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CKD and ACE Inhibition: A Contrarian View!
- 1. Sheffield Kidney Institute CKD and ACE Inhibition Facts and Fiction… Prof Meguid El Nahas, PhD, FRCP Professor of Nephrology, Sheffield Kidney Institue Chairman, Global Kidney Academy Sheffield, UK A Contrarian View!
- 2. Sheffield Kidney Institute RAS Inhibition in CKD The story of Single Issues Fanatics (SIF)…. The story of Big Pharma Promotion… The story of Lack of Critical Appraisal of Evidence by Nephrologists…
- 5. Sheffield Kidney Institute Loss AutoRegulation Afferent arteriolar Vasodilatation AII CKD = Glomerular Hyperfiltration
- 6. Sheffield Kidney Institute Loss AutoRegulation Afferent arteriolar Vasodilatation x ACEi ACEi Reduce Glomerular Hyperfiltration
- 8. Sheffield Kidney Institute RCTs Lewis, 1993 REIN, 1997 RENAAL, 2001
- 12. Sheffield Kidney Institute RAS Inhibition in CKD The story of Single Issues Fanatics (SIF)…. The story of Big Pharma Promotion… The story of Lack of Critical Appraisal of Evidence by Nephrologists…
- 13. Sheffield Kidney Institute Ask the 5Whats….!!!??? • What • What • What • What • What
- 14. Sheffield Kidney Institute RASi: 5 WHATs! 1. WHAT is the PURPOSE of RASi? 2. WHAT is the VALIDITY of RASi superiority? 3. WHAT is the UTILITY of RASi? 4. WHAT is the RISK v BENEFIT RASi? 5. WHAT is the COST v BENEFIT RASi?
- 15. Sheffield Kidney Institute RAS INHIBITION IN CKD 1.Lower BP ✓ 2.Slow CKD Progression 3.Reduce CV Morbidity/Mortality
- 16. Sheffield Kidney Institute RASi: 5 WHATs! 1. WHAT is the PURPOSE of RASi? 2. WHAT is the VALIDITY of RASi superiority? 3. WHAT is the UTILITY of RASi? 4. WHAT is the RISK v BENEFIT RASi? 5. WHAT is the COST v BENEFIT RASi?
- 17. Sheffield Kidney Institute Giatras et al, 1997
- 18. Sheffield Kidney Institute Casas et al, 2005
- 19. Sheffield Kidney Institute ACE Inhibition Is it independent of Changes in BP? NOT
- 20. Sheffield Kidney Institute RAS INHIBITION IN CKD 1.Lower BP ✓ 2.Slow CKD Progression 3.Reduce CV Morbidity/Mortality
- 21. Sheffield Kidney Institute ACE Inhibition Lowers Serum Creatinine: Decrease Doubling of serum creatinine Slow decline of 1/sCr slope Slow decline of eGFR
- 22. Sheffield Kidney Institute RCTs Lewis, 1993 REIN, 1997 RENAAL, 2001 mGFR ✖ ✖✔ In subgroup 177/352
- 23. Sheffield Kidney Institute ACE Inhibition Creatinine Homeostasis 1. Intake 2. Metabolism 3. Glomerular Filtration: 4. Tubular Secretion: Organic Cation Transporter (OCT) 1 and 2
- 24. Sheffield Kidney Institute Creatinine Secretion OCT1 OCT2 SLC22 CR
- 26. Sheffield Kidney Institute Tubular Secretion of NMN/Creatinine Stimulated by ACE inhibition • GFR: -6% • Tubular Secretion: +15%
- 27. Sheffield Kidney Institute REIN STUDY <45ml/min >45ml/min
- 28. Sheffield Kidney Institute ACE Inhibition Lowers Serum Creatinine: Decrease Doubling of serum creatinine Slow decline of 1/sCr slope Slow decline of eGFR Slow decline of mGFR???
- 29. Sheffield Kidney Institute ACE Inhibition Does RAS inhibition slow decline in GFR? NOT As GFR never Measured!!??
- 30. Sheffield Kidney Institute RAS INHIBITION IN CKD 1. Lower BP 2. Slow CKD Progression 3.Reduce CV Morbidity/Mortality
- 32. Sheffield Kidney Institute BP LTTC, BMJ, 2014
- 33. Sheffield Kidney Institute BP LTTC 2014
- 35. Sheffield Kidney Institute RAS INHIBITION IN CKD (independent of BP changes) Reduce CV Morbidity/Mortality NOT
- 36. Sheffield Kidney Institute RASi: 5 WHATs! 1. WHAT is the PURPOSE of RASi? 2. WHAT is the VALIDITY of RASi superiority? 3. WHAT is the UTILITY of RASi? 4. WHAT is the RISK v BENEFIT RASi? 5. WHAT is the COST v BENEFIT RASi?
- 37. Sheffield Kidney Institute Prevalence of cCKD NHANESIII 0% 5% 10% 15% 20% 25% 30% 35% 40% Prevalenc e (%) 20-39 40-59 60-69 70+ Age Group (years) <2% >30%
- 38. Sheffield Kidney Institute cCKD in the Elderly eGFR Kidney Attacks Kidney Attacks Heart Attack
- 41. Sheffield Kidney Institute AKI and RAS Prescriptions
- 42. Sheffield Kidney Institute Loss AutoRegulation Afferent arteriolar Vasodilatation AII CKD = Glomerular Hyperfiltration
- 43. Sheffield Kidney Institute Angiotensin II Atherosclerosis Older CKD = Glomerular Ischemia
- 44. Sheffield Kidney Institute X RASi Atherosclerosis Older CKD = Glomerular Ischemia
- 45. Sheffield Kidney Institute ONTARGET Mann et al, 2008
- 46. Sheffield Kidney Institute X Dual RASi Atherosclerosis X X
- 47. Sheffield Kidney Institute ACEi in Long Term DN Suissa et al, 2006 1
- 48. Sheffield Kidney Institute Ahmed et al, 2011 Older CKD STOP ACE
- 49. Sheffield Kidney Institute RASi: 5 WHATs! 1. WHAT is the PURPOSE of RASi? 2. WHAT is the VALIDITY of RASi superiority? 3. WHAT is the UTILITY of RASi? 4. WHAT is the RISK v BENEFIT RASi? 5. WHAT is the COST v BENEFIT RASi?
- 51. Sheffield Kidney Institute RAS INHIBITION IN CKD 1. Lower BP: ✓ 1. Slow CKD Progression 2. Reduce CV Morbidity/Mortality
Editor's Notes
- And when we look at the so-called CKD “epidemic” in the US; those with CKD are older people and again 35% of those over 70 have CKD.