A preliminary report of the HTK randomized multicenter study comparing kidney graft preservation with HTK and EuroCollins solutions

The main goal of transplantation is to restore good renal function and to improve the quality of life of thousands of dialysis patients, something which can only be achieved by providing them with well functioning grafts. Delayed renal allograft function is a serious problem. It is important to prevent this complication because it makes the diagnosis of acute rejection in the early postoperative period difficult, increases the necessity for diagnostic procedures, introduces dialysis treatments and prolongs hospital stay. The aetiology of delayed graft function (DGF) is multifactorial, and factors including donor management, technique used for organ procurement and preservation, age, anatomical variations in the graft, ischemia periods, use of cyclosporine A (CyA) or recipient immunological reactions have been implicated. Using different preservation solutions DGF rates vary from 30% to 60%. Recent clinical data have demonstrated better preservation and improved renal function posttransplant with HTK and University of Wisconsin (UW) solutions compared to EuroCollins solution. In a randomized multicenter study in collaboration with the Eurotransplant organ exchange organization, the efficacy of the HTK solution in renal transplantation was compared to EuroCollins and UW solutions in two parallel prospective randomized trials. The first preliminary results comparing HTK and EuroCollins solutions are reported here.     

Comparison of histidine-tryptophan ketoglutarate solution and University of Wisconsin solution in prolonged cold preservation of kidney allografts

Although University of Wisconsin (UW) solution is the standard preservation solution for organ transplantation, Histidine-Tryptophan Ketogluatarate (HTK) solution has been increasingly used. This study compared HTK or UW for cold static storage of kidney allografts. In all, 149 renal transplants were performed with cold ischemic times (CI) greater than 16 hr (UW 87, HTK 62) and a subset analysis was performed with CI over 24 hr (HTK 31, UW 38). Data from receiving renal transplant centers focused on delayed graft function (DGF), patient and allograft survival. In CI greater than 16 hr, graft and patient survival were comparable. HTK cohort had lower DGF. In CI greater than 24 hr, there was no difference in patient survival, a trend towards improved graft survival in HTK, and decreased rate of DGF in HTK. This data suggests that UW and HTK have at least similar efficacy in kidney preservation at longer ischemic times.     

Preservation solutions for static cold storage of kidney allografts: a systematic review and meta-analysis

Static cold storage is the most prevalent method for renal allograft preservation. Several solutions have been designed to counteract the detrimental effects of cold ischemia and reperfusion. The aim of this study was to appraise the evidence for the currently available preservation solutions. We performed a systematic literature search using MEDLINE, EMBASE, the Cochrane Library, the Transplant Library and trial registries. Inclusion criteria specified any comparative, prospective study for deceased donor renal allografts. Studies were assessed for methodological quality. The primary outcome was delayed graft function (DGF). Fifteen trials with a total of 3584 kidneys were included. Eurocollins was associated with a higher risk of DGF than University of Wisconsin solution (UW) in two randomized controlled trials (RCTs) and histidine-tryptophan-ketoglutarate (HTK) in two RCTs. UW was associated with an equal risk of DGF compared with Celsior in three RCTs and HTK in two RCTs. There was limited data regarding other comparisons and outcomes. The choice of preservation solution has an effect on the incidence of DGF, which might, in turn, affect long-term outcomes. Both UW and HTK have lower rates of DGF than Eurocollins. There is no difference in the incidence of DGF with the use of Celsior, HTK and UW. These findings are supported by registry data.     

Evaluation of preservation solutions by ESR-spectroscopy: superior effects of University of Wisconsin over Histidine-Tryptophan-Ketoglutarate in reducing renal reactive oxygen species

Despite the causative role of oxidative stress in renal ischemia-reperfusion (I-R) injury effects of preservation solutions on reactive oxygen species (ROS) release have not been sufficiently evaluated. We compared the effects of most common solutions in kidney transplantation, University of Wisconsin (UW) and Histidine-Tryptophan-Ketoglutarate (HTK). ROS formation in isolated perfused rat kidney was detected by electron spin resonance spectroscopy using spin label 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine. Donor kidneys from Lewis rats were pretreated with saline (controls), in therapeutic groups, kidneys underwent 18 h of cold storage (CS) preserved by HTK or UW solution. Experimental protocol included a stabilization period followed by additional I-R. Kidneys preserved by HTK produced highest ROS values in the control period after CS, whereas levels in UW and control group did not vary significantly. A peak release induced by additional I-R was also significantly highest in HTK kidneys, and UW did not differ from controls. During reperfusion, levels in HTK exceeded control and UW values. Renal vascular resistance, caspase-3-activity, and tissue hydration were enhanced in HTK compared with UW group, whereas ATP concentration was less reduced in UW-preserved tissue. These data show the greater antioxidative potential of UW solution, which also attenuated organ impairment after CS in the early reperfusion period.     

