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CASE REPORT

NEPHROTIC SYNDROME

CASE REPORT NEPHROTIC SYNDROME Carvin Herryanto Kyna Troeman Compiled by : (110100115) (110100204) Supervisor : dr.

Carvin Herryanto Kyna Troeman

Compiled by :

(110100115)

(110100204)

Supervisor :

dr. Nelly Rosdiana, MKed(Ped), SpA(K)

DEPARTMENT OF PEDIATRIC H. ADAM MALIK CENTRAL GENERAL HOSPITAL FACULTY OF MEDICINE UNIVERSITY OF SUMATERA UTARA MEDAN

2016

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FOREWORD

All praises to God for His grace and blessing that provide this opportunity and grant us the capability to complete a case report titled “Nephrotic Syndrome”. This case report is written as a requirement to complete the clinical rotation in Department of Pediatrics, Faculty of Medicine, University of Sumatera Utara. We would like to offer our sincere appreciation to our supervisor, dr. Nelly Rosdiana, MKed(Ped), SpA(K) for her supervision and constant support. Her invaluable help of constructive comments and suggestions throughout the process have contributed to the completion of this case report. We would also like to offer our appreciation to all the residents in Department of Pediatrics for their support and contribution to our case report. We realize that this case report is still far from perfection. Therefore, we would like to look forward to suggestions from the readers for the improvement of further works in the future. We hope that this case report can be useful and everybody is able to take benefit from it. Thank you.

Medan, February 2016

Writers

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CONTENTS

FOREWORD ..............................................................................................................

CONTENTS

.............................................................................................................

ii

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

  • 1.1 Background..........................................................................................................

  • 1.2 Objective..............................................................................................................

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

  • 2.1 Definition ...........................................................................................................

3

  • 2.2 Epidemiology .....................................................................................................

3

  • 2.3 Etiology ..............................................................................................................

3

  • 2.4 Pathogenesis ......................................................................................................

4

  • 2.5 Clinical Manifestations ......................................................................................

6

  • 2.6 Pathophysiology ................................................................................................

8

  • 2.7 Classification .....................................................................................................

10

  • 2.8 Differential Diagnosis ........................................................................................

10

  • 2.9 Diagnostic Evaluation ........................................................................................

11

 
  • 2.9.1 History .........................................................................................................

11

  • 2.9.2 Physical Examination ...................................................................................

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  • 2.9.3 Laboratory Evaluation and Imaging .............................................................

13

 
  • 2.9.4 Renal Biopsy ................................................................................................

14

  • 2.10 Treatment ...........................................................................................................

14

 
  • 2.10.1 Symptomatic Treatment ..............................................................................

15

 
  • 2.10.1.1 Diet ......................................................................................................

15

 
  • 2.10.1.2 Hypovolemia .......................................................................................

15

 
  • 2.10.1.3 Diuretics ..............................................................................................

15

 
  • 2.10.1.4 Thromboemboli ..................................................................................

16

 
  • 2.10.1.5 Antihypertensive Drugs ......................................................................

17

 
  • 2.10.1.6 Infections and Immunizations .............................................................

17

 
  • 2.10.1.7 Hyperlipidemia ....................................................................................

18

 
  • 2.10.1.8 Miscellanous .......................................................................................

18

 
  • 2.10.2 Specific Treatment ......................................................................................

18

 
  • 2.10.2.1 First Episode .......................................................................................

18

  • 2.10.2.2 Relaps Treatment ................................................................................

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  • 2.10.2.3 Frequent Relaps and Glucocorticoid Dependence ..............................

19

 
  • 2.10.2.4 Second Line Agents and Strategies .....................................................

19

 
  • 2.10.2.5 Management of Steroid-Resistant Nephrotic Syndrome ....................

20

 
  • 2.10.2.6 Steroid Side Effects………………………………………………….

20

2.11

Parental Education .............................................................................................

21

  • 2.12 Complication ......................................................................................................

21

  • 2.13 Prognosis ............................................................................................................

23

 

CHAPTER 3 CASE

24

3.1

Case

24

CHAPTER 4 DISCUSSION

35

CHAPTER 5 CONCLUSION

37

REFERENCE

38

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CHAPTER 1 INTRODUCTION

1.1. Background

Nephrotic syndrome is a common chronic disorder, characterized by alterations of permselectivity at the glomerular capilarry wall, resulting in its inability to restrict the urinary loss of protein. Nephrotic range proteinuria is defined as proteinuria exceeding 1000 mg/m 2 per day or spot (random) urinary protein-to-creatinine ratio exceeding 2 mg. The proteinuria in childhood nephrotic syndrome is relatively selective, constituted primarily by albumin. 1 Estimated on the annual incidence of nephrotic syndrome range from 2-7 per 100,000 children, of a higher incidence of nephrotic syndrome in children from Southeast Asia, as in Indonesia the incidence of nephrotic syndrome reported 6 per 100,000 children aged less than 14 years old per year. The condition is primary (idiopathic) in 95 per cent cases. An underlying disorder that might be identified in less than 5 per cent cases, includes systemic lupus erythematosus, Henoch Schonlein purpura, amyloidosis and infection with HIV, parvovirus B19 and hepatitis B and C viruses. 1,2 Nephrotic syndrome in children can be classified according to 3 groups:

secondary, congenital and infantile, and idiopathic. 3 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-Schönlein purpura, etc.) or not (e.g., Alport syndrome, focal sclerosis due to reduced nephronic mass resulting from renal scarring, etc.). 3 Congenital and infantile NSs are occurring 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. 3 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 age. INS is defined by the association of the

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clinical features of NS with renal biopsy findings of diffuse foot process effacement on electron microscopy and minimal changes (called minimal change disease (MCD)), focal segmental glomerulosclerosis (FSGS), or diffuse mesangial proliferation (DMP) on light microscopy. Most patients have histologic findings of MCD. The vast majority of patients with MCD (>90 percent) respond to glucocorticoid therapy whereas only 50 percent of those with DMP and 30 percent of those with FSGS are expected to do so. Clinical findings at presentation differentiate children with MCD from those with other glomerular pathology. The latter include: age younger than six years of age, absence of hypertension, absence of hematuria, normal complement levels, and normal renal function. However, onset of nephrotic syndrome in the first year of life, particularly in the first three months of life, is more likely to be due to a gene mutation and to be resistant to glucocorticoids. 3 Approximately 80% of children presenting with nephrotic syndrome will respond to prednisolone and this is the most important factor in terms of management and prognosis. Nephrotic syndrome is thought of as a relatively benign condition; however the mortality rate remains around 0.5-1%. There is significant acute and long term morbidity and almost half children presenting with an initial episode will develop frequently elapsing disease. 1

1.2.

