Emerging Paradigms in Chronic Kidney Ischemia.

The word paradigm derived from the Greek paradigma (pattern or example) encompasses basic assumptions, ways of thinking, and methodologies commonly accepted by community members. In 1962, the American physicist Thomas Kuhn introduced the term paradigm shift, describing a fundamental change in the basic concepts and experimental practices of a scientific discipline. Renovascular disease (RVD) presents a quintessential example of this transformation, a chronic condition where traditional and emerging paradigms converge, often resulting in uncertainty for nephrologists caring for these patients. Community-based screening studies have shown that atherosclerotic RVD affects as many as 7% of individuals >65 years old and its prevalence increases with age. Atherosclerosis is its primary cause in Western countries, with the remaining causes, including fibromuscular dysplasia and other vascular disorders, including renal trauma, Takayasu’s arteritis, renal artery dissection, thrombosis, and embolic occlusion. Importantly, patients with RVD frequently develop renovascular hypertension (RVH), which accelerates cardiovascular disease and renal dysfunction, increasing morbidity and mortality. The US Renal Data System Annual Data Report indicates that RVD remains an important cause of end-stage renal disease in this country. Restoration of renal blood flow (RBF) with percutaneous transluminal renal angioplasty (PTRA), later supplemented with endovascular stents, was established as a safe and definitive technique and became widely accepted as the primary therapy for management of atherosclerotic RVD. The number of PTRA procedures among Medicare beneficiaries more than doubled by the end of last century, rising from 7660 in 1996 to 18 520 in 2000. However, a review panel commissioned by the Centers for Medicare and Medicaid Services scrutinized the evidence related to renal revascularization and concluded that available trial evidence did not support the use of PTRA over medical therapy. This ongoing controversy over relative merits of highly effective medical therapy versus revascularization has largely subsided after publication of the 2014 CORAL trial (Cardiovascular Outcomes for Renal Artery Lesions). This multi-center, open-label, randomized, controlled trial concluded that renal artery stenting did not confer additional benefit over conventional medical therapy with respect to prevention of clinical cardiovascular events in patients with atherosclerotic RVD. This and other trials have led to a major reduction in PTRA procedures in recent years. These are currently limited mainly to individuals with failure of medical therapy to control hypertension, episodes of congestive heart failure, and rapidly progressive renal functional decline. An important corollary of this development has been a major increase in the number of medically treated RVD patients affected by chronic ischemic kidney disease. In parallel with the transition away from large vessel revascularization, experimental studies directly targeting vascular, glomerular, and tubular structures are illuminating the processes underpinning poststenotic kidney injury. Several of these are showing promise in arresting and reversing parenchymal kidney disease attributable to RVD. Therefore, we are entering an era in which basic discoveries highlight emerging pathogenic paradigms and may replace traditional paradigms based on large-vessel blood flow primarily. This in turn reflects a transition from the aim of outright cure or reversal of RVH, which is now managed primarily with medical therapy, to exploration of new therapies to attenuate renal tissue injury and promote its regeneration. The current review provides an overview of evolving paradigms in the pathogenesis and treatment of RVD and discusses ongoing efforts and future directions for treating RVD.