Comparison of histidine-tryptophan ketoglutarate and University of Wisconsin solutions as primary preservation in renal allografts undergoing pulsatile perfusion

INTRODUCTION: University of Wisconsin (UW) solution is the standard preservation solution for organ transplantation. Histidine-tryptophan ketogluatarate (HTK) solution has been used increasingly for kidney, pancreas, and liver transplantation. This study compared HTK and UW used during kidney procurement with subsequent pulsatile perfusion. METHODS: Between January and October 2003, 91 deceased renal and simultaneous kidney pancreas transplants were performed (UW, n = 41, and HTK, n = 50). There were no differences with regard to donor and recipient demographics or cold ischemia. RESULTS: Delayed graft function occurred in 3 (7%) of UW and 4 (8%) of HTK-preserved kidneys (P = NS). There were no significant differences between patient or graft survival. There was an anticipated difference between total preservative volumes used (HTK: 4.1 +/- 1.0 vs UW: 3.0 +/- 0.5; P < .005). CONCLUSION: UW and HTK appear to have similar efficacy in kidney preservation with pulsatile perfusion. HTK preservation solution can be used safely in conjunction with pulsatile preservation for cold storage of renal allografts.     

Increased Primary Non-Function in Transplanted Deceased-Donor Kidneys Flushed with Histidine-Tryptophan-Ketoglutarate Solution

Histidine-Tryptophan-Ketoglutarate (HTK) solution is increasingly used to flush and preserve organ donor kidneys, with efficacy claimed equivalent to University of Wisconsin (UW) solution. We observed and reported increased graft pancreatitis in pancreata flushed with HTK solution, which prompted this review of transplanting HTK-flushed kidneys. We analyzed outcomes of deceased-donor kidneys flushed with HTK and UW solutions with a minimum of 12 months follow-up, excluding pediatric and multi-organ recipients. We evaluated patient and graft survival and rejection rates, variables that might constitute hazards to graft survival and renal function. Two-year patient survival, rejection, renal function and graft survival were not different, but early graft loss (<6 months) was worse in HTK-flushed kidneys (p < 0.03). A Cox analysis of donor grade, cold ischemic time, panel reactive antibodies (PRA), donor race, first vs. repeat transplant, rejection and flush solution showed that only HTK use predicted early graft loss (p < 0.04; relative risk = 3.24), almost exclusively attributable to primary non-function (HTK, n = 5 (6.30%); UW, n = 1 (0.65%); p = 0.02). Delayed graft function and early graft loss with HTK occurred only in lesser grade kidneys, suggesting it should be used with caution in marginal donors.     

Experience with hystidine tryptophan ketoglutarate versus University Wisconsin preservation solutions in transplantation

We present our experience with histidine tryptophan ketoglutarate (HTK) and University Wisconsin (UW) preservation solutions in liver transplantation and a review of the literature in pancreas and kidney transplantation comparing these solutions. A group of 134 liver transplantations in 123 recipients was analyzed retrospectively. Grafts procured in adults were perfused with HTK in 63 cases and with UW in 71 cases. We compared results according to preoperative, intraoperative, and postoperative parameters, as well as complications and survival. No differences regarding donor and recipient data, intraoperative fresh frozen plasma (FFP) substitution, length of intensive care unit (ICU) stay, and ischemic damage of the graft were found. The rate of complications was comparable in both groups. However, the bilirubin was higher in the UW group. The rate of biliary complications was higher in the UW group (n = 8) versus the HTK group (n = 5). HTK ischemic type biliary lesions (ITBL) were only present in the UW group. Patient and graft survival were statistically nonsignificant. The data confirm that HTK and UW, with exception of biliary complications, are considered comparable in clinical liver transplantation. The same conclusion can be taken from the literature analyzed concerning renal transplantation, and in smaller groups of pancreas transplants, similar results were published.     

