Objectives: Atherosclerosis is becoming a more common problem for dialysis patients. Therefore, transplant surgeons are faced with the need to develop surgical techniques and procedures for severe atherosclerosis. This study aimed to clarify the clinical features, the usefulness of examinations, and operative procedures for kidney transplant recipients with the complication of severe atherosclerosis.

Materials and Methods: Among 220 kidney transplant candidates, 13 patients (severe atherosclerosis group) were predicted complications due to arterial calcifi-cation in the bilateral iliac arterial system using a computed tomographic scan. They were compared with the remaining 207 patients (mild atherosclerosis group) based on patient characteristics. The severe atherosclerosis group was evaluated by additional examination, anastomosis procedure of the graft artery, and patient outcome.

Results: The severe atherosclerosis group had significantly higher rates of mean recipient age, glycosylated hemoglobin A1c, past smoking, and administration of antithrombotics. Past vascular surgery related to atherosclerosis in the aortoiliac region had been performed in 8 patients from the severe atherosclerosis group. A three-dimensional computed tomography angiography and an intra-operative periarterial echography were useful to deter-mine the kidney transplant site. A balloon catheter effectively blocked blood flow. A polytetrafluoroethylene vascular graft was used for bypass between the graft artery and abdominal aorta. All kidney grafts of the severe atherosclerosis group were functioning well.

Conclusions: Kidney transplant for patients with severe atherosclerosis can be achieved successfully by additional examinations and vascular surgical techniques.

Key words : Arterial calcification, Computed tomography, Kidney transplantation, Vascular graft

Introduction

Atherosclerosis in dialysis patients has become a common problem owing to risk factors of chronic kidney disease, increasing age,¹ and complications from diabetes.² Kidney transplant is frequently contraindicated in patients on dialysis with severe atherosclerosis because it might be impossible to anastomose the graft artery to the iliac arteries due to calcification.³ If transplant surgeons encounter unpredictable atherosclerosis in the iliac arteries that was undetected during the preoperative exami-nation, successful kidney transplant is difficult to achieve. Furthermore, the number of kidney transplant candidates with severe atherosclerosis is anticipated to increase in the future. Therefore, transplant surgeons are faced with the need to develop surgical techniques and procedures to deal with severe atherosclerosis. However, systematic methods to evaluate atherosclerosis preoperatively and to determine optimal anastomosis of the graft artery have not yet been established.

In this study, we analyzed the clinical features of kidney transplant recipients with the complication of severe atherosclerosis, we clarified the usefulness of examinations and operative procedures for patients with severe atherosclerosis, and we analyzed their postoperative outcomes.

Materials and Methods

Patients
From January 2011 to March 2013, a total of 220 consecutive patients (living donor 208, deceased donor 12) underwent kidney transplant procedures at Nagoya Daini Red Cross Hospital. All candidates underwent a computed tomographic (CT) scan of the abdomen and pelvis. Among these 220 candidates, 13 patients were predicted to have complications associated with arterial anastomosis due to arterial circumferential calcification in the bilateral iliac arterial system, as detected by CT scan. These 13 patients (severe atherosclerosis group) were compared with the remaining 207 patients (mild atherosclerosis group) based on patient characteristics before kidney transplant. The severe atherosclerosis group was evaluated based on additional preo-perative and intraoperative exam-inations, anastomosis procedure of the graft artery, and patient outcome.

Statistical analyses
Patient characteristics were compared between the severe atherosclerosis group and the mild athero-sclerosis group (Table 1) in terms of numbers, percentages, mean values ± standard deviations, and median values with minimum and maximum as well as ranges. Continuous variables were assessed by an unpaired t test or the Mann-Whitney U test where appropriate.

Comparisons between categorical variables were assessed by the chi-square test with the Yates chi-square test or Fisher exact probability, where appropriate. A statistically significant difference was determined when two-tailed P was < .05.

Preoperative examinations
Ankle brachial pressure index
Lower extremity arteries of kidney transplant patients were palpated at the initial visit. In the case of a weak palpation of the femoral, popliteal, and dorsalis pedis arteries, an ankle brachial pressure index (ABPI) was performed to exclude peripheral arterial disease before kidney transplant.

