RENAL ARTERY STENOSIS Grand Rounds 10/11/2011
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
RESISTIVE INDEX Kidney International (2006) 70, 1543 1547
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.
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
RESULTS
RESULTS
MBG VS GFR CHANGE
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
TREATMENT OF ARAS Medical therapy Percutaneous Angioplasty / stent Surgical angioplasty
WHAT IS CRITICAL RAS?
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
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
PATIENT CHARACTERISTICS
PATIENT CHARACTERISTICS
RESULTS
RESULTS
EVENTS
SURVIVAL
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
FOLLOW UP TO ASTRAL Single center observational study Selected 127 pts who underwent intervention b/w 2003-2007 not included in ASTRAL Primary end point- rate of decline of gfr before and after revascularization Mean follow up 2.8yrs
RESULTS
STAR TRIAL
Primary end point- >20% decline in creatinine clearance Secondary end point- cardiovascular morbidity and mortality Study under powered to provide definite estimate of efficacy
RESULTS
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
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.
RESULTS
RESULTS
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
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
THANK YOU