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Vol. 30. Issue. 3.May 2010
Pages 271-380
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Acute rejection of pancreatic grafts
Rechazo agudo en el injerto pancreático
Ana Guitián Penaa, Ángel Alonso Hernándezb
a Servicio de Nefrología, Complejo Hospitalario Universitario de A Coruña, La Coruña, La Coruña, España,
b Servicio de Nefrología y Unidad de Trasplante Renal, Complejo Hospitalario Universitario de A Coruña, La Coruña, La Coruña, España,
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Dear Editor,  

 Simultaneous renal and pancreatic transplantation is the best treatment option for young patients (< 45 years) who have type 1 diabetes mellitus (DM) and advanced stages of diabetic nephropathy, in the absence of other cardiovascular risk factors, as long as the transplantation waiting time is not unreasonably prolonged.1  

 Due to the characteristics of this type of donors and recipients, patient and graft survival is similar to living donor transplant cases.2 The pancreatic graft in this case has a survival rate of around 70% five years after transplantation. We report a case of a 47-year-old man who underwent simultaneous pancreas and kidney transplantation and came in for follow-up; he was asymptomatic except for mild discomfort in the area of the pancreatic graft. He was sent from the outpatient clinic for admission in order to obtain laboratory data related to pancreatic injury. 

 His medical history included hypertension and type 1 DM with diabetic retinopathy and nephropathy; he had received Continuous Ambulatory Peritoneal Dialysis (CAPD) for 18 months. Ischaemic heart disease had been ruled out and he received pancreatic and kidney transplants 7.5 years ago, both of which are currently functional. 

 The donor was a 21-year-old man who died of multiple trauma, with the same blood group as the patient, and no HLA compatibility among those that were tested. The pancreas was transplanted with exocrine drainage into the duodenum. Both grafts were initially functional, the patient did not require insulin starting in the first 24 hours and plasma creatinine was 0.8mg/dl on the third day. Thymoglobulin induction was performed during the first 4 days after transplantation, and then suspended due to lymphopoenia and thrombocytopoenia. Tacrolimus was started, which, along with MMF and prednisone, became the patient’s maintenance immunosuppressive therapy. 

 On the current admission the patient has good blood glucose control and blood pressure. On physical examination, the patient had no pathological findings except for discomfort on palpation of the epigastric area. The main laboratory data obtained were: plasma creatinine 1mg/dl, amylase 440mg/dl, lipase 403 U and tacrolimus levels of 3.1ng/ml. Ultrasonography was performed which showed slight oedema of the pancreatic graft and resistive index (RI) within normal limits, without abnormalities in the renal graft. 

 The clinical symptoms were interpreted as being consistent with acute rejection of the pancreatic graft, probably related to low levels of the anti-calcineurin agent. In the first days after admission, the tacrolimus levels were adjusted to 10ng/ml and the patient was treated with 4 boluses of 6- methylprednisolone, with reduction but not normalisation of pancreatic enzymes. Treatment was initiated with thymoglobulin (3mg/kg) via a jugular catheter. This medication was poorly tolerated and the patient developed fever, myalgias, gastrointestinal intolerance, and general worsening, which improved with symptomatic treatment. The pancreatic enzyme levels normalised after three doses of thymoglobulin, and renal function remained stable. Prophylactic treatment with septrim and oral valganciclovir was started at the time of discharge. 

 Acute rejection is 1.5 to 2 times more common in combined pancreas- kidney transplantation than in simple renal transplantation. It also occurs later and is more often resistant to steroids.3 However, graft loss due to a pancreatic rejection is more uncommon in the case of combined transplantation than in either of the other two methods (pancreas after kidney and pancreas alone).4 Pancreatic rejection may or may not be associated with renal graft rejection and it can occur synchronously or asynchronously. Confirmation by renal biopsy is sufficient when it occurs simultaneously. 

 Pancreatic rejection initially occurs against acinar cells, such that the islets of Langerhans continue functioning at first. Thus, uncontrolled blood glucose is a late event in the course of acute pancreatic rejection, when more than 90% of the graft has been affected. In combined transplantation of the pancreas and kidney, renal graft rejection is more common and more serious than pancreatic rejection, and therefore monitoring of serum creatinine is usually used to detect rejection of both organs. However, up to 15% of cases of pancreatic rejection occur without any damage to the renal graft.5  

 In the case of enteric drainage, pancreatic function cannot be monitored via amylasuria, so it is important to pay attention to more nonspecific data, such as serum pancreatic amylase and lipase levels. Ultrasound-guided pancreatic biopsy does not require laparotomy, but it carries a 3 to 15% risk of non-diagnosis due to sampling failure.6 The diagnostic alternative is laparoscopic biopsy. Information provided by Doppler ultrasound or CT is often non-specific.  

Recipient risk factors have an impact on technical failure and patient and graft survival rates in bladder-drained pancreas transplants Gruessner RW; Dunn DL; Gruessner AC; Matas AJ; Najarian JS; Sutherland DE Transplantation 1994 Jun 15;57(11):1598-606.
Transplantation in the diabetic patient with advanced chronic kidney disease: a task force report. Gaston RS; Basadonna G; Cosio FG; Davis CL; Kasiske BL; Larsen J; Leichtman AB; Delmonico FL Am J Kidney Dis 2004 Sep;44(3):529-42. [Pubmed]
Simultaneous pancreas-kidney versus kidney-alone transplants in diabetics: increased risk of early cardiac death and acute rejection following pancreas transplants. Douzdjian V; Abecassis MM; Corry RJ; Hunsicker LG Clin Transplant 1994 Jun;8(3 Pt 1):246-51 [Pubmed]
Pancreas transplant outcomes for United States (US) and non-US cases as reported to the United Network for Organ Sharing (UNOS) and the International Pancreas Transplant Registry (IPTR) as of June 2004. Gruessner AC; Sutherland DE Clin Transplant 2005 Aug;19(4):433-55 [Pubmed]
Impact of acute rejection episodes on long-term graft survival following simultaneous kidney-pancreas transplantation. Reddy KS; Davies D; Ormond D; Tuteja S; Lucas BA; Johnston TD; Waid T; McKeown JW; Ranjan D Am J Transplant. 2003 Apr;3(4):439-44
Use of ultrasound and cystoscopically guided pancreatic allograft biopsies and transabdominal renal allograft biopsies: safety and efficacy in kidney-pancreas transplant recipients. Kuhr CS; Davis CL; Barr D; McVicar JP; Perkins JD; Bachi CE; Alpers CE; Marsh CL J Urol 1995 Feb;153(2):316-21
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