Histidine‐Tryptophan‐Ketoglutarate for Pancreas Allograft Preservation: The Indiana University Experience

Abstract

Histidine-tryptophan-ketoglutarate solution (HTK) has been scrutinized for use in pancreas transplantation.A recent case series and a United Network for Organ Sharing data base review have suggested an increased incidence of allograft pancreatitis and graft loss with HTK compared to the University of Wisconsin solution (UW). Conversely, a recent randomized, controlled study failed to show any significant difference between HTK and UW for pancreas allograft preservation. This study was a retrospective review of all pancreas transplants performed at Indiana University between 2003 and 2009 comparing preservation with HTK or UW. Data included recipient and donor demographics, 7-day, 90-day and 1-year graft survival, peak 30-day serum amylase and lipase, HbA1c and C-peptide levels. Of the 308 pancreas transplants, 84% used HTK and 16% UW. There were more SPK compared to pancreas after kidney and pancreas transplant alone in the HTK group. Donor and recipient demographics were similar. There was no significant difference in 7-day, 90-day or 1-year graft survival, 30-day peak serum amylase and lipase, HbA1c or C-peptide. No clinically significant difference between HTK and UW for pancreas allograft preservation was identified. Specifically, in the context of low-to-moderate flush volume and short cold ischemia time (≤10 h), no increased incidence of allograft pancreatitis or graft loss was observed.

Using HTK for Prolonged Pancreas Preservation Prior to Human Islet Isolation

“…The reasons for replacement of UWS by HTK can be partially related to economic considerations [25]. In agreement with numerous studies evaluating the effect of HTK on pancreas [2,4,6,7,26], kidney [27], and liver transplantation [3], the only islet studies that have been performed so far did not find any significant difference between HTK and UWS with regard to isolation and post-transplant outcome [12,13,28]. In contrast, several multicenter studies provided opposite results for pancreas [8], kidney [10,24], and liver transplantation [11].…”

“…Due to the low viscosity of HTK, some authors observed an enhanced clearance of the perfused organs compared with UWS, particularly when small vessels were used for flushing [4]. In this context, it has been speculated whether the adverse effect of HTK on graft survival is related to pancreas edema caused by using high perfusion volumes as recommended by the producer [4,7,26]. Although we did not observe obvious edema during gross inspection of the organ, the dry-to-wet weight ratio clearly indicated that the significantly higher weight of HTK-perfused pancreata was caused by a higher fluid content in the tissue.…”

“…Furthermore, the lower viscosity of HTK seems to facilitate enhanced clearance of organs from blood compared with UWS [4]. In pancreas transplantation, the majority of the current reports did not reveal any significant differences between UWS and HTK with respect to graft survival [2,[5][6][7]. Nevertheless, two studies analyzing more than 4000 pancreas transplants have raised concerns about the efficiency of HTK, particularly if utilized for prolonged cold ischemia time (CIT) [8,9].…”

Outcomes of Pancreas Allografts Procured Simultaneously With an Isolated Intestine Allograft

“…The distal stumps of the SMA and SMV on the pancreas allograft side should be carefully controlled and oversewn or tagged with a fine nylon suture. Most simultaneous intestine and pancreas procurements performed for the institutional analysis study group used histidine-trytophan-ketoglutarate as the preservation solution for both in situ flush and storage as described elsewhere (8,9).…”

Retrieval of the pancreas allograft for whole‐organ transplantation

“…Using clearance of the portal venous effluent to determine volume of flush ex vivo is not advisable for the pancreas because it is difficult to exsanguinate the spleen. In the last decade, it is become increasingly apparent that minimizing cold ischemia (<12 h) is one of the single most important predictors of success in pancreas transplantation irrespective of donor quality or method of preservation (36)(37)(38)(39)(40).…”