The clinical significance of platelet count among pediatric patients

with Nephrotic Syndrome : A case control study

Shanessa Budiarty, M.D.

2nd Year Pediatric Resident

Orpheus C. Monakil, M.D.

Adviser

Madeleine Grace Sosa, M.D.

Epidemiologist

1
The clinical significance of platelet count among pediatric patients with Nephrotic Syndrome

ABSTRACT

Objectives : To determine the relationship of initial platelet count between pediatric patients with steroid
responsive and steroid non responsive nephrotic syndrome admitted January 1997- May 2014 at UMC

Design : A case control study

Patients : Patients with Idiopathic Nephrotic Syndrome aged 1-18 years old

Methods : Demographic, hematologic, serologic and urinalysis findings were analyzed. Patient were
grouped into, group A (steroid non responsive) and group B (steroid responsive). Comparison of initial
platelet count between group A and group B were analyzed.

Results : A total of 90 pediatric patients with Idiopathic Nephrotic Syndrome were included in the study.
Most of the patients belong to the 1-5 years old age. Fifty-seven (63.3%) were males while there were 33
(36.7%) females with a 1.7 : 1 male to female ratio. Most patients consulted because of edema. Anemia
(53.2%) and leukocytosis (75.6%) were noted. Low albumin and hypercholesterolemia were consistent
with nephrotic syndrome. Majority of the patients (63.3%) showed urine albumin levels or a with
nephrotic range proteinuria. All variable were analyzed between group A and group B showed no
statistically significant difference. Platelet count is only 1 variable significant with Fishers exact p-value
of 0.005812.

Conclusion : Patient with increased platelet count had 1.3 times more likely to be steroid non responsive
than those normal platelet count.

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I. INTRODUCTION

A. Burden of Illness

Nephrotic syndrome (NS) is characterized by substantial loss of protein in the urine

(primarily albuminuria), leading to hypoproteinemia (hypoalbuminemia) and its result, edema.

Hyperlipidemia, hypercholesterolemia, and increased lipiduria are usually associated. Although not

commonly thought of as part of the syndrome, hypertension, hematuria, and azotemia may also

occur1. The annual incidence of NS in children in the USA and in Europe has been estimated to be 1

7 per 100,000 children, with a cumulative prevalence of 16 per 100,000 children2. There is

epidemiological evidence of a higher incidence of nephrotic syndrome in children from south Asia. In

the Philippines, nephrotic syndrome accounts for 10.2 cases per 100, 000 population and based on the

year 2000 statistics has a death rate of 2.1%3.

Nephrotic syndrome in children can be classified according to 3 groups : idiopathic,

secondary, congenital or infantile. . Idiopathic nephrotic syndrome (INS) is the most frequent form of

NS in children representing more than 90 percent of cases between 1 and 10 years of age and 50

percent after 10 years of age2. Secondary nephrotic syndrome is defined as nephrotic syndrome

associated with well-defined diseases that are inflammatory (e.g., lupus nephritis, acute postinfectious

glomerulonephritis, IgA nephropathy, Henoch-Schnlein purpura, etc.). Congenital or infantile NS

are occur before the age of one year and are mostly associated with infections (e.g., syphilis,

toxoplasmosis, etc.) or with mutations of genes coding for podocytes proteins and are steroid resistant

The most common form of NS in children is minimal change lesion (MCL). The vast

majority of patients with MCL (>90%) respond to steroid therapy. Other types of INS like focal and

segmental glomerulosclerosis (FSGS), diffuse mesangial proliferation (DMP), membranoproliferative

glomerulonephritis (MPGN) and membranous glomerulonephritis (MGN) are less steroid-responsive.

More than 90 percent of patients who respond to steroid therapy have MCL. MCL can accurately be

3
diagnosed based on presenting clinical findings in children younger than 6 years of age, absence of

hypertension, absence of hematuria, normal complement levels, and normal renal function4.

Thrombosis, a serious complication in children with nephrotic syndrome (NS), occurs in

28-42% patients, 8.1% among them have recurrent episodes of thrombosis.

The risk factors of thrombosis are increased thrombocyte aggregation, increased coagulation factors,
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hypovolemia, corticosteroid treatment, and increased platelet count (thrombocytosis) .

Thrombocytosis occurs in 57.5% of NS patients. Most children with idiopathic NS respond to initial

steroid treatment; however approximately 60-80% of cases will undergo relapse and half of them

have frequent relapses or steroid dependence, needing high dose steroid administration to achive

remission. During the relapse episode, NS patients tend to have increased platelet count compared to

that in the initial attack. Frequent relapse nephrotic syndrome (FRNS) patients may need long term

steroid therapy, i.e., 6-12 months, which may increase the risk of thrombocytosis8.

