CASE REPORT

Nephrotic Syndrome

Compiled by :
Jaspreet Kaur Roar (110100430)
Christy Sitorus (110100492)

Supervisor :
Dr Yazid Dimyati,Sp A (K)
Pediatric Departement
H. Adam Malik General Hospital
Faculty of Medicine
University of Sumatera Utara
Medan
2016

CONTENTS
CHAPTER 1 INTRODUCTION.................................................................

CHAPTER 2 LITERATURE REVIEW......................................................

2.1 Definition.......................................................................................
2.2 Epidemiology................................................................................
2.3 Etiology.........................................................................................
2.4 Clinical Manifestation...................................................................
2.5 Pathophysiology............................................................................
2.6 Classification.................................................................................
2.7 Differential Diagnose....................................................................
2.8 Diagnostic Evaluation...................................................................
2.9 Treatment.......................................................................................

2
3
4
4
6
8
10
10
12

CHAPTER 3 CASE REPORT.....................................................................

17

CHAPTER 4 DISCUSSION .......................................................................

27

CHAPTER 5 SUMMARY ..........................................................................

27

REFERENCES..............................................................................................

28

CHAPTER 1
INTRODUCTION
Nephrotic syndrome is a disorder of the kidneys that results from increased
permeability of the glomerular filtration barrier. It is characterized by 4 major clinical
characteristics

that

are

used

in

establishing

the

diagnosis:

proteinuria,

hypoalbuminemia, edema, and hyperlipidemia. (Andolino TP, 2015)

The estimated annual incidence of nephrotic syndrome in healthy children is 2
to 7 new cases per 100,000 children younger than 18 years of age, making it a
relatively common major disease in pediatrics. The peak age of onset occurs at 2 to 3
years except for the rare, congenital type of nephrosis. Approximately 50% of
affected children are ages 1 to 4 years; 75% are younger than age 10 years. In
addition, even the most benign form of the nephrotic syndrome is, by nature, a
recurrent disorder, so each new-onset case likely will continue to manifest disease for
some time. Nephrotic syndrome is one of the most frequent reasons for referral to a
pediatric nephrologist for evaluation, although its insidious onset frequently causes
delay in diagnosis. (Roth KS, 2002)

CHAPTER 2
LITERATURE REVIEW

2.1 Definition
Nephrotic syndrome, also known as nephrosis, is defined by the presence of
nephrotic-range

proteinuria,

edema,

hyperlipidemia,

and

hypoalbuminemia.

Nephrotic-range proteinuria in adults is characterized by protein excretion of 3.5 g or

more per day. However, because of the great range of body sizes in children, the
pediatric definition of nephrotic-range proteinuria is more cumbersome. (Lane JC,
2015)
Nephrotic-range proteinuria in children is protein excretion of more than 40
mg/m2/h. Because 24-hour urine collections are potentially unreliable and
burdensome, especially in young children, many pediatric nephrologists instead rely
on a single, first-morning urine sample to quantify protein excretion by the ratio of
protein to creatinine. (Lane JC, 2015)
Further definitions to clarify the course of nephrotic syndrome are shown in the table
below. (Indian Pediatric Nephrology Group, 2008)
Remission
Relapse
Frequent relapses
Steroid dependence
Steroid resistance

Urine albumin nil or trance (or proteinuria < 4 mg/m2/h) for 3

consecutive early morning specimens.
Urine albumin 3+ or 4+ (or proteinuria > 40 mg/m2/h) for 3
consecutive early morning specimens, having been in remission
previously.
Two or more relapses in initial six months or more than three
relapses in any twelve months.
Two consecutive relapses when on alternate day steroids or
within 14 days of its discontinuation.
Absence of remission despite therapy with daily prednisolone at
a dose of 2 mg/kg per day for 4 weeks.

2.2 Epidemiology
Indonesia is a densely-populated nation with more than 235 million people,
and a pediatric population 19 years and under of more than 88 million. It is assumed
that the ratio of pediatric nephrologists to pediatric population is approximately
1:3,684,210 with 19 trained pediatric nephrologists. Based on a multicenter study in
2000-2004 involving seven pediatric institutions, the top three kidney diseases
affecting children in Indonesia were nephrotic syndrome (35%), acute poststreptococcal acute glomerulonephritis (26%), and urinary tract infections (23%).
Other renal disease entities from most to least common included acute renal failure,
chronic renal failure, nephrolithiasis, enuresis, and congenital renal disease. Urinary
incontinence was an increasingly recognized problem. The underlying etiologies
identified were spinal dysraphism, malignant osteolytic vertebral lesions, nonneurogenic neurogenic bladder and anatomical abnormalities. More than 50% of
these children developed chronic renal failure. (Avner ED, 2009)
Among the causes of acute renal failure in older children, jengkol bean
intoxication was an important cause, accounting for 31% of children hospitalized for
acute renal failure in a large general hospital in Jakarta. Jengkol bean is widely
consumed in Indonesia, especially in rural areas. The pathophysiologic mechanism of
kidney injury includes obstruction of renal tubules by jengkolic acid crystals, as well
as a direct tovix effect on renal tubular cells. (Avner ED, 2009)
Studies on frequent relapsing nephrotic syndrome in Indonesian children have
shown an association with certain HLA class II haplotypes, including HLA-DRBI*12
(protective haplotype) and DQBI*02 (at risk haplotype). Other studies in Indonesian
children on genetic variants of the Th2 cytokine genes IL-I3 and IL-4 showed some
association with minimal change nephrotic syndrome. (Avner ED, 2009)