Three-dimensional computed tomography angio-graphy
A three-dimension CT angiograph (3D-CTA) was performed to confirm the course, blood flow, and any abnormalities (eg, stenosis or obstruction) of the aortoiliac arteries. The blood flow of bilateral aortoiliac arteries was compared with a 2-phase (early and late phase) 3D-CTA as necessary.

Direct invasive measurement of arterial blood pressure
Arterial blood pressure of the bilateral femoral artery was measured directly on one side of the external iliac artery by placing cannula needles through inguinal regions into bilateral femoral arteries under general anesthesia just before the operation.

Intraoperative examinations
Intraoperative periarterial echography
Abnormalities of the arterial wall were observed directly by ultrasonography using a 7.5-MHz probe to determine the optimal anastomotic site for the graft artery. Calcification, stenosis, and dissection in the recipient’s arteries were detected by B-mode echography, and arterial blood flow was estimated in real time by color Doppler echography.

Intraoperative angiography
In the case of low blood flow through the aortoiliac arteries, an intraoperative angiography under a mobile C-arm was performed to exclude arterial problems, such as dissection.

Surgical techniques
Arterial blood flow occlusion using a balloon catheter
Atraumatic soft jaw clamps for hemostasis were used to reduce damage to the arterial wall as much as possible. However, when vascular clamps were impractical because of a fear of dissection and shower emboli caused by careless hemostasis against severe calcification, a balloon catheter was used to occlude the arterial blood flow. Blood flow occlusion of the proximal artery was performed by an occlusion balloon catheter (11 mm in diameter) through a percutaneous or direct puncture of the external iliac artery via a 6F sheath.

Method for anastomosis of the graft artery
An endarterectomy was performed, if possible, via the anastomosis opening of the recipient’s artery before arterial anastomosis. The graft artery was anastomosed to the internal iliac artery by an interrupted suture of end-to-end anastomosis using 5-0 or 6-0 polyproethylene. In the case of anastomosis to the external iliac artery or common iliac artery, the graft artery was anastomosed by a continuous suture of side-to-end anastomosis with a parachute method using 5-0 or 6-0 polyproethylene after forming an opening by an aorta punch.

Interposition using a synthetic vascular graft
In cases where the optimal anastomotic site of the recipient’s arteries was too far, which would limit anastomosis of the graft artery, interposition using a vascular graft was considered. A polytetrafluo-roethylene (PTFE) vascular graft (5 mm in diameter) was anastomosed to the abdominal aorta by a continuous suture of side-to-end anastomosis using the parachute method. This involved using a 5-0 polyproethylene following a cross clamp after the activated clotting time was over 200 seconds by systemic administration of heparin. After vascular clamps were changed from the abdominal aorta to the PTFE vascular graft, the graft artery was anastomosed to the PTFE vascular graft by an interrupted suture of end-to-end anastomosis using 5-0 polyproethylene.

Results

Of the 220 kidney transplant procedures examined, 13 patients (5.9%) were defined as the severe atherosclerosis group because of arterial circum-ferential calcification in the bilateral iliac arterial system, identified by CT scan. Patients in the severe atherosclerosis group were compared with the remaining 207 patients (mild atherosclerosis group) on the basis of patient characteristics before kidney transplant (Table 1). We observed significant differences between the severe atherosclerosis group and the mild atherosclerosis group for mean age of recipients (60.2 ± 10.4 vs 46.5 ± 14.9 y), HbA1c (6.3 ± 0.9% vs 5.6 ± 0.7%), preemptive transplant (0% vs 37.2%), past smoking (61.5% vs 12.1%), and administration of antithrombotics before kidney transplant (76.9% vs 20.8%). Past vascular surgery related to atherosclerosis legions had been performed in 8 patients (61.5%) from the severe atherosclerosis group (Table 2). In these 8 patients, past vascular surgeries in the aortic and iliac regions had been performed in 4 and 5 patients, respectively.