B. Disease Causation

The glomerular capillary wall consist of three structural elements that constitute the

permselectivity barrier : endothelial cells separated by fenestrae, the glomerular basement membrane

made up of a network of matrix proteins, and specialised epithelial cells (podocytes) connected to

each other via an interdigitating network of slit diaphragms. Normally, proteins the size of albumin

(69 kd) and larger are excluded from filtration, a restriction that depends substantially on the integrity

of the slit diaphragms. In nephrotic syndrome, glomeruli appear greatly changed adjacent podocytes

appear fused together, assuming a flattened rather than foot-like morphology5.

Idiopathic nephrotic syndrome is associated with complex disturbances in the immune

system, especially T-cell mediated immunity. Steroid-resistant nephrotic syndrome can be associated

with mutations in NPHS2 (podocin) and WT1 genes, as well as other components of the glomerular

filtration apparatus, such as the slit pore, and include nephrin, NEPH1, and CD2 associated protein6.

4
 Although, the mechanism of edema formation in nephrotic syndrome is incompletely

understood, it seems likely that in most instances, massive urinary protein loss leads to

hypoalbuminemia, which causes a decrease in plasma oncotic pressure and transudation of fluid from

the intravascular compartment to the interstitial space. In the nephrotic state, serum lipid levels

(cholesterol, triglycerides) are elevated for 2 reasons. Hypoalbuminemia stimulates generalized

hepatic protein synthesis, including synthesis of lipoproteins. This is also why a number coagulation

factors are increased, increasing the risk of thrombosis. In addition, lipid catabolism is diminished as

a result of reduced plasma levels of lipoprotein lipase related to increased urinary losses of this

enzyme. Nephrotic syndrome is a hypercoagulable state resulting from multiple factors : vascular

statis, an increase in hepatic production of fibrinogen and other clotting factors, decreased serum

levels of anticoagulation factors, increased platelet production (as an acute phase reactant), and

increased platelet aggregation. The coagulopathy manifest with thromboembolic events6.

Nephrotic syndrome is characterized by heavy proteinuria, hypoalbuminemia (serum

albumin <2.5g/dL), hyperlipidemia (serum cholesterol >200 mg/dL) and edema. Nephrotic range

proteinuria is present if early morning urine protein is +3 or +4 (on dipstick test), spot

protein/creatinine ratio >2mg/mg, or urine albumin excretion >40mg/m2 per hour. Based on a study

done by Maravillosa, et al in our insitution on patients with idiopathic nephrotic syndrome diagnosed

with the aid of routine urinalysis,urine protein level of +2 to +4 has a high specificity of 91.67% with

a diagnostic accuracy of 33.33 to 53.85%7.

Adequate treatment of the initial episode, both in terms of dose and duration of

corticosteroids is important. The standard medication for treatment is prednisolone or prednisone. The

use of methylprednisolone, dexamethasone, betamethasone, triamcinolone, or hydrocortisone is not

recommended. Prednisone is initially given at a dose of 60mg/m2/day in a single dose for 4-6 weeks.

According to the statistics, 80-90% of children respond to steroid therapy within 3 weeks. Signs of

positive response to steroid therapy include diuresis, disappearance of edema and urine finding of

5
trace or negative protein. After the 4-6 week daily course, steroids are tapered to 40mg/m2/day given

every other day for 4 weeks(maintenance phase). After the four week maintenance phase, the steroid

is slowly tapered for 1-2 months until the patient is off the medications6.

Children who continue to have proteinuria (+2 or greater) after 8 week of steroid therapy

are considered steroid resistant, and diagnostic renal biopsy should be performed. A subset of patients

relaps while on alternate day steroid therapy or within 28 days of completing a successful course of

prednisone therapy. Such patients are termed steroid dependent. Patients who respond well to

prednisone therapy but relapse 4 times in a 12 mo period are termed frequent relapses6.

C. Review of Related Literature

Thromboembolic complications remain one of the most serious complications in patients

with nephrotic syndrome and are considered a major threat to nephrotic patients. Numerous factor are

involved in the occurrence of thromboembolic complications in NS. There is alteration in every

coagulation factor and inhibitor as well as decreased fibrinolytic activity. In addition, thrombocytosis

and platelet hyperactivity have been suggested to contribute to the thrombophilic diathesis

characteristic of NS.