2.3 Etiology
Commonly, the primary causes of nephrotic syndrome include kidney diseases
such as minimal-change nephropathy, membranous nephropathy, and focal
glomerulosclerosis. Secondary causes include systemic diseases such as diabetes
mellitus, lupus erythematosus, and amyloidosis. Congenital and hereditary focal
glomerylosclerosis may result from mutations of genes that code for podocyte
proteins, including nephrin, podocin, or the cation channel 6 protein. Nephrotic
syndrome can result from drugs of abuse, such as heroin. (Cohen EP, 2014)
Nephrotic-range proteinuria occurring in the third trimester of pregnancy is
the classical finding of preeclampsia. In that condition, also known as toxemia,
hypertension develops as well. It may occur de novo or it may be superimposed on
another chronic kidney disease. In the latter case, there will have been preexisting
proteinuria that will have worsened during pregnancy. (Cohen EP, 2014)
Medication can cause nephrotic syndrome. This includes the very infrequent
occurrence of minimal-change nephropathy with NSAID use, and the occurrence of
membranous nephropathy with the administration of gold and penicillamine, which
are older drugs used for rheumatic diseases; there have also been reports of focal
glomerulosclerosis in association with intravenous bisphosphonates. Lithium and
interferon therapy also are implicated in focal glomerulosclerosis of the collapsing
type. (Cohen EP, 2014)
2.4 Clinical Manifestation
Edema is the presenting symptom in about 95% of children with nephrotic
syndrome. Early on, the edema is intermittent and insidious, and its presence may not
be appreciated. A common story is for the child to present to a primary care
practitioner repeatedly for periorbital edema, which is ascribed to "allergies" until the
edema progresses. (Lane JC, 2015)

Edema usually appears first in areas of low tissue resistance (eg, the
periorbital, scrotal, and labial regions). It can progress rapidly or slowly. Ultimately, it
becomes generalized and can be massive (anasarca). The edema is pitting and
typically dependent in nature, being more noticeable in the face in the morning and
predominantly in lower extremities later in the day. (Lane JC, 2015)
A history of a respiratory tract infection immediately preceding the onset of
nephrotic syndrome is frequent, but the relevance to causation is uncertain. Upper
respiratory infections, otitis media, and other infections are often associated with
relapses of idiopathic nephrotic syndrome (INS) as well. Approximately 30% of
children have a history of allergy. A hypersensitivity event, such as a reaction to bee
sting or poison ivy, has been reported to precede the onset of INS in some cases.
(Niaudet P, 2004)
Children with nephrotic syndrome occasionally present with gross hematuria.
The frequency of macrohematuria depends on the histological subtype of nephrotic
syndrome.

It

is

more

common

in

patients

with

membranoproliferative

glomerulonephritis (MPGN) than in other causes, but its frequency in minimal

change nephrotic syndrome (MCNS) has been reported to be as high as 3-4% of
cases. (Lane JC, 2015)
Statistically, a higher percentage of patients with focal segmental
glomerulosclerosis (FSGS) have microhematuria than those with MCNS, but this is
not helpful in differentiating between types of nephrotic syndrome in the individual
patient. (Lane JC, 2015)
Given the risk of thrombosis in INS, renal vein thrombosis must be
considered in patients with significant hematuria. Rarely, a child can present with
other symptoms secondary to thrombosis, such as seizure caused by cerebral
thrombosis. (Lane JC, 2015)

A child might be brought to medical attention for symptoms of infection, such

as fever, lethargy, irritability, or abdominal pain due to sepsis or peritonitis. Peritonitis
can be mistaken for appendicitis or other cause of acute abdomen unless the child's
proteinuria and edema are appreciated. (Lane JC, 2015)
Anorexia, irritability, fatigue, abdominal discomfort, and diarrhea are
common. GI distress can be caused by ascites, bowel wall edema, or both.
Respiratory distress can occur, due to either massive ascites and thoracic compression
or frank pulmonary edema, effusions, or both. (Lane JC, 2015)
Except in rare cases of familial INS, no significant family history of kidney
disease or INS is usually noted. Children are typically healthy prior to onset of INS
and, except for the history of allergy and atopy noted above, do not usually have a
significant past medical history related to INS. (Lane JC, 2015)
2.5 Pathophysiology
The kidney uses a complex filtration system known as the glomerular
filtration barrier (GFB). It is composed of a glomerular basement membrane
sandwiched between a fenestrated endothelium and an epithelial layer made up of
podocytes and their foot processes, with interspersed filtration slits and slit
diaphragm. As part of the systems intrinsic design, it is charge and size specific,
allowing water and small solutes to pass through its pores into the urinary space. In
nephrotic syndrome, there is an effacement of the podocyte foot processes that can be
seen on electron microscopy. Disruption of this barrier leads to the proteinuria seen in
nephrotic syndrome. (Roth KS, 2002)
Nephrotic syndrome can be inherited from a number of genetic mutations that
lead to defects in various regions of the glomerular filtration barrier; presentation can
vary from isolated nephrotic syndrome seen in corticosteroid-resistant nephrotic
syndrome or focal segmental glomerular sclerosis (FSGS) to more involved

