1. Friday, December 9 th, 2011

2. A 2½-year-old male presents with a 3-day history of progressive eyelid swelling. He had a URI 1 to 2 weeks ago. He has no history of pruritus or bee stings. His mother reports a decreased number of wet diapers per day, no fever, and no gross hematuria. He exhibits bilateral periorbital swelling, mild scrotal edema, and mild pitting edema over the pretibial region on PE. Of the following, the MOST likely laboratory finding expected for this child is: A. depressed complement 1 esterase inhibitor value B. elevated bradykinin value C. elevated immunoglobulin E value D. elevated serum creatinine value E. large protein on urinalysis

3. The Nephrotic Syndrome Alterations of the glomerular capillary wall Proteinuria Hypoalbuminemia Edema Hyperlipidemia

4. Epidemiology 16 per 100,000 children Males: females = 2:1 during childhood Increased familial incidence African American and Hispanic have greater incidence and more severe disease

5. Classification Primary (Idiopathic)Secondary Minimal Change Nephrotic Syndrome (MCNS) Infections (Hepatitis B, C, HIV, malaria, toxo, syphilis) Focal Segmental Glomerulosclerosis (FSGS) Drugs (gold, NSAIDS, pamidronate, interferon, heroin, lithium) Membranous Nephropathy (MN)Malignancies (lymphoma, leukemia) Miscellaneaous (SLE, mesangioproliferative glomerulonephritis, IgA nephropathy, DM) 90% of cases are primary

7. Minimal Change Nephrotic Syndrome (MCNS) 85% of cases Fusion of epithelial foot processes

8. *Clinical Features Edema Visible when fluid retention > 3 to 5% of body weight Low tissue resistance areas first Periorbital (mistaken for allergy) Scrotal Labial Becomes generalized Anorexia Irritability Fatigue Abdominal discomfort Diarrhea

9. *Laboratory Findings Low plasma protein Low albumin <2.5 g/dL Hyperlipidemia ↑ VLDL, LDL, TG Normal HDL *Hyponatremia Due to hyperlipidemia and retention of water ( ↑ ADH) Low total calcium *Remember complement and renal function are normal!

10. Proteinuria Start with dipstick (1+, 2+, 3+, 4+) Quantitative measurement 24-hour urine collection >50 mg/kg/day or 40 mg/m 2 /hour = nephrotic Cumbersome Urine protein/creatinine ratio 2) >3 = nephrotic syndrome

11. *Treatment

12. Ancillary Therapy Diuretics to treat edema Loops and Thiazides *May induce hypovolemia, secondary renal failure, thromboembolism, or electrolyte disturbances If diuretics fail can give albumin infusion Effective in children with very low serum albumin (<1.5) ACE inhibitors Statins for hyperlipidemia Vaccinations Low-sodium diet

14. A 4-year-old boy presents periorbital and extremity edema. Laboratory evaluation shows normal electrolyte values, BUN of 14.0 mg/dL, creatinine of 0.3 mg/dL, and albumin of 1.6 g/dL. UA demonstrates 3+ protein; and negative blood. Microscopy results are normal. Additionally, complement component (C3 and C4) values are normal, and results of serologic testing for ANA, hepatitis B and C, and HIV are negative. Of the following, you are MOST likely to advise the parents that A. a renal biopsy is warranted to determine the optimal treatment B. disease relapse can be expected in fewer than 25% of those achieving remission C. patients who relapse have a similar prognosis as those who do not respond to steroids D. remission is expected in more than 75% of patients who receive corticosteroid treatment E. tacrolimus is the preferred treatment for patients who do not respond to corticosteroids

15. Course Responders 90% respond to steroids *Of those, 60% relapse Frequency of relapses decreases with time Rare after puberty Negligible risk of renal insufficiency Steroid-resistant More common after age 2 10% of cases Poor prognosis Renal function deteriorates Candidates for dialysis and transplant

16. A 6 yo female is admitted for swelling of her face and extremities. Vital signs and PE are normal except for generalized anasarca. UA shows 4+ protein with no casts or RBCs. Serum albumin is 1.3 g/dL, cholesterol is 550 mg/dL, and creatinine is 0.4 mg/dL. This patient is at greatest risk for: A. Centrilobular hepatic necrosis B. Cerebral edema C. Congestive heart failure D. Myoglobinuric renal failure E. Peritonitis

17. *Complications of Nephrotic Syndrome Signs of acute renal failure ( ↓ GFR, oliguria) Reversed with albumin infusion and diuresis Thrombosis Loss of antithrombin III and protein S Incidence is 3% Antiphospholipid syndrome

18. *Complications of Nephrotic Syndrome Infections Peritonitis Empiric coverage with aminoglycoside and ampicillin Cellulitis, meningitis, pneumonitis Anasarca and pulmonary edema Steroid use Stunting of growth Reduced bone mineral density

19. 4 yo male with swelling of face and extremities x 2 days. Other than swelling, physical exam and vital signs are normal. UA shows 4+ protein and 5 RBCs/HPF. Of the following, the best indicator of good outcome for this child is: A. Normal C3 complement value B. Normal serum creatinine C. Resolution of symptoms with prednisone treatment D. Serum cholesterol less than 500 mg/dL E. Urine protein/creatinine ratio less than 5

20. Prognosis *Best prognostic indicator is steroid responsiveness* 95% of kids who will respond to steroids do so within the first 4 weeks As a result, patients with suspected MCNS are started on Prednisone without a renal biopsy Persistence or recurrence of hematuria often is a sign of impending steroid resistance

21. You are treating a 9-year-old girl who has nephrotic syndrome with prednisone. Which of the following is the strongest indication for performing renal biopsy? A. Lack of response to therapy after 1 week B. Microscopic hematuria showing more than 5 RBCs/HPF C. Reduced serum concentration of C3 complement D. Serum albumin less than 1.5 g/dL E. Urine protein/creatinine ratio of 1 at presentation

23. Hematuria/Proteinuria, Dr. Vehaskari