous or compound heterozygous mutations in genes encoding podocyteproteins include the following:

NPHS1mutations – NPHS1 encodes for nephrin, an integral membraneprotein of the slit diaphragm of the podocyte. Although mutationsof this gene are most often associated with the Finnish type ofcongenital NS, about 10% of children with SRNS who present beforefive years of age will carry on NPHS1 gene mutation .

NPHS2 mutations – NPHS2 encodes for podocin, an integral membraneprotein found exclusively in glomerular podocytes. Homozygous andcompound heterozygous mutations of this gene are most frequentlyfound in children with familial SRNS and less commonly withsporadic SRNS. To date no mutations have been found in childrenwith steroid-sensitive NS . There is a strong regional bias with10 to 30 percent of cases of sporadic SRNS in children in theMiddle East and Europe having this mutation , whereas thefrequency of mutations is low in African-Americans . Thesechildren have early onset of disease, rapid progression to end-stage kidney disease and associated cardiac defects in somecases .

NPHS3 mutations – mutations in the phospholipase (epsilon gene(PLCE1 or NPHS3) are usually associated with congenital NS anddiffuse mesangial sclerosis, but may also occur in older patientswith SRNS .

WT1 mutations – mutations in the Wilm’s tumour suppressor gene hasbeen reported from Europe in both sexesmales (5 percent in malesand 9 percent in females) with sporadic SRNS but no mutations werefound in steroid-sensitive NS . Patients with this mutation withidiopathic SRNS are at increased risks for Wilm’s tumour .

APOL1 gene – variants in this gene in African-American patientsare associated with idiopathic FSGS and HIV nephropathy. Thisgene lies in close proximity to MYH9 gene on chromosome 22 .

Other genes include the following: ACTN4 gene encoding alpha-actinin 4; TRPC6 encoding the transient receptor potential cation

channel 6 and INF2 encoding a member of the formin family ofactin regulating proteins [22].

The above gene mutations are responsible for autosomal dominant NS withFSGS that present in adolescence and young adulthood.

Genetic testingChildren with genetic forms of SRNS are less likely to respond toimmunosuppression. It is therefore important to identify children withgenetic forms of SRNS to avoid undue exposure to immunosuppressivetherapy . Factors that increase the likelihood of a genetic form of SRNSinclude:

Family history of SRNS Onset of NS in the first year of life Parental consanguinity. Syndromic SRNS

In children suspected of having a genetic aetiology for their NS, astep-wise screening approach is recommended given the number ofdifferent gene defects .

Age of presentation- In congenital NS, screening for mutations for NPHS1 should

first be performed followed by NPHS2 mutations. For olderchildren, first screen for NPHS2 mutations.

Presence of extra renal anomalies.- In children with ocular abnormalities screen first for

LAMB2.- In those with ambiguous genitalia, begin with WT1

screening. Histological lesion.

- In children with diffuse mesangial sclerosis onhistopathology, screen for WTI or LAMB2 mutations.

Genetic testing for NPHS1, NPHS2 and WT1 mutations is commerciallyavailable. The National Institute of Health provides a voluntarylisting commercial and academic laboratory throughout the world thatoffers molecular genetic testing.(http://www.ncbi.nim.nih.gov/sites/genestests/lab?dls = gene tests).

Given that over 85% of children with idiopathic NS are steroid-sensitiveand only approximately a third of SRNS children have genetic mutations,only five percent of children with idiopathic NS will have genetic

mutations . Hence currently routine genetic testing for all childrenwith idiopathic NS is not recommended.

Syndromic SRNSNon-renal manifestations are helpful in determining the appropriate geneto test in syndromic forms of SRNS.

WTI mutations are responsible for several hereditary forms of NSincluding Frasier syndrome and Denys-Drash syndrome. Denys-Drash syndrome consists of a triad of progressive kidney diseaseassociated with diffuse mesangial sclerosis, malepseudohermaphroditism, and Wilm’s tumour. Frasier syndrome ischaracterised by the association of male pseudohermaphroditismwith female external genitalia and NS associated with FSGS .

