Management of Thrombophilia in Renal Transplant Patients

Renal allograft recipients with thrombophilia (a hypercoagulable state) are at higher risk for early allograft loss. Following an episode of allograft renal vein thrombosis in a patient subsequently diagnosed with protein C deficiency, we adopted universal screening for hypercoagulable risk factors. Patients with a history of a thromboembolic event underwent laboratory screening for thrombophilia. Eight patients with a defined hypercoagulable disorder or a strong clinical history of thrombosis even in the absence of hematologic abnormalities were treated with anticoagulation following renal transplantation. We reviewed the outcomes of these eight patients and all renal transplant recipients at our center who developed thrombotic complications after renal transplantation. Since the introduction of universal screening for hypercoagulable risk factors, 235 consecutive transplants were performed without allograft thrombosis. Eight patients with evidence of thrombophilia, recognized before renal transplantation, received perioperative heparin and postoperative oral anticoagulation. Two of these eight patients developed perinephric hematomas requiring evacuation, blood transfusion, and temporary withholding of anticoagulation. Of interest, two of the remaining 227 patients, not identified with thrombophilia before surgery, developed thrombotic complications after renal transplantation. A hypercoagulable disorder was subsequently documented in each. Identifying patients with thrombophilia before transplantation and defining their management presents many challenges. The risk of allograft thrombosis must be weighed against the risk of perioperative bleeding and the need for long-term anticoagulation. Recommendations for managing thrombophilia in renal transplant recipients are suggested based on our experience and review of the literature.     

Renal vein reconstruction with interposition allografts in cadaveric renal transplantation

Abstract. The short or injured renal vein in cadaveric transplantation is a surgical challenge. Over a 2-year period, we have performed ex vivo renal vein lengthening with an interposition vascular allograft in 17 recipients of cadaveric kidneys. Indications for renal vein extension allografts were a short right renal vein ( N = 12), procurement injury to the vein ( N = 4), and double renal vein ( N = 1). In six cases (35.3%), ex vivo renal artery reconstruction was performed in combination with the venous repair. Our preferred approach is to employ allograft material in ex vivo reconstruction under cold storage conditions. Bench surgery ranged from 10 to 30 min, and the mean in situ anastomosis time was 20 min. The mean length of renal vein prior to reconstruction was 12 mm, and the mean length of venous interposition allograft after revascularization was 27 mm. There were no episodes of vascular thrombosis or primary nonfunction. Three patients (17.6%) required postoperative hemodialysis for acute tubular necrosis, which was subsequently resolved. The mean serum creatinine at 1 month post-transplant was 1.7 mg/dl. These preliminary results suggest that ex vivo renal vein reconstruction with an interposition allograft is a safe and effective modality which should be added to the transplant surgeon's armamentarium in select cases.     

Interventional therapy of vascular complications following renal transplantation

Abstract:  Renal transplantation is accepted as the preferred treatment for most cases of end-stage renal disease. Postoperative vascular complications include stenosis or thrombosis of the transplant renal artery or arteriovenous fistulas after biopsy. Impaired arterial perfusion of the transplant may be the leading cause for graft dysfunction or refractory hypertension. Therefore, non-invasive imaging modalities are required to detect and locate vascular complications with high accuracy. Doppler ultrasound is suited as a screening method for the detection of impaired graft perfusion. Magnetic resonance imaging (MRI) is used for an accurate diagnosis of vascular complications and to support decision for appropriate surgical or interventional treatment. Minimal invasive techniques like percutaneous transluminal angioplasty and stent placement have evolved as safe procedures with a high technical success rate reducing substantial morbidity. They can be considered as an alternative to surgical treatment of transplant renal artery stenosis (TRAS). Embolization of severe arteriovenous fistulas is the method of choice if the feeding artery can be occluded through a microcatheter. In selected cases, even catheter-guided fibrinolytic treatment of arterial thrombosis might be considered, if instantaneous surgery is considered a high-risk procedure. This article reviews the imaging features of common vascular complications after renal transplantation with focus on MRI. In addition, interventional radiological techniques are described for the treatment of TRAS, acute thrombotic occlusion, and arteriovenous fistulas.     