Preoperative examination
Preoperative results are shown in Table 2. An ABPI was performed for all patients in the severe atherosclerosis group because it is a noninvasive examination. No patients were aware of their peripheral arterial disease before kidney transplant, which was confirmed by abnormally low ABPI values. A 3D-CTA was performed in 11 patients, all of whom had undergone past vascular surgeries. Reduced blood flow in the bilateral internal iliac arteries was detected in all 11 patients. If blood flows were different between the right and left iliac artery, 2-phase 3D-CTA (in patient 10) or direct invasive measurements of arterial blood pressure (in patients 3 and 10) were performed to determine which side was optimal for anastomosis of the graft artery.

Two-phase 3-dimensional computed tomography angiography
Patient 10 was a 66-year-old man with a past history of synthetic vascular graft replacement of the descending aorta for thoracic aortic dissection (DeBakey type IIIb). Because dissection in the descending aorta was left postoperatively, the right and left common iliac arteries were supplied with blood flow through true and false lumen, respectively. However, a usual 3D-CTA could not detect contrast effect differences between the bilateral common iliac arteries. Furthermore, there was no difference in arterial palpitation between the bilateral femoral arteries in the inguinal regions, and the bilateral ABPI was in the normal range (right, 1.08; left, 0.97) owing to a femorofemoral bypass. Accordingly, we compared the blood flow between the bilateral common iliac arteries using a 2-phase 3D-CTA (Figure 1). As a result, although there was no contrast effect difference between the bilateral common iliac arteries in the early phase, the contrast effect of the right common iliac artery that supplied true lumen through the descending aorta was more strongly enhanced than the left common iliac artery that supplied false lumen through the descending aorta in the late phase. Therefore, the right external iliac artery was chosen to anastomose the graft artery because the blood flow of this artery was more abundant than the blood flow of the left external iliac artery.

Direct invasive measurement of arterial blood pressure
Patient 3 was a 43-year-old man with a past history of stenting in the left common iliac artery and a left femoropopliteal bypass for peripheral arterial disease. In palpitation, the right femoral artery in the inguinal region was stronger than the left; conversely, the left dorsalis pedis artery was stronger than the right. A living-donor kidney transplant was scheduled before a deceased-donor pancreas transplant for type 1 diabetes. Because of blood flow differences between the bilateral external iliac arteries, a direct invasive measurement of arterial blood pressure (Figure 2) was conducted by placing cannula needles from the bilateral femoral arteries to the external femoral arteries under general anesthesia just before kidney transplant. As a result, there was no difference between the bilateral external iliac arteries (right, 104/53 mm Hg; left, 104/56 mm Hg). The left iliac fossa was selected for the kidney transplant side because of the planned pancreas transplant.

Intraoperative examination
Intraoperative periarterial echography
In prepara-tion of recipient’s arteries, an intra-operative periarterial echography (Figure 3) was performed for all patients. Any abnormalities in the recipient’s arteries were detected by placing an echo probe using a B-mode image directly onto the arterial wall of the anastomotic site. Additionally, the recipient’s arteries were observed by color Doppler echography to determine whether the blood flow was sufficient. As a result of the intraoperative periarterial echography, an optimal anastomotic opening was formed in a confined region with sufficient blood flow and without calcification, dissection, and stenosis.

Intraoperative angiography
Patient 1 was a 74-year-old man with severe calcification of the bilateral external iliac arteries; therefore, a balloon catheter was used instead of vascular clamps to occlude blood flow of the right external iliac artery. Because arterial blood flow decreased temporally before anastomosis of the graft artery, dissection of the right external iliac artery was suspected because of damage caused by dilation of the balloon catheter. An intraoperative angiography fortunately showed no such arterial problems.

Surgical techniques
Arterial blood flow occlusion using a balloon catheter
In the 13 kidney transplant recipients of the severe atherosclerosis group, hemostasis using vascular clamps could not be conducted in 2 patients (patients 1 and 7) because of calcification along the entire length between the common iliac artery and external iliac artery (Table 3). For these 2 patients, occlusion balloon catheters (11 mm in diameter) were required for proximal arterial blood flow occlusion (Figure 4). On the other hand, distal arterial blood flow was sufficient with loose hemostasis using vascular clamps.

