RENAL ARTERY STENOSIS. Grand Rounds 10/11/2011

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1 RENAL ARTERY STENOSIS Grand Rounds 10/11/2011

2 ARAS Prevalence- 0.5% overall population, 5.5% in ckd pts No correlation between ischemic nephropathy and severity of stenosis Increased risk of vascular events- CAD 67% vs 25%, CVA-37% vs 12%, PVD-56% vs 13%, CKD- 25% vs 2% (medicare database) Renovascular htn 5 yr survival 45%, 18% once on dialysis

3 RESISTIVE INDEX Kidney International (2006) 70,

4 FACTORS THAT PLAY ROLE IN RVD VEGF has been shown in animal models to be crucial for preservation of renal microvasculature and promotes vascular proliferation and endothelial repair. Hypoxia-inducible factor (HIF)-1, matrix metalloproteinases (MMP)-2, MMP-9, membranetype MMP (MT-MMP), plasminogen activator inhibitor (PAI)-1, tissue transglutaminase (ttg), and transforming growth factor (TGF)-beta are other factors shown to play a role.

5 CARDIAC RISK IN RAS Cardiotonic steroids are a group of steroids recently discovered in the plasma and urine of pts with CHF, CKD and MI. Object of the study is to test the effect of renal ischemia on marinobufagenin (MBG) in humans

6 RESULTS

7 RESULTS

8 MBG VS GFR CHANGE

9 CONCLUSIONS MBG levels are increased in RAS and treatment reduces levels In patients with b/l RAS decrease in MBG correlates with gfr change suggesting possible role of MBG in maintaining GFR in global ischemia

10 TREATMENT OF ARAS Medical therapy Percutaneous Angioplasty / stent Surgical angioplasty

11 WHAT IS CRITICAL RAS?

12 ASTRAL TRIAL-METHODS Multicenter, randomized, unblinded Medical treatment included antiplatelet, statins and bp control 403 in each arm Inclusion criteria- 59% had >70% stenosis or renal dysfunction creat >1.7 or both 6% from medical crossed over to intervention grp

13 END POINTS Primary end point Rate of progression of renal dysfunction (Using reciprocal creat over time) Secondary end points Renal events- AKI, dialysis, txp or nephrectomy Vascular events- MI, angina, stroke

14 PATIENT CHARACTERISTICS

15 PATIENT CHARACTERISTICS

16 RESULTS

17 RESULTS

18 EVENTS

19 SURVIVAL

20 CONCLUSIONS- ASTRAL No evidence of a worthwhile clinical benefit in the initial years after revascularization in patients with atherosclerotic renal-artery stenosis. No significant improvements in blood pressure or reductions in renal or cardiovascular events or mortality were seen

21 FOLLOW UP TO ASTRAL Single center observational study Selected 127 pts who underwent intervention b/w not included in ASTRAL Primary end point- rate of decline of gfr before and after revascularization Mean follow up 2.8yrs

22 RESULTS

23 STAR TRIAL

24 Primary end point- >20% decline in creatinine clearance Secondary end point- cardiovascular morbidity and mortality Study under powered to provide definite estimate of efficacy

25 RESULTS

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27 STAR TRIAL- CONCLUSIONS No statistically significant difference in progression of renal failure over 2 years in those treated with stenting and medication compared with those treated with medication only Stent-related complications occurred- 2 procedure-related deaths, 1 death secondary to an infected hematoma and 1 case of deterioration of renal function resulting in dialysis

28 WHAT S NEW.. Endothelin A receptor blockade Chronic ET-A receptor blockade would preserve the hemodynamics and function and slow the progression of injury in the stenotic kidney. Underlying mechanisms of renoprotection of ET- A blockade are associated with stimulation of the VEGF and HGF pathway 14 pigs unilateral stenosis induced gradually with coil insertion 7 treated with Endothelin A rp blockade and 7 as control. Also normal animal used as control.

29 RESULTS

30 RESULTS

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34 CONCLUSIONS Chronic ET-A blockade preserved the hemodynamics and function of the stenotic kidney despite the similar degree of renal artery stenosis and hypertension in RVD and RVDET-A pigs independent of blood pressure ET-A blockade also augmented renal expression of HGF, a pleiotropic growth factor with robust direct and VEGF-mediated angiogenic effects

35 TRAS Incidence -2-7% 3 main sites - At anastamosis surgical site - Distal site of anastamosis- cause unclear - Multiple stenosis in distal arterial brancheslikely sec to chronic rejection Risk factors- CMV and DGF No change in need of anti- hypertensives post intervention and overall graft survival remains unchanged. Ponticelli et al.transplant International, 2011

36 THANK YOU