nephrotic $ case study

8/12/2019 Nephrotic $ Case Study

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(A study in pediatric department


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Abstract:Background:

Children with nephrotic syndrome may have one or more relapse. These are diagnosed i

there is +++ or ++++ proteinuria for 3 or more days. Urine should be checked initially

twice weekly, then weekly after the first episode, and the families instructed to get i

contact should a relapse of proteinuria occur, or if there is ++ for more than 1 week. The objective of this study was to identify predictors of relapse and determine th

predictive score for relapse. Ninety-nine children with nephrotic syndrome visiting thpediatric nephrology outpatient clinic in Al- Kadhmia teaching hospital from 2010 to 201

were studied. This study was retrospective study. According to age ,5% ofpatients wer

N.S. less than 1 year , 17.5 % of patients were N.S. between 1-5 years & 77.5 % o

patients were N.S. equal or above 5 years. Regarding gender, 62.5 % patients wer

males while 37.5 % were females. Regarding relapses, 55 % of the patients ha

frequent relapse while 45 % of the patients had infrequent relapse. 65 % of th

patients were steroid sensitive, 35 % of the patients steroid resistant. In this study th

majority of patients were equal or more than 5 years, male, living in rural area, withonset between 1-5 years, steroid responsive, frequent relapse, having a follow up

between 1-2 years & having MCD on renal biobsy

Aim of study:1-Study demographic characteristics in patients with N.S. regarding age, gender &

residency

2-Study the characteristics of N.S. in those children regarding onset of the disease frequency of relapses & type of N.S. according to steroid sensitivity

3-Study the duration of follow up in patients with N.S.4-Study renal biopsy findings in patients with N.S.5-Study the atypical features in patients with N.S.


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Introduction:

Nephrotic Syndrome (NS) is a common childhood illness characterized by massiv

proteinuria, hyperlipidemia, hypoalbuminemia & edema. NS is a disease of relapse and it i

a major problem to manage the cases with frequent relapse. So it is very important to fin

out such children who are prone to develop frequent relapse

The observations that nephrotic syndrome, some was responsive to corticosteroids othernot and that its clinical course could be characterized by remission and relapse led t

several further observations that remain highly relevant to both the treatment and prognosi

of nephrotic syndrome today.

DEFINITIONS(1)

1. NEPHROTIC SYNDROME:

Oedema, serum albumin < 25 g/l, proteinuria > 40 mg/m2/hour or urine protein creatininratio > 200 mg/mmol.

2. REMISSION:

Urinary protein excretion < 4 mg/m2/hour or urine dipstix nil/trace for 3 consecutive days.

3. RELAPSE:

Urinary protein excretion > 40 mg/m2/hour or urine dipstix ++ or more for 3 consecutiv

days.

4. FREQUENT RELAPSES:

Two or more relapses within 6 months of initial response or four or more relapses within

any 12 month period.

5. STEROID DEPENDENCE:

Two consecutive relapses occurring during the period of steroid taper or within 14 days o

its cessation.

6. STEROID RESISTANCE:

Failure to achieve remission in spite of 4 weeks of standard prednisolone therapy


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EPIDEMIOLOGY

The annual incidence of nephrotic syndrome in most countries in the Western Hemispher

is estimated to range from 2 to 7 new cases per 100,000 children(2,3,4)

and the prevalence i

about 16 cases per 100,000 children(4)

. There is a male preponderance among youn

children, at a ratio of 2:1 to females, although this gender disparity disappears by

adolescence, making the incidence in adolescents and adults equal among males and

females (5, 6, and 7). The incidence of nephrotic syndrome has been fairly stable over the las

30 years, but there are suggestions that the histopathologic patterns may be changing. Fo

example, reports from different parts of the world indicate an increasing occurrence of focasegmental glomerulosclerosis (FSGS) not only after adjusting for variations in renal biops

practices but also based on then generous assumption that all patients who did not have

renal biopsy had minimal change nephrotic syndrome (MCNS)(5, 6, and 7)

. The incidence an

the histologic pattern of nephrotic syndrome are also affected by geographic location an

ethnic origin.

In this same study the authors found that although only 11% of Hispanic and 18% oCaucasian patients with nephrotic syndrome had FSGS, 47% of African American children

had this less favorable diagnosis(6)

. Age also correlates with both the frequency opresentation and the biopsy fi ndings associated with nephrotic syndrome.

