Renal transplant is the treatment of choice for end-stage renal failure. Since the first successful kidney transplant in 1954, advances in immunosuppression, surgical techniques, and posttransplant medical care have drastically improved the outcomes of this procedure. Despite these advances, surgical complications after renal transplant remain a challenge that can result in serious morbidity, graft loss, and recipient mortality. A significant proportion of surgical complications will have a vascular origin. Some of these vascular complications can cause irreversible damage to the transplanted kidney unless they are identified and treated urgently. In this review, common vascular complications of renal transplant are discussed, with emphasis on their mode of presentation, diagnosis, current management, and outcomes. Such knowledge can be useful for transplant clinicians, for prompt diagnosis and appropriate management of these complications.
Key words : False aneurysms, Renal artery thrombosis, Renal vein stenosis, Renal vein thrombosis, Transplant renal artery stenosis
Renal transplant is considered the gold standard treatment for end-stage kidney disease. The first successful renal transplant was performed in 1954 by Joseph Murray and colleagues.1 Since then, advances in immunosuppression, surgical technique, and protocol-driven management of transplant recipients have made renal transplant a safe procedure with durable long-term outcomes. Despite this progress, complications still occur following renal transplant. Of these, 5% to 10% can be categorized as surgical complications.2 Up to 30% of surgical complications will have a vascular origin.2,3 The major vascular complications of renal transplantation include renal artery thrombosis (RAT), renal vein thrombosis (RVT), transplant renal artery stenosis (TRAS), false aneurysms, and postbiopsy arteriovenous fistulae (AVF).
According to a case series published by Palleschi and colleagues, 3.5% of patients who received transplants from 1963 to 1979 had vascular complications.3 A single-center case series involving 2594 renal transplants performed from 1975 to 2017 reported vascular complications in 2.1% of recipients.4 In another case series by Emiroglu and colleagues published in 2001, the vascular complication rate was 1.8%.5 Tavakkoli and colleagues, in a more contemporary case series, reported a 1.3% incidence of immediate vascular complication following renal transplant.6 In an analyses of 1945 renal transplant recipients who received grafts exclusively from living related donors, Srivastava and colleagues reported a 1.29% incidence of vascular complications.7 According to available data, the overall vascular complication rate after renal transplant has generally been <5% in the past few decades. This is a major improvement compared with earlier data, where the incidence of vascular complications was estimated to be around 30%.5
Vascular complications that occur after transplant will invariably increase patient morbidity and occasionally may even lead to graft loss or recipient mortality. Bessede and colleagues associated the occurrence of a vascular complication with a reduction of graft survival by 3 years.8 Palleschi and colleagues reported that such complications can lead to graft loss in 1.66% and recipient mortality in 0.16% of patients.3 Thus, clinicians involved in renal transplant should be vigilant of these complications and thorough on the principles of their management. Appropriate treatment at an early stage may enable graft salvage in patients with RAT or RVT where seconds may affect the result. This review aimed to address the epidemiology, presentation, diagnosis, current management strategies, and outcomes of such vascular complications after renal transplant.
Renal Artery Thrombosis
Renal artery thrombosis is a rare but devastating complication of renal transplant. It occurs in less than 1% of all transplants.2 Generally, RAT occurs in the early postoperative period. The most common predisposing factor is technical error during renal artery anastomosis, such as a kink or torsion of the vascular pedicle or a missed intimal flap. Multiple donor renal arteries, end-to-end anastomosis of the donor artery to the recipient artery when there is a size discrepancy, posttransplant hypotension, hyperacute rejection, treatment unresponsive acute rejection, atherosclerosis of the donor or recipient arteries, and hypercoagulable conditions are other risk factors associated with this complication.2,3 Bessede and colleagues reported that back-bench reconstruction of the donor renal arteries before implantation was a significant risk factor for RAT.8
Thrombosis of the main renal artery will manifest with an abrupt reduction in urine output and acute deterioration of graft function.9 When multiple donor arteries are anastomosed, thrombosis involving one of the branches will result in segmental infarctions, which may be entirely asymptomatic or manifest as rising creatinine levels or new-onset hypertension. If the affected artery is a lower polar branch, it can precipitate ureteric ischemia and subsequent urine leaks.