Severe Renal Vein Stenosis of a Kidney Transplant with Beneficial Clinical Course after Successful Percutaneous Stenting

A 51‐year‐old renal transplant recipient presented with marked renal function deterioration 13 months after renal transplantation. After exclusion of ureteral obstruction, transplant artery stenosis and acute rejection, the diagnosis of a severe renal vein stenosis was made by an MR scan. After angiographic confirmation of the stenosis, treatment was attempted with percutaneous stent angioplasty. The long‐term clinical course was favorable, with marked improvement in renal function. Transplant renal vein stenosis is a rare, but potentially curable, cause of renal allograft functional deterioration.     

Renal allograft rupture with iliofemoral thrombophlebitis.

Spontaneous rupture of a renal allograft in the early posttransplant period is associated with tachycardia, hypotension, oliguria, swelling, pain, a falling hematocrit level, and tenderness at the transplant site. Occasionally, the ruptured allograft can be saved by control of the hemorrhage. Deep vein thrombophlebitis, a common occurrence after prolonged surgery and cortocosteroid therapy, is less common in renal allograft transplantation, but may be associated with renal vein thrombosis. The simultaneous occurrence of deep vein thrombophlebitis, renal vein thrombosis, and allograft rupture contraindicates anticoagulent therapy. We present a patient in whom ipsilateral deep vein thrombophlebitis developed eight days after a cadaveric renal allograft, followed in two days by hypotension, a falling hematocrit level, oliguria, and a painfall mass at the allograft site. Surgical exploration revealed a ruptured allograft with iliofemoral and renal vein thrombosis and profuse hemorrhage. A transplant nephrectomy was performed.     

Mechanisms of posttransplant hypertension

Summary Hypertension is a common problem in renal failure patients both before and after renal transplantation. The stable allograft can maintain salt, volume, and blood pressure homeostasis and is not intrinsically a hypertensive model. The causes of severe posttransplant hypertension are multiple. Renal vascular tone, body salt and volume status, and renin release are all connected and influenced by immunosuppressive medications, allograft function, and native kidney presence and function. The role of each of these in posttransplant hypertension is reviewed. In most cases, severe hypertension in the stable transplant patient without rejection or transplant renal artery stenosis is greatly improved following native bilateral nephrectomy. Transluminal angioplasty is the preferred initial treatment for transplant renal artery stenosis.     

Renal transplantation in allografts with multiple versus single renal arteries

Allograft with multiple renal arteries (MRA) is considered to have an increased post-transplantation risk due to vascular and urologic complications. The aim of this study is to investigate the outcome of living donor kidney transplantation using allograft with a single artery and recipients of allografts with multiple arteries. Seven hundred and eighteen consecutive adult kidney transplants done between 1998 and 2007, with living unrelated kidney donors, were enrolled in this retrospective analysis. Data from the group with MRA (n = 60) were compared with those from the group with single renal artery (SRA) (n = 658). Delayed graft function (DGF) was more frequent in recipients' allografts with more than 2 arteries when compared with SRA recipients (Odds Ratio: 1.2; 95% CI:1.08-1.9, P = 0.02), but there was no difference between SRA and allograft with two arteries. The incidence of acute rejection (AR) was not statistically greater in recipients with MRA. Renal artery stenosis (RAS) occurred more frequently in patients with MRA (8.3% vs. 5.9% and P = 0.02), but other vascular complications such as renal artery thrombosis and hematoma revealed no differences (P > 0.05). Urologic complications such as UVJ obstruction, urinary leakage and ureteropelvic obstruction were not statistically different between the groups. The actuarial 1-year allograft survival rate was comparable in both groups (93.6% vs 96.8%, P = 0.22). Allografts with more than two arteries were associated with increased DGF and RAS, but no surgical or urological complications were detected in our series. Our findings demonstrate that renal allograft transplantation with multiple arteries could be performed with reasonable complications and acceptable outcomes.     

Corner-saving renal artery anastomosis for renal transplantation

Renal transplantation is the preferred treatment for most patients with end-stage renal disease. Postoperative vascular complications that significantly affect graft loss include stenosis and renal artery thrombosis. Our transplant team has performed 1635 procedures since 1975. Since December 2003, we have performed a corner-saving technique for the renal artery anastomoses in 183 recipients. In this study, we retrospectively analyzed the outcome data from these procedures in 43 women and 140 men of overall mean age of 31.6 years (range, 7-66 years). Graft tissue was obtained from deceased donors in 47 and from living donors in 136 recipients. The mean age of the donors was 39.8 years (range, 6-67 years). The graft renal arteries were spatulated from the posterior walls of the renal artery to provide wide anastomoses. Using this technique, a renal artery stenosis occurred at 5 months after renal transplantation in 1 recipient (0.54%). It was treated successfully with balloon angioplasty and placement of an intraluminal stent. We did not encounter any instances of renal artery thrombosis during a mean follow-up of 20.6 +/- 11.6 months (range, 1-40 months). During follow-up, 5 recipients died, and 9 returned to hemodialysis. At the time of this writing, the remaining 169 recipients (92.3%) are alive with good graft function. In conclusion, owing to its low complication rate, we believe our new corner-saving technique to be the safest way to perform a renal artery anastomosis.     