A study by Farid, et al (2011) in Egypt, reported significant increase in platelet counts

among pediatric patients with nephrotic syndrome, both in relapse and in remission than in the

controls, with statistically highly significants differences (p<0.001), but there was no difference in

platelet count between the proteinuria and remission group (p>0.05). This supports the hypothesis

that platelets may play significant role in generating hypercoagulability in NS. The above findings

have informed the present policy of using antiplatelet drugs and low molecular weight heparin in

patient with NS. The indications for anticoagulants include significant thrombocytosis, resistant

oedema, severe ascites with dilated veins around the umbilicus, renal biopsy findings of fibrin

deposition inside the glomeruli and in between the tubules, and glomerulosclerosis.

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 In a study conducted in Iran by Mortazavi, et al (2008), thrombocytosis was found in

50% of patients with nephrotic syndrome at relapse period. There was no correlation between urinary

protein excretion and the haemostatic factors.

Another study conducted by Hafni, et al (2007) in Bandung, Indonesia , it was found that

the platelet level of frequent relapses of NS (FRNS)patients ( 517909.09) was higher than that of

infrequent relapses of NS (IFRNS)patients (416272.73). The occurrence of thrombocytosis in

children with FRNS was higher than that of children with IFRNS.

In a collaborative study by EL- Domiaty et al (1999) in Egypt, which included 20

children aged 2-12 years in the proteinuric phase of idiopathic NS. The study cases included two

groups : Group I : 8 patients in the initial attack of NS and group II: 12 patients in relapse (defined as

recurrence of edema, proteinuria, and hypoalbuminemia). At the time of study, all relapsers were off

steroid therapy for at least one month. Ten healthy children (7 males and 3 females of matching age

and sex served as a control group). Statistical analysis was done using conventional methods. The test

was considered significant if P 0.05. It was found that platelet count was higher in nephrotics

(platelet count range 260.000-750.000) than controls ( platelet count range 170.000-360.000);

relapsers had higher counts (platelet count range 280.000-750.0000) than nephrotics in initial attack

(platelet count range 260.000-400.000) and the differences were statistically significant (P< 0.005 and

P< 0.005 respectively). Mean difference was higher in nephrotic (389.500) than controls (256.000)

and relapsers had higher mean difference (445.833) than initial attack (305.000).

D. Definition of Terms 6

1. Nephrotic syndrome : edema, proteinuria >40mg/m2/hour or +2 to +4, plasma albumin <2.5

g/dl (25 g/L) and hypercholesterolemia

2. Nephrotic syndrome remission : urine albumin nil or trace (or proteinuria <4mg/m2/h) for

three consecutive early morning specimens

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 3. Steroid responsive : remission achieved after complete steroid therapy (induction therapy

with prednisone 60mg/m2/day for 6 weeks and tapered course 40mg/m2/day every other day

and discontinued over the next 2-3mo)

4. Steroid non responsive include steroid resistant, frequent relapse and steroid dependent.

Steroid resistant : Failure to achieve remission inspite of 4-6weeks prednisone

60mg/m2/day

Frequent relapse : 2 or more relapses within 6 months of initial response

Steroid dependent : Relapse while on tapered course or within 28 days of stopping

prednisone therapy

5. Platelet count : a test to measure how many platelets in blood. Platelets are parts of the blood

that help the blood clot. The normal number of platelets in the blood is 150.000-

400.000/mm3

E. Significance of the Study

A hypercoagulable state and thromboembolic complications are well known features of

NS. Increased plasma level of coagulation factors, decreased level of natural anticoagulant proteins,

and decreased fibrinolytic activity are reported in nephrosis. The role of platelets in promoting

hypercoagulability in NS may be of particular importance. Increased platelet adhesion, aggregate

formation and coagulation at injured vessels wall have been proposed as important mechanism in the

development of thrombosis. It has been postulated that platelet hyperactivity is also an important

feature of the prethrombotic state in patients with NS.

Studies have shown that increase platelet count is more commonly found in frequent

relapsing nephrotic syndrome, which puts them at risk for thrombosis. Therefore we should take more

precaution to the occurrence of thrombosis in patient with frequent relapsing nephrotic syndrome.

Thus, this study will attempt to the determine between platelet count of children with nephrotic

syndrome in relation to steroid response to treatment.

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II. OBJECTIVES

General Objective
To determine the relationship of initial platelet count between pediatric patients with steroid

responsive and steroid non responsive nephrotic syndrome.