Selection of recipient’s arteries for anastomosis of the graft artery. In the severe atherosclerosis group, arterial calcification detected by a plain CT scan was found not only in the external iliac arteries but also in the internal and common iliac arteries. An optimal arterial anastomotic site with no calcification and efficient blood flow was selected by direct palpation of the arterial wall and intraoperative periarterial echography. As a result, the recipient’s arteries used for anastomosis of the graft artery were the external iliac artery (n = 10, 76.9%), the internal iliac artery (n = 1, 7.7%), the common iliac artery (n = 1, 7.7%), and the abdominal aorta (n = 1, 7.7%) (Table 3).

Interposition using a synthetic vascular graft
Patient 13 was a 67-year-old man who underwent a previous operation of stenting in the right common external iliac artery, a femorofemoral bypass, a superficial temporal artery-middle cerebral artery bypass, and a percutaneous coronary intervention. Per that shown in the 3D-CTA, there was no anastomotic site for the graft artery in the iliac arterial system because of the stent in the right common external iliac artery and obstruction of the left common external iliac and bilateral internal iliac arteries. In addition, the 3D-CTA showed that the native renal arteries and splenic artery were narrow and irregular, making an orthotopic kidney transplant impossible. Therefore, the abdominal aorta was selected for the anastomotic site of the graft artery. The kidney graft was placed in the left iliac fossa near the side of the abdominal aorta. At first, the graft vein was anastomosed to the left external iliac vein in an end-to-side fashion. For anastomosis of the graft artery, a PTFE vascular graft (5 mm in diameter, 12 cm in length) was interposed to the abdominal aorta. The surgical procedure lasted for 7 hours and 10 minutes, the total ischemic time was 2 hours and 12 minutes, and the first urine was observed at 21 minutes (Figure 5).

Postoperative complications and prognosis
The median observation period after kidney transplant for the 13 patients was 677 days (range, 205-877 d). At last follow-up, all patients were alive and all kidney grafts were functioning; the latest mean serum creatinine level was 1.36 ± 0.46 mg/dL. Postoperative complications occurred in 2 of the 13 patients, which included a cerebral infarction on postoperative day 2 (patient 13) and Fournier gangrene during postoperative month 8 (patient 7). Both patients recovered from their complications.

Discussion

In this study, patients with severe atherosclerosis accounted for 5.9% of all kidney transplant recipients. However, kidney transplant candidates with severe atherosclerosis might be expected to increase in the future because of increased numbers of patients who are elderly¹ and diabetic.² Although kidney transplant candidates with severe athero-sclerosis are currently contraindicated for transplant because of the difficulty of anastomosis of the graft artery, these difficult kidney transplants will be demanded in the future as the number of these patients continues to increase. Because kidney transplant is built on the provision of valuable goodwill of the donor, the worst choice is to give up even if unexpected severe atherosclerosis lesions are encountered during the operation. Therefore, the method for arterial blood flow occlusion, the selection of the arterial anastomotic site, and the method for arterial anastomosis by careful preoperative and intraoperative examination are extremely important.

Kidney grafts in the severe atherosclerosis group in this study, except for 1 patient, were provided from living donors. Living-donor kidney transplants are advantageous because they provide sufficient preoper-ative examination time. Conversely, deceased-donor kidney transplant has the disadvantage of limited preoperative examinations because it is an emergency operation. Therefore, if severe atherosclerosis is found in candidates for deceased-donor kidney transplant, they can be easily removed from the candidate list because of this contraindication. However, candidates for deceased-donor kidney transplant procedures should also receive the benefits of transplant that candidates for living-donor kidney transplants have. We believe that this will become possible with thoroughly prepared support in transplant centers.

Vascular anastomosis is one of the most important factors for kidney transplant success. In a standard kidney transplant procedure, the position of the kidney graft is in the iliac fossa; if severe atherosclerosis exists, the position is in the iliac arterial system and anastomosis of the graft artery might be difficult. Moreover, if the recipient’s arterial blood flow is weak because of severe atherosclerosis, a kidney graft might result in primary nonfunction because of a lack of flow. Therefore, selection of the arterial anastomotic site is extremely important to ensure that there is no atherosclerosis and sufficient blood flow. After reconstruction with an aortic dissection and aortoiliac bypass, there might be a difference in blood flow between the right and left iliac arteries. Even if the arterial wall with severe atherosclerosis is covered with calcification, a strong tool to identify the anastomotic opening site for the graft artery is intraoperative periarterial echography. The methods for arterial blood flow occlusion and arterial anastomosis are important because hemostasis easily induces arterial dissection and shower emboli by careless maneuvering of vascular clamps. A balloon catheter is useful to occlude arterial blood flow in patients with severe atherosclerosis.