Comparison of Histidine-Tryptophan-Ketoglutarate and University of Wisconsin Preservation in Renal Transplantation

Histidine-tryptophan-ketoglutarate (HTK) is replacing University of Wisconsin (UW) solution as the preservation fluid for renal allografts in many centers, but recent large-scale data to support this transition are lacking. We conducted a retrospective analysis of patient and graft outcomes after renal transplantation at our center, comparing 475 consecutive living donor and 317 deceased donor transplants since the adoption of HTK with equal numbers of grafts preserved using UW solution. Data collected included donor and recipient age, race, sex, comorbidities and graft ischemia time. Graft and patient survival, as well as the incidence of delayed graft function (DGF), were studied by Kaplan–Meier and Cox regression analysis. No significant difference was seen in either patient or graft survival. Deceased donor kidneys in the HTK group had a higher incidence of DGF than the UW cohort, whereas this trend was reversed in the case of living donor organs. In multivariate analysis, HTK was associated with a significant risk reduction on the incidence of DGF. Prolonged preservation with HTK compared to UW was not associated with excess risk to the graft or patient. In summary, HTK demonstrated efficacy similar to UW in terms of patient and graft survival.     

Microcirculatory disturbances and leucocyte adherence in transplanted livers after cold storage in Euro-Collins,UW and HTK solutions

Integrity of the hepatic microcirculation and maintenance of endothelial cell viability are critical components in preventing primary non-function after liver transplantation. Therefore, hepatic microcirculation and leucocyte-endothelial interaction were studied in rat livers stored for 1 h in Euro-Collins (EC), University of Wisconsin (UW), and histidine-tryptophan-ketoglutarate (HTK) solutions and subsequently transplanted. One hour after transplantation surgery, the livers were exposed under an intravital fluorescence microscope. After injection of the leucocyte marker acridine orange (1 mol/kg), six pericentral fields were observed for 30 s and experiments were recorded continuously. The percentage of perfused sinusoids was reduced in the livers in the EC group (82.9%) in contrast to the UW (93.2%) and HTK groups (91.0%). Livers in the EC group showed a reduction in the diameters of pericentral sinusoids (7.3±0.2 m; mean±SEM) compared with the UW group (9.5±0.2 m; P<0.05) and HTK group (10.2±0.8 m; P<0.05), indicating substantial cell swelling in livers stored in EC solution. Permanent adherence of leucocytes was most frequently observed in the EC group (33.5±1%), while this phenomenon was less pronounced in the UW group (14.5+1.1%; P<0.05) and HTK group (16.3±0.7%; P<0.05). Conversely, temporary adherence of leucocytes was reduced in the EC group (19.7+1.3%) compared with the UW group (30.5+2.1%) and the HTK group (34.4+0.8%). Microcirculatory failure and cell swelling in the EC group might be due to the lack of osmotic substances or oxygen radical scavengers included in UW (allopurinol, glutathione) and HTK (mannitol) solutions. In conclusion, cold storage of livers in UW and HTK solutions results in better preservation of the microcirculation and prevention of adhesion of leucocytes after transplantation compared with the EC solution.     

Comparison of solutions for preservation of the rabbit liver as tested by isolated perfusion

The University of Wisconsin (UW) solution consists of a relatively complex mixture of agents. In this study we compared simpler preservation solutions, namely, histidine-tryptophan-ketoglutarate glutarate (HTK) and phosphatebuffered sucrose (PBS) with different compositions of UW solution in the isolated perfused rabbit liver model. Livers were stored cold for 24 and 48 h. After 24 h of preservation, the amount of bile produced in UW-preserved livers was significantly greater (P<0.05) than that in HTK-preserved livers. Also, there was less LDH released into the perfusate in UW-preserved livers. There was more edema and lower K+/Na+ rations in HTK-preserved livers than in UW-preserved livers (all data P<0.05). After 48 h of preservation, the differences between livers preserved in UW or HTK solution were less noticeable than at 24 h and bile production was similar. LDH and AST release were greater in HTK-preserved livers than in UW livers, but these differences were not statistically significant. Preservation in PBS for 48 h was worse than in either UW or HTK solution. Substitution of polyethylene glycol (PEG) for hydroxyethyl starch (HES) in 48-h UW-preserved livers was not effective. We conclude that solutions simpler in composition than UW solution may be effective in kidney transplantation but do not appear suitable for successuful liver preservation.     

A prospective randomized multicenter trial comparing histidine–tryptophane–ketoglutarate versus University of Wisconsin perfusion solution in clinical pancreas transplantation

