Approach to Nephrotic & Nephritic Syndromes

1. Approach to Nephrotic & Nephritic Syndromes • Academic Half-Day • Aug 2, 2012

2. Nephrology Olympics!

3. Name two NBA athletes with Nephrotic Syndrome

4. Proteinuria • Some protein in urine is normal (< 4mg/m2/hr or < 100 mg/m2/24h) • Non-pathologic • Postural (orthostatic) • Febrile • Exercise-induced • Pathologic • Tubular • Inherited (cystinosis, Wilson ds, Lowe syndrome) • Acquired (antibiotic, AIN, ATN, heavy metal poisoning) • Glomerular

5. Hematuria • Gross • Trauma - perform imaging and cystoscopy • Pain - rule out renal stones, mass, UTI • Painless - consider stones, mass, HSP, familial (thin BM), hematologic, other glomerular disease, systemic disease • Microscopic • Symptomatic - symptoms direct investigation • Isolated hematuria - rarely have significant renal disease (benign familial hematuria or hypercalciuria) • Asymptomatic hematuria and proteinuria - more worrisome, requires thorough evaluation by nephrology.

6. Edema • Differential diagnosis • Loss of oncotic pressure • decreased protein synthesis • increased protein loss • Increased capillary permeability • viral/bacterial • immune mediated • mechanical/thermal trauma • drugs • Increased hydrostatic pressure • congestive heart failure • lymphatic blockage

7. What is the term for extreme, generalized edema? ANASARCA

8. Golmerular Disease • Presents in one of 4 ways: • Acute Nephritic Syndrome • Nephrotic Syndrome • Rapidly Progressive Glomeruloneprhitis • Asymptomatic

9. Nephrotic Syndrome • Nephrotic range proteinuria • 3+ or 4+ • > 250 mg/mmol creatinine • > 40 mg/m^2/hr • Hypoalbuminemia • Hyperlipidemia • Hypercoagulable

10. Pathophysiology Glomerular Filtration Barrier

11. NEPHROLOGY AND INFECTIOUS DISEASE! What is this fictional doc’s specialty?

12. Etiology • Primary or idiopathic • Minimal change disease • FSGS • MPGS • Membranous nephropathy

13. Minimal Change Disease 85% of cases

14. FSGS 10-15% of cases

15. Membranous Nephropathy 4% of cases

16. In what event did this athlete win a bronze medal? 100m freestyle

17. Etiology • Secondary causes • Genetic • Metabolic • Infections • Drugs • Immunologic/Allergic • Malignancy • Glomerular hyperfiltration

18. Idiopathic Nephrotic Syndrome • 90% of childhood nephrotic syndrome • 85% of all cases due to MCD • Consider diagnosis other than MCD in: • Children < 1 year and > 10 years • Family history nephrotic syndrome • Extra-renal findings • More than minimal hematuria

19. Idiopathic Nephrotic Syndrome • Clinical manifestations: • Most common between age 2 and 6. • Often follows minor infection. • Mild edema progressing to generalized. • Ascites • Pleural effusions • Genital edema • Anorexia, abdo pain, diarrhea, irritability common.

20. What food item is known scientifically as Phaseolus vulgaris?

21. Diagnosis • Laboratory findings • Low serum albumin • High cholesterol, triglycerides, lipoproteins • Low serum sodium • Nephrotic range proteinuria • Indications for biopsy: • Age > 10, gross hematuria, hypertension • Renal insufficiency • Low C3 complement value • Persistent proteinuria following 4 week course of steroids

22. Treatment • Prednisone drug of choice. • Dose: 60 mg/m^2 per day divided TID • Continue daily for 4 weeks, then 40mg/m^2 as single dose on alternate days for 4 weeks. • 90% of MCD is steroid responsive • Of those, 60% relapse • Frequent relapsers can be treated with cyclophosphamide

23. Steroid-resistance • Up to 10% of all children with NS • Poor prognosis • Eventually leads to dialysis and renal transplant

24. Complications of Nephrotic Syndrome • Thromboembolic events • Loss of antithrombin III and protein S • Increase in fibrinogen concentration • Infection • Loss of factor B, low IgG, impaired Tcell function • Most common infection is peritonitis • Most common organisms are Strep pneumo or gram-negatives • Steroid side effects

25. Where did this duo rank in badminton at the 2012 Olympics? DISQUALIFIED for CHEATING!

26. Nephritic Syndrome • Results from inflammation within glomerulus • Characterized by • Hematuria, RBC casts, dysmorphic RBCs • Mild to moderate proteinuria • Azotemia, oliguria • Hypertension

27. Etiology

28. Rapidly Progressive Glomerulonephritis • Subset of nephritic syndrome • Medical emergency • Characterized by renal failure in days or weeks (months) • Classfication: • Type I - anti-GBM (idiopathic, Goodpasture’s) • Type II - immune complex (PIAGN, SLE, HSP) • Type III - pauci-immune (idiopathic, Wegener’s, microscopic polyangitis, drugs) • Treatment • Induction of remission (pulse steroids, cyclophosphamide 3-6 months) • Maintenance therapy (azathioprine) • Newer agents - Rituximab, MMF

29. Crescent BAD NEWS.

30. IgA Nephropathy • Most common cause of GN • Idiopathic or secondary (HSP, rheumatic ds, HIV, Celiac ds, chronic liver ds) • Variable presentation: • Asymptomatic hematuria and mild proteinuria • Recurrent episodes of gross hematuria • Nephrotic range proteinuria or RPGN • Hematuria coincident with URTI • Treatment depends on prognostic indicators • Watch & wait vs. immunosuppressive agents

31. Poststreptococus glomerulonephritis • Prototypic acute nephritic syndrome • Occurs 2-3 weeks after pharyngitis or skin infection with GAS (nephritogenic strain) • Typical history plus low C3, normal C4, and high ASOT, positive anti-DNase B • Self-limited disease - three phases • latent phase • acute phase • recovery phase • Supportive management of hypertension and edema • Indications for biopsy include normal complement level, failure to document strep infection, GFR < 30ml/min/1.73 m2

32. How much does the average adult kidney weigh? 120-140 grams!

33. References • Gordillio, R. and Spitzer, A. The Nephrotic Syndrome. Pediatr Rev, 2009;30: 94-105. • Beck, L. and Salant, D. Glomerular and Interstitial Diseases. Prim Care Clin Office Pract 2008;35:265-296. • Bergstein, J. A Practical Approach to Proteinuria. Pediatr Nephrol 1999;13:697-700. • Massengill, S. Hematuria. Pedatr Rev 2008;29:342-348. • Pais, P. and Avner, E. Nephrotic Syndrome. Nelson’s Textbook of Pediatrics, Ch 52:1801-1806. • Eison, T., Ault, B., and Jones, D. Post-streptococcal cute glomerulonephritis in children: clinical features and pathogenesis. Pedatr Nephrol 2011;16:165-180.