Transplant Renal Artery Stenosis: Underrecognized,Not So Rare,but Curable Complication

Transplant renal artery stenosis (TRAS) constitutes 75% of all vascular complications in kidney transplant recipients, being a significant source of graft dysfunction and loss. TRAS is a heterogeneous disease with different risk factors and causes. The incidence differs greatly, and it is likely it will increase because of the aging population of potential recipients and donors of renal grafts and the expanding use of extended-criteria donors. Prompt diagnosis and treatment of TRAS can prevent irreversible allograft dysfunction and loss. Current evidence of risk factors, diagnostic challenges, and therapeutic options are presented in this short review.     

Renal Vein Stenosis With Transudative Ascites From Graft After Renal Transplantation With Good Response After Percutaneous Stent Placement

Ascites sometimes occurs as a result of technical complications of transplant surgery or other medical reasons, including hepatic, cardiac, or oncologic pathology. Renal vein stenosis after renal transplant resulting in transudative ascites is rare; thus there are few if any data on such cases. Stent implantation seems to be a safe and elective approach to treatment of this rare condition. We present the case of a 22-year-old woman in whom massive ascites developed 33 months after renal transplantation. After the analysis of the ascites fluid and exclusion of transplant artery stenosis, graft rejection, infection, portal hypertension, and other possible etiologies, the final diagnosis of graft renal vein stenosis with transudative ascites derived from the graft was made based on imaging studies, including Doppler ultrasonography and computed tomography. The patient underwent angiographic stent placement, and the ascites markedly improved after the procedure. Renal vein stenosis complicated with ascites after renal transplantation is highly unusual; the patient's response to angiographic stent placement was beneficial, with satisfactory resolution of the blockage and ascites.     

Renal allograft rupture caused by acute tubular necrosis

Renal allograft rupture is a rare but potentially lethal complication of kidney transplantation. A renal allograft recipient receiving quadruple immunosuppressive therapy developed a spontaneous allograft rupture 13 days after kidney transplantation. Warm ischaemia time during the transplant was 80 minutes. The ruptured kidney graft could not be salvaged because of the patient's haemodynamic instability. The histopathological examination showed interstitial oedema with severe acute tubular necrosis with no signs of acute rejection. The most common causes of renal graft rupture are acute rejection and vein thrombosis, while acute tubular necrosis may only rarely be responsible for this complication. Renal graft rupture may be the result of interstitial damage attributed both to the prolonged warm ischaemia time during the transplant and to post-transplant acute tubular necrosis in the absence of graft rejection. In those patients whose haemodynamic status cannot be stabilized by appropriate aggressive haemodynamic support therapy, graft nephrectomy should be considered the only definitive treatment.     

Renal vein reconstruction with interposition allografts in cadaveric renal transplantation

The short or injured renal vein in cadaveric transplantation is a surgical challenge. Over a 2-year period, we have performed ex vivo renal vein lengthening with an interposition vascular allograft in 17 recipients of cadaveric kidneys. Indications for renal vein extension allografts were a short right renal vein (N=12), procurement injury to the vein (N=4), and double renal vein (N=1). In six cases (35.3%), ex vivo renal artery reconstruction was performed in combination with the venous repair. Our preferred approach is to employ allograft material in ex vivo reconstruction under cold storage conditions. Bench surgery ranged from 10 to 30 min, and the mean in situ anastomosis time was 20 min. The mean length of renal vein prior to reconstruction was 12 mm, and the mean length of venous interposition allograft after revascularization was 27 mm. There were no episodes of vascular thrombosis or primary nonfunction. Three patients (17.6%) required postoperative hemodialysis for acute tubular necrosis, which was subsequently resolved. The mean serum creatinine at 1 month post-transplant was 1.7 mg/dl. These preliminary results suggest that ex vivo renal vein reconstruction with an interposition allograft is a safe and effective modality which should be added to the transplant surgeon's armamentarium in select cases.     