Objective

The aim of this study is to explore more about the theoritical aspects on

nephrotic syndrome, and to integrate the theory and application of nephrotic syndrome case in daily life.

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CHAPTER 2 LITERATURE REVIEW

  • 2.1 Definition 3

Nephrotic syndrome is defined by the presence of nephrotic-range proteinuria, edema, hyperlipidemia, and hypoalbuminemia. While nephrotic-range proteinuria in adults is characterized by protein excretion of 3.5 g or more per day, in children it is defined as protein excretion of more than 40 mg/m 2 /h or a first- morning urine protein/creatinine of 2-3 mg/mg creatinine or greater.

  • 2.2 Epidemiology 1,4

Nephrotic syndrome can occur at any age. Causes vary by age, with children more likely to have primary causes, and adults more likely to have secondary causes. The prevalence worldwide is approximately 16 cases per 100,000 children with an incidence of 2 to 7 per 100,000 children. Males appear to be more affected than females at a ratio of 2:1 in children, but this predominance fails to persist in adolescence.

  • 2.3 Etiology 5 Nephrotic syndrome occurs at any age but is more prevalent in children,

mostly between ages 1½ and 4 yr. Congenital nephrotic syndromes appear during the first year of life. At younger ages, boys are affected more often than girls, but both are affected equally at older ages. Causes differ by age and may be primary or secondary. The most common primary causes are such as focal segmental glomerulosclerosis and membranous nephropathy. The secondary causes account for <10% of childhood cases but >50% of adult cases,most commonly are diabetic nephropathy and preeclampsia.

  • 2.4 Pathogenesis 6

The hallmark of nephrotic syndrome is massive proteinuria, leading to decreased circulating albumin levels. The initiating event that produces

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proteinuria remains unknown. However, strong evidence suggests that nephrotic syndrome, at least in part, has an immune pathogenesis. The effect of glucocorticoids on inducing remission in nephrotic syndrome implicates the immune system, and particularly T-lymphocytes, in the pathogenesis of the condition. Glucocorticoids, primarily acting through the nuclear factor kappaB (NF-κB) transcription pathway, have a variety of effects, including inhibiting cytokine production and inhibiting T-cell production and proliferation. A variety of studies provide further evidence of the role of T-cells in nephrotic syndrome. Patients with nephrotic syndrome in remission have alterations in the NF-κB pathway compared with healthy control subjects. NF-κB transcription is up-regulated in relapse of nephrotic syndrome compared with remission. Additionally, nephrotic syndrome has been reported in patients with Hodgkin lymphoma, a T-cell disease. Other observations in nephrotic syndrome include altered thymic regulation of T-cell differentiation and alterations in T-cell subsets in INS patients compared with healthy controls. In addition to T-cells, the recent reports of remission in nephrotic syndrome after treatment with rituximab, an anti-CD20 monoclonal antibody that results in complete depletion of B lymphocytes, implicate a role for B cells in the pathogenesis of nephrotic syndrome. A circulating factor may play a role in the development of proteinuria in nephrotic syndrome. This can be demonstrated by the rapid development of proteinuria in recurrence of nephrotic syndrome after kidney transplantation, the improvement in nephrotic syndrome in such patients after treatment with plasmapheresis, and the experimental induction of proteinuria in animals by plasma from patients with nephrotic syndrome. The nature of this circulating factor is not known. Various cytokines and molecules have been implicated, including the following :

Interleukin (IL)-2, IL-4, IL-12, IL-13, IL-15, IL-18

IL-2 receptor

Interferon-γ

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Tumor growth factor (TGF)-β Vascular permeability factor Nuclear factor (NF)-κB Tumor necrosis factor (TNF)-α Recently, investigators have found high circulating levels of soluble urokinase receptor (suPAR) in children and adults with FSGS. Treatment of FSGS with immunosuppressive medications led to lower levels of suPAR, and a decline in suPAR levels over 26 weeks of treatment was associated with reduction in proteinuria. Interestingly, suPAR levels were higher in patients with familial FSGS and those with podocin mutations (see below). suPAR might act as a glomerular permeability factor. The association of allergic responses with nephrotic syndrome also illustrates the role of the immune system in nephrotic syndrome. Nephrotic syndrome has been reported to occur after allergic reactions to bee stings, fungi, poison ivy, ragweed, house dust, jellyfish stings and cat fur. Food allergy might play a role in relapses of nephrotic syndrome; a reduced-antigenic diet was associated with improved proteinuria and complete remission in one study. Additionally, nephrotic syndrome is 3-4 times more likely in children with human leukocyte antigen (HLA)-DR7. Steroid sensitive INS has also been associated with HLA-B8 and the DQB1 gene of HAL-DQW2. A greater incidence of nephrotic syndrome is also observed in children with atopy and HLA-B12.

  • 2.5 Clinical Manifestations 3,4,7

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. 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

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pitting and typically dependent in nature, being more noticeable in the face in the morning and predominantly in lower extremities later in the day. 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 nephrotic syndrome 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 nephrotic syndrome in some cases.

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. 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. Given the risk of thrombosis in nephrotic syndrome, 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. 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. 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. Except in rare cases of familial INS, no significant family history of kidney disease or nephrotic syndrome is usually noted. Children are typically healthy prior to onset of nephrotic syndrome and, except for the history of allergy and atopy noted above,

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do

not

usually have

a significant past medical history related

to

nephrotic

syndrome.

 

2.6 Pathophysiology 8 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 (Figure 1). As part of the system’s 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. 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. 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

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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.

xii release that affects glomeruli and causes increased permeability and (2) immune system dysfunction that leads

Figure 1. Glomerular filtration barrier (GFB). A. Schematic diagram; B. normal GFB; and C. GFB in nephrotic syndrome. Note the effacement of the podocyte foot processes (P) with poor visualization of the slit diaphragm(S). FE:fenestrated endothelium. Electronmicroscopy images courtesy of Fadi El Salem, MD, Icahn School of Medicine at Mount Sinai, New York, NY.

2.7

Classifications 9

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In many long-term studies, the response to steroid medication used more often than anatomic pathology to determine the prognosis. Therefore, at this time, classification of nephrotic syndrome is based on the clinical response, namely:

Remission

Urine albumin negative or trace (or proteinuria < 4 mg/m 2 /h) for 3 consecutive early morning specimens in a

week

Relapse

Urine albumin >2+ (or proteinuria > 40 mg/m 2 /h) for 3 consecutive early morning specimens in a week, having

been in remission previously

Infrequent relapse

<2 times relapse within the first 6 months after the initial

response or <4 times per year of observation

Frequent relapse

>2 relapses in initial six months or >4 relapses in a year

Steroid dependence

Two consecutive relapses when on alternate day steroids

or within 14 days of its discontinuation

Steroid resistance

Absence of remission despite therapy with daily

prednisone at full dose of 2 mg/kg per day for 4 weeks.