We aimed to evaluate early pancreas transplant graft function after histidine–tryptophan–ketoglutarate (HTK) versus University of Wisconsin (UW) perfusion. Prospective randomized multicenter study including 68 pancreas transplantations stratified according to preservation fluid used (27 HTK vs. 41 UW). Primary endpoint was pancreas graft survival at 6 months. Serum α-amylase, lipase, C-peptide, HbA1C and exogenous insulin requirement were compared at several time points. Mean pancreas cold ischemia time was 10.8 ± 3.7 (HTK) vs. 11.8 ± 3.4 h (UW) ( P  = 0.247). Simultaneous pancreas–kidney transplantation was performed in 95.6% of the patients, pancreas transplantation alone in 2.9%, and pancreas after kidney transplantation in 1.5%. Six months graft survival was 85.2% (HTK) vs. 90.2% (UW) ( P  = 0.703). Serum amylase and lipase values did not differ between both the groups during the observation period. C-peptide levels were elevated in both the groups without significant differences at each time point. Higher exogenous insulin requirement early after transplantation in the UW group had resolved at 3 months. Six month patient survival was 96.3% (HTK) vs. 100% (UW) ( P  = 0.397). With a mean cold ischemia time of 10 h in this study, HTK and UW solutions appear to be equally suitable for perfusion and organ preservation in clinical pancreas transplantation.     

Histidine-tryptophan-ketoglutarate solution maximally preserves endothelium-derived hyperpolarizing factor-mediated function during heart preservation: comparison with University of Wisconsin solution.

BACKGROUND: The University of Wisconsin (UW) solution is used widely in heart preservation but has been demonstrated to be detrimental to the endothelial function. The present study compares the effect of histidine-tryptophan-ketoglutarate (HTK) and UW solutions on endothelium-derived hyperpolarizing factor (EDHF)-mediated function in porcine small coronary arteries. METHODS: An isometric force study was performed in a myograph and the membrane potential of a single smooth muscle cell was measured electrophysiologically. Small coronary arteries (diameter 457 +/- 15 microm) were incubated with UW (n = 8), HTK (n = 7) or Krebs solution (n = 15) at 4 degrees C for 4 hours. After washout, in the presence of indomethacin (Indo; 7 micromol/liter), N(G)-nitro-l-arginine (l-NNA; 300 micromol/liter) and oxyhemoglobin (HbO; 20 micromol/liter), bradykinin (BK; -10 to -6.5 log M)-induced relaxation was compared in U46619 (-8 log M) pre-contraction. EDHF-mediated hyperpolarization was elicited by BK (-6.5 log M) in the presence of Indo, l-NNA and HbO. RESULTS: BK-induced, EDHF-mediated relaxation was reduced from 93.6 +/- 2.8% to 79.7 +/- 4.6% after UW preservation (p = 0.01 by unpaired t-test and p = 0.005 by 2-way analysis of variance [ANOVA]), whereas HTK incubation did not decrease EDHF-mediated relaxation (87.0 +/- 6.5%, p = 0.3 by unpaired t-test and p = 0.6 by 2-way ANOVA, compared with control, and p = 0.001 by 2-way ANOVA, compared with UW). EDHF-mediated hyperpolarization (10.3 +/- 1.6 mV) was attenuated by UW exposure (3.4 +/- 0.6 mV, [p = 0.002] vs control), but not by HTK exposure (8.3 +/- 1.1 mV, [p = 0.3] vs control). CONCLUSIONS: HTK is superior to UW solution in protecting EDHF-mediated endothelial function in porcine small coronary arteries. The present findings supports the use of HTK solution in heart preservation.     

Low viscosity histidine-tryptophan-ketoglutarate graft flush improves subsequent extended cold storage in University of Wisconsin solution in an extracorporeal rat liver perfusion and rat liver transplantation model.

Adequate flushing for liver donation requires large fluid volumes delivered at a high flow. This can be achieved more effectively with crystalloid solutions than with colloid-based solutions. This study examined the combination of initial histidine-tryptophan-ketoglutarate solution (HTK) graft flush and subsequent storage in University of Wisconsin solution (UW) to that of the single use of each solution. Livers from inbred Wistar rats were procured using aortic perfusion with UW or HTK for initial perfusion and reflushed after 30 minutes using either solution. In a third group, after perfusion with HTK, organs were reflushed with UW. A 60-minute in-vitro recirculating perfusion was performed after 24 hours of cold storage in the subsequent solution, as well as allotransplantation after 18 and 24 hours of cold storage. In extracorporeal perfusion, the HTK flush followed by UW storage was superior compared to the single use of either UW or HTK solution, as measured by portal venous pressure, bile flow, liver enzymes released into the effluent perfusate, glycerol leakage, and histological examinations. These data were consistent with the transplantation study. Histological damage and enzyme release after 5-day survival were lowest in the HTK flush and subsequent UW storage groups following 18 hours of cold storage; likewise, the 5-day survival was superior following 24 hours of cold storage. In conclusion, the combined use of HTK solution for initial graft rinse and subsequent storage in UW solution resulted in a cumulative protection. Choosing low-viscosity HTK solution for the initial organ flush may represent a feasible improvement in liver preservation, which also further reduces the required amount of UW solution.     