Specific Objectives

1. To determine the demographic profile of children diagnosed with Nephrotic Syndrome

2. To describe the clinical manifestations of children with Nephrotic Syndrome

3. To determine the hematologic findings in children with Nephrotic Syndome

4. To determine urinalysis findings in children with Nephrotic Syndrome

5. To compare the initial platelet count of pediatric patients with nephrotic syndrome in relation

to there steroid responsiveness and steroid non responsiveness

III. PATIENTS AND METHODS

A. Study Design
This is a case control study

B. Study setting
De La Salle University Medical Center, a tertiary hospital in the city of Dasmarinas, Province

of Cavite.

C. Sample Size Determination

Calculate sample size as follows were mean platelet count of group A (steroid

responsiveness nephrotic syndrome) equal 416272.73 (SD 14576.35) and mean platelet count

for group B (steroid non responsiveness nephrotic syndrome) equal 517909.09 (SD

165670.30). The study need 45 patients each group to have 95% confidence level and 80%

power for detecting difference in platelet count equal to 101636.36.

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D. Study Population
Inclusion criteria :
Pediatric patients 1 to 18 years old with newly diagnosed Idiopathic Nephrotic Syndrome

and completed prednisone therapy with follow up from the year January 1997-May 2014.

Initial complete blood count and platelet count determination result

Criteria for diagnosis of Nephrotic syndrome are as follows :

1. urinalysis (protein)

2. serum total protein, albumin and globulin

3. serum cholesterol

4. 24 hour urine protein

Exclusion criteria :
Those lost to follow up will not be included in this study
Patient with incomplete data

E. Conduct of the study

Medical records of all patients with Idiopathic Nephrotic Syndrome seen at De La

Salle University Medical Center from January 1997- May 2014 were retrieved. Using an

extraction form the following data was retrieved, tabulated and analyzed.

1. Age and sex

2. Chief complaint

3. Signs and symptoms

4. Complete blood count

5. Serology test (Total protein, serum albumin, serum globulin and serum cholesterol)

6. Urinalysis (albumin)

7. Urine protein/albumin determination

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F. Statistical Analysis
Frequency distribution table used to describe demographic and clinical characteristics

of the patients. The study use chi square test to determine if difference in proportion with

increased platelet count between steroid responsive and non responsive patients. The Chi

square statistic is significant at the 0.05 level (p-value 0.05). The 95% confidence interval of

the difference also be computed. Fishers exact test was used for variables where Chi-square

could not be used. Since the reflected values are only those observed, expected cell will be

small if observed values or frequency in some variables of this 2x2 table is small.

G. Ethical consideration
A letter of informed consent of the study were given to the Medical Records of the

hospital. The study was submitted and approved by the Ethics Committee of the hospital prior

to retrieval of charts and data collection.

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 IV. RESULTS

A total of 90 pediatric patients with newly diagnosed Idiopathic Nephrotic Syndrome were

included in the study. Forty-five patients belong to group A (steroid non responsive) and 45 patients

under group B (steroid responsive).

A. Demographic Characteristics

Overall, most of the patients belong to the 1-5 years old age group followed by the 6-10 years old

age group with 59 (65.6%) and 18 (20.0%) patients, respectively. Among the 45 patients who belong to

group A (steroid non responsive) , 29 (64.4%) were 1-5 years old while group B (steroid non responsive)

had 30 (66.7%) patient belong to the same age group.

Fifty-seven (63.3%) were males while there were 33 (36.7%) females with a 1.7 : 1 male to

female ratio. Steroid non responsive patient had 28 (62.2%) males and 17 (37.8%) females with male :

female ratio of 1.6 : 1 while the steroid responsive group had 29 (64.4%) males and 16 (35.6%) females

with male : female ratio of 1.8 : 1. Chi square test done showed no statistically significant difference

between the 2 groups according to age and sex. (Table 1)

Table 1. Age and Sex Distribution

Nephrotic Syndrome
Demographic Steroid non Steroid
Total
characteristics responsive responsive
n % n % n % X2 Chi p value
Age
1-5 years old 29 64.4 30 66.7 59 65.6 3.239 0.3562
6-10 years old 11 24.5 7 15.6 18 20.0
11-15 years old 4 8.9 8 17.7 12 13.3
16-18 years old 1 2.2 0 0 1 1.1
Total 45 100 45 100 90 100
Sex
Male 28 62.2 29 64.4 57 63.3 0.04785 0.8269
Female 17 37.8 16 35.6 33 36.7
Total 45 100 45 100 90 100

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B. Clinical Presentation

Table 2 shows the chief complaint of the patients included in the study. Seventy-three

(81.1%) consulted because of edema. Thirty-four (75.5%) out of the 45 patients with steroid non

responsive came with chief complaint edema. No statistical different were noted between the 2

groups.

