External iliac vein to inferior vena cava bypass as an alternative management for external iliac vein stenosis and thrombosis in renal transplant recipients

Abstract

An man in his early 40s suffered from end-stage renal disease and underwent living donor renal transplantation. Doppler ultrasonography before surgery showed a normal iliac artery and vein without any thrombus. There was clear evidence of urine production intraoperatively. On the 5th postoperative day, there was no improvement in his renal function, and painless right leg oedema was noted. The clinical workup revealed pitting oedema without loss of arterial pulsation, discolouration or focal tenderness in the right leg. Serial Doppler ultrasonography examination showed thrombus progression from the right popliteal vein to the right external iliac vein around renal vein anastomosis despite anticoagulant administration with a downtrend of diuresis and worsening renal function. This condition led the patient to undergo surgical exploration on the 10th day post-transplantation. We decided to perform a thrombectomy and bypass the right external iliac vein to the inferior vena cava.

Background

Renal transplantation is currently the best treatment for end-stage renal disease. Postoperative renal transplantation complications are usually divided into vascular complications, ureteric complications, lymphocele formation, and general surgical problems such as bleeding and wound infections.¹ Vascular anastomosis is an essential part of the renal transplantation process, where in most cases, the allograft is anastomosed to the recipient’s iliac vessels.² Vascular complications are probably the most anticipated and likely to cause sudden renal allograft loss.¹ Therefore, a thorough evaluation of the recipient’s abdominopelvic vascularisation system is essential, generally using multiple imaging approaches, before the transplantation procedure.

Graft loss in an early stage resulting from artery or vein thrombosis accounts for a 2% incidence of all cases in renal transplantation.³ Iliac vein stenosis is a rare complication, with the resulting complications being thrombosis and graft dysfunction. Thrombosis development may have consequences, including deep vein thrombosis, pulmonary embolism and thrombus progression, resulting in graft loss.⁴ Early diagnosis and proper management are essential for maintaining the graft. However, information about the diagnosis approach and appropriate management regarding these cases is still limited, so a multidisciplinary approach is needed.

Case presentation

We present the case of a man in his early 40s who had been suffering from end-stage renal disease on routine haemodialysis for 7 years. He made the decision to have a renal transplant from a living donor. His baseline renal function was 48 mg/dL urea and 7.82 mg/dL creatinine. Before surgery, Doppler ultrasonography revealed a normal bilateral iliac artery and vein with no thrombus. At the time of surgery, the right iliac vessels were normal. Renal artery and renal vein were anastomosed end to side onto the internal iliac artery and external iliac vein, respectively. The operation went smoothly, and there was clear evidence of urine production intraoperatively. A right ureter double J stent was left in situ.

Postoperatively, his renal function shows no improvement, and haemodialysis was decided to be carried out on the 3rd postoperative day. Allograft Doppler ultrasonography was performed before haemodialysis, which showed no abnormalities. On the 5th postoperative day, painless right leg oedema was noted. The clinical workup revealed pitting oedema without loss of arterial pulsation, discolouration or focal tenderness in the right leg (see figure 1). On day 6 post-transplantation, his creatinine and urea were 7.35 mg/dL and 82.3 mg/dL, respectively. Laboratory examinations showed normal prothrombin time and activated partial thromboplastin time, with a D-dimer concentration of 0.11 mg/mL and fibrinogen 362 mg/dL.

Figure 1.

Clinical picture of right leg oedema after renal transplantation

Decreasing diuresis was shown with a value of 0.9 cc/kg/hour on the 1st postoperative day to 0.06 cc/kg/hour on the 9th postoperative day.

Investigations

Extensive Doppler ultrasonography examination was performed immediately on the 5th postoperative day to find the cause, which showed an acute thrombus in the right common femoral vein up to the right external iliac vein around renal vein anastomosis. Allograft examination showed normal renal vascularisation into the interlobar artery without indirect main arterial stenosis. Interlobar artery resistive indexes were relatively the same as an examination intraoperatively, with a value of 0.78 on average.

The patient was diagnosed with deep vein thrombosis of the right lower extremity based on the examination performed. Intravenous heparin was then administered continuously right after the diagnosis had been confirmed.

Heparinisation continued until 8 days postoperation without improvement of the right leg oedema. Doppler ultrasonography evaluation was then performed, which showed thrombus progression from the right popliteal vein to the right external iliac vein at the junction of renal vein anastomosis. Allograft ultrasonography also showed an elevation of interlobar artery resistive index with a value of 0.95 on average due to compliance disturbance. The formation of thrombi at renal and external iliac vein anastomosis was suspected of causing this disturbance. Heparin administration had failed to prevent progression and reduce the formed thrombus. A laboratory examination revealed that creatinine remained at level 7.34 mg/dL, and haemodialysis was needed on the first week post-transplantation, suggesting delayed graft function.