LAMB2 mutations are associated with Pierson syndrome characterisedby ocular manifestations and diffuse mesangial sclerosis .

SMARCAL1 mutations are associated with Schimke syndrome. This ischaracterised by T-cell deficiency, bone dysplasia,cerebrovascular disease and growth retardation. Patients developSRNS with FSGS that progress to end-stage kidney disease .

LMX1B mutations are associated with nail-patella syndrome. Lessthan half of nail patella syndrome patients have clinical kidneydisease characterised by microscopic haematuria and mildproteinuria, typically presenting in adolescence or youngadulthood .

No underlying genetic defects were identified in 50 to 60 percent ofpatients with SRNS in the Middle East and Europe []. The prevalence inother regions of the world, including Africa, is unknown. It ispossible that mutations in unidentified genes may be responsible forsome cases of SRNS .

Management of SRNSApproximately 20% of patients with SRNS will progress to end-stagekidney disease . Since disease prognosis is predicted closely by thelevel and persistence of proteinuria, the main aim is to achievecomplete remission of proteinuria, thereby reducing the complicationsassociated with NS, and preserving kidney function. Even partialremission confers a markedly better prognosis with kidney survival rates

over 90% after 5 -10 years explain what this means?. Genetic forms ofSRNS are usually refractory to all forms of immunosuppressive treatment.

Therapeutic options for SRNS include:

Immunosuppressive therapy: calcineurin inhibitors (cyclosporinand tacrolimus), mycophenolate mofetil, alkylating agents (e.g.cyclophosphamide), azathioprine, sirolimus, and the monoclonalCD19 antibody rituximab. What algorthym determines order of use?

Non immunologic therapy include: angiotensin converting enzymeantagonist and angiotensin receptor blockers.

In resistant cases with persistent hyperlipidaemia, cholesterollowering agent (e.g. HMG Co-enzyme A reductase inhibitors) areused to control hypercholesterolaemia.

Investigational treatments include plasmapheresis , galactoseand zinc but there has not been proven benefit or randomisedcontrolled trials using these agents.

Adequate randomised controlled trials have not yet been reported toprovide sufficient evidence to guide treatment of SRNS . To date theonly multicentre, open labelled, randomised study sponsored by theNatural Institute of Health conducted in the United States comparedcyclosporine versuswith combined mycophenolate mofetil and oral pulseddexamethasone . Proteinuria decreased in both groups with approximately40% achieving complete or partial remission after 1 year. Only 24% ofall 138 patients were still in remission 6 months later. The study waslargely underpowered, raising the possibility of a substantial type II(beta) error. The recommendation of the study was that mycophenolatemofetil with oral pulse dexamethasone be given in patients with baselineimpaired glomerular filtration rate since the cyclosporine group had agreater decline in glomerular filtration rate. This combination shouldalso be recommended in children who become dependent onimmunosuppression to maintain remission as cyclosporine (a calcineurininhibitor) in the long-term is nephrotoxic and withdrawal of treatmentresults in a high rate of relapse is it possible to give exact data forboth statements.

Tacrolimus is a macrolide antibiotic from the fungus Streptomycestsubukaensis . It is similar to cyclosporine, having relatively selective

inhibitory action in CD4 T-helper lymphocytes and is also a more potentsuppressor of pro-inflammatory cytokines . Tacrolimus has been shown todecrease proteinuria in patients who are cyclosporine-resistant, eventhough both agents are calcineurin inhibitors [], although remissionrates between the two agents are similar up to two years . Tacrolimusis associated with a lower relapse rate, fewer cosmetic side effects,and a lower blood cholesterol level please give data .

Oral cyclophosphamide, administered alone or in combination with oralglucocorticoids has limited efficacy in inducing remission .Intravenous cyclophosphamide with tapering doses of glucocorticoid givenmonthly for six doses induces remissions 40% - 50% of patients with SRNS.

