LETTERS TO THE EDITOR

 

Late venous thrombosis of renal allograft: two cases with different treatment and outcome

Trombosis venosa tardía del injerto renal: dos casos con tratamiento y seguimiento diferentes

 

 

Correspondence

 

 

Dear Editor:

Renal transplant (RT) patients have a higher incidence of thrombotic events and an increased risk of recurrence after the with drawal of anticoagulation. Thrombosis of the allograft vein is a well-described complication of renal transplantation. It can occur early after transplant, related to surgical technical complications or many years post-transplant associated to multiple inciting factors. The treatment includes surgery, thrombolytics and anticoagulation.

We present two cases of late allograft venous thrombosis with different treatments and outcome: conventional hipocoagulation leaded to renal failure but surgical thrombectomy allowedpatient improvement and renal function recovery. Based onthe cases, a review of the literature about pathophysiology, clinical presentation, diagnosis and treatment options of late venous thrombosis of renal allograft was made.

RT patients have a higher incidence (ranging 0.6-25%) of thrombotic events^1,2. Thrombosis of the allograft vein is a well-described early complication³, usually associated with acute rejection or surgical complications⁴. The typical presentation is that of a sudden painful and swollen allograft, haematuria and oliguria with deterioration of graft function^4,5. Partial vein thrombosis presents as a late event, with chronic oedema and progressive deterioration of renal function⁶.

Diagnosis can be made by Doppler ultrasound, computed tomography (CT) or magnetic resonance venogram⁷ and the treatment includes surgery, thrombolytics and anticoagulants⁷. The authors present two cases of late allograft venous thrombosis with different treatments and outcome.

 

Clinical cases

Case 1

A 63-year-old man, with chronic renal failure (CRF) secondary to adult polycystic kidney disease (APKD), was submitted to RT in 1988 and treated with cyclosporine (CsA), azathioprine (AZA) and prednisolone (P). Nineteen years after RT, serum creatinine (Cr) increased to 2.5 mg/dl and nephrotic proteinuria was documented. In 2007, chronic allograft nephropathy (CAN) was confirmed. One year latter, a rectal adenoma was diagnosed and after four months (on March 2009), he had acute diverticulitis complicated by peritonitis and needed surgery.

On July 2009, he was admitted with painful oedema of the right leg with one week of evolution. Doppler revealed femoral vein thrombosis and partial thrombosis of allograft vein, iliac and inferior vena cava (IVC). Renal function had declined (Cr: 5.84 mg/dl) and serum albumin was reduced (2.68 g/dL). Pulmonary embolism was excluded and anticoagulation with low molecular weight heparin (LMWH) was started, followed by accenocumarol. Renal function deteriorated and one week latter he started haemodialysis. The study for other neoplasms was negative. Three months latter, he is asymptomatic but remains on haemodialysis.

Case 2

A 58-year-old man, with CRF secondary to APKD, was submitted to RT in 1993. He was treated with CsA, AZA and P and renal function stabilized on Cr: 1.8 mg/dl, without proteinuria. Posttransplant erytrocytosis was documented in 1996 and treated with phlebotomies.

On May 2009, he was admitted with thrombosis of right popliteal vein. He had erytrocytosis (Hb: 18.3g/dL) and deterioration of renal function (Cr: 2.2 mg/dl). Anticoagulant treatment was maintained for 6 weeks, with improvement.

Three months latter, he was readmitted with oedema of right leg with two days of evolution. He maintained erytrocytosis (Hb: 16.9 g/dL) and allograft dysfunction (Cr: 2.02 mg/dl). Imagiological studies revealed thrombosis of femoral vein with extension to allograft and iliac veins, without involvement of IVC (figure 1). No neoplasic disease was found.

Figure 1. Thrombosis of renal graft vein.

 

He was treated with heparin without improvement, and started haemodialysis on the 3^rd day. Surgical thrombectomy was preformed and, one week latter, renal function recovered (to Cr: 1.8 mg/dl). He was discharged under oral anticoagulation and two months latter, he is asymptomatic with stable renal function (Cr: 1.79 mg/dl).

 

Discussion

Early allograft venous thrombosis accounts for one third of all graft losses within the first three postttransplant months⁵. Thrombosis occuring several months after RT is rare⁸ and is associated to inciting factors^5,7. RT patients have persistent hypercoagulable state that may play a role in latter thrombotic events (TE)². Clotting activation ismultifactorial, with classic risk factors associated to specific ones related to RT^1-4.

Allograft vein thrombosis is more frequent with some therapies, particularly with OKT3 and high doses of steroids^4,9. CsA role remains controversial^5,9. Our patients were treated with low doses of immunosuppression and is unlikely that therapy alone caused thrombosis.

Recurrent or de novo glomerulonephritis with proteinuria superior to 2 g/day¹⁰ (even without nephrotic syndrome) generates hypercoagulable states^1,4,7 and neoplasms increase the risk of thromboembolism by nearly five times in RT patients⁷.

Late renal vein thrombosis (RVT) was described following surgery, related to immobilization or hypovolemia, and associated with compression of the allograft vein^4,8. The first patient had nephrotic proteinuria, a neoplasic lesion and was recovering from surgery with prolonged immobilization. Either polycystic kidneys or adhesions could compress allograft vein and act as predisposing factors.

Posttransplant erythrocytosis affects 10-15% of RT recipients¹¹ and was pointed as the inciting factorfor thrombosis^2,5 in the second patient.

Few weeks after the first episode, we confirmed recurrence of venous thrombosis with extension to allograft vein. After anticoagulants withdrawal, the risk of TE recurrence is near 48% in RT recipients³, which is 10 times higher than in normal population^2,3.