Treatment

Despite heparin administration, persistent right leg oedema and renal function worsening led the patient to undergo surgical thrombectomy on the 10th day after transplantation to release the thrombus, which obstructs the venous drainage system and raises the interlobar artery’s resistance. A team of urologists carried out the procedure along with a cardiothoracic surgeon. During the procedure, renal and vascular exploration was performed to find the cause of vein thrombosis, which led the team to discover stenosis at the junction of the external iliac vein and renal vein anastomosis. This stenosis had caused thrombi to develop along the right external iliac vein to the right popliteal vein, which further made ipsilateral lower leg oedema. The thrombi occluding the renal vein outflow at the anastomosis junction resulted in increasing interlobar artery resistance.

We decided to make a bypass from the right external iliac vein to the inferior vena cava in order to reduce thrombus formation and restore the venous flow (see figure 2). This decision has been made intraoperatively considering the degree of vein thrombosis and stenosis. Artificial blood vessel made from polytetrafluoroethylene (PTFE) was used to make this new drainage. This artificial blood vessel had a diameter of 6 mm and a length of 15 cm approximately. The end-to-side anastomosis was made from the right external iliac vein to the artificial blood vessel, which connects to the inferior vena cava (see figure 3). This procedure was the first to be carried out in our centre and the first case reported to our knowledge.

Figure 2.

Intraoperative view showed artificial blood vessel was used to bypass the external iliac vein to inferior vena cava.

Figure 3.

External iliac vein to inferior vena cava bypass illustration in the case of external iliac vein stenosis (illustrated originally by author of this publication: Muhammad Radityo Hendarso).

Mechanistically, a bypass between the right external iliac vein and the inferior vena cava will aid the return of blood flow from the ipsilateral leg, hence reducing oedema. This bypass also helps decrease turbulence by reducing the volume of blood flow from the lower extremity through the stenotic segment. The possibility of new thrombus formation will be reduced as turbulence in the area of stenosis is decreased. Reduced thrombosis in the anastomosis area eventually results in adequate renal venous outflow, contributing to lower allograft’s resistive index. If a bypass was not performed, it was possible that a recurrent thrombus would form in the area of stenosis after discontinuation of anticoagulant therapy.

The operation went as planned, and the patient was admitted to the intensive care unit for 4 days. On day 1, the diuresis started to rise from 0.14 cc/kg/hour to 0.65 cc/kg/hour on day 3 post-thrombectomy and bypass surgery. However, the urea and creatinine values did not improve immediately, with 77.5 mg/dL and 9.28 mg/dL, respectively. The patient underwent haemodialysis three times after the surgery. An MRI was performed to evaluate the 7th day post-bypass surgery. It showed a partial thrombus at the right external iliac vein with 15% patency and a partial thrombus at the right renal vein at the anastomotic part of the external iliac vein with a 56% patency. The total thrombi were found in the main, superficial and deep right femoral vein. The heparinisation was continued after surgery to reduce the remaining thrombi.

The patient gradually improves and shows a significant development of clinical symptoms and renal function. The right leg oedema decreased significantly after the surgery. The patient was discharged 3 weeks after the bypass surgery with a diuresis value of 3.27 cc/kg/hour, urea of 18.2 mg/dL and creatinine of 3.57 mg/dL, without haemodialysis.

Outcome

The patient received oral warfarin medication for 4 months and routinely visited the hospital to control his post-transplantation condition. One month after the procedure, the patient got admitted to the hospital to undergo double J stent removal. Clinically, the right leg oedema gradually resolved with renal function improvement.

Four months after the procedure, the right leg oedema was barely seen without loss of arterial pulsation, discolouration or focal tenderness in the right leg. The renal function continued to improve with a creatinine level of 1.72 mg/dL. Doppler ultrasonography examination showed lower extremities’ vein system without any thrombus on the bilateral side. Two years after the procedure, the patient maintained a urea and creatinine level of 29.8 mg/dL and 2.04 mg/dL, respectively, without haemodialysis. The right leg oedema had also never occurred again.

Discussion

Iliac vein stenosis is a rare complication after renal transplantation, with the resulting complications being thrombosis and graft dysfunction.⁴ To our knowledge, this represents the first report of iliac vein stenosis and thrombosis after renal transplantation treated with anticoagulation, thrombectomy and vein bypass surgery.

