CASE REPORT

Nephrotic Syndrome

Compiled by :
Muhammad Fakhrur Rozi (120100163)

Supervisor :
dr. Tina Christina L. Tobing, M.Ked(Ped), Sp A(K)

Pediatric Departement
H. Adam Malik General Hospital
Faculty of Medicine Universitas 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 ....................................................................

10

2.8 Diagnostic Evaluation ...................................................................

10

2.9 Treatment ......................................................................................

12

3.0 Prognosis .......................................................................................

16

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

17

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

31

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

33

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

34

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 post-streptococcal 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, non-neurogenic 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
of CNS is 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.

11

Physical examination is done to detect infections and underlying systemic disorder,

e.g., systemic lupus erythematosus, Henoch Schonlein purpura, etc. Infections should
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

12

high molecular weight. Thrombin also is increased, while fibrinolytic activity and
circulating quantities of platelet adhesion inhibitors are decreased. As a 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

13

directly proportional to the rate of expansion of intravascular volume. Thus, too rapid
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/m2 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

14

adjunctive treatment, such as anticoagulation therapy, should be used judiciously. If

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

Methylprednisolone
sodium succinate

Nonsteroidal Agents
Cyclophosphamide

Dosage
2 mg/kg per day orally
(maximum, 60 mg/d)

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
30 mg/kg per week
In partial steroid-resistant cases,
intravenously;
this relatively high-dose regimen
combined with
may aid in moderating
prednisone 2 mg/kg on development of FSGS
alternate days for
variable duration
according to
underlying diseases
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

Levamisole

2.5 mg/kg per day

during remissions
5 to 10 mg/kg per day
chronically

Angiotensinconverting Enzyme
Inhibitors

Comments

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

16

Indomethacin

50 kg/day for short

term (<3 mo)

Mizoribine

2 to 5 mg/kg per day

for 24 wk

Mycophenolate
mofetil

25 mg/kg per day in

two divided doses for
up to 1 y

Reduces glomerular
hyperfiltration. Adverse effect:
hepatorenal toxicity
Reduces relapsing nephrotic
syndrome. Blocks purine
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

3.0 Prognosis
Mortality in minimal-change nephrotic syndrome is approximately 2%, with
the majority of deaths due to peritonitis or thrombus. 98% of children who have
minimal change nephrosis, most are steroid-responsive and can be expected to return
eventually to a normal state. Minimal-change nephrotic syndrome results in relapses;
about two thirds of patients experience at least a single relapse, with another third
possibly developing a protracted series of such relapses over many years

17

CHAPTER 3
CASE REPORT

3.1. Case Objective

The objective of this paper is to report a case of a 11 years 5 months 30 days
old boy with a diagnosis of Nephrotic Syndrome.

3.2. Case
AEP , boys aged 11 years 5 months 30 days , came to Haji Adam Malik
Hospital on June 27, 2016 with complaints of swelling throughout the body.

3.3. History of Disease

AEP, boys aged 11 years 5 months 30 days , came to Haji Adam Malik
Hospital on July 13, 2016 with a chief complaint swelling throughout the body and
low albumin serum. Swelling occurs in both feet , both hands , and scrotum . No
complaints before the onset of swelling . This complaint felt at first since a year ago
and relapse more than twice a year.
In July 27th 2015 his parents caught him in swelling thoroughout his body,
started from eye and a few weeks later sweeling appeared on foot. On July 28th 2015,
His parents brought him to RS.Haji Medan and hospitalized during one month. First
swelling the doctor also found nephrotic-range proteinuria, and the doctor diagnosed
the patient as nephrotic syndrome. On August 31st 2015, his urine was free from
protein and the medication was completed on December 4th 2015.
On February 15th 2016, swelling was found on his foot, bilaterally, but now
with additional symptom, ascites. Nephrotic-range proteinuria was found again (+++).
Then, patient came to RS.Haji Medan and he was treated without hospitalized. On April
2016 he finished his treatment.