Renal artery thrombosis that occurs 2 or more weeks after transplant is defined as late RAT.10 Late RAT is extremely rare and is usually the result of severe renal artery stenosis leading to secondary thrombosis or iatrogenic intimal damage to the vessel following cannulation for percutaneous endovascular interventions.2 The clinical presentation of late RAT is similar to early acute thrombosis. Slowly progressive thrombosis has been reported in the background of vasculitis, thrombophilic conditions, and hemolytic uremic syndrome.10
When RAT is suspected on clinical grounds, Doppler ultrasonography (DUS) of the graft is the first choice of imaging. It will show absent flow in the main renal artery and in the intrarenal segmental branches. A completely infarcted kidney will appear as a hypoechoic mass. Magnetic resonance angiography or digital subtraction angiography can be used to confirm the diagnosis.9,11 However, the information gained by such imaging should be weighed against the time lost for arranging them, as every passing second reduces the chances of graft salvage. Once the diagnosis is suspected, it should be treated as a surgical emergency. Urgent reexploration should be done to assess graft viability. If the graft appears salvageable, thrombectomy and correction of the root cause for the thrombosis should be done. This will usually require a reanastomosis.12 With prompt recognition and intervention, graft salvage has been reported in the literature. In their case series, Harraz and colleagues reported a 63% graft salvage rate for RAT treated by open surgery. The crucial steps in their operative strategy were to obtain vascular control, dismantle the arterial anastomosis, extract the thrombus, and perform perfusion of the graft with cold, heparinized saline and vasodilators, with venting of the perfusate through a venotomy, followed by reanastomosis.13 Aktas and colleagues reported 3 cases of salvaged renal transplants with RAT with open surgery.14 Their operative approach was similar to that reported by Harraz and colleagues. The short-term and long-term outcomes of such salvaged grafts appear to be acceptable.13,14
According to Tavakkoli and colleagues, the key to success in RAT is to maintain a high degree of suspicion in the early postoperative period. When there is doubt, immediate exploration and correction of any potential precipitating factors such as a kink or torsion in the renal artery before complete thrombosis sets in will improve the chances of graft salvage.6 However, in most cases, the graft is found to be nonviable on reexploration and the end result will be a graft nephrectomy. Graft nephrectomy for RAT is associated with significant mortality. Sepsis is the leading cause of death.15
The place for catheter-directed thrombolysis and percutaneous thrombectomy in the setting of early transplant RAT has not been well defined, but successful outcomes following percutaneous intervention for late RAT have been reported.16 Rouviere and colleagues reported successful revascularization of 3 of 4 transplanted kidneys with RAT after catheter-guided thrombolysis. They concluded that guided thrombolysis may be effective up to 24 hours from the onset of arterial thrombosis.17 However, thrombolytic agents should be judiciously used in the early transplant period as they can provoke catastrophic bleeding.9 Hedegard and colleagues recommended avoiding thrombolysis in the immediate 2 weeks after graft implantation. If endovascular thrombolysis is attempted in a case of RAT, and the procedure is successful, a cause for the thrombosis should be always looked for and appropriately addressed to prevent rethrombosis.18
Once RAT sets in, graft salvage is exceptionally rare; therefore, prevention is of the utmost importance. Excision of segments of the donor artery traumatized during organ retrieval, endarterectomy of atherosclerotic recipient vessel, avoidance of size mismatch between the donor and recipient vessels by performing end-to-side anastomosis, and adequate volume loading to avoid perioperative hypotensive episodes are some of the steps that have been proposed to prevent this complication.15
Renal Vein Thrombosis
