Extern conference A 1-year-3-month-old boy presented with generalized edema for 1 month 20 December 2007

History A 1-year- 3month-old boy Chief complaint : Generalized edema for 1 month Present history: He was no underlying disease. 1 month PTA, his mother noticed that her child had enlarged abdomen and edema of both feet and ankles. The patient’s body weight increased 4 kg in 2mo.

History - Normal urination and defecation, no gross hematuria - No previous history of fever, cough, sore throat and skin infection - No rash, no arthralgia - No dyspnea, no orthopnea - No chronic diarrhea

History Past history Caesarean section due to previous C/S birth weight 2616 gm, Apgar score 9,10 Family history No history of kidney disease in family Nutritional status Solid food 3 feeds Powdered milk 8 oz 3 feeds per day

Drugs and immunization No history of drug allergy No routine drug use Immunization Up to date Developmental history Say some words and walk History

Physical Examination Vital signs : T 36.9 C, PR140/min, BP 99/72 mmHg, RR 32/min GA : 1 3/12-year-Thai boy, uncooperative, not pale, no jaundice, no dyspnea, no cyanosis, puffy eye lids, generalized pitting edema 1+ Ht 80 cm (P50-75), BW 11 kg (P50-75), HC 46 cm (P25-50), Abdominal circumference 49 cm

HEENT : no dental caries no injected pharynx and tonsils Lungs : clear CVS : normal S1 and S2, no murmur Abdomen : soft, not tender, liver and spleen not palpable, no palpable mass, mild ascites, bowel sound active KUB: CVA-not tender, bimanual palpation-negative Genitalia: scrotal edema Others: unremarkable Physical Examination

PROBLEM LIST Generalized pitting edema for 1 month Weight gain 4 kg in 2 months

Generalized edema Nephrotic syndrome Acute or chronic glomerulonephritis Congestive heart failure Protein losing enteropathy Protein malnutrition DIFFERENTIAL DIAGNOSIS

Nephrotic syndrome PROVISIONAL DIAGNOSIS

Characteristic features of nephrotic syndrome 1.Generalized pitting edema 2.Hypoalbuminemia (≤2.5g/dl) 3.Hypercholesterolemia (≥250g/dl) 4.Heavy proteinuria (≥40 mg/m²/hr)

Question 1 “What is the initial investigation in this patient?”

INVESTIGATIONS AT INITIAL PRESENTATION Complete blood count Renal profiles, urinalysis and quantification for urinary protein excretion Serum albumin Lipid profiles

INVESTIGATIONS CBC(11/12/50) Hb 13.3 g/dl, Hct 39.9% WBC /ul ( N 32.2%, L 58.9%, M 4.8%, E 3.7%, B 0.4%) Plt 428,000 /ul Urinalysis(11/12/50) pH 7.0, spgr protein 4+, sugar neg, wbc 0-1/HP, rbc 1-2/HP

Blood chemistry(11/12/50) BUN 9 mg/dl, Cr 0.1 mg/dl Cholesterol 366 mg/dl Albumin 1.5 g/dl Na 131 mmol/L K 3.8 mmol/L Cl 104mmol/L HCO ₃ 24mmol/L INVESTIGATIONS

Urine 24 hrs Volume 440 ml (1.67ml/kg/hr) urine creatinine 31.3 mg/24hr urine protein 607 mg/24hr (50.6mg/m²/hr) INVESTIGATIONS

Diagnosis Nephrotic syndrome

Types of nephrotic syndrome Primary nephrotic syndrome(90%) Secondary nephrotic syndrome(10%)

Nephrotic syndrome Primary nephrotic syndrome(90%) Most common at age 2-6 yr (6 mo. patient has been reported) Male : female = 2 : 1

Distribution of primary nephrotic syndrome HistologyNo. of Patient (%) Minimal change disease Focal segmental sclerosis Membranoproliferative glomerulonephritis (MPGN) Mesengial proliferation Proliferative glomerulonephritis Membranous nephropathy Chronic glomerulonephritis unclassified 398 (76.5) 44 (8.5) 39 (7.5) 12 (2.3) 8 (1.5) 3 (0.6) 4 (0.8) * Adapted from a report of the International Study of Kidney Disease in Children

Nephrotic syndrome Secondary nephrotic syndrome(10%) Suspected in Age>8 yrs Hypertension Hematuria Renal dysfunction Extrarenal symptoms (rash, arthralgia, fever)

Secondary nephrotic syndrome Causes Infections Drugs Immunologic or allergic disorders Malignant disease Glomerular hyperfiltration

In this patient Primary nephrotic syndrome More common (90%) Lower age group Male No clinical suspection of secondary nephrotic syndrome

Management General Low salt, normal protein for age diet Salt poor albumin/diuretic if indicated Clear infection Education Immunization

Management Specific Prednisolone Cyclophosphamide Cyclosporin Levamisole

Indications for renal biopsy Pretreatment Macroscopic hematuria Persistent hypertension and microscopic hematuria Renal failure not attributable to hypovolemia Low plasma C3 Onset age < 6 months

Before start steroid therapy Complete physical examination CXR, PPD skin test Stool conc. for parasite Dental exam

In this patient Complete physical examination CXR: no infiltration PPD skin test: negative Stool conc. for parasite: not found 3 days Dental exam: no dental caries

CORTICOSTEROIDS 1. Nephrotic Syndrome Initial Diagnosis Prednisolone 60 mg/m2/day (max 80/day) for 4 weeks Response No Response Prednisolone 40 mg/m2/48 hours for 4 weeks Renal Biopsy *Discontinue *Steroid taper at 25% monthly over 4 months 2. Relapse

Progression Admit 11-14/12/50 V/S stable BW 11 – 11.1 kg Balanced I/O

Discharge 14/12/50 Home med Prednisolone[5] 4 tab oral OD pc Follow up OPD 2 weeks with urinalysis

Follow up 1. Nephrotic Syndrome Prednisolone 60 mg/m2/day (max 80/day) for 4 weeks Response No Response Prednisolone 40 mg/m2/48 hours for 4 weeks Renal Biopsy *Discontinue *Steroid taper at 25% monthly over 4 months

INDICATIONS FOR RENAL BIOPSY Steroid resistant Steroid dependence Frequent relapse

Definitions REMISSION: Urinary protein excretion < 4 mg/m2/hour or urine dipstix nil/trace for 3 consecutive days. RELAPSE: Urinary protein excretion > 40 mg/m2/hour or urine dipstix ++ or more for 3 consecutive days. FREQUENT RELAPSES: Two or more relapses within 6 months of initial response or four or more relapses within any 12 month period.

Definitions STEROID DEPENDENCE: Two consecutive relapses occurring during the period of steroid taper or within 14 days of its cessation. STEROID RESISTANCE: Failure to achieve remission in spite of 4 weeks of standard prednisolone therapy

Question 2 ‘What will you advice the patient’s caregiver ?”

Prognosis The prognosis depends on the cause of nephrotic syndrome. It is usually good in children. Minimal change disease responds very well to steroids and does not cause chronic renal failure. Focal segmental glomerulosclerosis frequently lead to end stage renal disease.

Prognosis Children who present with hematuria and hypertension are more likely to be steroid resistant Poor patient response to steroid therapy seems to be the finding most predictive of a poor outcome Frequent relapses are more common with young age of onset and in boys.

Patient Education Nephrotic syndrome is a chronic illness characterized by relapses and remissions Ensure normal activity and school attendance. Infections are an important cause of morbidity and mortality

Patient Education Live vaccines can be administered 6 weeks after cessation of corticosteroid therapy. Peer support and psychological counseling are important.