syndromes, such as nail-patella or Denys-Drash syndromes. Congenital nephrotic

syndrome (CNS) is usually seen within the first 3 months after birth. The classic form
ofCNSis the Finnish type (CNF), which is most frequently seen in Finland and has an
incidence of 1 in 8,200 live births, although this autosomal recessive condition has
been described in many other populations. CNF results from a mutation in the gene
encoding the protein nephrin, a key component of the slit diaphragm. CNS is also
caused by mutations of genes encoding other proteins of the glomerular basement
membrane, slit diaphragm, and podocyte. CNS can also be secondary to underlying
processes such as maternal lupus, neonatal autoantibodies to neutral endopeptidase,
and infections such as syphilis, toxoplasmosis, and cytomegalovirus. (Roth KS, 2002)
Most ongoing research into mechanisms of pathogenesis of idiopathic
nephrotic syndrome explores the roles of the immune system and the podocyte in
disease. Proposed theories include (1) T-cell dysfunction that leads to cytokine release
that affects glomeruli and causes increased permeability and (2) immune system
dysfunction that leads to the production of circulating factors (soluble urokinase
plasminogen activator receptor is one example) that alter podocyte structure and/or
function, resulting in proteinuria. B-cell involvement is also suggested by reports of
remission after administration of rituximab, an anti-CD20 antibody. However,
definitive evidence of the underlying mechanism of action is lacking at this time.
(Roth KS, 2002)

2.6 Classification
Nephrotic syndrome can be divided into primary (idiopathic) and secondary
causes. Idiopathic nephrotic syndrome refers to that which is not associated with
another identifiable systemic disease. Outside these 2 major groupings, there are 2
subsets that are based on age of presentation: CNS and infantile nephrotic syndrome.
Patients with the latter condition typically present between ages 3 months and 1 year.
Some prenatal signs that are nonspecific but may suggest CNF are an enlarged
placenta apparent on ultrasonogram in addition to elevated maternal serum and
amniotic fluid -fetoprotein levels. If CNF is suspected in families with known risk
factors, genetic testing can be performed. (Andolino TP, 2015)
Idiopathic nephrotic syndrome can be further subdivided based on histologic
information gathered via percutaneous renal biopsy. The 3 major subgroups are
MCNS (also known as minimal change disease), FSGS, and membranous
nephropathy (MN). MCNS is the most common form of nephrotic syndrome in
school-aged children. On light microscopy, the glomeruli appear histologically
normal, hence the name minimal change disease. Although light microscopy findings
are normal, inspection by electron microscopy reveals fusion of the foot processes.
FSGS describes what is found histologically: some glomeruli can be normal, whereas
others exhibit segmental areas of sclerosis or scarring. Diffuse thickening of the
capillary walls of the glomeruli are histologically characteristic of MN. There are
other glomerulopathies that can present with nephrotic syndrome, including IgA
nephropathy, lupus

nephritis,

and

membranoproliferative

glomerulonephritis

(MPGN), and often present with a nephritic/nephrotic picture, with hematuria in

addition to proteinuria. Aside from histologic features, children with nephrotic
syndrome can be further classified by their response to corticosteroid therapy.
(Andolino TP, 2015)

Secondary Causes of Nephrotic Syndrome (Andolino TP, 2015)

INFECTIONS
Hepatitis B
Human immunodeficiency virus
Syphilis
DISEASES OR CONDITIONS
Amyloidosis Lupus
IgA nephropathy
Membranoproliferative glomerulonephritis
MEDICATIONS/DRUGS
Lithium
Heroin
Gold
Pamidronate

Hepatitis C
Toxoplasmosis
Malaria
Henoch-Schnlein purpura
Lymphoma
Nonsteroidal anti-inflammatory drugs
Penicillamine
Interferon

Common Definitions of Patients With Nephrotic Syndrome (Andolino TP, 2015)

TERM
Remission
Relapse

Corticosteroid responsive
Corticosteroid resistant
Infrequent relapse
Frequent relapse
Corticosteroid dependent

DEFINITION
Urine protein:creatinine ratio <0.2 or
dipstick negative or trace reading for 3
consecutive days
Increase in first morning urine
protein:creatinine ratio to 2 or dipstick
reading of 2+ for 3 of 5 consecutive
days
Attainment of complete remission with
corticosteroid therapy
Inability to induce a remission within 4
weeks of daily corticosteroid therapy
13 Relapses annually
2 Relapses within 6 months after initial
therapy or 4 relapses in any 12-month
period
Relapse during taper or within 2 weeks of
discontinuation of corticosteroid therapy

10

2.7 Differential Diagnoses

Heart failure may cause a similar presentation to that of nephrotic syndrome.
In typical cases of heart failure, however, the patient will have a history of heart
disease and/or features of poor heart function on exam, such as a third heart sound
and even low blood pressure. In heart failure without kidney disease, there will be
little or no proteinuria. (Cohen EP, 2014)
Nephrotic syndrome with renal impairment, such as may occur in IgA
nephropathy, may cause secondary reduction in heart function, with cardiomegaly on
exam. Such cases would typically be hypertensive and there will be substantial
proteinuria on urinalysis. (Cohen EP, 2014)
Patients with cirrhosis may have substantial fluid retention, both as ascites and
as peripheral edema. Unless there is associated kidney disease, however, there will be
little or no proteinuria in cirrhosis. (Cohen EP, 2014)
Acute kidney failure (AKF) is a rare complication of idiopathic nephrotic
syndrome. Fever, rash, arthralgia and eosinophilia with a "bland" urinalysis (minimal
cellular elements) in the presence of AKF are typical for acute interstitial nephritis.
However, obvious clinical symptoms may be absent except for the AKF and
unremarkable urinalysis. Gross hematuria, flank pain, and thrombocytopenia may be
signs of renal vein thrombosis. Hemoconcentration in the patient with anasarca might
indicate intravascular volume depletion. (Lane JC, 2015)
2.8 Diagnostic Evaluation
A detailed evaluation is necessary before starting treatment with
corticosteroids. The height, weight, and blood pressure of the patient should be
recorded. Regular weight record helps monitor the decrease or increase of edema.
Physical examination is done to detect infections and underlying systemic disorder,
e.g., systemic lupus erythematosus, Henoch Schonlein purpura, etc. Infections should

