Abstract

Key words : Percutaneous balloon angioplasty, Renal transplantation, Stenting

Introduction

Transplant renal artery stenosis (TRAS) is the commonest vascular complication after renal transplant with a reported incidence of 1% to 23%. It is a known cause of graft dysfunction and posttransplant hypertension. Although a rare occurrence, severe TRAS can progress to renal artery thrombosis and graft loss.¹ Transplant renal artery stenosis should be suspected in those with deterioration of graft function when infection, rejection, and obstruction to urine flow are excluded. Early recognition and appropriate intervention for clinically significant TRAS are vital, as it is a potentially reversible cause of graft dysfunction.

Duplex ultrasonography is the first-line imaging modality in patients with suspected TRAS. Although strict duplex criteria for the diagnosis and grading of the severity of the condition have not yet been established, elevated peak systolic velocity in the renal artery (Figure 1), a drop in intrarenal resistive indices, and prolonged acceleration times in the renal and intrarenal arteries are considered sensitive indicators of existing stenosis.^2,3 Digital subtraction angiography is the gold standard of imaging, but at present noninvasive cross-sectional imaging techniques such as computed tomography angiography and magnetic resonance angiography provide comparable images. Depending on the location of the renal artery affected by the stenosis, Lacombe has classified TRAS as anastomotic, distal to the anastomosis, and recipient inflow artery stenosis. He further described 2 distal to the anastomosis TRAS morphological variants: focal and diffuse.⁴

Transplant renal artery stenosis presenting with graft dysfunction and refractory hypertension requires intervention. Progressive worsening of the stenosis on image surveillance is another acceptable indication for treatment.¹ Percutaneous balloon angioplasty (PBA) and stenting are first-line approaches of management. Because of the substantially higher risks of morbidity and mortality, surgery is reserved for lesions that are not amenable to percutaneous therapy.⁵ Endotherapy for TRAS has high clinical success rates, and the short-term and long-term graft outcomes after such treatment are extremely favorable.^6-8 However, because of its effects on blood pressure control, treatment of TRAS is controversial, with some studies reporting nonsignificant changes in blood pressure parameters and the need for antihypertensive drugs after intervention.⁹

Materials and Methods

This study aimed to present our experiences with the percutaneous treatment of clinically significant TRAS. Between October 1, 2010, and July 31, 2021, 1211 patients underwent kidney transplant at our center. Of these kidney transplant recipients, we identified 33 consecutive patients who underwent endovascular treatment for TRAS at the Royal Liverpool University Hospital (Liverpool, UK) by retrospective review of electronic patient records. All renal allografts were placed extraperitoneally in the right of the left iliac fossae. The donor renal artery was anastomosed to the recipient’s external iliac artery in all the cases, using an end-to-side technique.

Patients who were suspected to have TRAS on clinical grounds were initially screened with duplex ultrasonography. High renal artery velocities >180 cm/s, resistive index of <0.6, and renal artery-to-external iliac artery velocity ratio of >1.8 were considered as duplex criteria diagnostic of TRAS. Those with positive duplex findings or negative findings and a high clinical probability of TRAS underwent cross-sectional imaging with computed tomography angiography or magnetic resonance angiography before invasive angiography. All endovascular procedures were done under local anesthesia via a retrograde femoral approach. The femoral artery on the contralateral side of the transplanted kidney was preferentially used. Stenoses with >50% reduction of the luminal diameter on catheter angiography underwent treatment. All lesions were dilated using the PBA technique. All lesions treated after 2017 underwent primary stenting (Figure 2). Before 2017, lesions with significant residual stenosis after PBA or recurrent lesions were selectively stented.

After treatment, patients were followed in nephrology or renal transplant outpatient clinics. Data retrieved from electronic records were entered into a Microsoft Excel spreadsheet and analyzed using DATA Tab statistics software. Analysis of variance (ANOVA) was used to compare preintervention and postintervention serum creatinine values, and paired sample t test was used to compare the number of antihypertensive drugs before and after endovascular therapy. P < .05 was considered statistically significant. Our study was conducted in accordance with the guidelines of the 1975 Helsinki Declaration.

Results

Patient characteristics
Thirty-three patients underwent endovascular treatment for clinically significant TRAS during the study period. Most were men (25/33, 75.8%), and the median age of the group was 59 years (range, 27-56 y). The median time to diagnosis was 156 days (range, 4-2193 d), and the mean duration of follow-up was 69.82 months. The commonest presentation of TRAS was graft dysfunction (26/33, 76.8%). Additional patient characteristics are summarized in Table 1.

Lesion characteristics and procedure details
The commonest location for stenosis was at the anastomosis. Twenty-two patients (66.7%) had stenosis confined to this location (Table 2). Although not statistically significant, organs from deceased donors, recipient diabetes, and hypertension status were more commonly associated with anastomotic stenosis. Percutaneous balloon angioplasty was used as the primary modality of treatment in 19 patients (57.6%); the remaining 14 patients (42.4%) received stents. Four patients (12.12%) underwent repeat digital subtraction angiography for suspected restenosis (3 in the PBA group and 1 in the stented group). Recurrent stenosis was confirmed and treated in 3 patients (2 in the PBA group and 1 in the stented group). Procedure-related complications occurred in 3 patients (9.1%) (Table 3).