The most common age for presentation is 2 years, and 70% to 80% of cases occur in

children younger than 6(2, 3)

. To some extent age also predicts the histologic lesio

associated with nephrotic syndrome. Children diagnosed before age 6 represented 79.6% o

those with MCNS compared with 50% of those with FSGS and only 2.6% of those with

membranoproliferative glomerulonephritis (MPGN)(8)

. When these data were analyzed o

the basis of renal histology, the median ages at presentation were found to be 3 years foMCNS, 6 years for FSGS, and 10 years for MPGN

(8). Thus excluding the fi rst year of life

these data combined suggest that the likelihood of having MCNS decreases with increasin

age, whereas the likelihood of having the less favorable diagnosis of FSGS or MPGN

increases(8, 9)

.

The histologic lesion associated with nephrotic syndrome has important ramifications fo

the likelihood of response to steroid treatment. Although almost 80% of children diagnose

with nephrotic syndrome in a multicenter International Study of Kidney Diseases i

Children (ISKDC) study entered remission following an initial 8-week course usin

prednisone, when these children were analyzed based on histology, steroid responsiveneswas found in 93% of those with MCNS compared with only 30% of those with FSGS an

7% of those with MPGN(8, 10)

. In addition to histology, response to steroids also varies wit

geographic location and ethnicity. Whereas 80% of children in western countries will b

steroid responsive, studies from South Africa, Nigeria, and more recently Ghana show tha

only 9% to 50% of children with nephrotic syndrome are steroid responsive(11,12,13)

. Failur

to respond to steroid treatment has important ramifications for the risk of developin

progressive renal failure later in life. In a multicenter evaluation of 75 children with FSGS


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it was found that within 5 years after diagnosis, 21% had developed ESRD, 23% had

developed CKD, and 37% had developed persistent proteinuria, whereas only 11%

remained in remission (14)

. Thus once a child is given the diagnosis of FSGS, the risk fo

development of CKD or ESRD within 5 years is almost 50%.

ETIOLOGY

Nephrotic syndrome in childhood is largely primary or idiopathic, although a smal

proportion of cases are secondary to infectious agents and other glomerular and systemi

diseases. The etiology of nephrotic syndrome is also age dependent. Most cases appearin

in the first 3 months of life are referred to as congenital nephrotic syndrome (CNS) and ardue to genetic diseases. Although there has been no systematic study of the etiology o

nephrotic syndrome presenting in the rest of the first year of life (3 to 12 months), there ar

data suggesting that up to 40% of cases during this time may also be due to genetic cause(15)

. Beyond the first year of life and in the first decade, most cases are due to primary o

idiopathic nephrotic syndrome, whereas the proportion of secondary nephrotic syndrom

cases increases beyond the first 10 years of life (figure 1).


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Figure 1: Etiology of Nephrotic syndrome (16)


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Pathophysiology of the Nephrotic Syndrome

In addition to excessive loss of protein in the urine, the hallmarks of the nephrotic

syndrome include depression of certain serum proteins, edema formation, and a rise in

serum lipids. Loss of protein in the urine is the basic defect, and the fall in serum protein

production of edema fluid and hyperlipidemia stem from it (Fig. 2). Hypoalbuminemia i

the nephrotic syndrome is owing to the combination of increased urinary loss and increased

catabolism of albumin, chiefly in the kidney(17)

. The liver reacts to the low serum albumi

levels by increasing albumin synthesis, but in the nephrotic syndrome, the response i

inadequate(17)

. The hypoalbuminemia then leads to both hyperlipidemia and edem

formation.

Figure 2: Pathophysiology of edema (16)

Hyperlipidemia in the nephrotic syndrome stems from several different mechanisms. Ahigher level of low-density lipoprotein (LDL) cholesterol is the principal alteration in th

lipid profile, with increases chiefly in very low density lipoproteins (VLDL) an

apolipoproteins B, C-II, and C-III(18,19,20,21)

. The increase in apolipoprotein B is probably

related to both hypoalbuminemia and changes in colloid oncotic pressure. The increase inLDL and VLDL is not related to increased synthesis. Rather, it is owing to decrease

catabolism secondary to decreased binding of lipoprotein lipase to endothelial cells(19,22)

, t

reduced clearance of VLDL, and to a decrease in the VLDL receptor. In addition, lecithin


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cholesterol acyl-transferase is lost in the urine so that there is limited uptake of surplu

cholesterol (21). High-density lipoprotein (HDL) cholesterol shows little change so that th

LDL/HDL is increased. Triglycerides are thought to increase by augmented synthesis(23)

o

decreased catabolism(22)

. Lipoprotein a [Lp(a)] is increased by synthesis alone. Th

increased synthesis of fibrinogen, transferrin, albumin, and apoA-1 is regulate

transcriptionally(19)

.

