diabetic kidney disease: update gka master class istanbul 2011 · type 1 and type 2 dn have the...
TRANSCRIPT
![Page 1: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/1.jpg)
Sheffield Kidney Institute
Diabetic Kidney Disease: Update
GKA Master Class
Istanbul 2011
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Sheffield Kidney Institute
DKD: Challenging dogmas
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Sheffield Kidney Institute
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
![Page 4: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/4.jpg)
Sheffield Kidney Institute
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?
![Page 5: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/5.jpg)
Sheffield Kidney Institute
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?
![Page 6: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/6.jpg)
Sheffield Kidney Institute
Diabetic Nephropathy
• Microvascular
Disease
• Macrovascular
disease
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Sheffield Kidney Institute
Diabetic Nephropathy Microvascular
(Hyperperfusion/Hyperfiltration)
• Other microvascular
manifestations• Onset:
– Microalbuminuria– Overt Proteinuria/Albuminuria
• Declining kidney function (CKD)
• ESRD
![Page 8: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/8.jpg)
Sheffield Kidney Institute
Afferent arteriolar vasoconstriction
Afferent arteriolar vasodilatation
Angiotensin
II
Hyperglycemia
![Page 9: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/9.jpg)
Sheffield Kidney Institute
0
20
40
60
80
100
120
140
160
0 5 10 15 20 25 300
2
4
6
8
10
12
14
16
Course of Diabetic Nephropathy Natural History
ProteinuriaGFR
Clinically silent Clinically manifest
Cre
atin
ine
clea
ranc
e (m
L/m
in)
Microalbuminuria
Prot
einu
ria(g
/24
h)
Duration of diabetes (years)
![Page 10: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/10.jpg)
Sheffield Kidney Institute
Diabetic Nephropathy Macrovascular
Ischemic Disease
• Systemic Systolic Hypertension• CAD• PVD• NO / LITTLE PROTEINURIA• CKD• Declining Kidney Function
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Sheffield Kidney InstituteEl Nahas, KI 2010
![Page 12: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/12.jpg)
Sheffield Kidney Institute
0
20
40
60
80
100
120
140
160
0 5 10 15 20 25 300
2
4
6
8
10
12
14
16
Course of Diabetic Nephropathy Natural History
GFR
Clinically silent Clinically manifest
Cre
atin
ine
clea
ranc
e (m
L/m
in)
Microalbuminuria
Prot
einu
ria(g
/24
h)
Duration of diabetes (years)
Microalbuminuria
Albuminuria
![Page 13: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/13.jpg)
Sheffield Kidney Institute
Microvascular Macrovascular
Diabetic Kidney Disease
AGE
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Sheffield Kidney Institute
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
![Page 15: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/15.jpg)
Sheffield Kidney Institute
Conceptual Model for DKD
CKD death CKDCKD deathdeath
ComplicationsComplicationsComplications
MICROALBUMINURIAMICROALBUMINURIA
NormalNormalNormal Increased risk
IncreasedIncreased riskrisk
Kidney failure KidneyKidney failurefailure
DamageMA
DamageDamageMAMA
GFR
GFRGFR
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Sheffield Kidney Institute
Diabetic Nephropathy
• Microvascular
Disease
• Macrovascular
disease
![Page 17: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/17.jpg)
Sheffield Kidney Institute
Steno Hypothesis
Deckert
et al. 1989
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Sheffield Kidney Institute Minamino
and Komuro, 2008
Albumin
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Sheffield Kidney Institute
CKD
Albuminuria
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Sheffield Kidney InstituteEl Nahas, KI 2010
![Page 21: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/21.jpg)
Sheffield Kidney Institute
![Page 22: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/22.jpg)
Sheffield Kidney Institute
![Page 23: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/23.jpg)
Sheffield Kidney Institute
MA Regression
BSBP
BLip
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Sheffield Kidney Institute
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
![Page 25: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/25.jpg)
Sheffield Kidney Institute
DCCT
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Sheffield Kidney Institute
ACCORD
Ismail-Beigi
et al, 2010
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Sheffield Kidney Institute
![Page 28: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/28.jpg)
Sheffield Kidney Institute
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
![Page 29: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/29.jpg)
Sheffield Kidney InstituteLewis et al 1993
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Sheffield Kidney Institute
![Page 31: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/31.jpg)
Sheffield Kidney Institute
Management of Diabetic Microvascular
Disease
Key Elements
RAASInhibition
No Smoking Lipids Control
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Sheffield Kidney Institute
Afferent arteriolar vasoconstriction
Afferent arteriolar vasodilatation
Angiotensin
II
Hyperglycemia
![Page 33: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/33.jpg)
Sheffield Kidney Institute
CKD management guidelinesParameter 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
![Page 34: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/34.jpg)
Sheffield Kidney InstituteJASN, 2011
![Page 35: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/35.jpg)
Sheffield Kidney Institute
![Page 36: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/36.jpg)
Sheffield Kidney Institute
![Page 37: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/37.jpg)
Sheffield Kidney Institute
Management of Diabetic Macrovascular
Disease
Key Elements
AVOIDRAAS
Inhibition!!!!