Renal vein thrombosis, another early posttransplant complication with a poor outcome, has a prevalence of 0.5% to 4%.9 Technical defects such as torsion or kinking of the donor renal vein and endothelial injury sustained during organ procurement or reperfusion can precipitate thrombosis of the renal vein. As for venous thrombosis elsewhere in the body, prothrombotic conditions and external compression due to perigraft collections (such as hematomas, abscesses, and lymphoceles) have been linked to this complication. Grafts placed in the left iliac fossa seem to be at a greater risk of RVT, which has been attributed to compression of the left common iliac vein between the bony sacrum and the right common iliac artery.15 Proximal propagation of deep vein thrombosis of the ipsilateral lower limb can lead to late thrombosis of the renal vein.2 An RVT that occurs outside the early posttransplant period is a rare event, which can be secondary to severe acute rejection.13
Renal vein thrombosis will manifest as acute deterioration of graft function and a drop in urine output. Some patients may develop hematuria. Tenderness over the graft is a characteristic physical sign.2,6 The clinical picture may be confused with acute rejection; hence, imaging has an important role in confirming the diagnosis.15
Urgent noninvasive imaging with DUS is the first step, which will show absent or reduced flow in the renal vein with a high resistance flow pattern and a reversed diastolic flow in the renal artery (Figure 1).11 Magnetic resonance venography will provide better details, but it is rarely done due to time constraints.6
When the imaging is supportive of acute thrombosis of the renal vein, urgent reexploration and thrombectomy or retransplant are indicated.9 Similar to that shown with RAT, most patients with RVT will ultimately lose their grafts due to irreversible damage. However, with immediate intervention, usually within 1 hour after the onset of thrombosis, the graft can be salvaged. Lerman and colleagues reported a case of transplant RVT where the graft was saved after open thrombectomy and reimplantation of the kidney.19 In their study, Fathi and colleagues saved 3 of 7 allografts with RVT after open thrombectomy.20 Haberal and colleagues salvaged 2 of 4 grafts with RVT following surgery.12 When the graft is found to be unsalvageable on exploration, graft nephrectomy is required. This is to prevent progressive congestive swelling and graft rupture, which can lead to life-threatening hemorrhage.2
Graft salvage following endovascular inter-vention for RVT has been reported. Techniques such as intra-arterial thrombolysis, intravenous thrombolysis, a combination of both techniques, and percutaneous mechanical thrombectomy have been utilized for this purpose. Harraz and colleagues reported successful graft salvage following catheter-guided thrombolysis for late RVT occurring on a background of acute rejection.13 Even partial lysis of the thrombus by endovascular methods may enable salvage of a graft that is otherwise destined for nephrectomy.21 In the setting of partial RVT, the use of systemic anticoagulation may be sufficient to prevent thrombus propagation.22
Screening for prothrombotic conditions in potential renal recipients with risk factors for thrombosis and judicial use of perioperative anticoagulation are important strategies to prevent RVT.10 The literature also supports the use of aspirin for the prevention of RVT in renal transplant recipients.23
Transplant Renal Artery Stenosis
The incidence of TRAS ranges from 1% to 23%, and this wide range of incidence has been attributed to the lack of uniformity in defining the condition and different imaging techniques used to arrive at the diagnosis. Transplant renal artery stenosis is the most common vascular complication after renal transplant. It is usually diagnosed between 3 months and 2 years posttransplant, but early or late presentations beyond this timeframe are possible. This complication should be suspected in posttransplant patients with worsening or treatment-refractory hypertension. Episodic pulmonary edema in the absence of left ventricular dysfunction (“flash pulmonary edema”) is a rare mode of presentation. Transplant renal artery stenosis is occasionally diagnosed when an alternative diagnosis is looked for in the setting of graft dysfunction in the absence of rejection, drug toxicity, or obstruction to urine flow. An acute deterioration of function in the transplanted kidney after treatment has been started with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers is another rare presentation of TRAS. Occasionally, clinically silent stenoses are incidentally discovered on DUS performed for routine graft surveillance purposes.24