Edema formation is the symptom of the nephrotic syndrome that usually brings the patien

to clinical attention. Two possible mechanisms of action may contribute to the productio

of edema. The classic mechanism, now known as the underfill hypothesis, may manifest in

patients with low plasma volume and is usually seen in children with MCD(24, 25)

. In thi

instance, hypovolemia is the primary stimulus driving the kidney to retain sodium andwater and eventually resulting in edema formation as the result of the Starling forces (Fig

3).

Figure 3: hypothesis of nephrotic syndrome

However, most patients with the nephrotic syndrome are either normovolemic o

hypervolemic. Thus, the overfill hypothesis was constructed. According to this theory

sodium retention by the kidney is primary. Sodium retention leads to increased bloovolume and results in increased blood pressure. These changes then lead to alterations in

the Starling forces, which result in edema. Several factors result in sodium retention. Th

fall in colloid osmotic pressure results in decreased Kf, causing decreased sodium filtration

Distal tubular injury causes resistance to atrial natriuretic peptide, resulting in decreasenatriuresis

(26). Chronic tubulointerstitial disease is associated with decreased GFR an

sodium retention(24)

. Recent studies have shown that albumin directly stimulates th

sodium hydrogen exchanger 3 (NHE3) in the proximal tubule with increased sodium


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retention. Rostoker et al(27)

showed abnormal capillary permeability in patients with

nephrotic syndrome that resolved with steroid therapy. They proposed that a cytokine o

other vascular permeability factor might be responsible. In any case, such increased

vascular permeability could lead to edema.

History and Physical Examination

The clinical diagnosis of idiopathic nephrotic syndrome is often very simple. In a child wit

periorbital or generalized edema, the primary care physician can quickly make thi

diagnosis by documenting significant proteinuria with more than 2 albumin on urin

dipstick or a spot urine protein/ creatinine ratio greater than 2 mg/mg and serum albumin o

less than 2.5 g/dl. In addition, a careful history should exclude possible complications andidentify children with atypical presentations that might reflect other serious systemi

illnesses. It should include an evaluation of any abdominal distension, which is usually du

to ascites and sometimes edema of the anterior abdominal wall. Although severe distension

may be accompanied by abdominal discomfort, persistent abdominal pain may be due to

primary bacterial peritonitis (a potentially life-threatening complication), gut edema, o

relative gut ischemia due to hypoperfusion secondary to intravascular volume depletionOther causes of an acute abdomen should also be considered. A history of coughing o

breathing difficulties or both may indicate pleural effusion. Pulmonary edema, thougrarely found in idiopathic nephrotic children, should lead to consideration of secondary

causes of nephrotic syndrome that might cause significant intravascular fluid retention

Although a history of gross hematuria is unusual in nephrotic syndrome, microscopi

hematuria may be seen in up to 23% of patients with MCNS and in a higher percentage o

patients with other histologic variants(8)

. Severe intravascular volume depletion may caus

acute renal failure, and some children may present with oliguria or anuria. In such case

prompt intravascular volume repletion is important to correct prerenal acute renal failurand to prevent development of acute tubular necrosis. A history of possible systemi

symptoms including fevers, weight loss, night sweats, polyuria, polydipsia, hair loss, ora

ulcers, rashes, abdominal pain, and joint pain or swelling should also be elicited, becaus

they may be manifestations of systemic diseases such as systemic lupus erythematosus

Henoch-Schnlein purpura, or diabetes mellitus, which can all cause nephrotic syndrome

A medication history should also be taken in that medications such as NSAIDs, gold, and

penicillamine can also cause nephrotic syndrome. The history should exclude other cause

of generalized edema, such as chronic liver failure, heart failure, and malnutrition in area

of the world where clinical malnutrition is prevalent. Regarding physical examinationblood pressure should be carefully determined in nephrotic children; it can be either low

(due to intravascular volume depletion) or elevated (due to neurohumoral responses t

hypovolemia, intrinsic renal causes, or occasionally renal vein thrombosis). Hypertensio

has been reported in up to 21% of children 6 years and under with biopsy-confirme

MCNS, and may be present in up to 50% of children with other histologic types(8)

. A

careful examination of the abdomen should also be performed to exclude abdomina

tenderness or guarding that may be signs of bacterial peritonitis. In addition, extremitie


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should be examined to exclude warmth, tenderness, or pain that may suggest venou

thrombosis. Finally, obtaining a detailed family history is also important, because som

causes of nephrotic syndrome are familial, as previously discussed.

