Childhood Nephrotic Syndrome By Brent Lee Lechner, D.O. MAJ, MC, USA

Case #1 4 month old child Symptoms: Irritability Intermittent puffy eyes Poor Appetite Normal, uncomplicated pregnancy, labor and delivery

Case #1 Physical Exam: Length: 60 cm Weight: 8.0 kg BP: 90/60 HEENT: Negative Chest: Clear; RSR without murmur ABD: liver palpable, kidneys not felt Ext: 2+ pedal and periorbital edema

Case # 1 Urine Urinanalysis: Microscopy: pH: 6.0 2-3 RBCs/hpf SG: 1.030 20+ Granular Casts Blood (-) Glucose (-) Ketones (-) Protein (3+) LE(-) Nitrite (-)

Case #1: Questions What additional historic information would be helpful? Congenital infections or maternal infection history including: VDRL screen, STD, etc Large Placenta Birth Weight and Prematurity Elevated Alpha Fetal Protein during pregnancy Newborn screen: Elevated TSH, VDRL, etc

Case #1: Questions What additional laboratory data? Serum Total Protein and Albumin Serum Cholesterol Screen for congenital infections: VDRL, RPR, CMV serologies, toxoplasmosis, hepatitis and HIV screen Third world Countries: Peripheral Smear for malaria Complete Thyroid Studies Urine Protein/Creatinine Ratio SLE serologies: C3, C4, ANA – very rare

Case 1: Questions Infantile Nephrotic Syndrome What is the most likely diagnosis? Infantile Nephrotic Syndrome What are the causes?

Congenital Nephrotic Syndrome Differential Diagnosis Genetic Infections Idiopathic

Genetic Causes Finnish Type NPHS 2 mutation (Podocin) NPHS 1 mutation (Nephrin) Autosomal recessive disease Generalized edema, abdominal distention, ascites, umbilical hernias and widened cranial sutures and fontanelles Hypotonia TSH and T4 NPHS 2 mutation (Podocin) Associated with focal segmental glomerulosclerosis (FSGS) Usually presents at older age

Genetic Causes Denys-Drash Syndrome (WT1 gene mutation) Male pseudohermaphroditism (XY) Ambiguous external or internal genitalia Wilm’s Tumor Association Renal Failure by age 4-5 years Galloway-Mowat Syndrome (autosomal recessive) Anomalies (CNS and brain, ocular, limb, cardiac and diaphragmatic defects along with dysmorphic facies)

Infections Congenital Syphilis (GN + interstitial nephritis) Hematuria often present Penicillin: Curative Toxoplasmosis Congenital rubella (membranous GN) Cytomegalovirus (CMV) HIV Hepatitis B (membranous GN)

Idiopathic Diffuse Mesangial Sclerosis (DMS) Membranous nephropathy Older infant (3-4 months out) Membranous nephropathy Infantile Systemic Lupus Erythematous (SLE) Diffuse proliferative GN (6 weeks-6 months) Low complement and ANA (+) Very Rare

Case #2 30 month old child Symptoms: Swollen Eyes ten days after URI Previously well and without problems Irritability, poor appetite and protuberant abdomen

Case #2 Physical Exam HEENT: negative Chest: Clear; RSR without murmur Height: 90 cm Weight: 18 kg BP 105/70 HEENT: negative Chest: Clear; RSR without murmur Abd: soft, liver palpable 2 cm below right costal margin Extremities: 2+/4 pedal and pretibial edema

Case #2 Urine Urinanalysis Microscopy SG: 1.030 multiple granular casts pH: 6.0 Blood (-) Glucose(-) Ketones(-) LE (-) Nitrites (-) Protein (4+)

Case #2: Questions What additional laboratory data would be helpful ? Serum Total Protein and Albumin Urine Protein to Creatinine ratio Serum Cholestrol

Case #2: Questions What is the most probable diagnosis? Childhood Nephrotic Syndrome Minimal change lesion What findings would make minimal change nephrotic syndrome less likely? Age: less than 1 year old or teenager Hematuria, especially rbc casts Hypertension Azotemia, elevated serum creatinine

Case #2: Questions What is required to establish diagnosis ? Always Proteinuria Hypoalbumemia Frequently Edema Hypercholestrolemia

Case #2: Questions How would you treat this patient? Low sodium diet Prednisone 2 mg/kg qd (max 60 mg/d) Daily urine dipstick When trace or negative for 10 days then wean steroids over 6 week course Albumin and Lasix treatment: If hyponatremia, severe edema and scrotal or labial edema (patient cannot ambulate), or respiratory distress (pleural effusion)

Case #2: Questions Is this likely to be a relapsing disease and, if so, when would the first relapse be likely? 100 patients 95 Steroid Responsive 5 Early Steroid resistant 50 Steroid Responsive 30 Steroid Dependent One episode No reslapses 5 Late Steroid Resistant

Case #2: Questions For patients with a complicated clinical course (multiple relapses or steroid non-responsive, or steroid toxicity), what is the alternate therapies? Cyclophosphamide (2 mg/kg) for 12 weeks Cyclosporin A (6 mg/kg/d) for 12 weeks

Case #2: Questions What is the long-term prognosis? Very favorable prognosis 90% full remission by age 21 years old