11

be treated before starting therapy with corticosteroids. (Indian Pediatric Nephrology

Group, 2008)
Investigations recommended at the initial episode include: (i) urinalysis; (ii)
complete blood count, blood levels of albumin, cholesterol, urea and creatinine.
Estimation of blood levels of anti-streptolysin O and C3 is required in patients with
groass or persistent microscopic hematuria. Appropriate tests are performed, if
necessary, for associated conditions (e.g., chest X-ray and tuberculin test, hepatitis B
surface antigen, antinuclear antibodies). Urine culture is not necessary unless the
patient has clinical features suggestive of a urinary tract infection. (Indian Pediatric
Nephrology Group, 2008)
The primary laboratory feature of the nephrotic syndrome is a marked
proteinuria, in excess of 50 mg/kg per 24 hours. The excreted protein is
predominantly albumin, although immunoglobulins (Igs) also are lost. In
uncomplicated cases of idiopathic nephrotic syndrome, it is unusual to see gross
hematuria in the presence of proteinuria, although microscopic hematuria occurs in a
sizeable proportion of cases. For patients who have gross hematuria and proteinuria,
IgA nephropathy always must be a diagnostic consideration. (Roth KS, 2002)
In the presence of clinical edema, measurement of serum protein will yield
low values; the serum albumin is likely to be 2.0 g/dL (20 g/L) or lower. Albumin
concentrations as low as 0.5 g/100 mL can be seen, and the albumin/globulin ratio is
commonly less than 1.0. Concomitantly, and directly related to the reduced serum
protein, hypocalcemia is found frequently, as reflected in reduced total and ionized
fractions. However, hypocalcemia rarely is manifested clinically. (Roth KS, 2002)
Of much greater significance than hypocalcemia to patients who have
nephrotic syndrome is the increased concentrations of coagulation factors, especially
those of high molecular weight. Thrombin also is increased, while fibrinolytic activity
and circulating quantities of platelet adhesion inhibitors are decreased. As a

12

consequence of these changes, as well as the intravascular hypovolemia, affected

patients are at greatly increased risk of thrombosis. In addition, IgG in plasma is
reduced, which in combination with large steroid doses, may predispose to infection.
(Roth KS, 2002)
Children who become oliguric from diminished intravascular volume have a
tendency to develop hyperkalemia. The use of diuretics may complicate the
electrolyte disturbances further, necessitating close monitoring of serum electrolyte
levels during treatment. (Roth KS, 2002)
Minimal change nephrotic syndrome usually begins in early childhood. Such
children usually have normal blood pressure, no blood in the urine and normal blood
levels of urea and creatinine. Children fitting this description are treated with
prednisolone without the need for a biopsy. If the child does not show reduction in
urinary protein excretion after a sufficient period of time, a kidney biopsy may be
done. Children with blood in their urine, high blood pressure and reduced kidney
function require a biopsy. (Srivastava RN, 2005)
2.9 Treatment
The intuitive solution to the diminished oncotic pressure is to restore serum
albumin concentration to better than 2 g/dL (20 g/L) by intravenous infusion.
However, the effectiveness of this measure is reduced considerably because of the
hypoalbuminemia resulting from glomerular leakage of serum protein. The degree of
urinary loss can be illustrated by the hepatic rate of albumin synthesis, which in
adults can be as high as 12 to 14 g/d. If a patient becomes hypoalbuminemic at such
endogenous rates of replacement, it is apparent that replacement by infusion can only
be a temporary remedy. Nonetheless, for a patient who has pulmonary edema or renal
shutdown, intravenous albumin (1 g/kg of a 25% solution) can be very effective in
mobilizing fluid into the vascular space. The rate of increase in oncotic pressure is
directly proportional to the rate of expansion of intravascular volume. Thus, too rapid

13

an infusion will place the child at risk for congestive heart failure. Accordingly,
intravenous albumin should be infused continuously over 8 to 12 hours under close
supervision. (Roth KS, 2002)
As intravascular space expands, renal perfusion improves, and with it, the
opportunity to reduce accumulated fluid volume is enhanced. Administration of a
diuretic is the obvious means by which to maximize this opportunity. Keeping in
mind that a normal or low serum sodium concentration is likely to represent the result
of a dilutional effect, the choice of diuretic should be directed at sodium as well as at
water excretion. An ideal choice is a loop diuretic such as furosemide, which can be
administered at a dose of 1 to 2 mg/kg intravenously and acts within 15 minutes. A
portion of the calculated furosemide dose can be administered during the albumin
infusion or it all can be administered at the end of the infusion, depending on the
volume of urine output and the degree of edema. (Roth KS, 2002)
The child should be started on oral corticosteroid therapy after a negative
tuberculosis skin test result has been determined. Prednisone is the usual drug of
choice, and the recommended maximum daily dose is 60 mg/m 2 or 2 mg/kg. The
daily dose should be maintained for 4 to 6 weeks. Opinion varies regarding this
recommendation, ranging from daily treatment administered just long enough to
achieve remission to 6 weeks of daily treatment. Following remission, the dose
should be kept constant while changing to an alternate-day schedule for an additional
6 weeks. (Roth KS, 2002)
Fluid balance must be monitored closely in the early stages of treatment.
Optimal nutrition, including high-quality protein in amounts required for growth, is
essential because the demand for albumin replacement is increased. The child should
follow a no salt-added diet, with maintenance sodium provided for replacement
during diuresis. Daily weights are key to assessing the therapeutic progress. Other
adjunctive treatment, such as anticoagulation therapy, should be used judiciously. If