18

On June 9th 2016, Nephrotic-range proteinuria was found again (+++) and
the the patient was hospitalied for a week in RS.Haji Medan. On June 27th 2016, the
patient was refered to RSUPHAM and
On July 12nd 2016, the patient was hospitalized in RSUPHAM because of
his low albumin serum (1,7gr/dl).
History of Medication

: - Furosemide 2x20 mg
- Prednisone 4-4-4
- Captopril 2x12,5 mg
- Spirinolactone 2x12,5 mg
- Valsartan 1x20 mg
- Diet MBRG 1760 kkal dengan 60 gr protein

History of feeding

: 0-6 month: breast feeding only

History of immunization

: Patient had a complete immunization. BCG scar

was found on the right upper arm.

History of growth and development

:2 months of age head-lift,

3 porne alone at three month
6 months of age sit alone
8-9 months of age standing with holding
11-12 months of age standing without holding
15 months of age running

Physical Examination:
Present status:
Sensorium : Compos Mentis `
Body temperature: 36,7C
Body Weight : 33 kg
Body Length : 134 cm

19

BB/U : 84,6%, TB/U : 91%, BB/TB : 113%

Cyanosis (-), Anemic (-), Icteric (-), Dyspnea (-), Edema (+)

Localized status:
1. Head

:
Fontanels within normal limit. Head circumference : ?
Face

: edema (+)

Eye

: light reflex (+/+), isochoric pupil, pale inferior

palpebral conjunctiva (-/-), periorbital edema (+/+)

Ears

: both ear lobe in normal morphologic.

Nose : septum deviation (-), normal morphologic.

Mouth : cyanosis (-), normal morphologic.
2. Neck

:
Lymph node enlargement (-)

3. Thorax

:
Symmetrical fusiform, retraction (-)
Inter costae shown easily, vertebrae shown easily
HR: 82 bpm, regular, murmur (-/-)
RR: 24 bpm, regular, ronchi (-/-), wheezing (-/-)

4. Abdomen :
Soepel, shifting dullness (+), hepar, lien : unpalpable
5. Extremities

:
Pulse 82 bpm, regular,adequate p/v, felt warm, CRT < 3,
oedema (+/+).

6. Anogenital

:
Male, enlargement scrotum (+)

20

Differential diagnosis :

Relapsed-Nephrotic Syndrome + Hypocalcemia+Sepsis

Steroid-resistant

Nephrotic

Syndrome

Hypocalcemia+Sepsis
Acute Glomerulonephritic + Hypocalcemia+ Sepsis
Congestive Heart Failure + Hypocalcemia+ Sepsis
Working diagnosis

Relapsed-Nephrotic syndrome + Hypocalcemia+

Sepsis

Laboratory finding:
Complete blood analysis (July 12nd 2016)
Test

Result

Unit

References

Hemoglobin

12.9

g/dL

10,8 15,6

Erythrocyte

4.92

106/L

4,50 6,50

Leucocyte

20,580

/L

4.500 13.500

Thrombocyte

497,000

103/L

181 521

Hematocrite

39

33 45

Eosinophil

0.00

1,00 3,00

Basophil

0.2

0,00 1,00

Neutrophil

91.2

r%

50,00 70,00

Lymphocyte

7.40

20,00 40,00

Monocyte

1.20

2.00 8.00

Neutrophil

18.75

103/L

2.7 6.5

1,53

103/L

1.5 3.7

0,24

103/L

0.2 0.4

absolute
Lymphocyte
absolute
Monocyte
absolute

21

0,01

103/L

0 0.10

0,05

103/L

0 0.1

MCV

79

fL

69 93

MCH

26.2

Pg

22 34

MCHC

33.2

g/dL

32 36

RDW

13.5

11 15

MPV

8.2

fL

6.5 9.5

PDW

7.0

10.0 18.0

PCT

0.380

0.100 0.500

Eosinophil
absolute
Basophil
absolute

Calcium

6.8

mg/dL

8.4-10.2

Natrium

135

mEq/L

135-155

Potassium

4.3

mEq/L

3.6-5.5

Chloride

96

mEq/L

96-106

Liver and Renal Function

Albumin

1.7

g/dL

3,5 5,0

Blood Urea Nitrogen (BUN)

