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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT Table of Contents   
Year : 2006  |  Volume : 17  |  Issue : 1  |  Page : 58-61
Treatment of Tacrolimus-associated thrombotic microangiopathy in renal transplant recipient with fresh frozen plasma: A case report


Unit of Nephrology, Military Hospital of Tunis, Tunisia

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   Abstract 

Thrombotic microangiopathy (TMA) is a rare serious adverse reaction of calcineurin inhibitors, tacrolimus and cyclosporin. We report a case of a young male renal transplant recipient treated with tacrolimus, who developed TMA. Treatment included discontinuation of tacrolimus, increasing the dose of mycophenolate mofetil and infusion of fresh-frozen plasma. This was followed by normalization of renal function and dis­appearance of proteinuria. The remission has been sustained after a follow-up of nine months.

Keywords: Renal transplantation, Calcineurin inhibitors, Thrombotic microangiopathy, Tacrolimus

How to cite this article:
Kais H, Nourredine C, Raoudha B, Emira C, Tarek S, Fehmi S, Ezzedine B, Jalel H, Jamel M. Treatment of Tacrolimus-associated thrombotic microangiopathy in renal transplant recipient with fresh frozen plasma: A case report. Saudi J Kidney Dis Transpl 2006;17:58-61

How to cite this URL:
Kais H, Nourredine C, Raoudha B, Emira C, Tarek S, Fehmi S, Ezzedine B, Jalel H, Jamel M. Treatment of Tacrolimus-associated thrombotic microangiopathy in renal transplant recipient with fresh frozen plasma: A case report. Saudi J Kidney Dis Transpl [serial online] 2006 [cited 2020 Feb 19];17:58-61. Available from: http://www.sjkdt.org/text.asp?2006/17/1/58/32446

   Introduction Top


Thrombotic microangiopathy (TMA) is a well-recognized complication in renal trans­plant recipients, affecting 3 to 14 % [1],[2] of patients treated with calcineurin inhibitors. The risk of TMA is probably higher with cyclosporin than tacrolimus. [3]

The clinical manifestations of post­transplant TMA are variable. Frequently, TMA manifests as the hemolytic uremic syndrome (HUS) with renal failure, hemo­lytic anemia, schizocytes, and thrombo­cytopenia.[4] Rarely, TMA may be localized to the renal graft and present with impairment of renal function or delayed graft function, with few or no systemic manifestations of HUS.[5]

We report a case of a young man with localized TMA who presented with only elevated serum creatinine (Scr) and pro­teinuria.


   Case Report Top


A 14-year-old caucasian man presented with a history of typical HUS diagnosed at 10 years of age. After two years on hemodialysis, he received a living donor renal transplant in January 2003. After initial induction with antithymocyte globulin (ATG) and methylprednisolone for five days, post-transplant immunosup­pression consisted of prednisone at 10 mg daily, mycophenolate mofetil at 1 gm/day and tacrolimus at 5 mg/day (0.15 mg/kg/ day). Trough levels of tacrolimus (measu­red by enzyme immunoassay) were kept between 10 and 15 ng/ml for the two first months, followed subsequently by levels between 5 and 10 ng/ml.

Clinical improvement was obtained shortly after transplantation (Tx) and was characterized by a baseline serum creatinine (Scr) of 67 µmol/L.

One year and two months after Tx, the renal function deteriorated with Scr level at 124 µmol/L and he developed proteinuria of 1.35 grams per 24 hours. He was hospi­talized and at admission; the physical exa­mination was unremarkable. Laboratory investigations showed the following levels: white blood cell count (WBC) 3500/mm 3 , hematocrit 37 %, hemoglobin 12.1 g/dl, platelets 236,000/ mm 3 , blood urea nitrogen (BUN) 9.8 mmol/l, blood sugar 4.6 mmol/l, sodium 136 mmol/l, potassium 3.6 mmol/l and lactate dehydrogenase 340 U. Complement levels were within normal limits. Repeated peripheral smears showed no schizocytes. Tests for lupus anticoagulant and anticardiolipin antibodies were negative. Tacrolimus trough level was 11.1 ng/ml.

Renal graft biopsy showed features of thrombotic microangiopathy with glomerular thrombosis and acute thrombosis involving the arterioles [Figure - 1].

Treatment included discontinuation of tacrolimus, increase in the dose of myco­phenolate mofetil to 1500 mg/day, intro­duction of ramipril (2.5 g/day) and daily infusion of fresh-frozen plasma (30 ml/kg/day) for ten days.

One month after treatment, the Scr level was 90 µmol/l and protein excretion was in the normal range, and both have remained so for the last six months.


   Discussion Top


In all forms of TMA, the pathophysiology includes vascular endothelial cell activation and damage by white blood cell activation and platelet aggregation. Calcineurin inhi­bitors, particularly cyclosporine A [6] but also tacrolimus [7] possibly damage endothelial cells via the inhibition of prostacyclin (PGI2) and act to increase platelet aggregation.

In our patient, after confirmation of TMA, the priority was to distinguish between recurrence of HUS and tacrolimus-asso­ciated TMA. The other bacterial or viral causes were excluded. We opted for the second possibility for several reasons.