14

laboratory evidence is sufficient to consider coagulopathy, heparin may be used at a

dose of 50 U/kg intravenously and 100 U/kg every 4 hours intravenously for
maintenance. (Roth KS, 2002)
The small percentage of children who are not completely free of proteinuria
for at least 3 to 5 days or those whose proteinuria continues beyond 3 months are
classified as frequent relapsing/steroid-dependent or steroid-resistant patients,
respectively. For many such patients, different steroid-based strategies or alternative
treatments may be required. (Roth KS, 2002)
Long-term maintenance on daily or alternate-day low-dose oral prednisone
may be appropriate for patients who experience frequent relapses. Many children
remain in long-term remission on such a regimen with few, if any, adverse effects. If
the child can be kept in remission with relatively low steroid doses in the absence of
adverse effects, this approach is optimal because it is the least harmful of the
available choices. On the other hand, when high steroid doses are required for
maintenance or when steroid-related adverse effects supervene, alternative
medications are required because the child clearly has a steroid-resistant nephrotic
syndrome. (Roth KS, 2002)
Among the alternative medications are several immunosuppressive agents as
well as an antihelminthic and certain nonsteroidal medications. The usual choices are
cyclophosphamide and chlorambucil, each of which can be used to achieve an initial
remission or to render the steroid-resistant child relatively more steroid responsive.
(Roth KS, 2002)

15

Steroidal and Nonsteroidal Treatment (Roth KS, 2002)

Medication
Steroidal Agents
Predinisone

Dosage

Comments

2 mg/kg per day orally

(maximum, 60 mg/d)

Methylprednisolone
sodium succinate

30 mg/kg per week

intravenously;
combined with
prednisone 2 mg/kg on
alternate days for
variable duration
according to underlying
diseases

Daily for 6 wk, followed by

alternate-day dosing for 6 wk. This
12-wk regimen is more effective
than an 8-wk regimen in reducing
relapse. Adverse effects: growth
retardation, cataracts, osteoporosis
In partial steroid-resistant cases,
this relatively high-dose regimen
may aid in moderating development
of FSGS

Nonsteroidal Agents
Cyclophosphamide

2 mg/kg per day for 8

wk; prednisone 60
mg/m2 on alternate
days

Chlorambucil

0.2 mg/kg per day for 8

to 12 wk

Cyclosporine

5 mg/kg per day to

maximum 20 mg/kg
per day for up to 4 y
2.5 mg/kg per day
during remissions
5 to 10 mg/kg per day
chronically

Levamisole
Angiotensinconverting Enzyme
Inhibitors
Indomethacin
Mizoribine

50 kg/day for short

term (<3 mo)
2 to 5 mg/kg per day
for 24 wk

May induce steroid sensitivity in

later relapses. Adverse effects:
sterility, bone marrow depression,
sepsis, alopecia. To avoid
hemorrhagic cystitis, administer
medication early in the day and
encourage oral fluid intake
Same as for cyclophosphamide.
Adverse effects as for
cyclophosphamide; risk of marrow
depression may be higher
Effectively maintains remission, but
relapses occur on discontinuation.
Adverse effect: nephrotoxicity
May help to maintain remission in
steroid-dependent disease
Renoprotective by reducing
glomerular hyperfiltration. Adverse
effects: hypotension, cough
Reduces glomerular hyperfiltration.
Adverse effect: hepatorenal toxicity
Reduces relapsing nephrotic
syndrome. Blocks purine

16

Mycophenolate
mofetil

25 mg/kg per day in

two divided doses for
up to 1 y

biosynthesis, inhibits mitogenstimulated T- and B-cell

proliferation. Adverse effect:
hyperuricemia
Effective in conjunction with
prednisone to control diffuse
proliferative lupus nephropathy.
Primary adverse effects
are gastrointestinal. Generally well
tolerated

17

CHAPTER 3
CASE REPORT
3.1

Case
DW, 1 year 5 months old boy, with 14 kg of BW and 86 cm of BL, came to
RSUP Haji Adam Malik Medan on 8th July at 21.00. His main complaint is
swelling throughout the body. It has been experienced by patient for 17 days,
worsened in the last 4 days, swelling appeared mainly on his testis, and it
worsened at day. History of swelling on the eyes (+), both legs (+), testis (+) and
body (+). Shortness of breath has also been experienced for 1 week. Fever (+) in
the last 5 days, it was fluctuating fever and down with fever medication. Nausea
(-), vomit (-). History of low urine output was found, lasted for 1 week, urine
looked concentrated. Sandy urine was not found. History of urine with the color
of meat wash (-). Defecation within normal limit.

History of disease
DW was a patient of RS AFINA AZIZ diagnosed with Nephrotic Syndrome
that has been treated for 3 days.
History of medication:
Cefotaxim, Paracetamol
History of family:
History of family having same symptom and disease was not found.
History of feeding:
1 month of breast feeding.

