Renal function and atherosclerotic renovascular disease

Abstract

Renovascular disease (RVD) is a potentially reversible cause of renal failure and renovascular hypertension. However, in the absence of definitive clinical trials, there is a lack of evidence regarding its optimal management. We first addressed the central role of renal function in cardiovascular disease (CVD) in part I of this thesis. Renal function seems to have a strong relationship with atherosclerosis, a generalized process which starts early in life. In patients with manifest vascular disease, we demonstrated that with more severe atherosclerosis, the decrease in renal size and function with age was more pronounced than with less severe atherosclerosis. We also found that moderate to severely impaired renal function was an independent predictor of future CVD. In the second part of this thesis, imaging techniques of the renal artery are studied, with both MRI (magnetic resonance imaging) and angiography. MRI offers a means to assess anatomical as well as functional information about the kidney, in a non-invasive way. We measured the blood flow in the renal arteries in healthy volunteers with MRI, but found that in the relatively small and mobile renal arteries, this measurement was difficult, with limited reproducibility. Until the end of the 90s, stent placement was the treatment of choice for atherosclerotic renal artery stenosis (ARAS). However, a recurrent stenosis can occur in the stent. We found that in-stent stenoses can well be treated with balloon dilatation or placement of a second stent, with good technical success rates after a year. Part III describes the STAR trial, a multicenter randomized trial about the treatment of patients with renal impairment and ARAS. Stent placement has been proved to be a feasible technique in the treatment of ARAS, with good long term patency. However, evidence for the superiority of stent placement compared to medical treatment only in terms of renal function, is lacking. We randomized 140 patients with impaired renal function (creatinine clearance 50% ARAS to medical treatment only or medical treatment plus stent placement of the renal artery. In both groups, medical treatment consisted of blood pressure and lipid-lowering drugs and a statin. Patients were followed for 2 years and compared in terms of renal function. The primary end point was defined as >20% decrease in creatinine clearance. We found no statistically significant difference between the patients in the medication or the stent group. However, serious complications related to the stent placement procedure occurred in the stent group, with a mortality rate of 3%. Stent placement might be beneficial in patients with a unilateral stenosis, but this will need to be confirmed after a longer follow-up. The balance between preservation of renal function by improved medication and the adverse events following stent placement, is not in favor of stent placement. The findings of the STAR trial favor a conservative therapeutic approach to patients with ARAS, focused on cardiovascular risk factor management.