No Smoking Lipids Control
![Page 38: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/38.jpg)
Sheffield Kidney Institute
CKD management guidelinesParameter 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
![Page 39: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/39.jpg)
Sheffield Kidney Institute
![Page 40: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/40.jpg)
Sheffield Kidney Institute
![Page 41: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/41.jpg)
Sheffield Kidney Institute
ACEi
in Long Term DN
Suissa
et al, 2006
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Sheffield Kidney Institute
ONTARGET
Mann et al, 2008
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Sheffield Kidney Institute
Conceptual Model for CKD
CKD death CKDCKD deathdeath
ComplicationsComplicationsComplications
Screening Screening for CKDfor CKD
risk factors:risk factors:diabetesdiabetes
hypertensionhypertensionage >60age >60
family historyfamily historyUS ethnic US ethnic minoritiesminorities
CKD riskCKD risk reduction;reduction;
Screening forScreening for CKDCKD
DiagnosisDiagnosis & treatment;& treatment;
Treat Treat comorbidcomorbid
conditions;conditions; Slow Slow
progressionprogression
EstimateEstimate progression;progression;
TreatTreat complications;complications;
Prepare forPrepare for replacementreplacement
ReplacementReplacement by dialysisby dialysis
& transplant& transplant
NormalNormalNormal Increased risk
IncreasedIncreased riskrisk
Kidney failure KidneyKidney failurefailureDamageDamageDamage
GFR
GFRGFR
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Sheffield Kidney InstituteAhmed, A. K. et al, 2011
Changes in eGFR
after stopping ACEi/ARB in patients with advanced CKD
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Sheffield Kidney InstituteEl Nahas, KI 2010
![Page 46: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/46.jpg)
Sheffield Kidney Institute
![Page 47: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/47.jpg)
Sheffield Kidney Institute
![Page 48: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/48.jpg)
Sheffield Kidney Institute
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Sheffield Kidney Institute Gaede
et al, 2008
STENO 2Intensive Multi-Factorial Intervention
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Sheffield Kidney Institute Gaede
et al, 2008
Intensive Multi-Factorial Intervention
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Sheffield Kidney Institute
Intensive Multi-Factorial Intervention
Gaede
et al, 2008
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Sheffield Kidney Institute
Intensive Multi-Factorial Intervention
Gaede
et al, 2008
![Page 53: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/53.jpg)
Sheffield Kidney Institute
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
![Page 54: Diabetic Kidney Disease: Update GKA Master Class Istanbul 2011 · Type 1 and Type 2 DN have the same natural history • Microalbuminuria is an early stage of DN • Tight Glycemia](https://reader034.vdocument.in/reader034/viewer/2022042302/5ecdaedfeb22350b8479f581/html5/thumbnails/54.jpg)
Sheffield Kidney Institute
DKD
New Therapies
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Sheffield Kidney Institute
• 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
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Sheffield Kidney Institute
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Sheffield Kidney Institute
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Sheffield Kidney Institute
ASCEND
Mann et al, 2010
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Sheffield Kidney Institute JASN,2011
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Sheffield Kidney Institute
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Sheffield Kidney Institute
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Sheffield Kidney Institute
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Sheffield Kidney Institute
VITAL
De Zeeuw
et al, 2010
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Sheffield Kidney Institute
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Sheffield Kidney Institute April 2011
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Sheffield Kidney Institute
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Sheffield Kidney Institute
• 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
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Sheffield Kidney Institute
DKD: Challenging dogmas