Table 2. Chief complaint

Nephrotic Syndrome
Steroid non Steroid
Chief complaint Total
responsive responsive
n % n % n % X2 chi p value
Edema 34 75.5 39 86.7 73 81.1 4.085 0.1297
(generalized, periorbital,
facial, scrotal, bipedal)

Abdominal pain, distention 8 17.8 2 4.4 10 11.1

Others (vomiting, fever, 3 6.7 4 8.9 7 7.8

oliguria)
Total 45 100 45 100 90 100

Table 3 shows most of the patients had fever (n = 38 ) as a symptoms followed by cough,

abdominal pain, tea colored urine, vomiting and dyspnea.

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 Table 3. Signs and symptoms

Nephrotic Syndrome
Steroid non Steroid
Signs and symptoms* Total
responsive responsive
n % n % n % X2 chi p value
Fever
Positive 19 42.2 19 42.2 38 42.2 0 1
Negative 26 57.8 26 57.8 52 57.8
Total 45 100 45 100 90 100
Cough
Positive 10 22.2 12 26.7 22 24.4 0.2406 0.6237
Negative 35 77.8 33 73.3 68 75.6
Total 45 100 45 100 90 100
Abdominal pain
Positive 5 11.1 7 15.6 12 13.3 0.3846 0.5351
Negative 40 88.9 38 84.4 78 86.7
Total 45 100 45 100 90 100
Tea colored urine
Positive 7 15.6 5 11.1 12 13.3 0.3846 0.5351
Negative 38 84.4 40 88.9 78 86.7
Total 45 100 45 100 90 100
Vomiting
Positive 5 11.1 5 11.1 10 11.1 0 1
Negative 40 88.9 40 88.9 80 88.9
Total 45 100 45 100 90 100
Dyspnea
Positive 5 11.1 4 8.9 9 10 0.1235 0.7253
Negative 40 88.9 41 91.1 81 90
Total 45 100 45 100 90 100
*Note : One patient can have more than one sign/symptom enlisted

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C. Hematologic test
Table 4. shows the initial complete blood count results. Forty-seven out of the 90 (52.2%)

patients showed below the normal hemoglobin on their complete blood count . Forty (44.4%)

patients had below the normal hematocrit levels. Sixty-eight (75.6%) patients showed leukocytosis on

their complete blood count. Forty-six (51.1%) patients with Idiopathic nephrotic syndrome showed

thrombocytosis, 30 (66.7%) were steroid non responsive while 16 (35.6%) were steroid responsive.

On the other hand, majority of the patients with normal platelet count belong to the steroid responsive

group with 29 (64.4%) compared with 15 (33.3%) in the steroid non responsive group. Fisher exact

test showed with p-value of 0.005812 which mean that the difference of the platelet count between

the 2 groups is statistically significant.

Table 4. Complete Blood Count

Nephrotic Syndrome
Complete Blood Steroid non Steroid
Total
Count responsive responsive
n % n % n % X2 chi p value
Hemoglobin
Decreased 18 40.0 29 64.4 47 52.2 Fishers
Increased 17 37.8 11 24.5 28 31.1 0.0653
Normal 10 22.2 5 11.1 15 16.7
Total 45 100 45 100 90 100
Hematocrit
Decreased 17 37.8 23 51.1 40 44.4 1.914 0.3841
Increased 17 37.8 15 33.3 32 35.6
Normal 11 24.4 7 15.6 18 20.0
Total 45 100 45 100 90 100
White Blood
Count 0 1
Increased 34 75.6 34 75.6 68 75.6
Normal 11 24.4 11 24.4 22 24.4
Total 45 100 45 100 90 100
Platelet count
Increased 30 66.7 16 35.6 46 51.1 Fishers
Normal 15 33.3 29 64.4 44 48.9 0.005812
Total 45 100 45 100 90 100

15
 Table 5. shows that 85 (94.4%) patients have decreased level of total blood protein.
Eighty-eight (97.8%) patients showed decreased serum albumin levels, and 2 out of the 90 patients
showed normal levels of serum albumin despite having nephrotic syndrome. Forty-eight (53.3%)
patients showed normal serum globulin. Eighty-six (95.6%) patients had a decreased serum albumin
to globulin ratio. Seventy-eight (86.7%) patients showed increased serum cholesterol level. There are
no statistical significant difference between the two group.