Treatment outcomes
Endovascular treatment for TRAS elicited a statistically significant improvement in serum creatinine levels for up to 4 years of follow-up (P = .019, repeated-measure ANOVA; Figure 3). Those who had resistant hypertension as the presentation of TRAS had significant reductions in the number of antihyper-tensive agents used for blood pressure control after the intervention (P = .016, paired sample t test). At the end of follow-up, 21.2% of patients (7/33) with TRAS had graft failure, with 1 graft failure (3.0%) being a direct consequence of TRAS (Table 4). The overall contribution of TRAS as a cause for graft failure was 0.08% (1/1211).

Discussion

Transplant renal artery stenosis has a reported incidence of 1% to 23%. This wide range is attributed to the heterogeneity in defining the condition and the imaging techniques used for the diagnosis.¹ The condition has been reported as the commonest vascular complication after kidney transplant across multiple studies and accounts for nearly 75% of such complications.^1,10,11 An estimated 5% of cases with posttransplant hypertension is a result of TRAS.¹ The condition is a significant predictor of graft loss and recipient mortality.¹² Diagnosis of TRAS usually occurs between 3 months and 2 years after graft implantation, but earlier or later presentations outside this time frame are also possible.¹ The median time at diagnosis in our patient cohort was 156 days, and there was 1 case that was detected as early as posttransplant day 4.

Patients with TRAS can present with graft dysfunction, resistant hypertension, or episodic pulmonary edema.¹ In our series, the commonest presentation was graft dysfunction as evidenced by a rise in serum creatinine. Five patients were diagnosed with TRAS within the first 3 months of graft implantation. All of these patients had static serum creatinine after graft implantation. Stenosis of the transplant renal artery should be suspected in a renal transplant recipient with worsening or resistant hypertension (defined as elevated blood pressure that is not controlled by 3 classes of antihypertensive drugs). Hypertension was the second leading clinical presentation of TRAS in our study. Episodic pulmonary edema with normal left ventricular function or “Pickering syndrome” is a rare clinical manifestation in those with TRAS.¹³ This phenomenon was seen in 4 of our patients.

The anastomotic suture line was the commonest location for the stenosis in our series. Similar findings were noted in the study by Biederman and colleagues.¹⁴ Traditional risk factors that may predispose to anastomotic stenosis are technical errors, retrieval injuries, and end-to-end anastomosis technique.¹⁵ We found that TRAS affecting the anastomosis was more common in recipients who had diabetes or hypertension and in those who underwent deceased donor transplant procedures. However, these associations were not statistically significant. An endovascular intervention for lesions at the suture line has been associated with poor success rates and higher risks of complications.¹⁵ This was not replicated in our series, where all patients with TRAS affecting the arterial suture line underwent successful endovascular treatment.

Percutaneous balloon angioplasty for TRAS has reported success rates of 85% to 93% and 63% to 83% for improving graft function and blood pressure control.⁷ In their case series, Peregrin and colleagues noted that 65% of patients treated with angioplasty for TRAS had improvements in blood pressure parameters. However, none of their patients were completely weaned from blood pressure medications.¹⁶ A different study by Geddes and colleagues compared a group of TRAS patients who were treated against a group of patients who had conservative follow-up and reported no significant differences in the blood pressure parameters or the number of antihypertensive drugs between the 2 groups.⁹ In our series, we noted favorable outcomes after treatment in those who had resistant hypertension due to TRAS, as evidenced by a significant reduction in the number of antihypertensive drugs required to achieve satisfactory blood pressure control.

Satisfactory long-term graft outcomes following endovascular treatment for TRAS have been previously reported.^5-8,17 In their study, Halimi and colleagues reported that, at 8 years after PBA for TRAS, patient and graft survival rates were not different for those treated versus those who did not develop TRAS.⁶ This finding was replicated by Hurst and colleagues, who retrospectively analyzed the US Renal Data System and identified 823 renal transplant recipients with TRAS.¹² These studies highlight the reversible nature of TRAS-related allograft injury and dysfunction, provided that the condition is recognized and treated adequately.

The reported restenosis rate after PBA for TRAS ranges from 10% to 33%.¹⁵ Stenting of the lesion appears to reduce the risks of recurrent stenosis. A systematic review by Ngo and colleagues reported that the average patency rates for patients treated with PBA versus stenting were 73% and 90.4%.¹⁷ In our series, the overall restenosis rate was 9.1%. Our current practice is to primarily stent all lesions after balloon dilatation. Before 2017, we used a selective stenting policy and stenting was reserved for significant residual stenosis after PBA or for recurrent lesions.

Treatment-related complications occurred in 3 of our patients (9.1%), and all 3 required some form of intervention (Table 3). Our complication rate is similar to the results published by Ngo and colleagues,¹⁷ who reported a 9.9% complication after a pooled analysis of 760 patients with TRAS who underwent percutaneous treatment. The common complications identified in their study were renal artery dissection, renal artery thrombosis, and puncture site hematomas.

Conclusions

Our experience with endovascular treatment of TRAS showed that it is a safe and effective modality of intervention with sustained improvements in serum creatinine levels and a significant reduction in the number of antihypertensive agents required to control blood pressure. The main limitations of our study were the small sample size and the retrospective methodology.

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