Laboratory Evaluation

Diagnosis of nephrotic syndrome is confirmed by the triad of generalized edema

proteinuria, albuminuria (2on dipstick or urine protein/creatinine ratio 2 mg/mg), an

hypoalbuminemia (serum albumin

2.5 g/dl), although hypercholesterolemia is alscommonly present. In addition to documenting proteinuria, urinalysis with microscopy

should be carried out to look for hematuria and possible red blood cell casts. In patient

with a typical presentation, serum studies should include an evaluation of complete bloocount, electrolytes, blood urea nitrogen (BUN), creatinine, and albumin levels. For patient

at an older age at presentation or with atypical presentation, additional serum studies t

exclude secondary causes of nephrotic syndrome should include C3 and C4 complemenlevels; antinuclear antibody (ANA) and possibly anti-double-stranded DNA; HIV antibody

hepatitis A, B, and C serologies; and consideration of other viral serologies such as HIV

antibodies. Because immunosuppressive therapy is the mainstay of treatment for most caseof childhood nephrotic syndrome, many pediatric nephrologists recommend placing a PPD

(purified protein derivative) test to screen for occult tuberculosis before institutin

immunosuppression. This is particularly important in areas of the world where tuberculosi

is endemic and for recent immigrants from such regions. In addition, many nephrologist

obtain a varicella IgG titer before treatment to classify patients as varicella-naive ovaricella-immune, which can be of great aid when suspecting or confirming varicell

exposure in children who are immunocompromised during treatment. A varicella-naiv

patient receiving immunosuppressive treatment for nephrotic syndrome who is exposed t

varicella should be treated with varicella zoster immunoglobulin (VZIG) within 96 hours oexposure if possible

(28). This passive immunization can sometimes be lifesaving due to th

potential severity of a primary varicella infection in an immunocompromised host. Rena

ultrasound does not usually have a role in the evaluation of childhood nephrotic syndrome

However, in the setting of a nephrotic child who develops gross hematuriathrombocytopenia, or unexplained persistent hypertension, a renal ultrasound should b

considered to exclude possible development of renal vein thrombosis.

Renal Biopsy

More than 80% of children with idiopathic nephrotic syndrome will respond to steroitherapy by entering complete remission. Based on this statistic, an initial trial of 4 to

weeks of high-dose daily steroid therapy is usually prescribed in children under 10 beforconsidering renal biopsy. In general, renal biopsy is indicated only in the setting of atypica

features such as (1) age at onset (less than 1 year or more than 10), (2) SDNS or SRNS, (3

gross or persistent microscopic hematuria or presence of red cell casts, (4) abnorma

serologies, or (5) significant persistent renal failure. Due to the known nephrotoxicit

(interstitial fi brosis) of calcineurin inhibitors such as cyclosporine and tacrolimus, rena


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biopsy is also indicated before initiation of these second-line or third-lin

immunosuppressive agents, as well as approximately every 2 years as long as use of thes

medications continues.

Risk factors for relapses:

Infection is an important cause of relapse in MCNS, prevention & treatment of which could

reduce proteinuria without necessity of steroid(3)

. An Upper Respiratory Tract Infectio

(URTI) or a febrile episode often precipitates a relapse; occasionally there is no obviou

cause1. Asymptomatic UTI might be an important and under diagnosed cause of relapse(5

Role of Tuberculosis in inducing relapse remain controversial10. Young age and low leveof serum protein at onset are independent risk for relapse

(4). Relapse within the first year i

a powerful independent predictor of subsequent relapse and relapse within first 6 months o

presentation is highly predictive of subsequent course(6)

.


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COMPLICATIONS


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MANAGEMENT(29)

MANAGEMENT OF THE OEDEMATOUS STATE.

Bed rest

This is not required and usually not practical unless the child has gross oedema.

B. Diet

A normal protein diet with adequate calories is recommended. Previou

recommendations of high protein diet had not been shown to improve serum albumin

concentration.

Salt intake should be reduced during the oedematous state.

Antibiotics.

Children with nephrotic syndrome are more prone to primary bacterial peritonitisProphylactic oral penicillin at doses of 125 mg BD or 250 mg BD depending on the siz

of the child is recommended during relapse particularly with gross oedema in view o

the lack of home albuminuria monitoring and long distance from the hospital.

Pneumococcal vaccine can be considered. However, it must be cautioned that th

vaccine does not cover all strains of pneumococci and some children with nephrotic

syndrome have been shown to be poor responders to this vaccine.

Hypovolaemia.

Children with nephrotic syndrome can present with hypovolemia, the manisfestations o

which include abdominal pain, cold peripheries, poor pulse volume, hypotension, andhaemoconcentration.

The treatment is to infuse salt poor albumin at 0.5 to 1.0 g/kg/dose over one to tw

hours. If salt poor albumin is not available, other volume expanders like 5% albumin

plasma protein derivatives or human plasma can be used.

Fluid restriction

This is not usually recommended except in chronic oedematous states.


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Diuretics.