Vascular complication and Doppler ultrasonographic finding after renal transplantation

OBJECTIVES: Vascular complications are common after renal transplantation. In this study we correlated Doppler sonographic indices and transplant kidney function. METHODS: We reviewed data on 244 renal transplant patients. Doppler ultrasonographic evaluation was performed during the first 2 weeks after renal transplantation. We determined resistive index (RI) and pulsatility index (PI) in the interlobar arteries and thrombosis of renal and lower limb veins. Serum creatinine (Cr) and cyclosporine levels were evaluated prior to sonographic assessment. RESULTS: The mean age of the 142 male and 102 female patients was 36.31 +/- 3.30 years. Prevalence of real artery stenosis was 9.5%. In these patients the mean serum Cr level (2.21 +/- 1.83 mg/dL) was significantly higher than among patients with patent renovascular tributary (1.49 +/- 1.00 mg/dL; P=.03). RI and PI were also significantly correlated with serum Cr(P=.05 and .001, respectively). There was no relationship between cyclosporine level or panel-reactive antibody with RI and PI. Retransplant patients showed higher RI than first renal allograft recipients (0.72 +/- 0.16 vs 0.63 +/- 0.11; P=.006). Serum Cr level was higher among renal allograft recipients with Doppler evidence of thrombosis of the lower limb veins (3.1 +/- 0.98 mg/dL versus 1.56 +/- 1.13 mg/dL; P=.04). CONCLUSIONS: RI and PI are two valuable Doppler ultrasonographic markers to determine renal allograft function and related vascular complications.     

Endovascular interventions for managing vascular complication of renal transplantation

Renal transplantation is a well-established treatment for patients with end-stage renal disease. Although the procedure is commonly undertaken with a high rate of initial technical success, a low but significant risk of vascular complications can develop and ultimately threaten the transplanted kidney. Complications include transplant renal artery stenosis, extraparenchymal and intraparenchymal pseudoaneurysm and arteriovenous fistula formation, and stenosis of native iliac arteries due to aortoiliac occlusive disease. Historically, open surgical correction of these complications has been associated with high morbidity and the risk of graft loss. Endovascular approaches are better tolerated by renal transplantation patients and are used increasingly for management of vascular complications associated with kidney transplantation. We review the contemporary diagnosis and treatment of these complications using endovascular techniques.     

Screening for transplant renal artery stenosis in hypertensive recipients using digital subtraction angiography

Digital subtraction angiography was used in 10 renal allograft recipients with sustained hypertension after transplantation to detect transplant renal artery stenosis. Recipients with end-to-end vascular anastomoses were visualized adequately in the anteroposterior projection. Two cases of transplant renal artery stenosis were identified by digital subtraction angiography and then verified by catheter angiography. Patients with end-to-side vascular anastomoses may require additional oblique projections. Digital subtraction angiography is a safe, noninvasive and cost-effective screening procedure to diagnose transplant renal artery stenosis in most recipients. Catheter angiography can be applied more selectively to those recipients with stenosis observed by digital subtraction angiography or when more detailed imaging is required.     

Vascular complications of renal transplantation

From January, 1963, to May, 1979, 600 renal transplants were performed at the Cleveland Clinic. There were 21 vascular complications in this series (3.5 per cent). Arterial complications included renal artery thrombosis in 5 patients, renal artery stenosis in 9 patients, and anastomotic hemorrhage in 2 patients. Venous complications included renal vein thrombosis in 2 patients and hemorrhage in 3 patients. Although vascular complications led directly to graft loss in 10 patients, only 1 resulted in patient death.     

Left renal vein ligation for large splenorenal shunt during liver transplantation

Adequate hepatopetal portal vein blood flow is obligatory to ensure proper liver function after liver transplantation. Large collateral veins as shunts impair portal vein flow and even cause hepatofugal blood flow and portal steal syndrome. In particular, splenorenal shunts in liver transplant recipients can lead to allograft dysfunction and possible allograft loss or hepatic encephalopathy. Restoration of portal flow through left renal vein ligation (LRVL) is a treatment option, which is much easier compared to splenectomy, renoportal anastomosis and shunt closure, but bears the risk of moderate and temporary impairment of renal function. In addition, a patent portal vein is mandatory for LRVL. However, although LRVL has been reported to be an effective, safe and easy method to control portacaval shunts and increase hepatopetal flow in some studies, indications and safety are still not clear. In this review, we summarize existing studies on LRVL during liver transplantation.     

