1. Childhood Nephrotic SyndromeBy
Brent Lee Lechner, D.O.
MAJ, MC, USA

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

3. 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

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

5. 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

6. 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

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

8. Congenital Nephrotic Syndrome Differential Diagnosis
Genetic
Infections
Idiopathic

9. 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

10. 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)

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

12. 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

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

14. 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

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

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

17. 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

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

19. 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)

20. 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 Early Steroid resistant
50 Steroid Responsive Steroid Dependent
One episode
No reslapses Late Steroid Resistant

21. 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

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