Table 5. Serologic Test

Nephrotic Syndrome
Steroid non Steroid
Serologic Test Total
responsive responsive
n % n % n % X2 chi pvalue
Total Protein
Decreased 44 97.8 41 91.1 85 94.4 1.906 0.1676
Normal 1 2.2 4 8.9 5 5.6
Total 45 100 45 100 90 100

Serum Albumin
Decreased 44 97.8 44 97.8 88 97.8 0 1
Normal 1 2.2 1 2.2 2 2.2
Total 45 100 45 100 90 100
Serum Globulin
Normal 23 51.1 25 55.6 48 53.3 1.303 0.5213
Decreased 22 48.9 19 42.2 41 45.6
Increased 0 0 1 2.2 1 1.1
Total 45 100 45 100 90 100
Albumin/Globulin
ratio 43 95.6 43 95.6 86 95.6 0 1
Decreased 2 4.4 2 4.4 4 4.4
Normal 45 100 45 100 9 100
Total
Serum Cholesterol
Increased 40 88.9 38 84.4 78 86.7 0.3846 0.5351
Normal 5 11.1 7 15.6 12 13.3
Total 45 100 45 100 90 100

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D. Urinalysis
Table 6. shows the urine albumin level, majority of the patients (n=57) have +4 to +3 while

33 (36.7%) out of the 90 study population were noted to have trace to +2 urine albumin levels.

Quantitatively, all patients had nephrotic range proteinuria.

Table 6. Urine Protein

Nephrotic Syndrome
Steroid non Steroid
Urine Protein Total
responsive responsive
n % n % n % X2 chi p value
Albumin
+4 to +3 27 60.0 30 66.7 57 63.3 0.4306 0.5117
(trace to +2) 18 40.0 15 33.3 33 36.7

Total 45 100 45 100 90 100

Table 7 shows that those who increased platelet count has increased risk of steroid non

responsive. Patient with increased platelet count had 1.3 times more likely to be steroid non

responsive than those normal platelet count.

Table 7. Comparison of platelet count between steroid non responsive and steroid
responsive nephrotic syndrome.

Nephrotic Syndrome
Steroid non Steroid
Total
Platelet Count responsive responsive
95% CI
n % n % n % OR p-value
of OR
Increased 30 66.7 16 35.6 46 51.1 1.373 1.147, Fishers
Normal 15 33.3 29 64.4 44 48.9 6.533 0.005812
Total 45 100 45 100 90 100

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V. DISCUSSION

Nephrotic syndrome (NS) is one of the most frequent glomerular diseases seen in

children with the potential of progression to end stage renal disease. The mortality rate of NS was

40% before 1940, primarily due to infection, but this has been significantly reduced with the

introduction of steroid treatment and antibiotics. Steroids have long been used as the first line of

treatment in NS, however other immunesuppressives may be indicated when prednisolone fails to

induce or sustains remission.4

Every physician should be keen in taking a complete history and performing a thorough

physical examination before starting treatment with corticosteroid. The height, weight, and blood

pressure should be recorded. Regular weight record helps to monitor decrease or increase of edema.

Physical examination is done to detect infections and underlying systemic disorder (e.g systemic

lupus erythematous, Henoch schonlein purpura). Infection should be treated before starting therapy

with corticosteroids. Investigations recommended at the initial episode include urinalysis, complete

blood count, blood levels of albumin, cholesterol, urea and creatinine. Estimation of blood levels of

antistreptolysin O and C3 is required in patients with gross or microscopic hematuria. Urine culture is

not necessary unless the patient has clinical features suggestive of urinary tract infection.

Adequate treatment of the initial episode, both in terms of dose and duration of

corticosteroids, is important. Evidence from multiple studies suggest that appropriate therapy at the

first episode of nephrotic syndrome is an important determinant of the long term course of disease.

About 80% children with idiopathic nephrotic syndrome show remission of proteinuria

following treatment with corticosteroids (steroid responsive). Most patients have multiple relapses,

placing them at risk for steroid toxicity, systemic infections, and other complications. A small

proportion of patients who are steroid resistance are also risk for similar complications and renal

18
insufficiency. Focal segmental glomerulosclerosis (FSGS) is the main cause of steroid resistant NS

and accounts for 10-20% of end stage renal disease (ESRD) in children.12

This study aimed to compare initial platelet count of pediatric patients with nephrotic

syndrome and evaluate if it can be used as a biomarker for steroid responsiveness or steroid non

responsiveness.

Ninety children with INS were analyzed. There were slightly more male (63.3%) than

female (36.7%), with a 1.7 : 1 male : female ratio and within the age range of 1-5 years old. A number

of studies show Idiopathic NS is the most frequent form of NS in children representing more than 90

percent of cases between 1 and 10 years of age and show a male preponderance.