Diuretic therapy is not usually necessary in steroid responsive nephrotic syndrome but i

required should be used with caution as it can precipitate hypovolemia.Salt poor albumin of 20 - 25% concentration can be used in symptomatic grossly

oedematous states together with intravenous frusemide at 1-2 mg/kg to produce

diuresis. There is however, the danger of fluid overload with salt poor albumin infusion

and the childs urine output and blood pressure should be closely monitored.

Hypercholesterolaemia

There is insufficient evidence for a recommendation to be made as yet.

MANAGEMENT OF THE COMPLICATIONS OF NEPHROTIC SYNDROME

A.I nfections.Children with nephrotic syndrome are prone to infections particularly cellulitis &

primary peritonitis.

Should a child with nephrotic syndrome develop primary peritonitis, the antibiotic

recommended is parenteral penicillin and a third generation cephalosporin as it has bee

found that about half of primary peritonitis is due to Streptococcal pneumoniaeand th

other half to gram negative bacilli.

The parents and children should be advised and cautioned about contact with chickenpoxand measles, and if exposed should be treated like any immunocompromised child. I

varicella-zoster immunoglobulin (VZIG) is available, it should be given within 72 hour

after exposure to chickenpox. If VZIG is not available, some units recommend giving

single dose of intravenous immunoglobulin.

B.Immunisation.While the child is on corticosteroid treatment and within 6 weeks after its cessation, onl

killed vaccines may be safely be administered to the child. Live vaccines can b

administered 6 weeks after cessation of corticosteroid therapy

C.Acute renal failur eThis is a rare complication in children with steroid responsive nephrotic syndrome. Th

actual cause is not known although hypovolemia has been implicated. Intrarenal factor

have also been postulated to play a role.


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D.ThrombosisThis complication if suspected should be thoroughly investigated and treated to preven

fatal complications.

Treatment consists of anticoagulation with the various anticoagulants available. Th

duration of anticoagulation required is still controversial.

E.Acute Adrenal CrisisThis may be seen in children who have been on long term corticosteroid therapy

(equivalent to 18 mg/m2 of cortisone daily) when they undergo situations of stress

Adequate cover with corticosteroids during these periods of stress is recommended to b

given in 3 divided doses.

CORTICOSTEROIDS IN NEPHROTIC SYNDROMEAt I ni tial diagnosis

A paediatrician should be consulted before initiation of therapy in a child with newly

diagnosed nephrotic syndrome

Corticosteroids was found to be effective in inducing remission of nephrotic syndrom

from the 1940s, and has since then been used as first line therapy in the treatment o

idiopathic nephrotic syndrome although no controlled trial was ever conducted about it

efficacy

Controversy lies in the dosage and duration of corticosteroids used at initial diagnosis of th

nephrotic syndrome. Various regimes of corticosteroids have been used. The two regime

discussed were the modified ISKDC regime; and the so called longer initial steroidinduction regime proposed and studied by Ueda et al

(30) and Ksiazek and Wysznska

(31

who showed a 2 year relapse free rate of 50% for the long initial prednisolone dose versu

27.3% for the modified ISKDC regime.


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Modified ISKDC regime

Prednisolone dosage at:

60 mg/m2/day (maximum 80 mg/day) for 4 weeks 40 mg/m2/48 hours for 4 weeks only.

Long initial prednisolone regime:

Prednisolone dosage at:

60 mg/m2/day (maximum 80 mg/day) for 4 weeks 40 mg/m2/48 hours for 4 weeks. Reduced by 25% monthly over the next 4 monthsThe choice of using either regime was left to the individual attending paediatrician.

A child with nephrotic syndrome who fails to respond to an initial four week treatment with

corticosteroids should be referred to a paediatric nephrologist for a renal biopsy.

Relapse

The majority of children with idiopathic nephrotic syndrome will relapse(32, 33)

. A relapse i

defined by urine albumin excretion of > 40 mg/m2/hour or urine dipstix of 2+ or more for

consecutive days.

Treatment of relapse

Prednisolone at 60 mg/m2/day (maximum 80 mg) is to be given until remission defined a

urine dipstix is trace or nil for 3 consecutive days after which the prednisolone dose i

reduced to 40 mg/m2/48 hours for 4 weeks.

It has not been shown that giving more corticosteroids for treatment of relapses results in

longer period of remission.

Breakthrough proteinuria may occur with intercurrent infection and usually does not requir

corticosteroid therapy if the child has no oedema and remains well.


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Frequent r elapses and steroid dependence

An initial responder who has 2 or more relapses within 6 months of initial response or 4 o

more relapses in any 12 month period is said to have frequent relapses.

