Nephrotic Syndrome

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recent lecture given to medical officers (part of internal medicine update course) in hospital sultanah aminah johor bahru

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  • very helpful slides. Would be grateful if you can share to me to felicia.annette@gmail.com thank you
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  • thank you very much for sharing this. As a medical student, i benefit a lot from it in my presentation.
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  • This is informative. Can you send a copy to misc.inbox@gmail.com
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Nephrotic Syndrome

  1. 1. nephrology update <ul><li>15/5/2008 </li></ul><ul><li>YW Chow </li></ul>
  2. 2. Nephrology Update <ul><li>Glomerulonephritis </li></ul><ul><ul><li>Nephrotic syndrome </li></ul></ul><ul><ul><li>Nephritic syndrome </li></ul></ul><ul><li>CKD </li></ul><ul><li>Others- NSF, Fleet induce phosphate nephropathy, CIN </li></ul>
  3. 9. Definition of Nephrotic Syndrome <ul><li>Urine protein excretion </li></ul><ul><ul><li>> 40mg/m 2 /hr </li></ul></ul><ul><ul><li>Urine protein creatinine index>200mg/mmol </li></ul></ul><ul><ul><li>24 hr urine protein > 3g </li></ul></ul><ul><li>Hypoalbuminaemia <25g/l </li></ul><ul><li>Oedema </li></ul>
  4. 10. Minimal Change disease Focal Segmental glomerulonephrits
  5. 11. Minimal Change Disease
  6. 13. <ul><li>International Study of Kidney Disease in Children </li></ul><ul><ul><li>20.7% had SBP > 98th percentile </li></ul></ul><ul><ul><li>22.7% had microscopic haematuria </li></ul></ul><ul><ul><li>32.5% had transiently elevated serum creatinine </li></ul></ul>
  7. 14. <ul><li>ISKDC regime </li></ul><ul><ul><li>Prednisolone 60mg/m 2 /day (max 80mg/day)- 4 weeks </li></ul></ul><ul><ul><li>Prednisolone 40mg/m 2 /EOD- 4 weeks </li></ul></ul><ul><li>Long initial prednisolone regime </li></ul><ul><ul><li>Prednisolone 60mg/m 2 /day (max 80mg/day)- 4 weeks </li></ul></ul><ul><ul><li>Prednisolone 40mg/m 2 /EOD- 4 weeks </li></ul></ul><ul><ul><li>Reduce by 25% monthly over 4 months </li></ul></ul>Treatment
  8. 16. <ul><li>Remission- Urine protein < 4mg/m 2 /hr or urine dipstick nil/trace for 3 consecutive days </li></ul><ul><li>Relapse - urine albumin >40mg/m 2 /hr or urine dipstick 2+ or more for 3 consecutive days </li></ul><ul><ul><li>Treatment- Prednisolone 60mg/m 2 /day (max 80mg/day) till urine dipstick is trace/nil for 3 consecutive days then, </li></ul></ul><ul><ul><li>Prednisolone 40mg/m 2 /EOD- 4 weeks </li></ul></ul><ul><li>Frequent relapser - 2 or more in 6 mths, 4 or more 12 months </li></ul>
  9. 17. <ul><li>Steroid dependence - 2 consecutive relapses during period of steroid taper or within 14 days of its cesssation </li></ul><ul><li>Steroid resistance - failure to achieve remission in spite of 4 weeks of standard prednisolone therapy </li></ul>
  10. 18. <ul><li>Cycophosphamide- 2mg/kg/d 8 weeks </li></ul><ul><ul><li>Steroid dependent/ frequent relapser </li></ul></ul><ul><li>Cyclosporin- 3-5mg/kg/d </li></ul><ul><ul><li>Steroid resistant/ steroid dependent/ frequent relapser </li></ul></ul>
  11. 19. <ul><li>DVT prophylaxis </li></ul><ul><li>No live vaccine till 6 weeks after cessation of steroid therapy </li></ul><ul><ul><li>Pneumococcal </li></ul></ul><ul><ul><li>VZ </li></ul></ul><ul><li>IV human albumin 0.5-1.0/kg/dose over 1-2 hours + IV Frusemide 1-2mg/kg </li></ul><ul><li>Addisonian crisis- on > 18mg/m 2 /d prednisolone </li></ul><ul><li>No evidence- Statins, Low protein diet, Bed rest </li></ul>
  12. 20. FSGS
