May-Thurner Syndrome in Renal Transplantation

Abstract

Venous complications after renal transplantation are uncommon but are associated with significant morbidity and graft loss. Recipients with left common iliac vein compression due to an overlying common iliac artery (May-Thurner syndrome) may be predisposed to venous complications. We discuss the care of a living donor kidney transplant recipient who developed an occlusion of the iliac vein secondary to a combination of a hematoma and the underlying presence of May-Thurner syndrome. Endovascular stenting of the two areas of compression in the iliac vein was successful in restoring adequate venous return, while maintaining normal renal allograft function. A 63-year-old white male with a 40-year history of insulin-dependent diabetes mellitus and end-stage renal disease secondary to diabetic nephropathy underwent living donor kidney transplantation in January 1999. Preoperative evaluation revealed multiple medical problems including a history of hypertension, hypothyroidism, hyperlipidemia, peripheral vascular disease, and coronary artery disease. He had undergone coronary artery bypass grafting in 1988. After full evaluation, he was cleared by cardiology for transplantation. Of note, he had no signs or symptoms of venous insufficiency in either lower extremity. To preserve the right iliac vessels for a future pancreas transplant, the donor kidney was placed retroperitoneally in the left iliac fossa. The left internal iliac vein was ligated and divided to maximize exposure. The vascular anastomoses were done to the left external iliac artery and vein; the ureteroneocystostomy was done using the single anterior stitch technique. At the time of surgery, he was found to have severely diseased iliac arteries. Immediately after surgery, because of the potential high risk for thrombosis, he was prophylactically placed on a low-dose heparin drip (200 U/h). Immunosuppression consisted of antibody induction plus mycophenolate mofetil, tacrolimus, and prednisone. On postoperative day 1, the recipient was hemodynamically stable with a urine output of 3500 cc/24 h. His serum creatinine level dropped to 3.2 mg/dl, his hemoglobin was stable (9.3 gr), and his partial thromboplastin time was 60 sec, with the INR within normal limits. However, on routine follow-up EKG, he was found to have ST elevations that correlated with a progressive elevation of troponin levels (from 0.3 μg/L to 2.4 μg/L). After the appropriate cardiology consultation, the diagnosis of a non-Q wave myocardial infarction was made. Later in the day, the urine output dropped slightly, which prompted a renal transplant ultrasound. The duplex study revealed normal flow in the renal artery and vein. However, no flow was detected in the iliac vein above the anastomosis. In addition, there was reversal of venous flow within the iliac vein below the anastomosis. A small fluid collection was also seen anterior to the kidney. On postoperative day 2, his urine output was 2000 cc/24 h, his serum creatinine level increased from 3.2 mg/dl to 3.4 mg/dl, and he required 2 U of PRBC for a hemoglobin level of 8.8 gr. A repeat renal ultrasound was done and was unchanged from the previous day. However, he started noticing some swelling in the left lower extremity. We obtained a magnetic resonance angiogram (MRA) of the pelvis to rule out an intraluminal clot in the iliac vein versus extrinsic compression of the vein by a hematoma. The MRA showed no intraluminal clot; there was a 6.5×4.0×5.0-cm hematoma posteromedial to the renal graft. In addition, the MRA confirmed the absence of flow in the left common and external iliac vein proximal to the renal vein anastomosis (Fig. 1). Figure 1: MR angiogram after intravenous gadolinium contrast injection with visualization of both arteries and veins on the MIP images. An occlusion of the left external iliac vein is demonstrated proximal to the renal vein anastomosis with no visualization of intraluminal clots in the iliac system. Abbreviations used in figures: TxKD, transplanted kidney; RVA, renal vein anastomosis; RAA, renal artery anastomosis; ECV, extrinsic compression of the vein due to pelvic hematoma; *, site of compression due to May-Thurner syndrome.As the recipient returned from the radiology suite, he became anuric and the swelling of his left lower extremity worsened to the point of developing early signs of compartment syndrome. Because of the recent myocardial infarction we elected to attempt to treat this with endovascular stenting rather than reoperation. He was returned to the radiology suite; a venogram confirmed the MRA findings (Fig. 2), and a 14-mm × 4-cm Wallstent (Boston Scientific Technology Center, Minneapolis, MN) was deployed across the area of stenosis involving the external iliac vein just proximal to the renal vein anastomosis. Despite successful deployment of the stent, it was apparent that proximal and distal to the stent there were large collateral veins with an additional proximal venous outflow obstruction (Fig. 3). These findings were consistent with a chronic iliac venous occlusion process known as May-Thurner (6) or Cockett’s syndrome (9). An additional 14-mm × 6-cm Wallstent was deployed in the left common iliac vein with the upper end at the inferior vena cava and the distal end 4 mm from the previously placed stent. A follow-up venogram revealed brisk flow toward the inferior vena cava with no filling of collaterals and normal flow in the left transplant renal vein (Figs. 4 and 5). The patient