Lacombe classified TRAS according to the location of the stenosis, with focal stenosis at the recipient’s artery, the anastomotic suture line, or the donor renal artery.25 In some cases, the donor renal artery can be diffusely affected or there can be multiple stenoses at different locations. Different predisposing factors have been proposed depending on the locations and patterns of involvement (Table 1). The timing of symptoms can vary according to the location of the stenosis. Anastomotic stenosis that presents early is usually the result of a technical error in performing the anastomosis. Intimal damage sustained during organ retrieval or reperfusion of the allograft is another predisposing factor for narrowing at the suture line. Stenoses proximal or distal to the anastomosis will usually manifest comparatively later. The most common cause for narrowing of the artery in these locations is progressive atherosclerosis that affects the donor renal artery or recipient’s iliac vessels.9 Diffuse stenosis can be a consequence of vasculitis induced by rejection, but a definitive temporal relationship between TRAS and episodes of rejection is yet to be demonstrated.24
Digital subtraction angiography is the gold standard imaging modality for confirming the diagnosis of TRAS, but it is invasive. Doppler ultrasonography is preferred as the initial choice of imaging due to its availability, noninvasiveness, lack of radiation, and contrast exposure. Elevated peak systolic velocity (PSV) at the site of stenosis (Figure 2) with a poststenotic-to-prestenotic velocity ratio of 2:1 and low resistance indexes at the level of intrarenal arteries are the expected findings of TRAS on DUS.24 A PSV in the renal artery above 180 cm/second is supportive of TRAS.26 A PSV of >200 cm/second and a PSV ratio of >1.8 between the renal artery and the recipient’s external iliac artery were taken as diagnostic cutoff values for TRAS by de Morais and colleagues.27 In their study, Baxter and colleagues reported that a PSV of >250 cm/second was 100% sensitive and 95% specific of TRAS.28 Because of lack of consensus over exact DUS criteria for the diagnosis of TRAS and the operator dependability of ultrasound imaging, the diagnosis of TRAS should always be confirmed with another imaging modality before contemplation of the intervention. Magnetic resonance angiography is preferred for this purpose, and computed tomography angiography is an acceptable alternative.
Conservative management can be attempted in patients with TRAS who have stable renal function and hemodynamically insignificant stenoses on DUS (defied as PSV <180 cm/s, resistance index >0.5). Medical management of hypertension and imaging follow-up are required, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are the preferred antihypertensive agents. These drugs should be started cautiously with monitoring of renal function. Prompt withdrawal of these agents in the setting of worsening renal function can potentially reverse the drug-induced graft dysfunction. Patients with atherosclerotic narrowing of the native renal arteries and TRAS should be started on aspirin and statins.24
Renal dysfunction, uncontrolled blood pressure while on optimum medical therapy, stenosis of >70%, and progressively worsening stenosis on follow-up imaging are indications for intervention.24 Restoration of graft perfusion with percutaneous transluminal balloon angioplasty with or without stenting is the first-line management option (Figure 3). After endovascular intervention, renal function has been shown to normalize in 85% to 93% of patients and blood pressure has been shown to normalize in 63% to 83% of patients.9 The reported incidence of serious complications (such as arterial dissection, thrombosis, or rupture following angioplasty) is around 4%. The risk of recurrent stenosis ranges from 10% to 33%. The reported rates of restenosis are much less when angioplasty is combined with stenting.9,24 This was confirmed in a meta-analysis published by Ngo and colleagues, where they noted superior patency rates with stent placement for TRAS compared with angioplasty alone (90.4% vs 73%).29 Advances in endovascular therapy such as drug-coated balloons and drug-eluting stents have been also applied for the treatment of TRAS.30,31 However, robust studies that compare the outcomes of these devices against standard balloons and bare metal stents are yet to be published.