  13. 22. <ul><li>FSGS with nephrotic syndrome- No spontaneous remission. ESRD in 5-10 years </li></ul><ul><li>Presentation:- </li></ul><ul><ul><li>Nephrotic range proteinuria (70%) </li></ul></ul><ul><ul><li>Renal impairment (20-30%) </li></ul></ul><ul><ul><li>Elevated BP (30-45%) </li></ul></ul><ul><ul><li>Microscopic haematuria (50%) </li></ul></ul>
  14. 23. <ul><li>Poor prognostic indicators:- </li></ul><ul><ul><li>Proteinuria (high grade) </li></ul></ul><ul><ul><li>Renal impairment </li></ul></ul><ul><ul><li>Interstitial fibrosis </li></ul></ul><ul><li>Good prognostic indicator:- </li></ul><ul><ul><li>PR/CR </li></ul></ul>
  15. 24. <ul><li>Treatment </li></ul><ul><ul><li>Steroids- No RCT on steroid Tx. Remains first line </li></ul></ul><ul><ul><li>Prednisolone 1mg/kg/d X 4-6 months before declaring steroid resistant (4/12- collaborative group of societe de nephrologie) </li></ul></ul><ul><ul><li>responsive pt- taper over 3 months </li></ul></ul><ul><ul><li>unresponsive pt- taper over 4 weeks </li></ul></ul>
  16. 26. CR 33_47% vs 0% if untreated vs <20% in shorter steroid course Korbet, KI 2002 n CR(%) PR(%) NR f/up (yrs) Nagai et al 1994 9 44 11 44 2.5 Rydel et al 1995 30 33 17 50 5.2 Catrran et al 1998 17 47 0 53 11.2 Ponticelli et al 1999 80 36 18 46 7.0 Schwartz et al 1999 42 33 19 48 6.2
  17. 27. Korbet, KI, 2002 n CR(%) PR(%) NR Cytotoxics S.Responsive S. Resistant 43 183 54% 17% 23% 15% 25% 68% Cyclosporin S.Responsive S. Resistant 15 281 73% 29% 7% 22% 20% 49%
  18. 28. <ul><li>Cyclophosphamide </li></ul><ul><ul><li>2mg/kg/d or chlorambucil 0.1-0.2 mg/kg/d PLUS steroids 2-3 months </li></ul></ul><ul><ul><ul><li>70% remission </li></ul></ul></ul><ul><ul><ul><li>Decrease rate of relapse </li></ul></ul></ul><ul><li>Cyclosporin </li></ul><ul><ul><li>3-5mg/kg/d. C0 125-225ng/ml </li></ul></ul><ul><ul><li>Respond in 1 month </li></ul></ul><ul><ul><li>>75% will relapse within 2 months of taper/stopping </li></ul></ul>
  19. 29. Membranous GN
  20. 36. Diabetic Nephropathy
  21. 37. <ul><li>Definition </li></ul><ul><li>Progressive decline in GFR </li></ul><ul><ul><li>Accompanied by proteinuria </li></ul></ul><ul><ul><li>End organ complication- retinopathy </li></ul></ul><ul><ul><li>Epidemiology </li></ul></ul><ul><ul><ul><ul><ul><li>Leading cause of ESRD in US/ Malaysia </li></ul></ul></ul></ul></ul><ul><ul><li>2002: 45% of ESRD is d/t DN </li></ul></ul><ul><ul><li>Incidence of DN in Type 1 patients is declining </li></ul></ul><ul><ul><li>Incidence of DN in Type 2 patients is increasing </li></ul></ul>
  22. 38. Natural History
  23. 41. <ul><li>Glucose Control </li></ul><ul><li>HbA1C <7% </li></ul><ul><li>FBS <6mmol/l </li></ul><ul><li>DCCT </li></ul><ul><li>Insulin </li></ul><ul><li>Self management education </li></ul><ul><li>Self monitoring of blood glucose </li></ul><ul><li>Reduce risk of microalbuminuria and albuminuria with intensive Rx </li></ul>Strategies for Preventing/Slowing DN Progression
  24. 42. <ul><li>EDIC </li></ul><ul><li>Glucose control decreases micro and macroalbuminuria and new development of HPT </li></ul><ul><li>Thiazolidinediones </li></ul><ul><li>Fluid retention esp in patients with LVF </li></ul><ul><li>Metformin </li></ul><ul><li>Caution if creatinine increases </li></ul><ul><li>0.13 mmol/l </li></ul><ul><li>T1/2 of insulin is prolonged with decreased GFR </li></ul><ul><li>Dose adjustments required </li></ul>
  25. 43. <ul><li>Hypertension </li></ul><ul><li><130/80 </li></ul><ul><li>May require 3-4 drugs </li></ul><ul><li>ACEI / ARB </li></ul><ul><li>ACEI: Type 1 & 2 DM </li></ul><ul><li>ARB: Type 2 DM </li></ul><ul><li>Close monitoring of serum creatinine and K for 2-3 months. </li></ul><ul><li>If stable yearly monitoring </li></ul><ul><li>Serum Creatinine increase of 30% above baseline that stabilizes in 2-3 months predicts improved long term outcome </li></ul>
