1. Dr.Ruba Nashawati

2. Diabetes  Leading cause of ESRD  30% 40%  DN  DN Risk type I = type II

3. Type II 74% 1 st degree relative Type I 83% 1 st degree relative Familial Cluster

4. Renal Injury Hemodynamic Hyperperfusion Hyperproliferatio n Glucose balance 4

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6. Clinical syndrome Persistent Albuminuria >300 mg/24 hr Persistent Albuminuria >300 mg/24 hr  GFR HTN HTN Cardiovascular Morbidity And Mortality

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9. Glomerular Barrier Glomerular Barrier tubule Normally, the larger Proteins are excluded at the glomerular barrier  Normally, the larger Proteins are excluded at the glomerular barrier  Smaller proteins can pass, but are mostly Reabsorbed Reabsorbed 9

10. tubule Large Proteins are able to pass by the abnormal glomerular barrier Leaky Glomerular Barrier 10

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12. 12 PLASMA PROTEINS EXCRETION (mg/day) PLASMA PROTEINS EXCRETION (mg/day) Plasma proteins Nonplasma Proteins Albumin12Tamm-Horsfall protein 40 Immunoglobulin G3 Other non–renal <1 Immunoglobulin A1All Nonplasma proteins 40 Immunoglobulin M0.3 Light chains χ 2.3 λ 1.4 β -Microglobulins0.12 Other plasma proteins 20 All plasma proteins40 Total Proteins80 ± 24

13. 13 Proteinuria  Glomerular Hydrostatic Pressure Hyperperfusion  Capillary Pressure  Systemic Hypertension

14. Sites of action: 1. Podocytes 2. Mesangial cell 3. Endothelial cell 4. Renal vessels 5. Tubular cell

15. Hemodynamic Nonhemodynamic ( Mediates Cell ) 1. Proliferation 2. Hypertrophy 3. Matrix Expansion 4. Cytokine(TGF- β )synthesis

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18. often 1 st symptom DN often 1 st symptom DN 18

19. 19  Only Albumin  Insensitive in Microalbuminuria

20.  Easy  Yearly  Control DM patient 20

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24.   Albumin excretion  (30 to 300 mg/day)  persists over 3-6 month 24

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28.  Indications for Renal Biopsy  Further investigation including a renal biopsy should be considered  (Fig. 29.22):  n If retinopathy is not present in type 1 diabetes with proteinuria  or moderately impaired renal function (absence of  retinopathy does not exclude DN in type 2 diabetes).  n If the onset of proteinuria has been sudden and rapid,  particularly in type 1 diabetes, and if the duration of type  1 diabetes has been less than 5 years or if the evolution has  been atypical, for example, without transition through the  usual stages, particularly the development of nephrtic syndrome  without previous microalbuminuria.  n If macroscopic hematuria is present or an active nephritic  urinary sediment is found that is suggestive of GN, such  as acanthocytes and red cell casts; the sediment in DN  typically is unremarkable apart from some occasional  erythrocytes.  n If the decline of renal function is exceptionally rapid or if  renal dysfunction is found without significant proteinuria  (first, of course, renovascular disease must be excluded

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30. Reduce the rate of Progression of Nephropathy + Minimize the risk for CV events

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32. Diabetic Nephropathy

33. corrected Good Glycemic Control ACEi

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35. Hypertensive + Diabetic Normotensive + Nondiabetic + Ratio>30mg/g 35

36.  Don’t prevent Proteinuria  Reverse the progression of Proteinuria 60% 36

37.  Stop  Cr >30%  K AKI  CKD = not contraindication 37

38. Check Creatinine day 3 week 2 38

39. Loop diuretics Thiazide Aldosterone Antagonist 39

40. Only Nonhydropyridin CCB (Diltiazem, Verapamil) Are Anti Proteinuric 40

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42. Aliskiren 42

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45. 45 Strict DM+DN  HBA1c 7.0% Type I Evidence Based

46. More aggressive in 1. Young 2. Short DM Duration 3. High Life Quality 4. Risk Of Hypoglycemia 46

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48. 1. Usually  HDL +  Tg 2. Type II +Non-Dialitic  statine 3. ESRD  too late 48

49. 1. DM  LDL <100mg/dl 2. DM +CVD  <70mg/dl 49

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51.  Low Protein Diet 0.8g/Kg/Day  K + Na Restriction  Life Style Modification 51

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53.  Peroxisome Proliferation Activated Receptors  Thiazolidinedione (Pioglitazone) +ARBs  MMF  Fish Oil 53

54. 54 TakeHomeMessagesTakeHomeMessages

55.  Early discover  DM control  ARBs /ACEi as Detected 55

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