Pulse intravenous methylprednisolone used in combination with oralcyclophosphamide reported remission rates of 65% after an averagefollow-up of six years in one study but not in other studies whereresponse rates were in the region of 40% . In some studiesdexamethasone has been used instead of methylprednisolone in view of itscost effectiveness. This form of treatment is still used as first lineintensive therapy in many centres, particularly in developing countries.It ensures compliance, is cost effective and nowadays shows improvedsuccess with the addition of calcineurin inhibitors (unpublished data).

There is limited data in the use of rituximab in SRNS. Several caseseries have reported that rituximab used in combination withglucocorticoids and/or calcineurin inhibitors improves remission ratesin patients with SRNS whilst one study showed no effect . In childrenwith idiopathic nephrotic syndrome, rituximab can maintain short–termremission with withdrawal of prednisone and calcineurin inhibitors.Rituximab can be safely and repeatedly used as a prednisone andcalcineurin inhibitor–sparing therapy in a considerable proportion ofchildren with steroid dependent forms of idiopathic nephrotic syndrome.Further study is needed to identify patients who will benefit most fromrituximab therapy. To date these has been one death due to lungfibrosis reported in a child with NS treated with rituximab. Otherserious adverse effects commonly seen with rituximab therapy includehypertension, fever, serious infections, and progressive multifocalleukoencephalopathy .

Adjunctive therapiesAngiotensin converting inhibitors used alone or in combination withangiotensin receptor blockers have been shown to have anti protein urineeffects, even in the absence of hypertension. In the patients with SRNSwho develop hypertension, these are the preferred agents. Angiotensinreceptors blockers are often substituted for angiotensin convertingenzyme inhibitors in patients who develops side-effects to the latter,such as chronic cough . Both agents have also been shown to haverenoprotective effects by inhibiting pathways of fibrosis and thusslowing progression of kidney disease .

In patients with persistently elevated fasting low-density cholesterol,a low-fat diet together with cholesterol lowing drug therapy isindicated. The most commonly used agents are HMG-CoA reductaseinhibitors and in adults with NS beneficial effects on dyslipidaemia hasbeen shown to impact the progression of chronic kidney disease .

Kidney Disease: Improving Global Outcomes (KDIGO) guidelines formanagement of children with SRNSIn 2012, the Kidney Disease: Improving Global Outcomes (KDIGO),developed guidelines for the management of children with SRNS .

Calcineurin inhibitors together with low dose corticosteroid therapyshould be administered for at least six months. If there is no responseto treatment, calcineurin inhibitor treatment is withdrawn. If there isa response to treatment either complete or partial, treatment iscontinued for at least 12 months. Most patients responded to treatmentwithin 3-6 months. All children should receive angiotensin convertingenzymes inhibitors or, if intolerant, angiotensin receptor blockers.There is no consensus with regard to the optimum duration of treatment.In the case of calcineurin inhibitors, treatment is continued to 2-3years and if biopsy shows evidence of nephrotoxicity, patients may beswitched to less toxic agents such mycophenolate mofetil or rituximab.Patients should be monitored every month until there is response totreatment and thereafter away 2-3 months. Sometimes patients who failin regimen of therapy may respond to another.

For patients unresponsive to the above treatment regimen, mycophenolatemofetil, high-dose pulse steroids, or a combination of the two, isrecommended. Alkylating agents are not recommended for children withSRNS . There is insufficient data to support the use of rituximab. In

developing countries where cost is a major consideration, high dosepulse therapy using methylprednisolone in combination withcyclophosphamide after 2-4 months is used as first line therapy in manycentres or pulse cyclophosphamide given intravenously over six months .

Complications of Nephrotic Syndrome

Complications of idiopathic NS may arise as a result of the diseaseitself or secondary to treatment. In children with secondary forms ofNS, these may include complications of the primary disease causing theNS.