Steroid sensitive

Remission occurs in the full dose of prednisone for 4

weeks

  • 2.8 Differential Diagnosis 10,11

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. 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. 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. 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

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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.

  • 2.9 Diagnostic Evaluation 2,12,13

The clinical distinction between nephrotic syndrome and nephritic syndrome can be ambiguous; therefore, on rare occasions, diseases that normally present with a nephritic presentation may actually present with a more nephrotic picture. To establish a diagnosis of nephrotic syndrome, initial laboratory evaluation includes: 12 (1) quantification of proteinuria by either 24-hour urine collection (normal <150 mg/day, nephrotic range >3.5 g/day) or spot urine protein-to-creatinine ratio; (2) urinalysis (fresh urine) with microscopy to check for the presence of cellular casts or other abnormalities; and (3) basic blood biochemistries to assess the presence of hyperlipidaemia, hypoalbuminaemia, or a hypercoagulable state. Once heavy proteinuria (and a diagnosis of nephrotic syndrome) is established, the cause may be suggested from standard history and physical examination, particularly in patients with a systemic disease. The history of the present illness may be key in identifying the cause. Cases in which the history, physical examination, and laboratory evaluation are non-diagnostic for the cause should be discussed with a kidney specialist. Other laboratory tests may be needed to aid the diagnosis, and a renal biopsy is usually needed in adult patients. This test should always be performed in consultation with a nephrologist.

2.9.1 History

Patient history should attempt to elicit a history of long-standing diabetes, end-organ damage (e.g., retinopathy), malignancy, SLE, HIV infection, multiple myeloma, connective tissue diseases, or amyloidosis. A full medication history should be taken, as some medications (e.g., pamidronate, lithium, gold, penicillamine, or non-steroidal anti-inflammatory drugs [NSAIDs], and very rarely interferon alfa, lithium, heroin, mercury, or

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formaldehyde) may be associated with nephrotic syndrome. Illicit use of Chinese herbs or mercurial skin-lightening creams must be considered. The principal symptoms of nephrotic syndrome are oedema and foamy urine. The oedema, which starts in the periorbital, face, or legs, may be severe, involving the entire body. Patients may also have symptoms suggestive of occult malignancy (e.g., cough, weight loss, night sweats, or tarry stools), SLE (e.g., rash, photosensitivity, or arthralgias), or Fabry's disease (e.g., painful neuropathy). Family history of Fabry's disease, amyloidosis, or any other renal disease should be noted. Previous known renal disease should always be considered as a cause: progression, relapse, or disease transformation (e.g., class changes in lupus) may lead to the development of nephrotic syndrome.

  • 2.9.2 Physical Examination

Patients generally have mild oedema of the legs or severe oedema involving the entire body (anasarca). Swelling is more likely to involve the face, particularly peri-orbital oedema, than in patients with other causes of oedema such as CHF or severe hepatic disease. Patients may get white banding of the nails from hypoalbuminaemia (known as Muehrcke's lines). Protein malnutrition leads to a loss in lean body mass in heavy proteinuria, but this is often concealed by weight gain due to simultaneous oedema. Additionally, patients may get xanthelasmata from severe hypercholesterolaemia. These physical findings are useful for aiding diagnosis of nephrotic syndrome, but they are not useful for determining the cause. Physical findings that may be useful in determining the cause include rash (consistent with SLE), easy bruising and neuropathy (consistent with amyloidosis), haem-positive stool (consistent with GI malignancy), or fundoscopic examination that reveals evidence of diabetic retinopathy.

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Proteinuria should be quantified by either 24-hour urine collection or spot urine protein-to-creatinine ratio (mg/micromol). Spot ratios are largely replacing 24-hour urine collection, as the ratio of milligrams of protein to milligrams of creatinine is roughly equivalent to the 24-hour excretion of protein. A result of >3.5 g/24 hours, or PCR >300 mg/micromol, is diagnostic for nephrotic-range proteinuria. A fresh urine sample (spun sediment) should ideally be evaluated under a microscope for the presence of cellular casts or other abnormalities that may either confirm the diagnosis of nephrotic syndrome or suggest another cause. 12 All patients should have an assessment of basic blood biochemistries including renal function, FBC, lipid profile (typically total and LDL cholesterol levels are elevated in nephrotic syndrome) and serum albumin. Thyroid hormone testing may be abnormal. Other laboratory tests that are indicated to differentiate the cause of nephrotic syndrome, and that may prevent the need for renal biopsy, include serum free light chains and urine protein electrophoresis, HIV test, serum complement level, syphilis test (RPR), hepatitis serologies, complement (C3, C4, and total haemolytic complement), cryoglobulins, or antinuclear antibodies (ANA) screening. If mercurial nephropathy is suspected, a mercury blood analysis is indicated. Imaging studies may be needed if malignancy is suspected (e.g., as a cause of membranous nephropathy). Underlying adenocarcinomas of the GI tract/abdomen are a well-recognised association, although the link between malignancy and nephrotic syndrome is wider than that. The choice of imaging and other studies will depend on the clinical presentation. Renal ultrasound can assist in some diagnoses (e.g., small asymmetric kidneys in focal segmental glomerulosclerosis secondary to congenital renal dysplasia). An ultrasound (or other renal imaging) is invariably performed before a renal biopsy. As there is a small risk of post-biopsy bleeding, and a very small risk of needing renal arterial embolisation, or nephrectomy, to arrest this, it is also prudent to use this imaging to assess the risk of end-stage renal disease in the

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event of post-biopsy bleeding requiring nephrectomy: the risk is higher if there is a single kidney or if the biopsy is of a good-sized kidney when the contralateral kidney is small. These risks must be weighed against the importance of discovering, and potentially treating, the underlying cause.