21

mg/dL

9-21

Ureum

45

mg/dL

19-44

Creatinine

0.73

mg/dL

0.7-1.3

Imunoserologi
CRP Kuantitatif

<0.7

mg/dL

<0.7

Procalcitonin

0.15

ng/mL

<0.05

22

Urinalisa
Protein

Positif 3

Negatif

Urobilinogen

Negatif

Negatif

Nitrit

Negatif

Negatif

Leukosit

Negatif

Negatif

Darah

Negatif

Negatif

Eritrosit

3-5

lbp

<3

Leukosit

2-4

lbp

<6

Epitel

3-6

lbp

Casts

Granular 2-4

lbp

Kristal

Negatif

lbp

Therapy

P/ IVFD NaCl 0,9% 4gtt/i

Ceftriaxone 1gr/12hr/IV
Prednison 5-5-6
Captopril 2x12.5mg
Spirinolaktone 2x12,5mg
Valsartan 1x20mg
Furosemid 2x20 mg
Albumin 20% 100 cc & Albumin 25% 85 cc
Diet MBRG 1760 kkal protein 60 gr

Negatif

23

FOLLOW UP
July, 12nd 2016 until July, 15th 2016
S

Oedema (+) Fever (+)

Sensorium

CM, T: 38,8C

Head

Face: Oedema (+).

Eyes: isochoric pupil, pale inferior palpebral conjunctiva
(-/-), icteric sclera (-/-), light reflexes (+/+), periorbital
edema (+/+).
E/N/M are normal.
Lymph node enlargement (-)

Neck

Thorax

SF, retraction (-). Heart rate 82 beats/min, regular,

Murmur (-). Respiratory rate 24 breaths/min, regular,
ronchi (-/-)

Abdomen

Bigger appearance, peristaltic (+) normal. Kidney, liver

and spleen undetermined, shifting dullness (+)

Extremities

Pulse 82 times/min, regular, blood pressure 100/60

mmHg, adequate pressure and volume, warm, CRT <
3. Oedema (+) at lower extremities.

Relapsed-Nephrotic Syndrome dd/ Steroid Resistent- Nephrotic Syndrome

+ Susp.Sepsis

Inj.Ceftriaxone 1gr/12 hr/IV

Prednison 5-5-6

Captopril 2 x 12,5 mg

Valsartan 1 x 20 mg

Inj.Furosemide 2x20mg

Spironolactone 2x12.5mg

Diet MB RG1760 kcal, protein 60 gr

24

Urine Dipstick
LEU/NIT/

URO /PRO/PH/BLO/ SG /KET/ BIL /GLU

12/ + /0,2(3,5)/ +++ /5,0/ - /1.020/

- /1(170)+/

Laboratorium Result
Albumin

: 1.7 mg/dL

BUN

: 21 mg/dL

Urea

: 45 mg/dL

GFR : 103.97 (96.5-136.9)

Creatinin : 0.73 mg/dL

CRP Quantitative : <0.7 mg/dL
Procalcitonin : 0.15 ng/mL
R/ Blood culture, urine culture, scheduled for cyclophosphamide A
treatment until hemodinamicaly stable
R/ Albumin Subtitution (July 13rd 2016)
Albumin Subtitution = (2.5 1.7) x 0.8 x 33 = 21.12 g
25% Albumin

= 21.15/25 x 100% = 84.4 cc

20 % Albumin

= 21.15/20 x 100% = 105.75 cc=100 cc

July, 17th 2016

S

Oedema (+ ) Seizure (+) Fever (+) Histeria (+) Restless (+)

1st seizure : 11.30 AM for 2 minutes
2nd seizure : 15.00 PM no more than 5 minutes

Sensorium

CM, T: 38.8C

Head

Face: Oedema (+).

Eyes: isochoric pupil, pale inferior palpebral conjunctiva
(-/-), icteric sclera (-/-), light reflexes (+/+), oedema
superior palpebra (+/+).
E/N/M are normal.
Lymph node enlargement (-)

Neck

25

Thorax

SF, retraction (-). Heart rate 106 beats/min, regular,

Murmur (-). Respiratory rate 20 breaths/min, regular,
ronchi (-/-)

Abdomen
Bigger appearance, peristaltic (+) normal. Kidney, liver
and spleen undetermined, shifting dullness (+)

Extremities

Pulse 106 times/min, regular, blood pressure 120/60

mmHg, adequate pressure and volume, warm, CRT <
3. Oedema (+) at lower extremities.
A

Relapsed-Nephrotic Syndrome dd/ Resistant Steroid Nephrotic Syndrome+

Seizure ec dd/Thrombosis or Electrolyte disturbances + Susp.Sepsis

IVFD NaCl 0.9% 4cc/hr

Head Elevation midline position 30

Inj.Ceftriaxone 1gr/ 12 hr IV

Prednison 5-5-6

Captopril 2 x 12,5 mg

Valsartan 1 x 20 mg

Inj.Furosemide 30mg/ 12 hr IV

Spironolactone 2x12.5mg

Diet MB RG 1760 kcal, protein 60 gr

Stesolid supp.10mg

Hypocalcemia correction: 0.5 cc/kg= 15 cc ca gluconas in 15 cc

D5% within 20 minutes.