Re-induction of any relapse with corticosteroids is as described in the section 3.4.2 on

relapse i.e. Prednisolone at 60 mg/m2/day (maximum 80 mg) until urine dipstix is nil/trac

for 3 consecutive days, after which the prednisolone dose is reduced to 40 mg/m2/48 hour

for 4 weeks .The prednisolone is now tapered instead of discontinued at the end of the re

induction regime. The rate of tapering depends on the patient and the paediatrician in

charge. The prednisolone is then kept on as low an alternate day dose as possible for 6

months. This low dose alternate day prednisolone should preferabley not exceed 0.

mg/kg/dose.

Should a child relapse while on low dose alternate day prednisolone, the child should be re

induced as for a relapse; the prednisolone is again tapered to low dose alternate da

prednisolone. Cyclophosphamide should be considered if the nephrotic syndrome is steroi

dependent and the child shows signs of steroid toxicity

CYCLOPHOSPHAMIDE

A renal biopsy is notneeded prior to cyclophosphamide therapy.

Cyclophosphamide therapy is indicated for the treatment of steroid dependent nephroti

syndrome with signs of steroid toxicity like stunting of growth, cataracts, striae, severcushingoid features and osteoporosis and should be started when the child is in remission

following induction with corticosteroids.

Various trials have shown the superiority of cyclophosphamide with prednisolone versu

prednisolone alone in maintaining prolonged remission.(33, 34)

Various dose and duration o

oral cyclophosphamide have been used. The report by APN (35)

demonstrated a 2 yea

remission rate of 67% for cyclophosphamide at 2 mg/kg/day for 12 weeks against 22% fo

8 weeks given for children with steroid dependent nephrotic syndrome. Ueda et al(36)

in later paper comparing the 8 week versus 12 week duration of cyclophosphamide however

showed no difference. Concern was expressed about the side effects of cyclophosphamid

particularly on the gonads.

A total cumulative dose of cyclophosphamide of 168 mg/kg was adopted for the treatmen

of steroid dependent nephrotic syndrome i.e. 2 mg/kg/day for 12 weeks or 3 mg/kg/day fo


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8 weeks. While the child is on cyclophosphamide, prednisolone therapy which can b

further reduced and discontinued once the child completes the cyclophosphamide therap

and remains in remission. Regular fortnightly review with full blood counts and urinalysi

should be carried out while the child is on oral cyclophosphamide.

RELAPSES POSTCYCLOPHOSPHAMIDE

Relapses after a course of cyclophosphamide is treated as for relapses after the initia

diagnosis of nephrotic syndrome if the child does not exhibit any further signs of steroid

toxicity.

Should the relapse occur soon after a course of cyclophosphamide when the child is stil

steroid toxic, or the child again becomes steroid toxic after multiple relapses, then

paediatric nephrology opinion should be sought.

Options available here are not many but fortunately this group of patients make up only

about 10 20% of children with nephrotic syndrome. The available options availabl

include:

A second course of cyclophosphamide Cyclosporine can also be used on a very selective basis by paediatric nephrologists and

has been shown to maintain remission in 80% of these patients.

Levamisole

URINE ALBUM IN MONITORING

It is advocated that monitoring of urine albumin excretion be done regularly either at hom

with urinary dipstix or at the nearest health centre.


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Diagram 1: Summery of treatment in children with nephrotic syndrome(16)

PROGNOSIS

The single most important prognostic factor for maintenance of long-term normal rena

function in nephrotic syndrome is the patients initial response to corticosteroids. Althougchildren who enter complete remission during an 8-week initial course of ora

corticosteroids have an excellent prognosis, the prognosis for those who fail to ente

remission is more guarded. Overall, close to 80% of newly diagnosed children treated wit

corticosteroids will achieve complete remission(10)

. Steroid responsiveness varies by rena

histologic type, with 93% of children with MCNS being steroid responsive compared with


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56% with mesangial proliferative glomerulonephritis (IgM nephropathy in some centers)

30% with FSGS, 7% with MPGN, and 0% with membranous nephropathy.5 In addition, th

frequency of steroid responsiveness generally decreases with increasing age at presentation

Among children with SSNS, relapse is common. It is estimated that 70% of children with

nephrotic syndrome will experience one or more relapses. However, the frequency o

relapses decreases over time. A large study of children with MCNS reported a gradua

increase in the number of nonrelapsing patients over time, such that 8 years after diseas

onset 80% of children were relapse-free(35)

. In addition, 75% of those children with n

relapses in the first 6 months after treatment either had rare relapses or continued in

remission for their entire clinical course. Risk factors for frequent relapses or a steroid

dependent course have not been carefully studied, but the literature suggests that an age oless than 5 years at onset and a prolonged time to initial remission are possible risk factor(36, 37)