First, typical HUS does not generally recur in the transplanted kidney.[8]

Second, recurrent HUS manifests commonly as systemic TMA and occurs earlier after TX [9]

Our patient presented with localized TMA, with only worsening renal function and proteinuria, fourteen months after trans­plantation (Tx). This presentation was in favor of tacrolimus-associated TMA.

Among risk factors described in literature,[9] like pre-transplantation HUS, anticardio­lipin antibodies, vascular rejection, cytomega­lovirus or parvovirus B19 infection, only the factor V Leiden mutation is mentioned as a possible risk factor for Cyclosporin­associated TMA after renal Tx.[10] The search for this factor has not been done in our patient.

We preferred withdrawal of tacrolimus without switching the patient to cyclosporin due to fear of recurrence.[11] Mycophenolate mofetil, considered as an alternative therapy [12] was increased to 1.5 g/day. Yango et al have reported a case of successful treatment of tacrolimus-associated TMA with sirolimus conversion and plasma exchange.[13] Conve­rsely, Barone et al reported on a transplant patient on solitary immunosuppression with sirolimus who developed biopsy-proven TMA.[14]

Our patient did not undergo plasma exchange and treatment was only with fresh frozen plasma administration. Schwimmer et al suggest that patients with localized TMA do not require plasma exchange for graft salvage. [9] In his study, 89 % of patients with localized TMA did not require plasma exchange, and none of the patients had early TMA-related graft loss.

 
   References Top

1.Zent R, Katz A, Quaggin S, et al. Thrombotic microangiopathy in renal transplant recipients treated with cyclosporin A. Clin Nephrol 1997; 47(3): 181-6.  Back to cited text no. 1    
2.Young BA, Marsh CL, Alpers CE, Davis CL. Cyclosporine-associated thrombotic microangiopathy/hemolytic uremic syn­drome following kidney and kidney­pancreas transplantation. Am J Kidney Dis 1996 ; 28(4): 561-1.  Back to cited text no. 2    
3.Gomez-Navarro B, Contreras H, Ramos F, et al. Two forms of thrombotic micro­angiopathy in renal transplant recipients. Transplantation 2004; 78(2):294-5.  Back to cited text no. 3    
4.Bren AF, Kandus A, Buturovic J, et al. Cyclosporine-related hemolytic-uremic syndrome in kidney graft recipients: clinical and histomorphologic evalu-ation. Transplant Proc 1998 ; 30(4): 1201-3.  Back to cited text no. 4    
5.Zarifian A, Meleg-Smith S, O'donovan R, Tesi RJ, Batuman V. Cyclosporine­associated thrombotic microangiopathy in renal allografts, Kidney Int 1999; 55(6): 2457-66.  Back to cited text no. 5    
6.Giroux L, Smeesters C, Corman J, et al. Hemolytic uremic syndrome in renal allografted patients treated with cyclosporine. Can J Physiol Pharmacol 1987 ; 65(6): 1125-31.  Back to cited text no. 6    
7.Burke GW, Ciancio G, Cirocco R, et al. Microangiopathy in kidney and simul­taneous pancreas/kidney recipients treated with tacrolimus: evidence of endothelin and cytokine involvement. Transplantation 1999; 68(9): 1336-42.  Back to cited text no. 7    
8.Bassani CE, Ferraris J, Gianantonio CA, Ruiz S, Ramirez J. Renal transplantation in patients with classical haemolytic­uraemic syndrome. Pediatr Nephrol 1991; 5(5): 607-11.  Back to cited text no. 8    
9.Schwimmer J, Nadasdy TA, Spitalnik PF, Kaplan KL, Zand MS. De novo thrombotic microangiopathy in renal transplant recipients: a comparison of hemolytic uremic syndrome with localized renal thrombotic microangiopathy. Am J Kidney Dis 2003; 41(2): 471-9.  Back to cited text no. 9    
10.Van den Berg-Wolf MG, Kootte AM, Weening JJ, Paul LC. Recurrent hemolytic uremic syndrome in a renal transplant recipient and review of the Leiden experience. Transplantation 1988; 45(1): 248-51.  Back to cited text no. 10    
11.Abraham KA, Little MA, Dorman AM, Walshe JJ. Hemolytic-uremic syndrome in association with both cyclosporine and tacrolimus. Transpl Int 2000; 13(6): 443-7.  Back to cited text no. 11    
12.Said T, al-Mousawi M, Samhan M, Lao M. Cyclosporin conversion to CellCept in a cadaveric renal allograft recipient with hemolytic uremic syndrome. Transplant Proc 1999; 31(8): 3295-7.  Back to cited text no. 12    
13.Yango A, Morrissey P, Monaco A, Butera J, Gohh RY. Successful treatment of tacrolimus-associated thrombotic micro­angiopathy with sirolimus conversion and plasma exchange. Clin Nephrol 2002; 58(1): 77-8.  Back to cited text no. 13    
14.Barone GW, Gurley BJ, Abul-Ezz SR, Gokden N. Sirolimus-induced thrombotic microangiopathy in a renal transplant recipient. Am J Kidney Dis 2003; 42(1): 202-6.  Back to cited text no. 14    

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Correspondence Address:
Harzallah Kais
Unit of Nephrology Military Hospital of Tunis 1008 Tunis
Tunisia
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PMID: 17297539

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    Abstract
    Introduction
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