Percutaneous transluminal renal stenting for transplant renal artery stenosis.
Five randomized clinical trials [1–5] demonstrated that renal revascularization was not associated with improvement in blood pressure or renal function, or reduction in clinical events compared with medical therapy in patients with atherosclerotic renal artery stenosis (ARAS). These studies raised skepticism about renal revascularization among physicians and payors, leading some to recommend therapeutic nihilism . In contrast, in this issue of Catheterization and Cardiovascular Interventions, Sharma et al demonstrate unequivocal benefit of renal revascularization for transplant renal artery stenosis (TRAS) . What lessons should we learn from this study? First, there are important differences in the pathophysiology of TRAS and ARAS. Early TRAS within the first year after surgery is usually due to a mechanical problem that arises during surgery, vessel injury leading to early thrombosis, or intimal proliferation leading to stenosis. Clinical manifestations include rapid renal dysfunction and acute severe hypertension, which must be differentiated from rejection, obstruction, and infection by appropriate urinary markers and imaging studies. These clinical manifestations are identical to the 2-clip Goldblatt model in which there is global renal ischemia and intense activation of the renin-angiotensin system leading to renovascular hypertension, excretory dysfunction, volume overload, and even pulmonary edema. Several years after surgery, late TRAS may be due to progressive atherosclerotic stenosis in the anastomosis or iliac artery proximal to the graft, contributing to insidious renal dysfunction and hypertension. Late TRAS bears a closer relation to severe bilateral ARAS, in which atherosclerotic risk factors are highly prevalent, and the entire renal mass is in jeopardy. These patients may have multiple causes of renal dysfunction (including longstanding parenchymal disease from hypertension or diabetes) and hypertension (including essential hypertension), and recommendations for revascularization should be individualized on the basis of renal ischemia and parenchymal disease . Second, the effects of treatment for TRAS and ARAS reflect the differences in pathophysiology. Successful revascularization of early TRAS, as demonstrated by Sharma et al, usually results in deactivation of the reninangiotensin system, and immediate improvement in renal function, hypertension, and volume status, consistent with classic renovascular hypertension. This type of profound response is highly unusual in patients with ARAS, although it may be observed in some patients with renal fibromuscular dysplasia. In contrast, patients with late TRAS or ARAS may have variable responses of blood pressure and renal function, depending on underlying comorbidities (diabetes, hypertension, or other causes of chronic kidney disease) and the extent of parenchymal disease. In patients with global renal ischemia (TRAS or bilateral ARAS), the renal benefits of revascularization may be readily apparent by the effects on urine output and creatinine, but in many patients (particularly those with unilateral ARAS), direct measurements of GFR may be needed to detect improvement in renal function, since serum creatinine may be too insensitive . Finally, there are several interesting technical observations in this study. All six patients with available information about the surgical anastomosis had TRAS involving an end-to-end anastomosis between the renal artery and the hypogastric artery. It would be interesting to know if rates of anastomotic stenosis are lower for end-to-side connections with the external iliac artery. From a technical standpoint, it is worth noting that the high success rate for access to the transplant renal artery using a femoral crossover approaches, given the inferior origin of the hypogastric artery in most patients. Likewise, a brachial artery approach could also be used. Although balloon-expandable stents are used for ARAS and were used in this study for TRAS, one wonders about the value of selfexpanding stents to allow better conformability with the renal and hypogastric artery, or the use of covered stents to address concerns about disruption of the anastomosis.