18

History of pregnancy :
Patients mother was 25 years old during pregnancy. The gestational age was
aterm. There was no illness during pregnancy.
History of birth :
Baby was spontaneously born assisted by a midwife and cried spontaneously.
Body weight was 3000 gram.
History of immunization:
Complete immunization
History of Growth and Development:
The patients mother said that DWgrew normally. DW had developed sitting at the
age of 6 months old, standing at the age of 10 months old and walking at the age of
15 months old.
Physical Examination :
General status
Body weight: 14 kg, Body length: 86 cm,
BW/A: Z score 3
BL/A: Z score >3
BW/BL: 2 < Z score < 3
Presens status
Sensorium

: Compos Mentis

Blood Pressure

: 90/60 mmHg

Heart Rate

: 140 beats/min

Respiratory Rate : 38 breaths/min

Body Temperature : 36,5oC

19

Anemic (-); icteric (-), cyanosis (-),edema (-), dyspnea (-)

Localized status
Head :
Eyes

: isochoric pupil, pale inferior palpebral conjunctiva (-/-),

icteric sclera (-/-), light reflexes (+/+), oedema superior palpebra (+/
+)

Face

: oedema (-), Bleeding (-/-)

Ears

: within normal range

Nose

: within normal range

Mouth

: within normal range

Neck :
JVP (-), lymph node enlargement (-)
Thorax :
Symmetric fusiform; retraction (-); HR: 140 beats/min, regular, murmur (-);
RR: 38 breaths/min, regular, ronchi (-), breath sound: vesicular, additional sound
(-)
Abdomen :
Bigger appearance, umbilical protrusion, soepel, peristaltic (+) normal. Kidney,
liver and spleen undetermined, skin pinch returns quickly, shifting dullness (+).
Extremities :
Pulse 140 times/min, regular, blood pressure 90/60 mmHg, adequate pressure and
volume, warm, CRT < 3. Oedema (+) at lower extremities.
Anogenital : Male. Scrotum Oedema (+).
Differential Diagnosis
-

Nephrotic syndrome
Glomerulonephritis

20

Laboratory finding:
Complete blood analysis (July 8th 2016)
Test
Hemoglobin
Erythrocyte
Leucocyte
Thrombocyte
Hematocrite
Eosinophil
Basophil
Neuthrophil
Lymphocyte
Monocyte
MCV
MCH
MCHC

Result
10,2
3,93
24,260
376,000
33
0,00
0.10
60.90
28.30
5.70
77
26
33.6

Liver
Carbohydrate

Test
Albumin
Blood Glucose

Metabolism
Renal

(ad random)
Blood Urea

Unit
g%
106/mm3
103/mm3
103/mm3
%
%
%
%
%
%
Fl
Pg
g/dL

References
10,8-15,6
4,50-6,50
4,500-13,500
181,000-521,000
33-45
1.00-5.00
0.00-1.00
25.00-60.00
25.00-50.00
1.00-6.00
69-93
22-34
32-36

Result
0,9
82

Unit
g/dL
mg/dL

References
3,5-5,0
<200

15

mg/dL

9-21

32
0,34
125
4,2
103

mg/dL
mg/dL
mEq/L
mEq/L
mEq/L

19-44
0,7-1.3
135-155
3,5-5,5
96-106

Nitrogen
(BUN)
Ureum
Creatinine
Natrium (Na)
Potassium (K)
Chloride

Electrolyte

Dipstick Urine :
LEU/ NIT/ URO/ PRO/ pH/ BLO/ SG/ KET/ BIL/ GLU
-/

- / +4 / 6,5 / - / 1,020/ - / - /

Working diagnosis
-

Nephrotic syndrome

21

Therapy
-

IVFD D5% NaCl 0,9% 20 gtt/minute/micro

Inj. Ceftazidim 25 mg/BW/12h => 300 mg/ 12h (IV)
Inj. Lasik 1 mg/BW/12h => 12 mg/ 12h (IV)
Spironolacton 2 x 12,5 mg
Diet 1100 kcal with 10gr protein

Planning Assesment:
-

Lipid Profil
Chest X-Ray ( AP & L)

FOLLOW UP
July, 9th 2016
S
Oedema (+) Fever (-)
O Sensorium
CM, T: 36,9C
Head

Neck
Thorax
Abdomen

Face: Oedema (-).

Eyes: isochoric pupil, pale inferior palpebral conjunctiva
(-/-), icteric sclera (-/-), light reflexes (+/+), oedema
superior palpebra (+/+).
E/N/M are normal.
Lymph node enlargement (-)
SF, retraction (-). Heart rate 120 beats/min, regular,
Murmur (-). Respiratory rate 20 breaths/min, regular,
ronchi (-/-)
Bigger appearance, umbilical protrusion, soepel,
peristaltic (+) normal. Kidney, liver and spleen

22

Extremities

undetermined, shifting dullness (+)

Pulse 120 times/min, regular, blood pressure 100/60
mmHg, adequate pressure and volume, warm, CRT < 3.
Oedema (+) at lower extremities.

A
P

Nephrotic Syndrome
- IVFD D5% NaCl 0,9% 20 gtt/minute/micro
- Inj. Ceftazidim 25 mg/BW/12h => 300 mg/ 12h (IV)
- Inj. Lasik 1 mg/BW/12h => 12 mg/ 12h (IV)
- Spironolacton 2 x 12,5 mg
- Diet 1100 kcal with 10gr protein
- Fluid Balance/6 hours
- Morning urine Dipstick

July, 10th 2016

S
Oedema (+ ) Fever (-)
O Sensorium
CM, T: 36,7C
Head

Neck
Thorax
Abdomen
Extremities

Face: Oedema (-).

Eyes: isochoric pupil, pale inferior palpebral conjunctiva
(-/-), icteric sclera (-/-), light reflexes (+/+), oedema
superior palpebra (+/+).
E/N/M are normal.
Lymph node enlargement (-)
SF, retraction (-). Heart rate 110 beats/min, regular,
Murmur (-). Respiratory rate 20 breaths/min, regular,
ronchi (-/-)
Bigger appearance, umbilical protrusion, soepel,
peristaltic (+) normal. Kidney, liver and spleen
undetermined, shifting dullness (+)
Pulse 110 times/min, regular, blood pressure 100/70

23

mmHg, adequate pressure and volume, warm, CRT < 3.