Clinically, 73 (81.1%) consulted because of edema, which is similar to study done by

Sahana.10 Thirty-four patients with steroid non responsive and 39 patients with steroid responsive had

edema. This have a p-value of 0.1297, which shows that the difference is statistically not significant.

Most of the patients had fever as a symptom followed by cough, abdominal pain, tea colored urine,

vomiting and dyspnea.

The hematologic and serologic findings characteristic were described. The complete

blood count of the study population showed that the difference is statistically not significant. In a

study done by Sahana, 74% of patients had anemia. In nephrotic syndrome, many nonalbumin

proteins are excreted in the urine, including transferrin and erythropoietin (EPO). Urinary losses of

EPO can cause EPO-deficiency anemia and prevent the normal increase in plasma EPO level in

response to anemia and hypoxia in NS. Similarly, tranferrinuria and increased transferrin catabolism

can cause hypotransferrinemia, and in some cases, iron deficiency anemia.11

Sixty-eight out of 90 patients have leukocytosis, which is can be explained why patients

with nephrotic syndrome are prone to infections. Thirty-four patients of each group had leukocytosis.

The most common forms of infection in nephrotic syndrome are cellulitis, peritonitis and sepsis.

19
Patients with nephrotic syndrome are known to have functional abnormalities in their immune

system. These abnormalities include low serum IgG due to urinary losses of IgG, altered T-cell

functions and presence of edema.6

Most of the patients showed thrombocytosis, 30 patients under group steroid non

responsive and 16 patients under group steroid responsive showed p-value of 0.005812. It shows that

the difference is statistically significant, which means that increased platelet count more likely to be

steroid non responsive than those normal platelet count. According to a study by Gulleroglu et al.,

mean platelet count in the steroid resistant group was significantly higher than steroid sensitive group.

It is can be explained why patients with nephrotic syndrome are prone to develop thrombosis

complications.14 This is related to destabilization of platelets by hyperlipidemia and intravascular

volume depletion (which can worsen with aggressive diuresis). The majority of studies on platetet in

NS revealed hyper-aggregation tendency to various aggregating agents in both nephrotic adults and

children. Platelet hyper-aggregability in NS has a multifactorial genesis. This is probably connected

to hypoalbuminemia, hypercholesterolemia and hyperfibrinogenemia. Hypoalbuminemia might

increase cyclooxygenases efficiency to form the pro-aggregatory thromboxane A2 in the presence of

a higherconcentration of free arachidonic acid that is normally bound to albumin. 13 Yashida and Aoki

found that enhanced platelet aggregation in NS was normalized in vitro by the addition of albumin to

patientss platelet rich plasma and in vivo by the correction of hypoalbuminemia by treatment. Shattil

et al. demonstrated that the acquisition of cholesterol by platelets in vitro is associated with increased

platelet sensitivity to aggregating agents. Other study done by El domiaty et al., revealed that a

significant correlation between ADP induced platelet hyperaggregability and the degree of

hypoalbuminemia as well as hypercholesterolemia.

With regards to other serologic tests such as TPAG, serum cholesterol, no

statistically significant difference was also noted. The reason why many patients had low albumin

levels can be explained by the fact that abnormality in nephrotic syndrome is an increased

20
permeability of the glomerular capillary wall, which leads to massive proteinuria and

hypoalbuminemia. Hypercholesterolemia is typically seen in nephrotic syndrome due to diminished

lipid catabolism as a result of reduced plasma levels of lipoprotein lipase.

The urinalysis results of the study population showed the urine albumin levels, majority

of the patients have +3 urine albumin levels, while 35(38.9%) of these patients showed urine albumin

level of trace to +2. Based on study by Maravillosa in 2012 revealed that the level of protein on

routine urinalysis is not accurate in measuring nephrotic range proteinuria, that is, the degree of

proteinuria based on dipstick is not directly related to the quantitative value of urine protein. Thus, 24

hour urine protein also recommended, which still remains the gold standard of diagnostic

examination. The mechanism of proteinuria is due to glomerular structural changes with greater

injury and leakage of all plasma proteins.

21
VI. CONCLUSION

Ninety patients with newly diagnosed nephrotic syndrome were included in the study to

compare initial platelet count between steroid responsive and steroid non responsive.

This study showed that most of the patients nephrotic syndrome belong to the 1-5 years

old age. There is noted male preponderance with a male : female ratio of 1.7 : 1. There are no

statistically significant difference between the 2 groups according to age and sex. Edema was the

most common chief complaint in study population.

On the initial complete blood count showed that both groups had anemia and

leukocytosis. However, thrombocytosis was higher in group steroid non responsive than steroid

responsive.