Iliac vein stenosis risk factors include the initial insertion of femoral dialysis catheters, postoperative fluid collection, haematoma, urinoma and lymphocele.⁵ Local inflammatory response and subsequent vessel stenosis can be triggered by post-transplantation fluid collections or haematoma. Owing to the left iliac vein’s recurrent compression due to the over-riding of the right iliac artery (May-Thurner or Cockett syndrome) before transplantation, iliac vein stenosis may also occur before transplantation.⁴

In our patient, none of these post-transplantation and pre-transplantation risk factors was observed. In May-Thurner syndrome, chronic trauma may lead to intimal proliferation with scarring and septal formation.⁶ In renal transplant recipients, a similar fashion can occur; local inflammatory reactions due to chronic extrinsic pressure will cause a repeated endothelial injury resulting in vascular stenosis.⁴ Intimal proliferation and fibrosis may also result from faulty suturing, intimal dissection and surgical clamp injury.⁶ In our case, the latter cause of stenosis most likely preceded, given the incidence of stenosis occurring acutely after transplantation.

The consequences of iliac vein stenosis include thrombosis and graft dysfunction.⁵ Recipients of renal transplants have a higher risk than the general surgical population of venous thrombus formation because of the acquired hypercoagulable state. This situation appears to be multifactorial, which is thought to be influenced by corticosteroid and immunosuppressant agents.⁷ The patients may present various clinical features, including varying degrees of allograft dysfunction and ipsilateral leg oedema. Unexplained graft dysfunction combined with the ipsilateral leg swelling may indicate a process of iliac vein stenosis. Other causes of renal allograft dysfunction should be excluded, including acute graft rejection, ureteral obstruction and nephropathy caused by a virus.⁶ While renal vein thrombosis may occur with haematuria, it is unlikely to occur in iliac vein thrombosis cases and may provide some indication that the physician may perform an alternative diagnostic approach.⁸

Identifying iliac vein thrombosis in renal transplant recipients is crucial because prompt and appropriate therapy can save the renal allograft. Ipsilateral leg swelling, decreased graft function as indicated by decreased serum creatinine, oliguria or delayed graft function should prompt urgent diagnostic workup. Doppler ultrasound may be used for identifying pathologies around the iliac vein in an acute setting. Loss of venous flow or reverse diastolic arterial flow is an indirect sign of acute venous obstruction in renal transplant recipients. In contrast to chronic venous stenosis, which is not accompanied by acute thrombosis and pressure overload on the renal vasculature, the ultrasound examination only shows impaired venous flow. When ultrasound evaluation shows no sign of allograft dysfunction, CT angiography or MR angiography can be conducted.⁶ This additional imaging can also be used to evaluate treatment outcomes in the iliac vein and thrombus setting. As in our case, we use MRI to assess the vein patency and the remaining thrombi after surgical exploration.

The current management of iliofemoral vein stenosis and thrombosis aims to remove the already formed thrombus, prevent new thrombus formation and increase venous patency. Chopra et al⁸ have developed a management algorithm for suspected deep vein thrombosis in renal transplant recipients. A suspected vein thrombosis must be distinguished whether the thrombus causes occlusion or not. If non-occlusive, then initial anticoagulation therapy can be given and evaluated by serial ultrasound. A more aggressive therapeutic approach can be achieved by administering anticoagulants, venograms, and catheter-directed thrombolysis with or without stent insertion when occlusive or thrombus progression has occurred. No improvement means operative re-exploration must be done.⁸

Unfortunately, systemic and catheter-guided thrombolysis raises serious bleeding risk when large doses of thrombolytic medications are used. After circulatory exclusion, surgical thrombectomy of iliac veins combined with loco-regional thrombolysis of veins below the groin has been shown to have a low risk of bleeding complications.⁹ Surgical reconstruction/venoplasty with or without endovascular stenting should be done if iliac vein stenosis is present.⁴

In our case, despite continuous anticoagulation administration, our patient did develop thrombus progression from serial Doppler ultrasound examination and worsening allograft function; thus, the option for surgery is then taken. We chose thrombectomy and bypassing over venous reconstruction in this case because the length of the renal vein allograft was so short that if venous reconstruction was performed, it was feared that it would cause more damage to the renal vein, causing postoperative tension in the anastomotic area and increasing the possibility of leakage. Bypass surgery was also expected to be less invasive than venous reconstruction, with a good outcome.

There has never been a publication discussing the use of vein bypass to manage iliac vein stenosis and thrombosis in renal transplant recipients. Currently, vein bypass is used in chronic iliac vein occlusion cases due to high restenosis rates and not in a renal transplant recipient. An artificial vascular graft with PTFE was used because of the lower thrombosis incidence and higher long-term patency rate.¹⁰

To achieve the lowest resistance, we have decided to bypass the external iliac vein distal to the stenosis to the inferior vena cava so that the highest flow can occur. This bypass was intended to decrease the volume of blood flow from the lower extremity through the stenotic segment in the anastomotic area. Reduced blood flow volume would lead to reduced turbulence and prevent new thrombus formation. Reduced thrombosis in the anastomosis area eventually results in adequate renal venous outflow, lowering allograft’s resistive index and overcoming the unilateral leg oedema problem.

