Paradigm Shifts in Atherosclerotic Renovascular Disease

Abstract

Results of recent clinical trials and experimental studies indicate that whereas atherosclerotic renovascular disease can accelerate both systemic hypertension and tissue injury in the poststenotic kidney, restoring vessel patency alone is insufficient to recover kidney function for most subjects. Kidney injury in atherosclerotic renovascular disease reflects complex interactions among vascular rarefication, oxidative stress injury, and recruitment of inflammatory cellular elements that ultimately produce fibrosis. Classic paradigms for simply restoring blood flow are shifting to implementation of therapy targeting mitochondria and cell-based functions to allow regeneration of vascular, glomerular, and tubular structures sufficient to recover, or at least stabilize, renal function. These developments offer exciting possibilities of repair and regeneration of kidney tissue that may limit progressive CKD in atherosclerotic renovascular disease and may apply to other conditions in which inflammatory injury is a major common pathway.

Differences in GFR and Tissue Oxygenation, and Interactions between Stenotic and Contralateral Kidneys in Unilateral Atherosclerotic Renovascular Disease

“…They emphasize the importance of pursuing novel strategies to reverse inflammatory and profibrotic injury in ARAS as we have proposed (25).…”

Association between Mitochondrial DNA Copy Number in Peripheral Blood and Incident CKD in the Atherosclerosis Risk in Communities Study

“…First, mitochondrial dysfunction in kidney cells has been implicated in the pathogenesis of CKD [3][4][5] and proposed as a therapeutic target for atherosclerotic renovascular disease. 8,17 Mitochondrial dysfunction can be a consequence of oxidative stress. 18 In functional studies, exposure to hydrogen peroxide, a reactive oxygen species, resulted in damage to the DNA replication enzyme (polymerase g) in the mitochondria and a reduction in mtDNA copy number.…”

Three Decades of Atherosclerotic Reno-vascular Disease Management - Changing Outcomes in an Observational Study

“…Indeed, although less revascularization procedures have been performed per year in the post-ASTRAL period compared to earlier years, the percentage of newly diagnosed ARVD patients who undergo revascularization is significantly higher in this last cohort, reflecting a selected population. Forgoing investigations for ARVD may be the correct option in the large majority of patients in whom revascularization will not lead to benefit, either due to functionally insignificant RAS [24] or irreversible renal parenchymal injury [25]. However, there is a concern that reduced enthusiasm for investigation may lead to missed opportunities for timely diagnosis of ARVD [9].…”