  • 2.9.4 Renal biopsy

In children, almost all cases of nephrotic syndrome are due to minimal change disease; therefore, many paediatric nephrologists treat the patient for minimal change disease and perform a renal biopsy only if the patient is unresponsive to treatment. In adults, minimal change disease is relatively uncommon and patients usually require a renal biopsy for definitive diagnosis, as history, physical examination, and laboratory evaluation are often not useful for differentiating the underlying cause. Early consultation with a kidney specialist is recommended, and it may be wise to discontinue any anticoagulation therapy early, if the patient is taking it, to avoid delaying a renal biopsy. This must be pondered carefully and a full risk- benefit analysis should be undertaken. Contraindications to percutaneous renal biopsy include:

Bleeding diathesis resistant to correction

Multiple, bilateral renal cysts Renal tumour Hydronephrosis Active renal infection Small kidneys secondary to chronic irreversible disease Severe and resistant hypertension

2.10 Treatment 2,4,5,14 Children with the first onset of nephrotic syndrome should be treated in the hospital for the acceleration of clinical examinations, evaluation and arrangement of diet, reduction of edema, initiation of steroid, and education of parents.

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  • 2.10.1 Symptomatic Treatment

    • 2.10.1.1 Diet

High-protein diet is considered a contraindication because it will increase the burden of the glomerulus to remove protein metabolism residual (hyperfiltration) and cause glomerular sclerosis. Low-protein diet will cause protein energy malnutrition and growth retardation. Therefore, normal protein diet (RDA=1.5-2 g/kg/day) is advisable for nephrotic syndrome patients. Salt restriction is advised for the prevention and the treatment of edema. A very low salt diet is only necessary in cases of massive edema. Fluid restriction is recommended for moderate to severe hyponatremia (plasma sodium concentration less than 125meq/l). A reduction of saturated fat is recommended. Carbohydrates should be given preferentially as starch or dextrin-maltose, avoiding sucrose, which increases lipid abnormalities.

  • 2.10.1.2 Hypovolemia

Hypovolemia occurs as a consequence of rapid loss of protein and is sometimes aggravated by the use of diuretics. This complication needs emergency treatment by rapid infusion of plasma (20 ml/kg) or albumin 20% (1 g/kg) administrated with control of heart rate, respiratory rate, and blood pressure.

  • 2.10.1.3 Diuretics

Fluid restriction is recommended for severe edema. Loop diuretic, such as furosemide 1-3 mg/kg/day, is usually given. If necessary, it can be combined with spironolactone (aldosterone antagonists, potassium-sparing diuretics) 2-4 mg/kg/day. Before administering diuretics, we need to exclude the possibility of hypovolemia. On the use of diuretics over 1-2 weeks, it is necessary to monitor blood electrolytes, such as potassium and sodium. When diuretics are not successful (refractory edema), it usually occurs because of hypovolemia or severe hypoalbuminemia (≤ 1 g / dL). In that case, 20- 25% albumin infusion at a dose of 1 g / kg for 2-4 hours may be given to draw fluid from the interstitial tissues and ends with intravenous furosemide administration of 1-2 mg / kg. If the patient is not capable in terms of cost, plasma 20 ml / kg / day slowly 10 drops / minute can be given to prevent complications of cardiac decompensation. When needed, albumin suspension can be given in one

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day interval to allow fluid shifts and prevent fluid overload. When ascites is very severe that it interferes breathing, recurrent ascites puncture can be done. Scheme of giving diuretics in patients with edema is shown below.

Response (-) Response (-) Response (-) Response (-) Response (-)
Response (-)
Response (-)
Response (-)
Response (-)
Response (-)

Figure 2.1. Algorithm in diuretic administration

2.10.1.4 Thromboemboli

Nephrotic patients are at risk for thromboembolic complications. Prevention of this complication includes regular ambulation, avoidance of hemoconcentration due to hypovolemia, avoidance of central venous catheter if possible, and early treatment of sepsis or volume depletion. There are no controlled trials on the efficacy and safety of prophylactic anticoagulation to prevent thromboembolic complications in children with nephrotic syndrome. However, several authors propose prophylactic measures in children with risk factors. For example, prophylactic warfarin therapy may be given to patients with a plasma albumin concentration below 20 g/l, a fibrinogen level over 6 g/l, or an antithrombin III level below 70 % of normal. Patients at risk may also be treated with low-dose aspirin and dipyridamole, although there is no evidence that it is beneficial. Heparin is given initially if thrombi do occur, alone or with thrombolytic agents. Anticoagulation is most often initiated with low molecular weight heparin,

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such as enoxaparin at a starting dose of 1 mg/kgBW every 12 h, with the antifactor Xa assay as a therapeutic drug monitoring. Its pharmacokinetics is more predictable than unfractionated heparin, and it is given subcutaneously, avoiding venous catheter. In situations where short half-life and reversible anticoagulation is necessary, unfractionated heparin is utilized. The heparin dose necessary to obtain a therapeutic effect is often greater than normal due to decreased antithrombin III level.

  • 2.10.1.5 Antihypertensive Drugs

Any arterial hypertension has to be carefully controlled, using preferably a β-blocker or a calcium channel blocker during acute episodes. In cases of permanent hypertension, an angiotensin-converting enzyme inhibitor is preferred.

  • 2.10.1.6 Infections and Immunizations

Prophylaxis of S. pneumoniæ with oral penicillin is often applied in patients during the initial treatment with corticosteroids. Pneumococcal vaccine may be performed. It is effective even in children receiving high doses of steroids, and it is not associated with an increased risk of relapse. In cases of peritonitis, antibiotics against both S. pneumoniæ and gram-negative organisms are started after peritoneal liquid sampling. Varicella is a serious disease in patients receiving immunosuppressive treatment or daily corticosteroids. Varicella immunity status should be checked in these patients. In cases of exposure, early preventive treatment by acyclovir must be instituted. Varicella vaccination is safe and effective if the child is in remission even if he/she is on low-dose alternate-day steroids.

  • 2.10.1.7 Hyperlipidemia

Persistent hyperlipidemia is a risk factor for atherosclerosis and may play a role in the progression of chronic renal failure. Experience with hypolipidemic drugs in nephrotic patients is still limited, but it seems that statins are effective and able to decrease hypercholesterolemia. Although long-term side effects of these drugs are not known, it is reasonable to consider a lipid lowering regimen in children with a persistent nephrotic syndrome.

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2.10.1.8

Miscellaneous

 

Calcium

metabolism

may

be altered by the urinary loss of 25-

hydroxycholecalciferol and its carrier protein. Preventive treatment with vitamin D supplements is therefore useful, but does not completely prevent bone loss. Thyroxine substitution may be indicated, but only in patients with documented hypothyroidism due to urinary loss of iodinated proteins .

  • 2.10.2 Specific Treatment

    • 2.10.2.1 First Episode

Prednisone (or prednisolone, used interchangeably): 60 mg/m 2 once daily or in 2–3 divided doses (~2 mg/kg/day, max. 60 mg/day) for 4–6 weeks followed by 40 mg/m 2 (~1.5 mg/kg, max. 40 mg) on alternate days as a single morning dose for the next 4–6 weeks with or without taper. Some authors recommend prolonged glucocorticoid therapy for 6 months after the initial, intense therapy. A focus of infection must always be searched and treated. Control of underlying infection can achieve remission in some cases.