. More recently Tsai et al. reported a higher incidence of the DD (homozygou

deletion) genotype for the angiotensin converting enzyme (ACE) gene in SDNS and SRNS

children compared with SSNS children, suggesting a potential role for ACE in regulatin

clinical response to steroids(38)

. Initial steroid resistance clearly identifies a subset o

patients at high risk for progressive kidney disease. It is estimated that 40% to 50% ochildren with SRNS will progress to CKD or ESRD within 5 years of diagnosis, despit

aggressive immunosuppression. Among children with nephrotic syndrome due to FSGSwho progress to ESRD, renal transplantation can also pose serious challenges. Nephroti

syndrome recurs in the allograft in up to 30% of children with FSGS and leads to graft los

in about 50% of such patients(39)

. Among children with FSGS due toNPHS2 mutations, th

risk for recurrence has been controversial(40)

. The introduction of antibiotics and steroids in

treating nephrotic syndrome has led to a significant reduction in mortality, from 60% t

70% to less than 5%. In an ISKDC series of 521 children with nephrotic syndrome, 1

deaths were reported, resulting in a mortality rate of 1.9%(41)

. Of note, 9 of these 1children had either early relapses or SRNS and 6 (60%) died from infections, confirming

infection as an important cause of mortality in nephrotic syndrome. Nephrotic syndrome i

one of the most common forms of renal disease seen in children. Although the introductio

of antibiotics and refinement of immunosuppressive medications have greatly decrease

mortality and improved the quality of life for children with this disease, neither th

mechanism(s) of action nor the target cell for these therapies is known. In spite of this, th

prognosis for long-term maintenance of normal renal function is excellent unless complet

remission cannot be achieved. Hopefully our growing understanding of the pathobiology o

nephrotic syndrome will lead to development of more effective therapies in the future.


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Patients & methods:

Data were collected from patients recording files

Study design: reterospective Period of study : from 1of march 20131 of May 2013 Place: Al- Kadhimia teaching hospital in pediatric nephrology clinic Number of patients: 40 Parameters : Age, Gender, Residency, duration of follow up , characteristics o

nephrotic syndrome , biopsy, atypical feature

Categorization: The patient categorized as follows:o Group 1: remissiono Group 2: relapse. The children with relapse were further grouped according

to clinical course as

o Group 3: steroid responders:

infrequent relapses (IFR) with 2 relapses in 6 months or 3 relapsesin a year frequent relapses (FRNS) with 2 relapses in 6months or 3 relapses

in a year

o Group 4: steroid nonresponders (SNR) comprising those who have notattained remission with 4 weeks of daily steroid therapy at 2 mg/kg/day.

Inclusion criteriaA.Children with nephrotic syndrome, aged 112 years, following up at our

hospital for at least 1 years

B.Children in remission to determine the occurrence of relapse or notC.Children in relapse to see if they were respond to steroid or not

Exclusion criteria:o Children who not complete thier follow up for at least 1 year in our hospital


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Results: 40 children with nephrotic syndrome visiting the pediatric nephrologclinic, Al- kadhimia teaching hospital, were eligible for the study

o Regarding the distribution of patient with nephrotic syndrome accordingto age as in table 1 , 2 patients (5%) were N.S. less than 1 year ,

patient (17.5 %) were N.S. between 1-5 years & 31 patient (77.5 %) wer

N.S. equal or above 5 years.

o Regarding the Demographic data in patients with nephrotic syndrome as in table 2

25 (62.5 %) patients were males while 15 were females (37.5 %) 22 (55 %) of patients reside a rural area while 18 (45 %) o

patients reside an urban area

o Regarding the Characteristics of nephrotic syndrome: as in table 3 2 (5 %) of the patients had onset of N.S. within 1 year , 23 (57.

%) of the patients had onset of N.S. between 1- 5 years & 15 (37.

%) of the patients had onset of N.S. equal & above 5 years

2 (5 %) of the patients had frequent relapse while 38 (95 %) of thpatients had infrequent relapse

26 (65 %) of the patients were steroid sensitive , 14 (35 %) of thpatients steroid resistant

o Regarding the duration of follow up: as in table 4 6 (15 %) of the patients were followed for 1 year , 17 (42.5 %) o

the patients were followed for 1- 2 years , 13 (32.5 %) of th

patients were followed for 2- 4 years & 4 (10 %) of the patient

were followed for equal & above 4 years

o Regarding renal biopsy characteristics in 17 patients with nephroticsyndrome : as in table 5

12 (70.6 %) of the patients had MCD , 2 (11.8 %) of the patienthad FSGN & 3 (17.6 %) of the patients had MPGN