There are several complications directly related to the nephrotic statein children with idiopathic NS or as a complication of treatment. Thecommon ones include inter alia:

Infection

Thromboembolism

Renal impairment

Anasarca

Hypovolemia

Hypercholesterolaemia

Hyperglycaemia

(i) Infection

Factors predisposing to an increased risk of infection in children withNS include:

Reduced serum concentration of immunoglobulin .

Impaired ability to make specific antibodies .

Decreased levels of alternative complement pathway factor Band D .

Immunosuppressive treatment.

The most frequently encountered infections include:

Upper respiratory tract infections.

Urinary tract infections

Peritonitis.

Pneumonia.

Acute gastroenteritis.

Empyema.

Children with NS are at increased risk of developing bacterialinfections, especially with encapsulated bacteria, due in part to lossof opsonizing factors . Ascites and pleural effusions provide a naturalculture medium for bacterial growth thus predisposing to pneumonia,empyema, and peritonitis . Other serious infections includesepticaemia, meningitis and cellulitis .

Common gram positive organisms include Streptococcus pneumonia, Streptococcushaemolyticus and alpha-haemolytic Streptococcus . In developing countries gramnegative organism such as Escherichia coli and Klebsiella pneumonia are alsocommon .

The mortality rate in children with infections primarily due to NS hassignificantly decreased following the use of antibioticsdies andglucocorticoids?? . To prevent serious complications and death frompneumococcal infections, all children with NS should receivepneumococcal vaccine if not previously immunised.

Viral infections, particularly varicella, can cause significantmorbidity and mortality in patients with NS . Vaccination is effectivein preventing varicella infections and for children already infectious,treatment with high dose acyclovir is indicated.

(ii) Thromboembolism

Factors that increase the risk of thromboembolism in children with NSinclude:

Hemoconcentration

Immobility (common in patients with anasarca).

Infection

Hypercoagulable state (due to thrombocytosis; decreaselevels of antithrombin III, decreased proteins, andplasminogen from increased urinary loss; increased plateletactivation, hyperfibrinogenemia; high molecular weightfibrinogen moieties in the circulation) .

The incidence of thrombotic complications is between 2 and 3 percent .Both arterial and venous thrombosis has been reported with common sitesbeing the pulmonary artery, renal vein, deep leg veins, inferior venacava, and femoral iliac artery . Other sites include the cerebral andmeningeal arteries, mesenteric and hepatic veins .

Thromboembolic complications may be associated with significant mobilityincluding pulmonary embolism and renal vein thrombosis . Pulmonaryembolic episodes are usually silent . Many pulmonary embolisms inchildren with NS should be suspected if they present with pulmonary orcardiovascular symptoms and can be confirmed by angiography orradioisotope scanning .

Prophylaxis anticoagulation is not recommended unless the patient has ahigh risk for thrombosis or a previous thromboembolic event. Factorsthat increase the risk for thrombosis include:

Serum albumin concentration less than 2g/dL (20g/L).

Fibrinogen greater than 6g/ L.

Antithrombin III level less than 70 percent normal.

(iii) Acute Kidney Injury

Children with NS can have reduced glomerular filtration rate because ofone or more of the following mechanisms:

Hypervolaemia.

Glomerular injury due to the underlying glomerularpathology.

Progression to chronic kidney (I-IV) leading to end-stage kidney disease(stage V) occurs in some patients, especially in childrenwith SRNS.

(iv) Anasarca

This is associated with the following complications:

Scrotal or vulvar oedema resulting in inability to walk.

Large pleural effusions and/or ascites leading to impaireddiaphragmatic moment resulting in respiratory distress.

(v) Hypovolemia

This is most common in children with minimal change disease resulting ina decrease glomerular filtration rate. Clinical signs includedtachycardia, signs of peripheral vasoconstriction (cold, clammyperipheries with reduce volume pulses), and oliguria. Laboratoryfindings include raised plasma renin, aldosterone, and norepinephrinelevels . Typically hypovolemia occurs during the first presentation ora severe relapse. Overzealous use of diuretic, sepsis andgastroenteritis can lead to hypotension and, if severe, shock.

