29 This dataset was extended to nearly 4000 patients and found 4 year unadjusted survival for those with and without significant RAS to be 57% and 89%, respectively. Survival related to the grade of stenosis, with even mild/moderate lesions (<50%) having significant impact on survival.30 Although these figures are compelling, they do not prove a causal relationship as the presence of stenosis may portent a more diffuse atherosclerotic process. Analysis of over 16 million Medicare claims between 1992 and 2004 confirms increased all cause mortality in patients with ARVD,

with adjusted hazard ratios for death compared with the general population as high as 2.28.31 A complex interplay buy Nutlin-3a between ARVD and the heart is well defined. In all, 95% of patients with ARVD have an abnormality of cardiac structure or function32

and have high mortality from cardiac causes in prospective study.33 A 2005 review of over 1 million Medicare patients showed increases in numbers of all cardiovascular events in those diagnosed with ARVD with annual atherosclerotic heart disease incidence 30.4% compared with 7.4% the general population, Selleckchem p38 MAPK inhibitor CCF (19.5% vs 5.6%), cerebrovascular disease events (17.6% vs 5.3%) and death (16.6% vs 6.3%). These risks were typically highest in the first 6 to 9 months after diagnosis. A review of 146 000 incident US dialysis patients aged over 67 found that patients with ARVD as the primary cause of renal failure, and those with ARVD associated with an alternative renal pathology had higher hazard ratios for cardiovascular events when compared with the remainder of the dialysis

population.34 Proteinuria represents tubulo-interstitial and glomerular injury, and is recognized in many, if not all forms of renal disease as a predictor of progressive dysfunction. Patients with ARVD can have histological patterns discrete from direct ischaemic responses, for example, focal segmental glomerulosclerosis35 and atheroembolic disease. High level, even nephrotic range36 proteinuria can be found in ARVD with increases relating to significantly lower Mannose-binding protein-associated serine protease glomerular filtration rate (GFR),37 but not to arterial patency.38,39 A negative correlation between renal functional outcome and proteinuria has been demonstrated.33 The absence of correlation between level of proteinuria and degree of stenosis suggests down-stream parenchymal damage is the major determinant of outcome. This suggestion is supported by a retrospective review of 83 patients who underwent revascularization, where proteinuria of >0.6 g/day was found to be an independent risk factor for lack of functional improvement or deterioration of function following revascularization.40 Over three decades renal revascularization techniques have evolved from surgical, to angioplasty and more recently, endovascular stenting. The heterogeneity of techniques makes comparison of published data challenging. RCT were limited by small patient numbers and short follow-up periods.