ABSTRACT: Percutaneous transluminal angioplasty with stenting is now an established modality for treatment of atherosclerotic renal artery stenosis. However, the rate of restenosis can be as high as 20%. While intravascular brachytherapy has proven efficacy in coronary artery in-stent stenosis, its role in the treatment of renal artery in-stent stenosis is not well understood. We report a case of recurrent in-stent renal artery stenosis treated successfully by brachytherapy with excellent follow up results at 22 months.

       Percutaneous transluminal angioplasty (PTA) and stent placement in the renal artery is a safe and effective procedure for the treatment of atherosclerotic renal artery stenosis (RAS). It has been shown to result in reduction of blood pressure and medication requirement in patients with renovascular hypertension.¹ However, up to one-fifth of patients receiving PTA and stenting for RAS develop in-stent restenosis (ISR).²
       Treatment of ISR in renal arteries remains a challenge with restenting and angioplasty, especially in patients who have aggressive disease. Intravascular brachytherapy (IVBT) has been shown to be effective in coronary and peripheral arteries. Its use in renal arteries is not yet FDA-approved, though case reports in the literature have shown its feasibility in renal arteries.^3–6 We describe a case where IVBT was successfully used to treat recurrent in-stent stenosis in the renal artery with good results at 22-month follow up.

Case Report.
       Our patient is a 66-year-old female with coronary artery disease status post-percutaneous intervention to a diagonal lesion, peripheral vascular disease with 60–70% bilateral carotid artery stenosis and bilateral renal artery stenosis, hypertension, hyperlipidemia, idiopathic thrombocytopenic purpura, chronic obstructive pulmonary disease, ongoing tobacco abuse and a strong family history of coronary artery disease. Her medications included aspirin, clopridrogel, cilostazol, isosorbide mononitrate, metoprolol and atorvastatin. Physical examination revealed a blood pressure of 154/78, with the presence of bilateral carotid and femoral bruits. Laboratory studies were within normal level, with a creatinine of 0.8 mg/dl, except for a chronically low platelet count of approximately 90,000.
       Initial diagnosis of renal artery stenosis was made in 2001 at an outside hospital during work-up for bilateral flank pain and hypertension. The patient underwent PTA of both renal arteries with relief of

Figure 1

symptoms. Her symptoms of “renal angina” recurred over the next few months, and a follow-up renal angiogram showed severe restenosis of both renal arteries. In February 2002 she underwent bilateral renal artery stent placement at the outside hospital. In September 2002 she presented to our hospital with recurrent left flank pain and was found to have 75–80% severe in-stent restenosis of the left renal artery with a 70–80 mm Hg pressure gradient. This was treated with a Slalom 5.0 x 20.0 mm balloon (Cordis Corp., Miami, Florida), followed by placement of a Genesis 5.0 x 18.0 mm stent (Cordis).
       In December 2002 she developed right-sided flank pain and was found on renal angiography to have an 80–90% right renal artery stenosis with a 80–100 mm gradient, which was treated with angioplasty and

Figure 2

stenting, with good symptom relief. Her left renal artery then showed 30% diffuse in-stent restenosis. In August 2003 she redeveloped left flank pain, and a renal Doppler ultrasound revealed a peak

Figure 3

systolic velocity of 2.1 m/second upon interrogation of the left renal artery. Renal angiography revealed 70% diffuse in-stent restenosis which, was confirmed with intravascular ultrasound of the left renal artery (Figures 1 A and B). This was then treated with a 6.0 x 20.0 mm Genesis stent (Figures 2 A–D), with 10–20% residual stenosis. Two weeks later, intravascular brachytherapy with Gamma radiation (Checkmate Cathete, Cordis) was administered to the left renal artery with a total in-dwell time of 32 minutes (Figure 3). IRB approval for compassionate use of intravascular brachytherapy was obtained prior to treatment.

Figure 4

       The patient has since remained symptom-free and repeat renal Doppler ultrasound studies in August 2004 and May 2005 have confirmed no restenosis in the left renal artery, with normal peak systolic velocity and intrarenal waveforms. A follow-up computed tomography angiogram of the renal arteries performed in October 2005 for evaluation of flank pain revealed patent left and right renal arteries (Figure 4).

Discussion
       Proliferative response from neointimal hyperplasia following stent placement can cause lumen loss. Intravascular brachytherapy has emerged as an effective tool for the prevention of in-stent restenosis by inhibiting neointimal proliferation. Radiation causes cell death both directly and indirectly by ionizing the DNA and causing double-stranded breaks, and by also ionizing intracellular water, generating injurious free radicals. Radiation-induced dilatative remodeling also contributes to preserving the vessel lumen.⁷ The type, dose and duration of radiation have not yet been standardized for the treatment of renal arteries with brachytherapy. The large lumen size may translate to a lesser dose to the vessel wall due to increased distance from the brachytherapy catheter. Risks of endovascular radiation in the coronary arteries have included late thrombosis, edge effect, accelerated atherosclerosis and recurrence of late restenosis. Whether similar effects can manifest in the renal arteries is not yet known.
       Our patient had undergone a PTA and stent placement to the left renal artery prior to presentation at our institution. She presented with in-stent stenosis and we elected to treat this with restenting, as renal artery brachytherapy had very limited follow up in the few case reports in the literature until our present case. However, when the restenosis recurred, we performed brachytherapy, since no other suitable options were available. PTA produced suboptimal results, and the left renal artery had to be re-stented. Given the good long-term results we have demonstrated, PTA with provisional stenting and brachytherapy can be considered a first-line therapy for renal artery in-stent stenosis.
       Renal artery brachytherapy is a viable option in the treatment of renal artery in-stent stenosis. We present the excellent intermediate-term follow-up results in a patient with aggressive disease. Long-term follow up of similarly-treated patients is imperative to closely monitor for any adverse effects of the local radiation therapy.