  • 2.10.2.2 Relapse Treatment

About 70 % of patients with INS will have one or more relapses. Treatment is directed to suppress proteinuria and restore normal serum protein concentrations and to reduce the frequency of future relapses, both with minimal short- and long-term adverse effects. Prednisone remains the only medication to effect remission quickly in patients with glucocorticoid-sensitive, relapsing INS. Prednisone 60 mg/m 2 per day usually achieves urinary remission within 7–10 days. Once urine is protein- free for three consecutive days, daily prednisone is switched to a single morning dose of 40 mg/m 2 (~1.5 mg/kg) on alternate days for 4 weeks and then stopped.

  • 2.10.2.3 Frequent Relapses and Glucocorticoid (Steroid) Dependence

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Upon achieving remission with daily high-dose prednisone, patient is switched to alternate-day prednisone as above. However, there is no clear consensus about the best long-term approach. Option 1: identification of a “threshold” dose of prednisone. Alternate-day prednisone is tapered to 0.5 mg/kg every 48 h. If stable, taper is continued until a dose is reached that still prevents relapses. When a relapse occurs, aim at a maintenance dose just above the last dose where the patient relapsed and continue this dose for 6 months. Option 2: introduction of second-line agent, usually in conjunction with prednisone tapering, intended to minimize long-term glucocorticoid adverse effects.

  • 2.10.2.4 Second-Line Agents and Strategies

Second-line agents are introduced to avoid long-term glucocorticoid related adverse effects or as alternative for glucocorticoid resistance. Treatment with second-line drugs depends on availability and affordability, adverse effect profile, physician comfort and family preference. Literature and common practice suggest efficacy of (oral) alkylating agents in patients with frequently relapsing or glucocorticoid-dependent nephrotic syndrome (oral cyclophosphamide [POCY], chlorambucil). The reported duration of remission after POCY varies. Early relapses after an alkylating agent are more common in SDNS and FSGS than in FRNS. Although affordable and widely available, there are concerns of drug safety, specifically gonadotoxicity, bone marrow suppression, and severe infection.

  • 2.10.2.5 Management of Steroid-Resistant Nephrotic Syndrome (SRNS)

Chances of remission diminish drastically after 3 weeks of high-dose daily prednisone treatment. Preparations should be made for a kidney biopsy and genetic testing to avoid excess glucocorticoid toxicity. Kidney biopsy is mandatory in patients who do not achieve remission after 4 weeks of prednisone treatment with or without a short course (3 pulses) of 10 mg methylprednisolone.

xxiii

The majority of patients with SRNS will have FSGS, diffuse mesangial proliferation, or MCNS by biopsy. The differential diagnoses include membranoproliferative (mesangiocapillary) glomerulonephritis (MPGN) and membranous nephropathy (MN). Children (or adolescents) with pathogenic mutations of genes encoding structural podocyte proteins do not benefit from immunosuppressive therapies but require supportive treatment and frequent monitoring. Examples are podocin (NPHS2) (in children), A-actinin 4 (ACTN4), and transient receptor potential cation channel type 6 (TRPC6) mutation (in adolescents and young adults). Methylprednisolone or dexamethasone pulses with cyclophosphamide have been used in patients where induction of remission has been difficult to achieve (so called Mendoza protocol). The 2012 KDIGO guideline advises against the use of cytotoxic agents for SRNS. In an attempt to minimize overall toxicity, the following modified protocol is proposed for patients with SRNS:

Glucocorticoid pulse therapy with IV methylprednisolone (3 pulses of 10 mg/kg Q 48 h) or PO/IV dexamethasone (three doses of 1.5–3 mg/kg or 50– 100 mg/m 2 Q 3 days). Alternate-day PO prednisone. Calcineurin inhibitor (tacrolimus or CSA), to be started in the upper dose range with target (trough) plasma concentrations (C0) of 5–10 or 150–250 ng/ml, respectively. If patient enters remission, taper prednisone. Adjust CNI dosage according to therapeutic effect. In case of CNI toxicity, consider reducing CNI dose or switch to alternative CNI. Addition of MMF may spare glucocorticoid or CNI. Rituximab does not appear to be effective in the majority of patients resistant to glucocorticoids and other second-line agents.

  • 2.10.2.6 Steroid side effects

Side effects of prolonged steroid therapy are well known and are

observed in children with a steroid- dependent course. Growth retardation is

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observed with prolonged daily steroid therapy, and alternate- day therapy may preserve growth. However, when the dose needed to maintain remission is too high, growth may be impaired Osteoporosis has been reported in adults who had suffered from nephrotic syndrome during childhood. However, a study in children and adolescent with steroid-dependent nephrotic syndrome failed to find a deleterious effect of alternate-day steroid therapy on bone mineral content. Biyikli et al. reported that steroid treatment causes a dose-dependent decrease in bone formation, as shown by the changes in osteocalcin and alkaline phosphatase levels and low 25-hydroxyvitamin D levels. A randomized controlled trial com- pared vitamin D and calcium supplements with no prophylaxis in children receiving high-dose steroid therapy during a relapse. The other side effects include weight gain, cataracts, behavior disturbances, and hypertension.

  • 2.11 Parental Education

Nephrotic syndrome is a significant diagnosis and the family needs to be aware that the risk of relapse is >80% and they should know how to detect and treat it. Making adequate information available for the family is essential. All carers should receive the Childhood Nephrotic Syndrome booklet or equivalent notebook to record daily urine results. They should be shown how to do this before discharge.