Allograft renal vascular thrombosis--lack of increase with cyclosporine immunosuppression

Several recent reports have demonstrated an increased incidence of allograft renal vascular thrombosis in patients receiving cyclosporine alone or as part of multiple drug regimens when compared with patients receiving azathioprine (AZA) and prednisone (P). To determine whether CsA therapy is indeed a risk factor for renal artery or vein thrombosis, we examined the incidence of these complications in 224 adult renal allograft recipients who were prospectively randomized and stratified by risk to treatment with either CsA-P (n = 117) or AZA-P-antilymphocyte globulin (n = 107) between September 1980 and October 1983, and in 452 adult and 87 pediatric patients on triple (AZA-P-CsA) or quadruple (AZA-P-CsA-ALG) therapy protocols between July 1984 and November 1987. In the randomized trial, one of 107 AZA-P-ALG patients (0.9%) and two of 117 CsA-P patients (1.7%) developed renal vein thrombosis (P = 0.94), and there were no cases of arterial thrombosis. Though CsA levels were elevated in one of the two CsA-treated patients at the time of their events, and both these patients demonstrated other predisposing factors for thrombosis. In the triple/quadruple therapy era, there were no cases of renal vein thrombosis, and the only case of renal artery thrombosis occurred in a pediatric recipient who was not receiving CsA at the time. These data, when taken together with a critical review of the conflicting literature, strongly suggest that factors other than immunosuppression with CsA, including surgical technique, allograft rejection, use of multiple artery and/or pediatric donor kidneys, and postoperative hypotension, are important in the pathogenesis of allograft renal vascular thrombosis. It seems possible, however, that high initial dosing of CsA might trigger this complication in the early posttransplant period when other predisposing factors are present.     

Successful renal transplantation in the right iliac fossa 2 years after serious deep venous thrombosis in a patient with systemic lupus erythematosus

Deep venous thrombosis (DVT) possibly occurs in the perioperative period, and induces serious complications such as a pulmonary embolism. On the other hand, allograft renal vein thrombosis leads to a high incidence of graft loss. We experienced a case in which a serious DVT occurred prior to renal transplantation; however, a successful renal transplantation in the right iliac fossa was performed after 2 years of anticoagulant therapy. It is suggested that the external iliac vein even after suffering from DVT can be anastomosed to an allograft vein successfully, when enough blood fl ow or a lower venous pressure is confirmed. However, one should be aware of the risk factors and the adequate management of thrombosis in renal transplantation because of the serious complications of DVT and the poor prognosis of allograft vein thrombosis.     

Analysis of vascular complications after renal transplantation

Purpose

Despite medical and surgical advances, vascular complications remain common after renal transplant, occurring among 3%-15% of patients. These complications may compromise graft function. This study sought to evaluate the frequency and management of vascular complications after renal transplant.

Materials and Methods

We retrospectively analyzed the 1843 transplantations performed at 2 centers by our team since November 1975. The 1349 male and 494 female patients had an overall mean age of 31.5 ± 11.2 years; (range, 3-66). Grafts were obtained from a living-related donor in 1406 (76.29%) or a deceased donor in the remaining 437 (23.71%). The mean donor age was 40.7 ± 13.7 years (range, 2-76). Of 1843 transplants, multiple vascular anastomoses were performed in 155 cases (8.4%), including 130 involving renal arteries and 25 renal veins.

Results

Forty-seven vascular complications (2.55%) were observed in 43 procedures (2.33%), most frequently renal artery stenosis (n = 14). It was followed by allograft renal artery kinking (n = 7), renal vein kinking (n = 7), renal artery thrombosis (n = 5), renal vein laceration (n = 4), renal artery laceration (n = 3), renal vein thrombosis (n = 2), renal artery disruption (n = 2), renal and iliac vein obstructions owing to pressure from a lymphocele (n = 1), renal artery and vein obstruction owing to pressure from a hematoma (n = 1), or an arteriovenous fistula after percutaneous graft biopsy (n = 1). Fifteen of these 47 complications were treated by interventional radiologic procedures.

Conclusion

The vascular complication rates in our patients were somewhat lower than those reported in the literature. A thorough understanding of how complications impair allograft function and survival is essential for adequate treatment. Interventional radiology is invaluable in the postoperative management of transplant-related complications.