Oedema (+) at lower extremities.
A
P

Nephrotic Syndrome
- IVFD D5% NaCl 0,9% 20 gtt/minute/micro
- Inj. Ceftazidim 300 mg/ 12h (IV)
- Inj. Lasik 12 mg/ 12h (IV)
- Spironolacton 2 x 12,5 mg
- Diet 1100 kcal with 10gr protein
- Fluid Balance/6 hours
- Morning urine Dipstick

July, 11th 2016

S
Oedema (+) Fever (+)
O Sensorium
CM, T: 37,8C
Head

Neck
Thorax
Abdomen
Extremities

Face: Oedema (-).

Eyes: isochoric pupil, pale inferior palpebral conjunctiva
(-/-), icteric sclera (-/-), light reflexes (+/+), oedema
superior palpebra (+/+) .
E/N/M are normal.
Lymph node enlargement (-)
SF, retraction (-). Heart rate 118 beats/min, regular,
Murmur (-). Respiratory rate 24 breaths/min, regular,
ronchi (-/-)
Bigger appearance, umbilical protrusion, soepel,
peristaltic (+) normal. Kidney, liver and spleen
undetermined, shifting dullness (+)
Pulse 118 times/min, regular, blood pressure 100/80
mmHg, adequate pressure and volume, warm, CRT < 3.
Oedema (+) at lower extremities.

Nephrotic Syndrome

24

IVFD D5% NaCl 0,9% 20 cc/hours

Inj. Ceftazidim 300 mg/ 12h (IV)
Inj. Lasik 12 mg/ 12h (IV)
Spironolacton 2 x 12,5 mg
Milk diet 100cc/3 hours (Oral)
Fluid Balance/6 hours
Morning urine Dipstick
Recheck Complete Blood Count, Albumin, Electrolyte,

Procalcitonin.
Urine & blood Culture

July, 12th 2016

S
Oedema (+), Fever (-)
O Sensorium
CM, T: 37,3C
Head

Neck
Thorax
Abdomen
Extremities

Face: Oedema (-).

Eyes: isochoric pupil, pale inferior palpebral conjunctiva
(-/-), icteric sclera (-/-), light reflexes (+/+), oedema
superior palpebra (+/+).
E/N/M are normal.
Lymph node enlargement (-)
SF, retraction (-). Heart rate 118 beats/min, regular,
Murmur (-). Respiratory rate 24 breaths/min, regular,
ronchi (-/-)
Bigger appearance, umbilical protrusion, soepel,
peristaltic (+) normal. Kidney, liver and spleen
undetermined, shifting dullness (+)
Pulse 118 times/min, regular, blood pressure 110/70
mmHg, adequate pressure and volume, warm, CRT < 3.
Oedema (+) at lower extremities.

A
P

Nephrotic Syndrome
- IVFD D5% NaCl 0,9% 20 cc/hours
- Inj. Ceftazidim 300 mg/ 12h (IV)
- Inj. Lasik 12 mg/ 12h (IV)
- Spironolacton 3 x 12,5 mg
- Milk diet 100cc/3 hours (Oral)
- Fluid Balance/6 hours
- Morning urine Dipstick

25

Follow Urine & blood Culture

July, 13th 2016

S
Oedema (+)
O Sensorium
Head

Neck
Thorax
Abdomen
Extremities

CM, T: 37,2C
Face: Oedema (-).
Eyes: isochoric pupil, pale inferior palpebral conjunctiva
(-/-), icteric sclera (-/-), light reflexes (+/+), oedema
superior palpebra (+/+).
E/N/M are normal.
Lymph node enlargement (-)
SF, retraction (-). Heart rate 120 beats/min, regular,
Murmur (-). Respiratory rate 20 breaths/min, regular,
ronchi (-/-)
Bigger appearance, umbilical protrusion, soepel,
peristaltic (+) normal. Kidney, liver and spleen
undetermined, shifting dullness (+)
Pulse 120 times/min, regular, blood pressure 100/70
mmHg, adequate pressure and volume, warm, CRT < 3.
Oedema (+) at lower extremities.

A
P

Nephrotic Syndrome
- IVFD D5% NaCl 0,9% 20 cc/hours
- Inj. Ceftazidim 300 mg/ 12h (IV)
- Inj. Lasik 12 mg/ 12h (IV)
- Inj. Furosemid 20 mg/6 hours
- Inj. Prednison 2 mg/BW (IV) => 2-2-1
- Spironolacton 3 x 12,5 mg
- Milk diet 100cc/3 hours (Oral)
- Fluid Balance/6 hours
- Morning urine Dipstick
- Follow blood Culture

July, 14th 2016

S
Oedema (+)
O Sensorium
Head

CM, T: 36,8C
Face: Oedema (-).
Eyes: isochoric pupil, pale inferior palpebral conjunctiva

26

Neck
Thorax
Abdomen
Extremities

(-/-), icteric sclera (-/-), light reflexes (+/+), oedema

superior palpebra (+/+).
E/N/M are normal.
Lymph node enlargement (-)
SF, retraction (-). Heart rate 110 beats/min, regular,
Murmur (-). Respiratory rate 24 breaths/min, regular,
ronchi (-/-)
Bigger appearance, umbilical protrusion, soepel,
peristaltic (+) normal. Kidney, liver and spleen
undetermined, shifting dullness (+)
Pulse 110 times/min, regular, blood pressure 110/70
mmHg, adequate pressure and volume, warm, CRT < 3.
Oedema (+) at lower extremities.