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o Regarding atypical features in patients with nephrotic syndromein 40patients: as in table 6

10 (25 %) of the patients were hypertensive 7 (17.5 %) of the patients had a hematuria at initial diagnosis 8 (20 %) of the patients had a raised in blood urea 0 (0 %) of the patients had a raised in serum creatinine

Tables:

Table number (1) .. Distribution of patient with nephrotic syndrome according to

age group

age Number of patients (%)

< 1 2 5

1-5 7 17.5

5 31 77.5Total 40 100 %

Table number (2) .. Demographic data of patient with nephrotic syndrome

Number of patients (%)

Gender

25 62.5

15 37.5Residency

rural 22 55

urban 18 45

Total / each 40 100 %

Table number (3) .. Characteristics of nephrotic syndrome

Number of patients (%)

Onset of disease

< 1 2 5

1-5 23 57.5

5 15 37.5relapses

frequent 2 5


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infrequent 38 95

Types of NS

sensitive 26 65

Resistant 14 35

Total / each 40 100 %

Table number (4) .. Duration of follow up

age Number of patients (%)

< 1 6 15

1-2 17 42.5

2-4 13 32.5

4 4 10Total 40 100 %

Table number (5) .. Renal biopsy characteristics in 17 patients with nephrotic

syndrome

biopsy Number of patients (%)

MCD 12 70.6

FSGN 2 11.8

MPGN 3 17.6

Total 17 100 %

Table number (6). Atypical features in patient with nephrotic syndromein 40patients

feature Number of patients (%)hypertension 10 25

hematuria 7 17.5

blood urea 8 20 serum creatinine 0 0


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Discussion:

o In this study, the distribution of patient with nephrotic syndromaccording to age as in table 1, the majority (77.5 %) were N.S. equal o

above 5 years.

This study similar to other study were the majority of patien(67%) were between equal or above 5 years. (43)

o In this study, the Demographic data in patients with nephrotic syndrome as in table 2

(62.5 %) patients were males while were (37.5 %) females (55 %) of patients reside a rural area while (45 %) of patient

reside an urban area

Which is nearly similar to other study : (67.9 %) patients were males while were (32.1 %) female

(42)

(60 %) of patients reside a rural area while (40 %) opatients reside an urban area

(43)

o In this study, the Characteristics of nephrotic syndrome: as in table 3

(5 %) of the patients had onset of N.S. within 1 year , (57.5 %) othe patients had onset of N.S. between 1- 5 years & (37.5 %) o

the patients had onset of N.S. equal & above 5 years

(55 %) of the patients had frequent relapse while (45 %) of thpatients had infrequent relapse

(65 %) of the patients were steroid sensitive , (35 %) of thepatients steroid resistant

Which is nearly similar to other study :(43) (3 %) of the patients had onset of N.S. within 1 year , (6

%) of the patients had onset of N.S. between 1- 5 years &

(30 %) of the patients had onset of N.S. equal & above 5

years

(50 %) of the patients had frequent relapse while (50 %) othe patients had infrequent relapse


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(70 %) of the patients were steroid sensitive , (30 %) of thpatients steroid resistant

o In this study, the duration of follow up: as in table 4 (15 %) of the patients were followed for 1 year , (42.5 %) of th

patients were followed for 1- 2 years , (32.5 %) of the patient

were followed for 2- 4 years & (10 %) of the patients werfollowed for equal & above 4 years

Which is nearly similar to other study :(42) (12 %) of the patients were followed for 1 year , (40 %) o

the patients were followed for 1- 2 years , (30 %) of th

patients were followed for 2- 4 years & (18 %) of th

patients were followed for equal & above 4 years

o In this study, renal biopsy characteristics in 17 patients with nephroticsyndrome : as in table 5

(70.6 %) of the patients had MCD , (11.8 %) of the patients haFSGN & (17.6 %) of the patients had MPGN

Which is differ to other study :(44) Minimal change disease (85%), mesangial proliferatio

(5%), and focal segmental glomerulosclerosis (10%).

o In this study, atypical features in patients with nephrotic syndromein 40patients: as in table 6

(25 %) of the patients were hypertensive (17.5 %) of the patients had a hematuria at initial diagnosis (20 %) of the patients had a raised in blood urea Which is nearly similar to other study :(43)

(22.5 %) of the patients were hypertensive (22.2 %) of the patients had a hematuria at initial diagnosis (30 %) of the patients had a raised in blood urea


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Conclusions:

In this study the majority of patients were equal or more than 5 years, male, living inrural area, with onset between 1-5 years, steroid responsive, frequent relapse, having

follow up between 1-2 years & having MCD on renal biobsy

nephrotic $ case study

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