Inj.Phenytoin LD 20mg/kg BW (300 mg of phenytoin) in 20cc

Nacl 0.9% within 60 minutes. Twelve hours later maintenance
dose 5mg/kg BW (75 mg of phenytoin in 20 cc Nacl 0.9% within
60 minutes) / 12 hr

Urine Dipstick
LEU/NIT/

URO / PRO /PH/BLO/ SG /KET/BIL /GLU

26

/ + /0,2(3,5)/ +++ /6,0/ - /1.030/ - / + / Glucose Stick

112 mg/dL
Laboratorium Result
Hb/ Ht/L/T : 11.3/34/20,320/508,000
Albumin

: 2,5

U/ Cr

: 28/0.48

GFr

: 153

Ca/ Na/ K/ Cl : 7.8/ 139/ 3.3/ 100

R/ Schedulded for Cyclophosphamide treatment until hemodynamically
stable and Non-contrast Head CT-Scan
July, 18th 2016 06.30 AM
S

Oedema (+) Seizure (-) Fever (-)

Sensorium

CM, T: 36,7C

Head

Thorax

Face: Oedema (+).

Eyes: isochoric pupil, pale inferior palpebral conjunctiva
(-/-), icteric sclera (-/-), light reflexes (+/+), oedema
superior palpebra (+/+).
E/N/M are normal.
Lymph node enlargement (-)

Abdomen

SF, retraction (-). Heart rate 103 beats/min, regular,

Murmur

Neck/

(-). Respiratory rate 20 breaths/min, regular, ronchi (-/-)

Peristaltic (+) normal. Kidney, liver and spleen

undetermined, shifting dullness (+)
Pulse 103 times/min, regular, blood pressure 120/80
mmHg, adequate pressure and volume, warm, CRT <
3. Oedema (+) at lower extremities.

27

Relapsed-Nephrotic Syndrome dd/ Resistant-steroid Nephrotic Syndrome +

Seizure ec Thrombosis dd/ Electrolyte Disturbances
+ Sepsis.

IVFD Nacl 0.9% 4cc/hr

Prednison 3-5-6

Captopril 2 x 12,5 mg

Valsartan 1 x 20 mg

Diet MB RG 1760 kcal, protein 60 gr

Urine Dipstick
LEU/NIT/

URO / PRO /PH/BLO/ SG /KET/BIL /GLU

/ + /0,2(3,5)/ ++ /6,0/ - /1.030/ - / + / R/ Inj. Midazolam Continious, Head CT-Scan

27th July 2016: The patient was allowed to go home and get controll once a month.

28

CHAPTER 4
CASE DISCUSSION

THEORY
CASE
Definition : Nephrotic syndrome is a Urinary protein ( +++ ) ~
clinical

condition

characterized

by Hypoalbuminemia : 2 g / dl

severe proteinuria mainly albuminuria

Edema ansarka ( + )

( > 1g / m2 / 24h ) , hypoproteinemia ,

(serum albumin < 2,5gr / dl ) edema and
hypercholesterolemia ( > 250 mg / dl )

Epidemiology:

Boy , age : 11 years 6 months 0 days

The incidence of primary SN in children

around 2-7 per 100000 children , and will
be bnayak found in boys ( 2 : 1 ) . The
primary nephrotic syndrome most often
occurs in 1.5 to 5 years of age .