felt an immediate relief of pain and left lower extremity tightness. Before and throughout the procedure, he was kept on fenoldopam mesylate (Carzopam; SmithKline Beecham Pharmaceuticals, Philadelphia, PA) drip for prevention of radiocontrast medium renal injury. Figure 2: Axial MR image with proton density technique showing a large hematoma with a fluid/fluid level posteromedial to the transplanted kidney and compressing the adjacent iliac vessels.Figure 3: Left iliac venogram demonstrating extrinsic compression of the left common iliac vein proximal to the renal vein anastomosis. Abbreviation: CV, collateral vein.Figure 4: Left iliac venogram after deployment of metallic Wallstent in distal common iliac vein. Abbreviation: MTS, May-Thurner syndrome site (proximal left iliac vein).Figure 5: Left iliac venogram after successful deployment of both metallic Wallstents. Absence of collateral veins. Abbreviation: RV, renal vein.On postoperative day 3, his lower extremity pain resolved and the swelling was minimal. The urine output dramatically improved (150–200 cc/h). The troponin level normalized within 24 h. A follow-up renal ultrasound confirmed the patency of the left common iliac vein with antegrade flow below the renal vein anastomosis. On postoperative day 10, the patient was discharged home in stable condition with a serum creatinine of 1.9 mg/dl. Two months later, he underwent a cadaver pancreas transplant to the right iliac fossa from which he recovered uneventfully. May and Thurner first described the iliac compression syndrome in 1956 as an obstruction of the left common iliac vein by the overlying right common iliac artery (6). They also described changes found in the intima of the left common iliac vein: these spurs are secondary to the compression and chronic vibratory pressure of the right common iliac artery on the venous endothelium. These spurs were composed of fibrocytes, collagen, and numerous capillaries; were found in 22–28% of autopsies; and had three different morphologic presentations: lateral, central, and fenestrated. In addition to the right common iliac artery as a cause of extrinsic venous compression, a tortuous left common iliac artery (7) and the left internal iliac artery (8) have been found responsible for the obstruction of the left iliac vein. May-Thurner syndrome has been diagnosed in 2–5% of patients undergoing evaluation for venous disorders of the lower extremity. It is more common in women (70%) than men (30%) and generally presents in the third to fifth decades of life. Based on the 22–28% frequency of spur formation found at autopsy, it is clear that the majority of the patients are asymptomatic. Left lower extremity swelling and pain are the most common symptoms. However, patients can present with varicosities, chronic venous stasis ulcers, iliac vein thrombosis, pulmonary embolus, and phlegmasia cerulea dolens. In the setting of May-Thurner syndrome, a new onset of symptoms or a worsening of the previous condition usually represents the presence of acute iliac vein thrombosis. Renal vein thrombosis is a rare complication of the transplanted kidney (1,3), occurring in 1.1% of extraperitoneal primary transplant recipients in our series. However, it is associated with a high incidence of graft loss; 17 (65%) of 26 of our patients lost their graft. There are many possible causes of transplant renal vein thrombosis of which May-Thurner syndrome is one (4,5). Others include improper placement of the kidney in the iliac fossa, rotation of an intraperitoneally placed kidney, a narrowed venous anastomosis, a short and long renal vein (kinking and twisting of the vein), hematological complications (hypercoagulable state), and extrinsic compression (lymphocele or hematoma). Nerstrom et al. (2) reported a higher incidence of renal allograft vein thrombosis in the left iliac fossa. These findings were thought to be due to the presence of iliac vein compression syndrome (2,5). In addition to the early postoperative vascular complications, undetected chronic iliac vein compression in a renal transplant recipient can lead to renal vein hypertension, progressive renal dysfunction, and late graft loss. Our patient had two different areas of extrinsic compression of the iliac vein. The proximal left external iliac vein (proximal to the renal vein anastomosis) was acutely compressed by the pelvic hematoma, and the proximal left common iliac vein was chronically compressed by the right common iliac artery (May-Thurner syndrome). This chronic compression of the left common iliac vein diverted the venous outflow mainly to the left internal iliac vein and to the numerous pelvic collaterals. In retrospect, the ligation and division of the left internal iliac vein (not routinely done in our center) compromised venous return, thus potentially worsening the symptoms early after the surgery. Of importance, a sudden disruption of the venous outflow proximal to the renal vein anastomosis, either by an intraluminal clot or extrinsic compression, would ultimately lead to renal vein thrombosis and graft loss immediately after transplantation. In our case, the large and numerous pelvic venous collaterals present secondary to May-Thurner syndrome prevented further disastrous complications after the kidney transplant. Conservative management of May-Thurner syndrome in nonrenal transplant patients is associated with poor results (9). Different surgical techniques with mixed results have been described in the literature (10–14). At the present time, the most