A
P

Nephrotic Syndrome
- IVFD D5% NaCl 0,9% 20 gtt/min/micro
- Inj. Ceftazidim 300 mg/ 12h (IV)
- Inj. Lasik 12 mg/ 12h (IV)
- Inj. Prednison 2 mg/BW (IV) => 2-2-1
- Spironolacton 3 x 12,5 mg
- Milk diet 100cc/3 hours (Oral)
- Fluid Balance/6 hours
- Morning urine Dipstick
- Follow blood Culture

27

CHAPTER 4
DISCUSSION
The patient is a 1 years 5 months old boy. Nephrotic syndrome often occurs in
93% in children compared to adults.
The patient was admitted to the hospital with a chief complaint of swelling
throughout the body. Interstitial edema is a common clinical expression of Nephrotic
Syndrome. Expansion of the interstitial compartment is secondary to the
accumulation of sodium in the extracellular compartment, due to an imbalance
between oral or parenteral sodium intake and urinary sodium output, along with
alterations of fluid transfer across the capillary walls.
Edema is the presenting symptom in about 95% of children with nephrotic
syndrome. Early on, the edema is intermittent and insidious, and its presence may not
be appreciated. A common story is for the child to present to a primary care
practitioner repeatedly for periorbital edema, which is ascribed to "allergies" until the
edema progresses. One of the clinical manifestations of nephrotic syndrome is edema
usually appears first in areas of low tissue resistance (eg, the periorbital, scrotal, and
labial regions). It can progress rapidly or slowly. Ultimately, it becomes generalized
and can be massive (anasarca). In this case, Patients has a history of swelling on the
eyes first then it is followed by general swelling throughout the abdomen and to the
extremities causing the edema to be massive (anasarca).
Patient was diagnosed with nephrotic syndrome due to hypoalbuminemia.
Hypoalbuminemia is a low level of albumin (a protein) in the blood due to
proteinuria. Low albumin in the blood causes fluid to move from the blood into the
tissue, causing swelling. The kidney perceives the decrease of fluid in the blood and
aggressively retains as much fluid and salt as it can. This contributes to the body's
fluid-overload state.

28

Nephrotic Syndrome due to Hypercholesterolemia (high level of cholesterol in

the blood). Hypercholesterolemia, high blood cholesterol, is common in nephrotic
syndrome). In addition to albumin, other important enzymes involved in cholesterol
metabolism slip through the glomeruli, which contribute to high blood cholesterol.
Laboratory criteria of nephrotic syndrome are proteinuria, hypoalbuminemia ,
hyperlipidemia, edema and one of minor criteria such as hematuria. In this patient,
based on laboratory result, the urinary protein test result is positive 1, and blood was
found in the urinalysis with 30-40 erythrocyte confirming hematuria.
The management for nephrotic syndrome is prednisone 2 mg/kg per day for 46 weeks, followed by 1.5 mg/kg per day on alternating days for another 4-6 weeks.
Some children with childhood nephrotic syndrome develop high blood pressure and
may need to take additional medications to lower their blood pressure. Loop diuretics,
such as furosemide 2 mg/kg per day, can be used to treat fluid overload and edema.
Prophylactic penicillin can be used to prevent streptococcal or staphylococcal
infection secondary to decreased complement levels. Besides, a low salt diet is used
to try to prevent further fluid retention and oedema.

29

CHAPTER V
SUMMARY
DW, 1 years 5 months old, male, was admitted to the Pediatric Departement
of H. Adam Malik General Hospital on 8th July, 2016. With his main complaint is
swelling throughout the body. Based on anamnesis, physical examination, and
laboratory assesment, he was diagnosed with Nephrotic Syndrome and was given
treatment of the followings:
-

IVFD D5% NaCl 0,9% 20 gtt/min/micro

Inj. Ceftazidim 25 mg/BW/12h => 300 mg/ 12h (IV)
Inj. Lasik 1 mg/BW/12h => 12 mg/ 12h (IV)
Inj. Prednison 2 mg/BW (IV) => 2-2-1
Spironolacton 3 x 12,5 mg
Milk diet 100cc/3 hours (Oral)

30

REFERENCES
Andolino TP, Reid-Adam J, 2015. Nephrotic Syndrome. Pediatrics in Review, 36(3):
117-125
Avner ED, Harmon WE, Niaudet P, Yoshikawa N, 2009. Pediatric Nephrology 6 th
Edition. German: Springer.
Cohen EP, Sinnakirouchenan R et al, 2014. Nephrotic Syndrome. Accessed from:
http://emedicine.medscape.com/article/244631-overview Last access: November 3rd
2015
Indian Pediatric Nephrology Group, 2008. Management of Steroid Sensitive
Nephrotic Syndrome: Revised Guidelines.
Lane JC, Langman CB, Finberg L, Spitzer A, Windle ML, 2015. Pediatric Nephrotic
Syndrome. Accessed from: http://emedicine.medscape.com/article/982920-overview
Last access: November 3rd 2015
Niaudet P. Steroid-Sensitive Idiopathic Nephrotic Syndrome in Children. Avner E,
Harmon W and Niaudet P. Pediatric Nephrology. 5th ed. Philadelphia: Lippincott,
Williams & Wilkins; 2004.
Roth KS, Amaker BH, Chan JCM, 2002. Nephrotic Syndrome: Pathogenesis and
Management. Pediatrics in Review, 23(7): 237-247
Srivastava RN, Bagga A, 2005. Nephrotic Syndrome in Children. Accessed from:
http://www.aiims.edu/aiims/departments/pediatrics/Nephro%2006%20pdf/Nephrotic
%20Syndrome%20in%20Children.pdf Last access: November 7th 2015