  26. 45. <ul><li>Lipids </li></ul><ul><li><100mg/dl (2.6 mmol/l) </li></ul><ul><li><70mg/dl (1.8 mmol/l) for patients with cardiovascular disease </li></ul><ul><li>Dietary Protein Restriction </li></ul><ul><li>Controversial </li></ul><ul><li>0.8g/kg/d </li></ul><ul><li>Weight Loss </li></ul><ul><li>Improves insulin sensitivity </li></ul><ul><li>Potentially slows DN progression </li></ul>
  27. 46. Lupus Nephritis
  28. 50. IgA Nephropathy
  29. 51. <ul><li>Isolated microscopic haematuria </li></ul><ul><li>Macroscopic haematuria </li></ul><ul><li>RPGN </li></ul><ul><li>Nephrotic syndrome </li></ul><ul><li>Proteinuria > 1g </li></ul>
  30. 52. <ul><li>Isolated microscopic haematuria </li></ul><ul><ul><li>No specific treatment </li></ul></ul><ul><ul><li>Follow-up is mandatory </li></ul></ul><ul><li>Macroscopic haematuria </li></ul><ul><ul><li>?Tonsillectomy </li></ul></ul><ul><li>RPGN </li></ul><ul><ul><li>Immunosuppression </li></ul></ul>
  31. 53. <ul><li>Nephrotic syndrome </li></ul><ul><ul><li>Minimal change in biopsy </li></ul></ul><ul><ul><li>Treat as MCD </li></ul></ul><ul><li>Proteinuria > 1g </li></ul><ul><ul><li>ACEI + ARB (COOPERATE) </li></ul></ul><ul><ul><li>Target BP 125/75 </li></ul></ul><ul><ul><li>Fish oil </li></ul></ul><ul><ul><li>Immunosuppresion- Steroids, Cycolphosphamide , MMF </li></ul></ul>
  32. 54. Chronic Kidney Disease
  33. 57. <ul><li>1 Stage 5 </li></ul><ul><li>200 Stage 3 & 4 </li></ul><ul><li>5,000 Stage 1, 2 </li></ul>CKD Burden
  34. 59. Acute Kidney Injury
  35. 60. Epidemiology <ul><li>AKI </li></ul><ul><ul><li>5-20% </li></ul></ul><ul><ul><li>A/W mortality </li></ul></ul><ul><ul><ul><li>ICD - 21.3% with AKI vs 2.3% without AKI </li></ul></ul></ul><ul><ul><li>Increase length of stay </li></ul></ul><ul><ul><ul><ul><ul><li>Uchino S, JAMA, 2005 </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Liangos O, cJASN, 2006 </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Xue JL, JAMA, 2005 </li></ul></ul></ul></ul></ul>
  36. 61. YW Chow, MMJ, 2007 <ul><li>0.48% (1994) vs 1.1% (2004) </li></ul><ul><li>55-57 y/o </li></ul><ul><li>sepsis- 41% (1994) vs 37.9% (2004) </li></ul><ul><li>Mortality- 56.4% (1994) vs 44.5% (2004) </li></ul><ul><li>ICU Mortality- 78.3% (1994) vs 68.5% (2004) </li></ul>
  37. 69. Treatment of AKI <ul><li>Pharmacological </li></ul><ul><ul><li>No effect- Dopamine, Frusemde </li></ul></ul><ul><ul><li>Potential benefits- Atrial natriuretic peptide, Fenoldopam </li></ul></ul><ul><li>Timing of initiation of RRT? </li></ul><ul><li>Modality of RRT- IHD, CRRT, SLEDD? </li></ul>
  38. 70. CRRT Machine (Prismaflex) Sustained low efficiency daily dialysis/diafiltration
  39. 71. <ul><li>Aggressive resuscitation (Rivers, NEJM 2001) </li></ul><ul><ul><li>Protocol driven resuscitation </li></ul></ul><ul><li>Management of sepsis </li></ul><ul><ul><li>Recombinant activated protein C (PROWESS) </li></ul></ul><ul><ul><li>Vasopressin (VASST) </li></ul></ul><ul><ul><li>Corticosteroids (CORTICUS) </li></ul></ul>
  40. 72. <ul><li>Hemodynamic monitoring </li></ul><ul><ul><li>Pulmonary art catheter- no benefit/ increase mortality (ARDSNet, FACTT, ESCAPE) </li></ul></ul><ul><li>Glycaemic control in critically ill- intensive sugar control </li></ul><ul><ul><li>Reduce AKI%, ICU stay, Mortality </li></ul></ul><ul><ul><li>increase ventilatio free days </li></ul></ul>

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