(vi) Growth

Children with NS can develop growth retardation due to:

a) Malnutrition

b) As a complication of long-term steroid treatment

(v) Hypercholesterolaemia

Total serum lipids (including cholesterol and triglycerides) areelevated with the increase in serum cholesterol inversely correlated tothe serum albumin concentration. Dyslipidaemia is an expected findingin children with NS and resolves when patients are in remission .Children with SRNS often have persistent dyslipidaemia. In adultpatient, persistent dyslipidaemia has been associated with prematureatherosclerosis and an increased risk of coronary artery disease.

(vii) Hyperglycaemia

Hyperglycaemia is not a complication of NS per se but related to the useof steroids especially in combination with calcineurin inhibitors(particularly tacrolimus).

Diet in nephrotic syndrome

During relapses, patients should have a sodium restricted, no addedsalt, diet. Once in complete remission, this can be stopped. Inpatients with anasarca, fluids must be restricted, but the patients mustbe carefully monitored for excessive intravascular volume depletion.Protein restriction is only implemented in patients with severe acutekidney injury or chronic kidney disease when severe azotaemia ispresent. This must however not be to the detriment of growth.

Activity

Most children with NS can be managed on an ambulatory basis and normalactivity is recommended for admission includes:

Anasarca, especially when resistant to outpatient therapy and/oraccompanied by respiratory compromise, massive ascites, orscrotal/perineal or penile oedema.

Severe hypertension. Anuria or oliguria > 24 hours. Severe acute kidney injury. Infections such as septicaemia, peritonitis chest infections, etc.

Vaccines in nephrotic syndrome

Routine childhood immunisation is safe in all children with NS inremission live virus strains are contraindicated during steroid therapyand for a minimum of one month afterwards . Care must be taken inchildren with frequently relapsing NS who may need to restart steroidtreatment shortly after vaccination. Pneumococcal vaccine recommendedat first presentation and should be repeated every 3-5 years while thepatient continues to have relapses. Yearly influenza vaccination isrecommended to present serious illness in the immune compromised patientand present relapses following infection. Varicella vaccine is safe inchildren with NS in remission and one month after steroid treatmentpost-exposure prophylaxis with varicella-zoster immunoglobulin is

recommended in the non-immune patient. Patients contracting theinfection should be treated with acyclovir and carefully monitored .

Long-term monitoring

Ambulatory monitoring of the child's condition and response to treatmentis a very important aspect of the overall management of NS. Homemonitoring of urine protein and fluid status is an important aspect ofmanagement. Parents and/or caregivers should be trained to monitorfirst morning urine proteins at home with urine dipstick. Weight shouldbe checked every morning as well and a home logbook should be keptrecording the patient’s daily weight, urine protein, and steroid dose ifthe child is receiving steroids.

Families and patients are instructed to call for any oedema, weightgain, or urine dipsticks testing 2+ or more for protein for more than 2days. Rapid detection of relapse of proteinuria by home testing ofurine can allow early initiation of steroid treatment before oedema andother complications develop. Urine testing at home is also useful inmonitoring response (or nonresponse) to steroid treatment.

Is there any role for transplant in these children?

Conclusion

Childhood NS is one of the commonest forms of kidney disease and SRNSposes the greatest challenge to those caring for children with NS.Optimally this condition should be managed by a team of experts preparedto provide on-going care to these children. To date there are notsufficient and randomised controlled trials to guide treatment of SRNS.Complications of the disease that arise during relapses as well as fromthe treatment require an anticipated approach to management. Treatmentguidelines proposed for the management of this disease and itscomplications are aimed to assist those caring for these patientsalthough more large randomised trials are needed to provide evidencebased validation of treatment protocols.

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Figure 1: Estimated glomerular filtration rate in mls/1.73m2/min usingthe modified Swartz transformation formula for creatinine inchildren during the course of the disease in the patient.

Figure 2: Serum albumin levels in mmol/l during the course of thedisease in the patient.