Reconstruction of the iliac artery using a synthetic vascular graft^4,5 or fresh arterial graft⁶ is useful at the time of a simultaneous kidney transplant. If the iliac artery has been already reconstructed by a synthetic vascular graft, it is possible to anastomose the graft artery into a synthetic vascular graft during a kidney transplant.³

Orthotopic kidney transplant is another posi-tioning site option of the kidney graft.⁷ However, atherosclerotic lesions extend to native renal and splenic arteries in orthotopic kidney transplants because atherosclerosis is a systemic disease. Actually, in the case of patient 12, the idea of orthotopic kidney transplant was abandoned because the renal and splenic arteries were narrow and irregular. This patient also had no adequate arteries in the pelvic cavity for anastomosis. Therefore, the graft artery was anastomosed to the abdominal aorta via a synthetic vascular graft. The positioning of a kidney graft in the iliac fossa, anastomosis of a graft vein, and ureteroneocystostomy were performed as usual, owing to their interposition using a synthetic vascular graft. A previous report of kidney transplant anastomosed to the aorta using a synthetic vascular graft reported 2 cases in 1 article⁸; thus, our report is only the second to be published. Of the various types of synthetic vascular grafts, PTFE is the most commonly used⁹ because it is thin and flexible. The autograft-like saphenous vein is also selected for interposition, except the synthetic vascular graft. However, the risk of obstruction due to a synthetic vascular graft is considered to be low because renal artery blood flow is abundant and the synthetic vascular graft for interposition is short.⁸ Another method considered for our patient 12 was a surgical procedure to interpose the graft artery to the femorofemoral bypass. However, this off-the-wall idea increases the risk of obstruction because the total length of the synthetic vascular graft is long. To directly anastomose a synthetic vascular graft to the abdominal aorta, a preoperative plain CT scan and 3D-CTA and intraoperative palpitation and periarterial echography to the recipient’s arteries make it possible to identify a localized site on the arterial wall with less calcification.

Almost all patients with severe atherosclerosis had been administered antithrombotics before kidney transplant because of a past history of peripheral arterial disease. In addition, heparin was also administered systemically in case of hemostasis of the aorta over a long period of time. Therefore, one must pay attention to the bleeding tendency during an operation in patients with severe atherosclerosis. In fact, in patient 12, we were forced to perform a reoperation for postoperative bleeding because of oozing of peeled periarterial tissue. Inflammatory adhesions were highly observed around severe atherosclerosis, and much time and effort in the operation were spent peeling off the adhesions. This is the most careful point in an operation in patients with severe atherosclerosis. However, patient 12 received a thrombectomy for thrombotic occlusion of the femorofemoral bypass during the operation despite systemic administration of heparin. In addition, a cerebral infarction occurred on postoperative day 2, and antithrombotic treatment was impossible to restart because of postoperative bleeding. As stated above, close attention must be paid to patients with severe atherosclerosis in terms of contradictory bleeding complications and a tendency for thrombus formation. Furthermore, we experienced a complication of a severe diabetes-induced infection that progressed from a perianal abscess to Fournier syndrome, even up to necrotizing fasciitis in patient 7. Although we observed these risk complications, all kidney transplant recipients with severe atherosclerosis were alive and all kidney grafts were functioning well at the last follow-up. Thus, the usual concept that patients with severe atherosclerosis are contraindicated for kidney transplant might be no longer relevant.

In conclusion, kidney transplant for patients with severe atherosclerosis can be achieved successfully by additional examinations and vascular surgical techniques. However, we must recognize that atherosclerosis is a systemic disease and be aware that not only vascular anastomosis but also systemic management is carefully reviewed in the peri-operative period.

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