  • 2.12 Complication

The main complications of nephrotic syndrome are hypovolaemia, infection and thrombosis. The initial examination of children with nephrotic syndrome needs to include an assessment of their intravascular volume. Whilst these children may be very oedematous, they may also be intravascularly depleted. Signs of intravascular depletion are cool peripheries (capillary refill time > 2 secs), a core- peripheral temperature gap of > 2ºC and tachycardia. Hypotension is a late sign of hypovolaemia, but paradoxical hypertension may be present. A urinary sodium of < 10 mmol/l is a useful investigation to confirm hypovolaemia.

xxv

Patients with nephrotic syndrome are at risk for the development of a variety of complications, which include thrombosis, infections, dyslipidemia (explored in the previous section), and renal dysfunction. Venous thrombosis is more common in patients with nephrotic syndrome compared with arterial thrombosis; thrombosis, when present, may occur in the renal vein, sagittal sinus, or pulmonary artery. Thrombosis in this patient population is multifactorial. Patients may have a hereditary risk factor (such as Factor V Leiden mutation) that predisposes them to clot formation. They may be intravascularly depleted as a result of nephrotic syndrome that may be exacerbated by diuretic use to control edema. When combined with the urinary loss of coagulation cascade regulators (such as anti-thrombin III) and an increase in hepatic production of procoagulant factors (such as fibrinogen, factor V, and factor VIII), conditions that favor thrombus formation result. Thrombocytosis and platelet aggregation also occur in nephrotic syndrome and may play a role in thrombosis. In addition to urinary loss of hematologic factors, there is also loss of immunoglobulins. This loss of circulating antibodies puts nephrotic children at risk for bacterial infections, particularly those with encapsulated bacteria (eg, Streptococcus pneumoniae, Haemophilus influenzae, and Group B streptococcus). Peritonitis caused by S. pneumoniae is a well-described infection in children with nephrotic syndrome. Patients may also experience serious infections like cellulitis and pneumonia, and can develop sepsis. These children must be vaccinated against these bacteria because of waning immunity over time as a result of their underlying diagnosis. Current recommendations call for administration of the 23- valent pneumococcal polysaccharide vaccine for all children older than 2 years with nephrotic syndrome. The vaccine should be administered at least 8 weeks after the last dose of the 13-valent pneumococcal conjugate vaccine, with an additional dose of the 23-valent pneumococcal polysaccharide vaccine 5 years after the first dose in patients who have ongoing disease. Patients undergoing treatment for nephrotic syndrome with immunosuppressants are also at continued risk of infections, and febrile illnesses in this population require close follow-up. Beyond the urinary loss of albumin and immunoglobulins, nephrotic syndrome also causes the loss of other important proteins, including vitamin D–

xxvi

binding protein and thyroid-binding globulin. This loss may cause vitamin D deficiency and increase the potential for metabolic bone disease. Although hypothyroidism is more of a frequent problem in patients with CNS, in whom proteinuria is heavy and long-standing, general practitioners should recognize this

as a potential issue in children who are resistant to corticosteroids or who have frequent relapses.

Renal

dysfunction

can occur in the setting of nephrotic syndrome,

especially with patients presenting with hypovolemia. Preceding illness, aggressive diuretic use, or sepsis with hypotension may result in decreased renal bloodflow, causing a decrease in the glomerular filtration rate. Acute kidney injury in most of these cases is reversible with remission of the nephrotic syndrome and adequate volume repletion.

2.13 Prognosis 4,13 For patients with minimal change pathology, prognosis is very good, with most patients going into remission following corticosteroid treatment For patients with focal-segmental glomerulosclerosis, prognosis is grave:

generally will progress to end-stage renal disease requiring dialysis and kidney transplant. In all cases, prognosis may be worsened by the following:

  • - Superimposed opportunistic infection

  • - Poorly controlled hypertension

  • - Significant renal impairment

  • - Persisting nephrotic range proteinuria unresponsive to treatement

  • - Thromboses in cerebral, pulmonary, peripheral, or renal veins

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3.1 Case

CHAPTER 3 CASE REPORT

ND, female, 16 years and 5 months, was admitted on January 26, 2016 with chief complaint such as swollen eyes and swelling on the entire body. Patient also complain for petechiae found in the abdomen and the feet 2 months ago. Patient was referred from Pirngadi General Hospital Medan without any clear diagnose. History of swelling on the eyes (-), face (-), both legs (-), and body (-). History of medication (-). Nausea (+), vomit (+), fever (-). History of reduced urine output (-). History of urine with the color of meat wash (+) 1 month ago without any pain or other complaint during urination. Defecation within normal limit.

History of Disease

  • - Initially, the patient’s complaint was swollen eyes. It was first experienced 2 months ago. Then, patient’s face and body slowly became swollen.

  • - Then, patient was taken to Pirngadi Hospital after the complaint appeared. The mother of the patient said that patient didn’t get any medication and then was referred to Adam Malik Hospital without any clear diagnose.

  • - History of hematuria (-). History of dyspnoe (-) and abdominal pain (-). History of cough (-) and flu (-).

  • - This patient has been treated under supervision of Pediatric Nephrology Division of RSUP HAM with nephrotic syndrome as the diagnosis.

History of Medication:

No history of medication

History of family:

No family history of the same disease

History of Feeding:

xxviii

Patient was breast milk and formula milk from birth to 6 months, then was given breast milk and milk porridge from 6 to 9 months, and was given breast milk, milk porridge and moistured rice from 9 months to 1,5 years old.

History of Immunization: The patient’s mother said that she was not clear about the immunization of ND.

History of Growth and Development: The patient’s mother said that ND grew normally. ND had developed sitting at the age of 7 months, crawling at the age of 9 months, standing at the age of 1 year old and walking at the age of 2 years old.

Physical Examination

General status

Body weight: 39 kg, Body height: 161 cm, Body weight in 50th percentile according to age: 55 kg Body length in 50th percentile according to age: 164 cm Body weight in 50th percentile according to body height: 51 kg BW/age: 39/55 x 100% = 70,9% BH/age :161/164 x 100% = 98.1% BW/BH: 39/51 x 100% = 76,47%

Presens status

Sensorium Blood Pressure Heart Rate Respiratory Rate

: Compos Mentis : 150/90 mmHg : 110 x/i : 22 x/i

Body Temperature : 37,0 o C Anemic (-); icteric (-), cyanosis (-), edema (-), dyspnea (-)

Localized status

Head :

xxix

Eyes

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

Face

icteric sclera (-/-), light reflex (+/+), edema (-/-) : edema (-), inferior and superior palpebral edema (-/-), bleeding

Ears

(-/-) : within normal limit

Nose

: within normal limit

Mouth

: within normal limit

Neck :

JVP R-2 cmH 2 O, lymph node enlargement (-)

Thorax :

Symmetric

fusiform; retraction

(-);

HR:

110

bpm, regular, murmur

(-);

RR: 22 bpm, regular, ronchi (-), breath sound: vesicular, additional sound (-)

Abdomen :

Soepel, peristaltic (+) normal, liver and spleen impalpable, skin pinch returns

quickly, ascites (-)

Extremities :

Pulse 110 bpm, regular, adequate pressure and volume, warm, CRT < 3”.

pitting edema (-)

Differential Diagnosis

  • - Nephrotic syndrome

  • - Glomerulonephritis

  • - Urinary Tract Infection

Working Diagnosis

  • - Nephrotic syndrome

Management

  • - Inj. Methylprednisolone FD 60 mg/ m 2 / hari ; Methylprednisolone tab 4 mg 6-5-5