Surgery for TRAS is reserved for patients with lesions that are inaccessible to percutaneous angioplasty or as a salvage procedure after failed angioplasty. Resection of the stenotic segment and revision of the anastomosis, bypass using reversed saphenous vein graft, patch angioplasty, and local endarterectomy are surgical techniques that have been described for TRAS. Surgery has a success rate of 63% to 92% but at the cost of significant morbidity. The rate of graft loss after surgical intervention for TRAS is as high as 15% to 20%, and the mortality risk is around 5%.24
Transplant Renal Vein Stenosis
Similar to TRAS, stenosis of the transplanted renal vein has been reported as a cause for graft dysfunction. It seems to be a much rare phenomenon, with limited literature.32-35 External compression from perigraft fluid collections or the recipient’s iliac artery, injury to the renal vein during organ procurement, infection, rejection, and coexisting intrarenal AVFs have been reported as risk factors for this condition.32,34
The presentation is with deteriorating graft function, and the diagnosis is clinched once more common causes for such graft dysfunction, such as rejection, hydronephrosis, and TRAS, are excluded. Doppler ultrasonography may depict the presence of a stenosis in the renal vein, with elevated flow velocities at the site of narrowing and turbulent flow just distal to this point. Resistance to intrarenal blood flow will be evident with the reduced diastolic flow in the renal artery and elevated resistance indexes in the intrarenal branch arteries.32,34 Computed tomography angiography, magnetic resonance venography, and conventional venography can confirm the diagnosis.33,34
The management of this condition is with relief of external pressure on the renal vein when it is the provoking factor or with balloon angioplasty with or without stenting when there is a fibrotic stricture in the vein wall.32-35 Transplant renal vein stenosis is a rare cause for graft loss and occurs when long-standing venous congestion causes irreversible graft damage.34
Extrarenal False Aneurysms
The incidence of extrarenal false aneurysms after renal transplant is less than 1%. They are a consequence of partial disruption of the arterial anastomosis due to technical error or infection.9,36 Although rare, such pseudoaneurysms of transplant renal artery may arise distal to the anastomosis, secondary to an infection, or as a result of arterial laceration during a percutaneous biopsy.36,37 Presentation is with abdominal pain, a pulsatile abdominal mass, or hypotension due to hemorrhage. A large extrarenal pseudoaneurysm can compress the renal artery and cause hypertension or graft dysfunction, as shown for TRAS.9
Doppler ultrasonography is the first choice of imaging. In B mode ultrasonography, a false aneurysm will appear as an extrarenal cyst. Enabling color flow imaging will demonstrate the characteristic to-and-fro flow pattern within the cyst. Computed tomography angiography and magnetic resonance angiography can be performed to obtain additional anatomic details prior to intervention.
Small, asymptomatic extrarenal false aneurysms that are free from infection can be managed expectantly.36 Large lesions or lesions associated with an infection will require intervention to prevent rupture. A size cut-off of 2.5 cm has been proposed as the threshold for intervention.38 Treatment options include open surgery or endovascular techniques such as stenting, thrombin injection, and coiling. Stenting is an attractive alternative to open surgery. However, the deployment of stents across the anastomosis will invariably disrupt allograft perfusion.37 With recent advances in the field of endovascular therapy, innovative techniques such as the use of “kissing stents” can be utilized to cross an anastomotic pseudoaneurysm with the preservation of organ perfusion.39
Treatment of extrarenal false aneurysms that occur after transplant is extremely challenging, and most patients with this condition will require a graft nephrectomy.38 However, there are reported cases of graft salvage, where the pseudoaneurysm was treated by stenting or percutaneous thrombin injection and the kidney was autotransplanted. When a patient presents with life-threatening bleeding from rupture of an anastomotic false aneurysm, a covered stent can be deployed in the iliac artery for hemostasis, and autotransplant or graft nephrectomy can be done as a secondary procedure, depending on the clinical scenario.37
Occasionally for definitive treatment of an anastomotic false aneurysm, especially those caused by infection, ligation of the external iliac artery may be required. This can threaten the viability of the ipsilateral lower limb, and, in such instances, vascular reconstruction will be necessary. When infection is suspected, antibiotic/silver-impregnated grafts and extra-anatomical bypass with femoro-femoral crossover grafts are recommended as surgical options to restore limb perfusion.38,40 There are reported cases of major limb loss after failed vascular reconstruction for such extrarenal false aneurysms.36