accepted operation is the full dissection and elevation of the right common iliac artery over the compressed area, followed by venotomy, thrombectomy (if thrombus is present), excision of the intimal spurs, and vein patch angioplasty (15). If the left internal iliac artery is the cause of the venous obstruction, it can be safely divided (8). With recent advances in noninvasive endovascular techniques, the implantation of a self-expanding metallic endoprosthesis in the setting of venous obstruction has become an alternative to surgical therapy. The use of metallic Wall- stents in iliofemoral venous stenosis has been associated with primary and secondary 4-year patency rates of 50% and 75%, respectively (16). In recent reports (17–19), the implantation of metallic stents in patients with May-Thurner syndrome was associated with 100% primary short-term patency rates. Catheter-directed thrombolysis, angioplasty, and endoluminal stenting has been advocated by some authors as an effective mode of treatment for iliofemoral venous thrombosis (20–24). The potential advantages of this treatment modality over the standard anticoagulation treatment (heparin) are the avoidance of surgical thrombectomy, prompt alleviation of painful lower extremity edema, preservation of valve function, prevention of postphlebitic syndrome, and prevention of pulmonary emboli. The overall clinical and technical success rate of catheter-directed therapy according to Semba and Dake is 85% with short-term primary patency rates of 95%(20). The complications related to the procedure reported by the same authors were minor. Surprisingly, there were no pulmonary emboli or deaths reported. Based on their experience, they no longer use baseline ventilation-perfusion scans or prophylactic inferior vena cava filters in noncomplicated patients, although others do (22). Patients treated with catheter-directed therapy, angioplasty, and stenting are kept on Coumadin (INR=2–3) for 6 to 9 months. In our case, because the renal allograft acts as a distal fistula, the anticoagulation should be shortened to 3 to 6 months. The follow-up required is a duplex ultrasound at 1 month, 3 months, 6 months, and then annually. The clinical outcomes of these small retrospectives series are very encouraging. However, to date, no double-blind, prospective, randomized studies have been done comparing the efficacy, cost, and incidence of delayed complications of iliofemoral venous thrombosis of catheter-directed thrombolysis with standard anticoagulation therapy. The use of iodinated contrast for placement of endovascular stents can potentially worsen the degree of acute tubular necrosis immediately after renal transplantation. The two valid alternatives to iodinated contrast would be CO2 and gadolinium-based angiograms. The quality of the images in CO2 angiograms are not as good as in iodinated angiograms. In addition, to obtain high-quality images with gadolinium, a significantly higher dose of gadolinium has to be administered, potentially increasing the risk of nephrotoxicity. In our patient, good definition of the images was of critical importance. Therefore, we used iodinated contrast with fenoldopam as an adjunct to maximize renal blood flow. The care of our patient immediately after surgery was challenging. The worsening renal function early postoperatively, the presence of a pelvic hematoma obstructing the left iliac vein, the retrograde venous flow on the left distal external iliac vein, and the worsening left lower extremity symptoms warranted immediate action. Our first inclination was surgical exploration. However, based on his ongoing myocardial infarction and the fact that the venous outflow seemed to be compromised due to extrinsic compression, we opted for a noninvasive stenting of the compressed area. The presence of iliac vein thrombosis early after transplantation would have prompted us to explore the patient surgically, perform a thrombectomy, and repair any potential technical problem. This approach would be justified based on the assumption that the thrombosis is directly related to the surgery. In the presence of iliac vein thrombosis, May-Thurner syndrome cannot accurately be confirmed with imaging studies until the thrombus has been extracted or lysed. However, if we suspect clinically and radiographically that May-Thurner syndrome may be the cause of iliac vein thrombosis after renal transplantation, then catheter-directed thrombolysis and stenting would be a valid alternative to surgery. In retrospect, if we had surgically reexplored our patient, we would have most likely missed the compression of the right common iliac artery on the proximal left common iliac vein because this area is not routinely dissected at the time of renal transplantation. In this instance, the noninvasive technique not only allowed us to stent the area compressed by the hematoma but to diagnose and successfully treat the proximal iliac vein compression. In conclusion, venous complications after renal transplantation are rare, but they are associated with significant morbidity and early graft nephrectomy. Asymptomatic patients with iliac vein compression syndrome may become symptomatic after renal transplantation, potentially leading to serious lower extremity venous complications, renal vein thrombosis, and graft loss. Iliac vein compression caused by a hematoma or May-Thurner syndrome in a renal transplant recipient can be safely and successfully managed noninvasively with the prompt deployment of endovascular metallic stents.