Diabetic Kidney Disease: Update. GKA Master Class. Istanbul 2011
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1 Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011
2 DKD: Challenging dogmas
3 Old Dogmas Type 1 and Type 2 DN have the same natural history Microalbuminuria is an early stage of DN Tight Glycemia control delays ESRD ACEi/ARBs are the treatment of choice for all diabetics with kidney disease
4 Case study 1 42 year old with history of type1 DM BP: 142/96mmHg Serum Creatinine 210umol/l egfr = 32ml/min Proteinuria 2.9g/24h PCR = 290mg/mmol ACR = 200mg/mmol What is the treatment of choice?
5 Case study 2 76 year old man Hypertension for 18 years Known IHD and intermittent claudication Type 2 DM since 2003 BP: 178/86mmHg Serum Creatinine 210umol/l egfr = 32ml/min Proteinuria: 0.8g/24h PCR: 80mg/mmol ACR: 60mg/mmol What is the treatment of choice?
6 Diabetic Nephropathy Microvascular Disease Macrovascular disease
7 Diabetic Nephropathy Microvascular (Hyperperfusion/Hyperfiltration) Other microvascular manifestations Onset: Microalbuminuria Overt Proteinuria/Albuminuria Declining kidney function (CKD) ESRD
8 Afferent arteriolar vasoconstriction Angiotensin II Afferent arteriolar vasodilatation Hyperglycemia
9 Course of Diabetic Nephropathy Natural History Creatinine clearance (ml/min) Clinically silent GFR Microalbuminuria Clinically manifest Proteinuria Proteinuria (g/24 h) Duration of diabetes (years) 0
10 Diabetic Nephropathy Macrovascular Ischemic Disease Systemic Systolic Hypertension CAD PVD NO / LITTLE PROTEINURIA CKD Declining Kidney Function
11 El Nahas, KI 2010
12 Course of Diabetic Nephropathy Natural History Creatinine clearance (ml/min) Clinically silent GFR Microalbuminuria Clinically manifest Microalbuminuria Albuminuria Proteinuria (g/24 h) Duration of diabetes (years) 0
13 Diabetic Kidney Disease Microvascular Macrovascular AGE
14 Old Dogmas Type 1 and Type 2 DN have the same natural history Microalbuminuria is an early stage of DN Tight Glycemia control delays ESRD ACEi/ARBs are the treatment of choice for all diabetics with kidney disease
15 Conceptual Model for DKD Complications Normal Increased risk Damage MA GFR Kidney failure CKD death MICROALBUMINURIA
16 Diabetic Nephropathy Microvascular Disease Macrovascular disease
17 Steno Hypothesis Deckert et al. 1989
18 Albumin Minamino and Komuro, 2008
19 CKD Albuminuria
20 El Nahas, KI 2010
21
22
23 MA Regression BLip BS BP
24 Old Dogmas Type 1 and Type 2 DN have the same natural history Microalbuminuria is an early stage of DN Tight Glycemia control delays ESRD ACEi/ARBs are the treatment of choice for all diabetics with kidney disease
25 DCCT
26 ACCORD Ismail-Beigi et al, 2010
27
28 Old Dogmas Type 1 and Type 2 DN have the same natural history Microalbuminuria is an early stage of DN Tight Glycemia control delays ESRD ACEi/ARBs are the treatment of choice for all diabetics with kidney disease
29 Lewis et al 1993
30
31 Management of Diabetic Microvascular Disease Key Elements RAAS Inhibition No Smoking Lipids Control
32 Afferent arteriolar vasoconstriction Angiotensin II Afferent arteriolar vasodilatation Hyperglycemia
33 CKD management guidelines Parameter Target Agent used BP 130/80 mmhg or 125/75 in DM and those with proteinuria. Start with ACEI or ARBs if proteinuria or DM microalbuminuria caution in the elderly and those with atherosclerosis. Monitor egfr within 1-2 weeks of initiation, review if egfr decreases by 15%, stop at 25%. Proteinuria Lowest achievable ACEi/ ARBs scholesterol Refer to national guidelines Lifestyle Standard CV risk reduction measures, including salt restriction Avoid NSAIDs, COX2s and radiocontrast agents
34 JASN, 2011
35
36
37 Management of Diabetic Macrovascular Disease Key Elements AVOID RAAS Inhibition!!!! No Smoking Lipids Control
38 CKD management guidelines Parameter Target Agent used BP 130/80 mmhg or 125/75 in DM and those with proteinuria. Start with ACEI or ARBs if proteinuria or DM microalbuminuria caution in the elderly and those with atherosclerosis. Monitor egfr within 1-2 weeks of initiation, review if egfr decreases by 15%, stop at 25%. Proteinuria Lowest achievable ACEi/ ARBs scholesterol Refer to national guidelines Lifestyle Standard CV risk reduction measures, including salt restriction Avoid NSAIDs, COX2s and radiocontrast agents
39
40
41 ACEi in Long Term DN Suissa et al, 2006
42 ONTARGET Mann et al, 2008
43 Conceptual Model for CKD Complications Normal Increased risk Damage GFR Kidney failure CKD death Screening for CKD risk factors: diabetes hypertension age >60 family history Sheffield US ethnic Kidney Institute minorities CKD risk reduction; Screening for CKD Diagnosis & treatment; Treat comorbid conditions; Slow progression Estimate progression; Treat complications; Prepare for replacement Replacement by dialysis & transplant
44 Changes in egfr after stopping ACEi/ARB in patients with advanced CKD Ahmed, A. K. et al, 2011
45 El Nahas, KI 2010
46
47
48
49 STENO 2 Intensive Multi-Factorial Intervention Gaede et al, 2008
50 Intensive Multi-Factorial Intervention Gaede et al, 2008
51 Intensive Multi-Factorial Intervention Gaede et al, 2008
52 Intensive Multi-Factorial Intervention Gaede et al, 2008
53 Old Dogmas Type 1 and Type 2 DN have the same natural history Microalbuminuria is an early stage of DN Tight Glycemia control delays ESRD ACEi/ARBs are the treatment of choice for all diabetics with kidney disease
54 DKD New Therapies
55 Vasoactive substances Renin antagonsist DN Endothelin antagonists DN Growth Factors/Hormones antagonists: TGF- 1: Neutralising antibodies, DN GH: Antagonist/Somatostatin DN Signal Transduction manipulations: PKC: Ruboxistaurin DN PPAR agonists Glitazones DN ECM Modulators: Heparinoids:Sulodexide DN LMW heparin DN MMP inhibitors XL784 DN Anti-Fibrotics (miscellaneous): Pirfenidone DN
56
57
58 ASCEND Mann et al, 2010
59 JASN,2011
60
61
62
63 VITAL De Zeeuw et al, 2010
64
65 April 2011
66
67 Vasoactive substances Renin antagonsist DN Endothelin antagonists DN Growth Factors/Hormones antagonists: TGF- 1: Neutralising antibodies, DN GH: Antagonist/Somatostatin DN Signal Transduction manipulations: PKC: Ruboxistaurin DN PPAR agonists Glitazones DN ECM Modulators: Heparinoids:Sulodexide DN LMW heparin DN MMP inhibitors XL784 DN Anti-Fibrotics (miscellaneous): Pirfenidone DN
68 DKD: Challenging dogmas
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