The treatment of RVT includes anticoagulants, thrombolytics and thrombectomy. Most cases of early post-surgical RVT are treated with thrombectomy, but in the late posttransplant it has low success rate¹². Some authors advice surgical thrombectomy only when a surgical cause is identified and there aren't adhesions that make surgery unsafe⁷. The first 10-14 posttransplant days are considered the timing for an open approach. Beyond that time, a percutaneous approach is recommended⁷.

Mechanical thrombectomy can lead to pulmonary embolism (PE)¹³, specially if the thrombus has extension to the IVC, as in our case 1.

Alternative treatments for late RVT include anticoagulation with heparin/LMWH or drug-induced thrombolysis⁷. Thrombolytic agents have proved better results, with complete lysis in 40-60% of patients, compared to 10% of those treated with heparin¹⁴.

Thrombolytics are more efficient when thrombi are less than 5 days-old¹⁵, but the most effective agent and the optimal duration of treatment remain uncertain⁷.

A combined approach of percutaneous mechanical and chemical thrombectomy has been used^7,13. It is advocated in RVT beyond the second week posttransplantation or when prolonged thrombolysis is contraindicated^7,13.

In our first case, post-peritonitis adhesions made surgical approach difficult, the organized thrombus reduced thrombolysis efficacy and the high probability of irreversible damage (in a graft with CAN) contributed to the decision for a conservative treatment. In our second patient, thrombectomy was really efficient, allowingallograft recovery.

In conclusion, renal vein thrombosis in late pos-transplant period is not an indication to graftectomy neither a definitive evidence of graft failure. Therapies such as thrombolysis or thrombectomy must be considered, as they may allow better outcomes.

 

C. Freitas¹, M. Fructuso¹, M. J. Rocha¹, M. Almeida², S. Pedroso²,
I.S. Martins², L. Dias², A. Castro Henriques², R.Almeida² y A. Cabrita^1
1Department of Nephrology. Hospital de Santo António. Porto (Portugal)
²Department of Transplantation. Hospital de Santo António. Porto (Portugal)

 

Referencias Bibliográficas

1. Biesenbach G, Janko O, Hubmann R, Gross C, Brucke P. The incidence of thrombovenous and thromboembolic complications in kidney transplant patients with recurrent glomerulonephritis is dependent on the occurrence of severe proteinuria. Clin Nephrol 2000;54:382-7.        [ Links ]

2. Poli D, Zanazi M, Antonucci E, Bertoni E, Salvadori M, Abbate R, et al. Renal transplant recipents are at high rik for both symptomatic and asymptomatic deep vein thrombosis. J Thromb Haemost 2006;4:988-92.        [ Links ]

3. Zanazzi M, Poli D, Antonucci E, et al. Venous thromboembolism in renal transplant recipients: high rate of recurrence. Transplant Proc 2005;37:2493-4.        [ Links ]

4. Bakir N, Sluiter WJ, Ploeg RJ, Van Son WJ, Tegzess AM. Primary renal graft thrombosis. Nephrol Dial Transplant 1996;11:140-7.        [ Links ]

5. Lim WH, Van Schie G, Warr K. Chronic renal vein thrombosis in a renal allograft. Nephrology 2003;8:248-50.        [ Links ]

6. Herrera RO, Benítez AM, Abad HJM. Renal vein partial thrombosis in 3 recipients of kidney transplantation. Arch Esp Urol 2000;53:45-8.        [ Links ]

7. Melamed MJ, Kim HS, Jaar BG, Molmenti E, Atta MG, Samaniego MD. Combined percutaneous mechanical and chemical thrombectomy for renal vein thrombosis in kidney transplant recipients. Am J Transplant 2005;5:621-6.        [ Links ]

8. Du Buf-Vereijken PWG, Hilbrands LB, Wetzels JFM. Partial renal vein thrombosis in a kidney transplant: management by streptokinase and heparin. Nephrol Dial Transplant 1998;13:499-502.        [ Links ]

9. Bedani PL, Galeotti R, Mugnani G, et al. Successful local arterial urokinase infusion to reverse late postoperative venous thrombosis of a renal graft. Nephrol Dial Transplant 1999;14:2225-7.        [ Links ]

10. Carrasco A, Díaz C, Flores JC, Briones E, Otipka N. Late renal vein thrombosis associated with recurrence of membranous nephropathy in a renal allograft: a case report. Transplant Proc 2008;40:3259-60.        [ Links ]

11. Vlahakos DV, Marathias KP, Agroyannis B, Madias NE. Posttransplant erythrocytosis. Kidney Int 2003;63:1187-94.        [ Links ]

12. Jordan ML, Cook GT, Cardella CJ. Ten years of experience with vascular complications in renal transplantation. J Urol 1982;128:689-92.        [ Links ]

13. Kim HS, Fine DM, Atta MG. Catheter-directed thrombectomy and thrombolysis for acute renal vein thrombosis. J Vasc Interv Radiol 2006;17:815-22.        [ Links ]

14. Gurewich V. Thrombolytic treatment of venous thromboembolism. Vasc Surg 1977;11:341-3.        [ Links ]

15. Jeff MR, Charles HC, Jaime T, et al. Selective low-dose streptokinase infusion in the treatment of acute transplant renal vein thrombosis. Cardiovasc Intervent Radiol 1986;9:86-9.        [ Links ]

 

 

Correspondence:
Cristina Freitas,
Department of Nephrology,
Hospital de Santo António,
Largo Profesor Abel Salazar,
4099-001, Porto, Portugal
E-mail: crislmf@yahoo.com.br