Etiology:

Primary idiopathic nephrotic syndrome,

I. Congenital Nephrotic Syndrome

minimal change nephrotic syndrome

Inherited as an autosomal recessive or

because

the

reaction

maternofetal,

resistant to all treatment , edema since

neoantus and has a very poor prognosis
and would die a first monthinstance of
life.
II. Secondary nephrotic syndrome :
1. Malaria parasite kuartana or others

29

2. Collagen disease SLE, or HSP

3. Chemicals like trimetadion , paradion,
penicillamine .
4. Amilioidosis , sickle cell disease , etc.
III . Idiopathic nephrotic syndrome
This classification is known based on
renal biopsy. 3 abnormalities are found
the most frequent forwading with their
prevalency:
1. Minimal change nephrotic syndrome
(MCNC ).The most frequent type of 70
%
2. Focal segmental glomerulosclerosis
(FSGS ) , the incidence of about 10 % .
This type is usually the type that precedes
MCNC
Symptoms and sign:

Oedema anasarka (+)

1. Oedema anasarka

Heavy proteinuria (+++) ~

2. Heavy proteinuria >40mg/m2/hours

Hypoalbuminemia : 2,0g/dl

3. Marked hipoalbuminemia <2g/dl

4. Hyperchlesterolemia >220 mg/dl
Therapy:

IVFD NaCl 0.9% 4cc/hr

- Take a rest untill edema cure

Prednison 5-5-6

-Methyl prednisolone 60mg/m2/day for

Captopril 2 x 12,5 mg

28 days (Initial/full dose prednisone)

Valsartan 1 x 20 mg

- Reduction dose 40mg/m2/day for 3days

Inj.Furosemide 30mg/ 12 hr IV

for 28 days (single morning alternate

Spironolactone 2x12.5mg

days)

30

- Fluid restriction:
Loop diuretics such as furosemide 1-3
mg

kg /

day,

spironolactone

combined
an

with

Diet MB RG 1760 kcal, protein

60 gr

aldosterone

antagonist , a diuretic potassium-sparing)

2-4 mg / kg / day
-Severe hypoalbuminemia ( 1 gr/dL),
should be given 20-25 % albumin
infusion at a dose of 1 g / kg for2-4 hours
-Diet
normal protein according to the RDA
(recommendeddaily allowances ) is 1.52 g / kg / day . Low-salt diet ( 1-2 g / day)
only required for children suffering from
edema .
Prognosis:
*Depend on the adequate therapy and the
response of therapy
Remission : negative or trace proteinuria
( proteinuria < 4 mg / m2
LPB /h ) 3 consecutive days in one week
Relapse : 2+ proteinuria ( proteinuria
> 40 mg / m2LPB / h ) 3 days
successively in 1 week
Relapse is rare : less than 2 x relapse
within the first 6 months after

Frequent relapses

31

initial response to or less than 4 x per

year of observation
Relapses often ( frequent relapses ) :
2 x relapse within the first 6 months
after an initial response or 4 x within a
period of 1 year
Steroid dependent : 2 x consecutive
relapse during steroid dosedecreased (
alternating) or within 14 days after
treatmentterminated
Steroid Resistant : no remission on
medication prednisonefull dose (full
dose) 2 mg / kg / day for 4 weeks .
Sensitive Steroid : remission occurred in
dose prednisonefull for 4 weeks

32

CHAPTER 5
SUMMARY
AEP , boys aged 11 years 6 months 0 days , was diagnosed with nephrotic syndrome.
Therapy: /
-

IVFD NaCl 0.9% 4cc/hr

Head Elevation midline position 30

Inj.Ceftriaxone 1gr/ 12 hr IV

Prednison 5-5-6

Captopril 2 x 12,5 mg

Valsartan 1 x 20 mg

Inj.Furosemide 30mg/ 12 hr IV

Spironolactone 2x12.5mg

Diet MB RG 1760 kcal, protein 60 gr

Stesolid supp.10mg

Hypocalcemia correction: 0.5 cc/kg= 15 cc ca gluconas in 15 cc D5% within

20 minutes.

Inj.Phenytoin LD 20mg/kg BW (300 mg of phenytoin) in 20cc Nacl 0.9%

within 60 minutes. Twelve hours later maintenance dose 5mg/kg BW (75 mg
of phenytoin in 20 cc Nacl 0.9% within 60 minutes) / 12 hr

Albumin

33

34

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 6th
Edition. German: Springer.
Cohen EP, Sinnakirouchenan R et al, 2014. Nephrotic Syndrome. Accessed from:
http://emedicine.medscape.com/article/244631-overview Last access: July 25rd 2016
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: July 23rd 2016
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: July 22th 2016