Intrarenal Arteriovenous Fistulas
Intrarenal arteriovenous fistulas can complicate about 10% to 16% of posttransplant renal biopsies.41 A communication between an intrarenal artery and an adjacent vein can be created when the biopsy needle penetrates through the walls of both structures. Preexisting hypertension and nephrocalcinosis have been reported as risk factors for this postbiopsy complication.42 However, there are no strong associations with factors such as the size of the biopsy needle used, serum creatinine at the time of biopsy and the concurrent use of aspirin. Most patients with iatrogenic postbiopsy AVF will be asymptomatic. Some patients may develop hematuria. Hypertension, graft dysfunction, and high output cardiac failure are rare presentations.42,43 The graft dysfunction and hypertension in the setting of such AVF can be explained by intrarenal shunting of blood, with ischemic injury to the renal parenchyma.37 Clinical examinations will be unremarkable in most patients; however, in special circumstances, a thrill may be palpable over the transplant, with a continuous bruit heard on auscultation.42
Doppler ultrasonography is the imaging modality of choice for the diagnosis. An abnormal turbulent flow will be seen in an intrarenal artery and an adjacent vein. The feeding artery will have a low-resistant, high-velocity Doppler waveform, and the draining vein will have a pulsatile, arterialized flow pattern.11,44 Magnetic resonance angiography and computed tomography are alternative noninvasive imaging options.
In 80% of cases, spontaneous resolution of these fistulae can be expected. Indications for intervention are gross hematuria that fails to settle or the presence of graft dysfunction, hypertension, or cardiac decompensation that can be attributed to the fistula. The absence of such complications warrants a conservative management approach.42 For those who require intervention, endovascular coil embolization of the feeding artery to the fistula is the preferred treatment option.41,43 Selective embolization of the feeder is preferable to nonselective embolization, as it is associated with less renal parenchymal loss.37 According to Lorenzan and colleagues, super-selective embolization of such fistulae in a background of graft dysfunction can lead to significant improvements in serum creatinine levels.44 Although minimally invasive, embolization of such lesions can be rarely associated with serious complications such as thrombosis or dissection of the renal artery, pulmonary embolism, and acute limb ischemia due to embolic material reaching the pulmonary circulation or lower limb arteries.45 Lesions that require intervention but are not amenable for embolization therapy may require surgery in the form of partial nephrectomy.46 However, open surgery will invariably result in significant loss of mass in the transplanted kidney.39
Vascular compilations are uncommon after renal transplantation, but their consequences can be devastating. Doppler ultrasonography is an excellent screening tool when such complications are suspected. Both RAT and RVT require immediate intervention once the diagnosis is suspected if the graft is to be saved. Selected patients with TRAS can be managed conservatively; for those who require intervention, angioplasty with stenting is the preferred treatment option. Management of extrarenal anastomotic false aneurysms can be extremely challenging, and there is high risk of graft loss. Biopsy-related AVFs of the transplanted kidney are common, and most of these will resolve spontaneously without adverse sequelae. In the minority that requires intervention, selective angio-embolization is associated with excellent outcomes.
Volume : 20
Issue : 4
Pages : 333 - 341
DOI : 10.6002/ect.2021.0303
From the Department of Renal Transplant, Royal Liverpool University Hospital, Liverpool, United Kingdom
Acknowledgements: The author has not received any funding or grants in support of the presented research or for the preparation of this work and has no declarations of potential conflicts of interest. The author is a fellow in renal transplantation at the Royal Liverpool University Hospital.
Corresponding author: Thilina Gunawardena, 164, Kensington, Kensington Field, Liverpool, L7 8XE, UK
Figure 1. Reversed Diastolic Flow on Doppler Ultrasonography in an Intrarenal Artery in a Suspected Case of Renal Vein Thrombosis
Table 1. Risk Factors for Transplant Renal Artery Stenosis Depending on the Location of the Stenosis
Figure 2. Elevated Peak Systolic Velocity on Doppler Ultrasonography in a Case of Transplant Renal Artery Stenosis
Figure 3. Digital Subtraction Angiography of Transplant Renal Artery Stenosis