Direct renal vein to inferior vena cava bypass might also help the allograft in this case. It would, however, have little effect on thrombus formation in the external iliac, femoral and popliteal veins. It was feared that the patient would have persistent or recurrent unilateral leg oedema. During surgical exploration, the length and calibre of the renal vein allograft were also taken into account, which had a shorter and smaller calibre than the external iliac vein, making bypassing more difficult with a high risk of failure.

This case showed that vein bypass might effectively manage vein thrombosis and stenosis complications after renal transplantation in conjunction with thrombectomy and postoperative anticoagulant administration with good outcomes. A multidisciplinary approach is crucial to diagnose better and treat the complication.

Patient’s perspective.

I was diagnosed with kidney failure for the first time 7 years ago. I have been undergoing routine hemodialysis twice a week since then. Doing this at a productive age is very difficult, particularly if you have to undergo hemodialysis during working hours.

I made the decision to have a living donor kidney transplant. I first underwent some initial tests before undergoing the operation before it was considered suitable for a kidney transplant. As a transplant donor, my wife also has a similar test.

The feeling after the surgery was good; other than post-surgery discomfort, I have no significant complaints. However, the doctor told me on the third postoperative day that my urine product had decreased along with the transplanted kidney that did not work correctly, so I went back to hemodialysis. I was afraid that the transplantation had failed.

On the fifth day after surgery, my right leg had swelling. I was anxious because, before the surgery, I had never felt the complaint. The team of doctors then did a thorough examination of my condition. From the Doppler ultrasound results, it was said that there was a thrombus in my vein, causing a blockage. The doctor explained that this was a complication of the kidney transplant procedure that I had just undergone. They then decided to give me an anticoagulant medication to prevent and reduce the progression of the thrombus. I was also asked to wear medical stockings on my right leg, hoping that it would help reduce the swelling. I had been treated for three days, but there was no improvement, either in my right leg swelling or in the transplanted kidney function that I had just received.

I underwent the second Doppler ultrasound, which showed an increasing thrombus in my vein. My worries are increasing, especially that my wife has been discharged from the hospital and cannot accompany me because she has to rest after surgery. The doctors’ team began to explain to me that surgery must be taken because my urine production continued to decrease, accompanied by a worsening thrombus image from the Doppler ultrasound results. If an aggressive approach is not taken immediately, there is a risk of damage to the kidney graft that was just implanted. I was afraid to hear it even though the team of doctors had described to me all the problems that could have happened before the surgery.

I spoke to my wife and family about this so that a decision could be made immediately. My wife was shocked to know this, mostly because she donated her kidney to me in the hopes that I could live without having to undergo hemodialysis. However, she is very supportive and fully supports the doctors’ decision. Thus, on the tenth day after my kidney transplantation, I had the second surgery.

After the second surgery, I woke up in the intensive care unit, and the doctors explained that the procedure was going well. They found a narrowing in my veins, which caused thrombus formation and caused swelling of my right leg. Because the narrowing was severe, the doctors told me that they had to make a new blood vessel to bypass and improve my venous blood flow. They said that this new blood vessel was artificial and had never been performed before in any kidney transplant recipient. Which means I got not only a new kidney but also a new blood vessel.

On the seventh day after the bypass surgery, I underwent an MRI examination to see my treatment progress. It showed that the thrombus which blocked my veins was still there. However, the doctors explained that the thrombus was unable to dissolve quickly, and it took time to reduce the swelling in my right leg. They continued the anticoagulant medication after the surgery, and I still use medical stocking on my right leg.

Gradually my urine product started to increase, followed by improved transplant kidney function. After the operation, I still underwent hemodialysis three times. In the third week after the bypass surgery, my right leg swelling started to get better, and I was allowed to go home. The doctor said that I was progressing very well, and I was pleased to hear that. After the discharge, I am still taking medicine from the doctor, especially the anticoagulant medication, for four months.

One month after the bypass surgery, my right leg’s swelling was no longer visible, and I was relieved because the complications were handled well. The nephrologists decided that I did not need hemodialysis anymore. My wife and I are delighted with the results of our kidney transplantation. We are very grateful to the doctors’ team, who had done such an amazing job!

Learning points.

• Iliac vein stenosis is a rare complication after renal transplantation, with the resulting complications being thrombosis and graft dysfunction.

• A multidisciplinary approach is needed to manage these cases because information about the diagnostic approach and appropriate management is still limited.

• Identifying iliac vein stenosis and thrombosis in renal transplant recipients is crucial; thorough physical, laboratory and radiological examinations are needed.

• Iliac vein stenosis and thrombosis after renal transplantation should be managed in a stepwise approach.

• Vein bypass can be one effective management for vein stenosis complication after renal transplantation in conjunction with thrombectomy and postoperative anticoagulant administration.

Ethics statements

Patient consent for publication

Obtained.