  • - Valsartan 1x80 mg

  • - Vit K 10 mg / IM for 3 days

  • - Amoxicilin 3x500 mg

xxx

  • - Diet MB R6 1900 kkal + 80 gram protein

Diagnostic Planning

  • - Complete Blood

  • - Biopsy

  • - Urinalysis

  • - LFT, RFT

  • - Albumin

  • - Electrolyte

  • - Blood glucose

  • - Total cholesterol

xxxi

Laboratory Finding: January 26, 2015

Hematology

Result

Normal

Hemoglobin

g/dL

11.50

11.3 – 14.1

Erythrocyte

Erythrocyte 3.76 4.40 - 4.48

3.76

4.40 - 4.48

Leucocyte

Leucocyte 24.40 4.5 - 13.5

24.40

4.5 - 13.5

Hematocrit

%

34.40

37 - 41

Thrombocyte

Thrombocyte 479 150 - 450

479

150 - 450

MCV

fL

91.50

81 - 95

MCH

pg

30.60

25 - 29

MCHC

g %

33.40

29 - 31

RDW

%

12.60

11.6 - 14.8

Neutrophil

%

87.10

37 - 80

Lymphocyte

%

11.10

20 - 40

Monocyte

%

1.80

2 - 8

Eosinophil

%

0.00

1 - 6

Basophil

%

0.000

0 – 1

 

Renal

Result

Normal

Ureum

mg/dL

51.7

<50

Creatinin

mg/dL

0.82

0.70 - 1.20

 

Electrolyte

Result

Normal

Sodium (Na)

mEq/L

142

135 - 155

Potassium (K)

mEq/L

3.3

3.6 - 5.5

Chloride (Cl)

mEq/L

104

96 - 106

xxxii

Urinalysis

Result

Normal

Color

Yellow

Yellow

Glucose

Negative

Negative

Bilirubin

Negative

Negative

Ketone

Negative

Negative

Specific gravity

1.010

1.005 - 1.030

pH

6.0

5 - 8

Protein

Positive 1

Negative

Urobilinogen

Negative

Nitrite

Negative

Negative

Leucocyte

Positive

Blood

Positive

Negative

Urine sediment

Erythrocyte

LPF

30-40

<3

Leucocyte

LPF

3-6

<6

Epithelial

LPF

1 – 3

Casts

LPF

Negative

Negative

Crystal

LPF

Negative

FOLLOW UP

xxxiii

 

26 January 2016

S

Pre orbital edema (+), nausea (-),vomit (-), fever (-)

Sens: CM, Temp: 37.0 o C

Body weight: 39 kg, Body height: 161 cm.

Head:

Eyes

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

icteric sclera (-/-), light reflex (+/+)

Face

: edema (-), inferior and superior palpebral edema (-/-), bleeding (-/-)

Ears

: within normal limit

Nose

: within normal limit

Mouth : within normal limit

Neck:

O

JVP R-2 cmH 2 O, lymph node enlargement (-) Thorax:

Symmetric fusiform; retraction (-); HR: 110 bpm, regular, murmur (-); RR: 22 bpm, regular, ronchi (-), breath sound: vesicular, additional sound (-)

Abdomen:

Soepel, peristaltic (+) normal, liver and spleen impalpable, skin pinch returns

 

quickly, ascites (-)

Extremities:

Pulse 110 bpm, regular, adequate pressure and volume, warm, CRT < 3”, pitting

edema (-)

A

Nephrotic syndrome

   

Management:

  • - Inj. Methylprednisolone FD 60 mg/ m 2 / day ; Methylprednisolone tab 4 mg

6-5-5

P

  • - Valsartan 1x80 mg

  • - Vit K 10 mg / IM for 3 days

  • - Amoxicilin 3x500 mg

  • - Diet MB R6 1900 kkal + 80 gram protein

xxxiv

 

27 January 2016

S

History of swollen eyes (+),nausea (-),vomit (-), fever (-)

Sens: CM, Temp: 36.9 o C

Body weight: 39 kg, Body height: 161 cm.

Head:

Eyes

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

icteric sclera (-/-), light reflex (+/+)

Face

: edema (-), inferior and superior palpebral edema (-/-), bleeding (-/-)

Ears

: within normal limit

Nose

: within normal limit

Mouth : within normal limit

Neck:

O

JVP R-2 cmH 2 O, lymph node enlargement (-) Thorax:

Symmetric fusiform; retraction (-); HR: 108 bpm, regular, murmur (-); RR: 20 bpm, regular, ronchi (-), breath sound: vesicular, additional sound (-)

Abdomen:

Soepel, peristaltic (+) normal, liver and spleen impalpable, skin pinch returns

 

quickly, ascites (-)

Extremities:

Pulse 108 bpm, regular, adequate pressure and volume, warm, CRT < 3”, pitting

edema (-)

A

Nephrotic syndrome

   

Management:

  • - Inj. Methylprednisolone FD 60 mg/ m 2 / day ; Methylprednisolone tab 4 mg

6-5-5

P

  • - Valsartan 1x80 mg

  • - Vit K 10 mg / IM for 3 days

  • - Amoxicilin 3x500 mg

  • - Diet MB R6 1900 kkal + 80 gram protein

xxxv

 

28 January 2016

S

History of swollen eyes (+),nausea (-),vomit (-), fever (-)

Sens: CM, Temp: 36.7 o C

Body weight: 39 kg, Body height: 161 cm.

Head:

Eyes

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

icteric sclera (-/-), light reflex (+/+)

Face

: edema (-), inferior and superior palpebral edema (-/-), bleeding (-/-)

Ears

: within normal limit

Nose

: within normal limit

Mouth : within normal limit

Neck:

O

JVP R-2 cmH 2 O, lymph node enlargement (-) Thorax:

Symmetric fusiform; retraction (-); HR: 88 bpm, regular, murmur (-); RR: 20

bpm, regular, ronchi (-), breath sound: vesicular, additional sound (-)

Abdomen:

Soepel, peristaltic (+) normal, liver and spleen impalpable, skin pinch returns

 

quickly, ascites (-)

Extremities:

Pulse 88 bpm, regular, adequate pressure and volume, warm, CRT < 3”, pitting

edema (-)

A

Nephrotic syndrome

   

Management:

  • - Inj. Methylprednisolone FD 60 mg/ m 2 / day ; Methylprednisolone tab 4 mg

6-5-5

P

  • - Valsartan 1x80 mg

  • - Vit K 10 mg / IM for 3 days

  • - Amoxicilin 3x500 mg

  • - Diet MB R6 1900 kkal + 80 gram protein

  • - Waiting for kidney biopsy schedule

xxxvi

 

29 January 2016

S

History of swollen eyes (+),nausea (-),vomit (-), fever (-)

Sens: CM, Temp: 36.5 o C

Body weight: 39 kg, Body height: 161 cm.