With regards to other serologic tests such as TPAG, serum cholesterol, no statistically

significant difference was also noted. The urinalysis results of the study population showed the urine

albumin levels, majority of the patients have +4 to +3 urine albumin levels. Quantitatively, all

patients had nephrotic range proteinuria.

Nephrotic patient with increased platelet count are 1.3 times more likely to be steroid non

responsive than those with normal platelet count. Thus, pediatric nephrotic syndrome patient with

increased platelet count should be monitored closely so as to identify whether there patient are

actually non minimal change NS patient which necessitated renal biopsy for histologic diagnosis and

prognosticative.

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VII. RECOMMENDATION

This study is limited since it was done retrospectively. It is recommended that a larger

sample size be used in order to further validate the data provided in this study. Other parameters such

as prothrombin time (PT), partial thromboplastin time (PTT), and mean platelet volume are also

recommended as to further assess the hypercoagulable state in patients with nephrotic syndrome.

23
 REFERENCES

1. Safaei, et al. Spectrum of childhood Nephrotic Syndrome in Iran : A single center study.
Indian Journal Nephrology.Vol 19. Number 3. Page 87-90. July 2009

2. Davin, et al. Nephrotic Syndrome in children from Bench to treatment. International

Journal of Nephrology. (2011).

3. Cabrera, B. A Correlation analysis of urine protein dipstick levels and serum albumin in
children with Nephrotic Syndrome: A Case Control Study. Book of Abstracts. Philippine
Pediatric Society 2002-2005. 165-166

4. Madani,A. An estimation of steroid responsiveness of Idiopathic Nephrotic Syndrome in

Iranian children. Journal of Pediatrics. Vol 20. Number 2. Page 199-205. June 2010

5. Eddy,et al. Nephrotic Syndrome in childhood. The Lancet. Vol 362. Page 629-639. August
2003

6. Kliegman, et al. Nelson Textbook of Pediatrics,Quezon Philadelphia, PA. Saunders. 19th

edition,
2007.
7. Maravillosa, G. Predictive Value of Protein Level on Routine Urinalysis among Children
with
Nephrotic Syndrome: A Cross- Sectional Study. Unpublished. October 2012.

8. Hafni, et al. Thrombocytosis in childhood relapsing Nephrotic Syndrome. Pediatrica

Indonesiana. Vol 47. Number 3. Page 100-103. May 2007

9. Haycock, G. The child with nephrotic syndrome. Clinical Paediatric Nephrology, Oxford
New York . 3rd edition, 2003. Page 341-366.

10. Sahana, KS. Clinical profile of Nephrotic Syndrome. Journal of Evolution of medical and
dental science. 2014. Vol 3. Issue 4. January 27. P863-870

11. Vaziri, ND. Erythropoeitin and transferrin metabolism in Nephrotic Syndrome. Am J

Kidney Dis. 2001 Jul;38(1):1-8

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12. Mortazavi et al. Steroid responsive pattern and outcome of pediatric nephrotic syndrome : a
single-center experience in Nortwest Iran. Department of Pediatric Nephrology, Tabriz
University of Medical Sciences, Tabriz, Iran. May 2011. p167-171.

13. El Domiaty et al. Study of Beta-thromboglobulin in children with nephrotic syndrome.

Alexandria Journal of Pedaitrics, volume 13, Number 2, July 1999.

14. Gulleroglu K et al. Clinical importance of mean platelet volume in children with nephrotic
syndrome. Ren Fail. Feb 2014.

25
APPENDIX A- EXTRACTION FORMS

Date of admission : ______________

Name :

Age (years) : Sex : Male Female

Chief complaint :

Signs/ Symptoms :

Fever Abdominal distention Dysuria Others

Periorbital edema Abdominal pain Tea colored urine
Facial edema Vomiting Bipedal edema
Dyspnea LBM Pallor
Cough Decreased appetite Easy fatigability

Nephrotic syndrome work up :

Total protein : _____ 24 h urine protein : ____

Serum Albumin : _____
Serum Globulin : _____ Serum cholesterol : _____
Albumin/Globulin : ______

Initial urinalysis result upon admission

Albumin +4 / +3 / +2 / +1 / trace
WBC
RBC

Intitial complete blood and platelet count upon admission:

Hemoglobin
Hematocrite
WBC
Platelet count

Admitting Diagnosis : Date of discharge :

26
After complete prednisone therapy :

Urine albumin : _____

Remission - urine albumin nil or trace (or proteinuria <4mg/m2/h) for three consecutive
early morning specimens

yes (steroid responsive)

no (steroid resistant)

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28