Head:

Eyes

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

icteric sclera (-/-), light reflex (+/+)

Face

: edema (-), inferior and superior palpebral edema (-/-), bleeding (-/-)

Ears

: within normal limit

Nose

: within normal limit

Mouth : within normal limit

Neck:

O

JVP R-2 cmH 2 O, lymph node enlargement (-) Thorax:

Symmetric fusiform; retraction (-); HR: 88 bpm, regular, murmur (-); RR: 20

bpm, regular, ronchi (-), breath sound: vesicular, additional sound (-)

Abdomen:

Soepel, peristaltic (+) normal, liver and spleen impalpable, skin pinch returns

 

quickly, ascites (-)

Extremities:

Pulse 88 bpm, regular, adequate pressure and volume, warm, CRT < 3”, pitting

edema (-)

A

Nephrotic syndrome

   

Management:

  • - Inj. Methylprednisolone FD 60 mg/ m 2 / day ; Methylprednisolone tab 4 mg

6-5-5

P

  • - Valsartan 1x80 mg

  • - Vit K 10 mg / IM for 3 days

  • - Amoxicilin 3x500 mg

  • - Diet MB R6 1900 kkal + 80 gram protein

  • - Waiting for kidney biopsy schedule

xxxvii

 

29 January 2016

S

History of swollen eyes (+),nausea (-),vomit (-), fever (-)

Sens: CM, Temp: 36.5 o C Body weight: 39 kg, Body height: 161 cm.

Head:

Eyes

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

icteric sclera (-/-), light reflex (+/+)

Face

: edema (-), inferior and superior palpebral edema (-/-), bleeding (-/-)

Ears

: within normal limit

Nose

: within normal limit

Mouth : within normal limit

Neck:

JVP R-2 cmH 2 O, lymph node enlargement (-) Thorax:

O

Symmetric fusiform; retraction (-); HR: 88 bpm, regular, murmur (-); RR: 20

bpm, regular, ronchi (-), breath sound: vesicular, additional sound (-)

Abdomen:

Soepel, peristaltic (+) normal, liver and spleen impalpable, skin pinch returns

 

quickly, ascites (-)

Extremities:

Pulse 88 bpm, regular, adequate pressure and volume, warm, CRT < 3”, pitting

edema (-)

 

Renal biopsy :

Macroscopic : two pieces of tissue received ; one centimetre length, grey colour. Microscopic : kidney glomerulus tissues was seen fibrotic with a part covering the glomerulus lumen, tubules are dilated and filled with amorf eosinophilic mass, stroma fibrous is edematous and fibrotic.

Conclusion : Focal Glomerulo Sclerotic

A

Nephrotic syndrome

   

Management:

  • - Inj. Methylprednisolone FD 60 mg/ m 2 / day ; Methylprednisolone tab 4 mg

6-5-5

P

  • - Valsartan 1x80 mg

  • - Vit K 10 mg / IM for 3 days

  • - Amoxicilin 3x500 mg

  • - Diet MB R6 1900 kkal + 80 gram protein

  • - Patient was sent home and scheduled to control in pediatric policlinic

xxxviii

CHAPTER 4

DISCUSSION

According to research, 90% of children with nephrotic syndrome have idiopathic nephrotic syndrome while in this patient, Patient was classified into idiopathic nephritic syndrome. Approximately 30% of children have a history of a respiratory tract infection immediately preceding the onset of nephrotic syndrome. Upper respiratory infections, otitis media, and other infections are often associated with relapses of nephrotic syndrome as well. Besides, children have a history of allergy and hypersensitivity event, such as a reaction to bee sting or poison ivy, has been reported to precede the onset of nephrotic syndrome in some cases. Patient admit that there is no history of sore throat, fever and influenza that happened. 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).

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 4-6 weeks, followed by 1.5 mg/kg per day on alternating days for another 4-6

xxxix

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. This patient is given Prednisone 60 mg/m 2 , Valsartan 1x80 mg, Diet MB 1900 kcal + 80 gr protein, Amoxicilin 3x500 mg and Vit K 10 mg for 3 days.

CHAPTER 5 CONCLUSION

xl

ND, female, 16 years and 5 months, was admitted on January 26, 2016 with chief complaint such as swollen eyes and swelling on the entire body. Patient was referred from Pirngadi General Hospital Medan without any clear diagnose. Patient does not have a history of swelling on the palpebrae, face, legs, and body. Patient received management with Prednisone 60 mg/m 2 , Valsartan 1x80 mg, Amoxicillin 3x500 mg, Vit K 10 mg for 3 days and diet MB 1900 kcal + 80 gr protein. Patient was diagnosed with Nephrotic syndrome.

REFERENCE

xli

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  • 2. Alatas H, Tambunan T, P. Trihono P, O. Pardede S. Konsensus Tata Laksana Sindrom Nefrotik Idiopatik Pada Anak.

  • 3. Lane, J.C., Langman, C.B., Finberg, L., Spitzer, A., Windle, M.L. 2015. Pediatric Nephrotic Syndrome. Accessed from : http://emedicine.medscape.com/article/98290-overview . [Accessed 30 January 2016].

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  • 6. Elie, V., Fakhoury, M., Deschênes, G., Jacqz-Aigrain, E. 2012. Physiopathology of idiopathic nephrotic syndrome: lessons from glucocorticoids and epigenetic perspectives.

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56. Accessed from : http://www.ncbi.nlm.nih.gov/pubmed/21710250

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  • 7. Keddis, MT. and Karnath, BM. The Nephrotic Syndrome. Review of Clinical Signs. 2007;38;25-30.

  • 8. Andolino, PT. and Reid-Adam, J. Nephrotic Syndrome. Pediatrics in Review. 2015;36(3);117-125.

  • 9. Togawa A e. [Nephrotic syndrome: pathophysiology, classification and diagnostic criteria]. - PubMed - NCBI. 2016. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15500118 . [Accessed 05 February 2016]

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  • 10. Cohen, E.P., Sinnakirouchenan, R. 2014. Nephrotic Syndrome. Accessed from: http://emedicine.medscape.com/article/244631-overview [Accessed 30 January 2016].

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  • 12. Childhood Nephrotic Syndrome. National Institute of Diabetes and Digestive and Kidney Diseases. 2014;14.

  • 13. Nephrotic Syndrome in Pediatrics Patients. Pediatric Clerkship.

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