Initial experience using histidine-tryptophan-ketoglutarate solution in clinical pancreas transplantation

BACKGROUND: The colloid-based University of Wisconsin (UW) preservation solution has been used extensively in clinical pancreas transplantation. Experimental studies support the use of the crystalloid-based histidine-tryptophan-ketoglutarate (HTK) preservation solution for this purpose. AIM: We report our initial experience with HTK for pancreas allograft preservation and compare this to a contemporary experience with UW solution in conventional multiorgan deceased donors (<50 yr). MATERIALS AND METHODS: Retrospectively collected information on 33 pancreas transplants between September 2001 and October 2002 were analyzed for early graft function and complications up to 30 d after procurement and storage in either HTK or UW solutions. During multi-organ recovery, either UW solution (4-5 L) or HTK solution (8-10 L) was used for aortic perfusion and subsequent back-table flush and storage. Exocrine drainage of 31 pancreas allografts was enteric, while the bladder was used for drainage in two cases. Patient outcomes were analyzed according to the preservation solution used. Sixteen pancreata were used in combination with a kidney allograft (SPK), seven were used in patients after prior kidney transplantation (PAK), while 10 were used in patients who were not in renal failure (PTA). RESULTS: The UW group consisted of 17 patients (10 SPK, three PAK, four PTA) with a mean donor age of 29.5 +/- 10.7, and a mean cold ischemia time of 15.1 +/- 2.1 h. The mean post-transplant pancreas and kidney function on days 1 and 10 were amylase (315 and 99 IU/L), lipase (1727 and 346 IU/L), glucose (121 and 100 mg/dL) and creatinine (5.01 and 1.77 mg/dL). Patient and graft survival was 100% at 1-month post transplant. In the HTK group there were 16 patients (six SPK, four PAK, six PTA) with a mean donor age 21.9 +/- 5.7 and a mean cold ischemia time 14.0 +/- 1.3 h. The mean post-transplant pancreas and kidney function on days 1 and 10 were amylase (588 and 126 IU/L), lipase (4711 and 441 IU/L), glucose (97 and 109 mg/dL) and creatinine (5.28 and 2.42 mg/dL). Patient survival was 100% while graft survival was 94% at 1-month post-transplant. CONCLUSIONS: Early graft function and complications are comparable with HTK and UW solutions for pancreas allograft preservation.     

Evaluation of rat liver apoptotic and necrotic cell death after cold storage using UW,HTK, and Celsior

BACKGROUND: The benefit of Celsior in liver graft preservation is controversial. In the isolated perfused rat liver model, we compared the effects of Celsior, University of Wisconsin (UW), and histidine-tryptophan-ketoglutarate (HTK) preservation solutions on liver cell death. METHODS: Rat livers were stored at 4 degrees C for 0, 8, 16, or 24 hr in either Celsior, UW, or HTK and reperfused for 90 min (37 degrees C). Bile secretion and perfusate levels of liver enzymes and histone-associated DNA fragments were measured. Apoptosis and oncotic necrosis were analyzed in biopsies by DNA gel electrophoresis, hematoxylin and eosin histology, and enzyme histochemistry for lactate dehydrogenase (LDH) and 5'-nucleotidase (5'-NT). RESULTS: Perfusate flow rate through the liver during perfusion did not significantly differ among preservation solutions. Bile secretion was best preserved in UW livers after 16-hr (versus HTK livers) and 24-hr storage (versus HTK and Celsior livers). Enzyme leakage from UW livers was lower compared with HTK livers after 8-hr storage (serum glutamic oxaloacetic transaminase [SGOT], LDH) and with Celsior and HTK livers after 16-hr (SGOT, LDH) and 24-hr storage (SGOT, serum glutamic pyruvic transaminase, LDH, purine nucleoside phosphorylase). In situ LDH and 5'-NT activities were best preserved in UW livers (up to 24 hr), whereas enzyme activities declined remarkably in HTK livers (after 8 hr) and Celsior livers (after 16 hr of cold storage). Although perfusate DNA fragment levels were repeatedly lowest from Celsior livers, apoptotic DNA laddering and the number of fragmented nuclei in hematoxylin and eosin sections was not different among livers after 8, 16, or 24 hr of storage. CONCLUSIONS: Celsior and UW are equally effective in preventing rat liver cell death after 0-16 hr of cold preservation as compared with the less effective HTK solution. After 24-hr cold storage, rat livers were best preserved in UW. Furthermore, there was no significant difference in mode of cell death (apoptosis or oncotic necrosis) after storage in any of the three solutions.     

Comparison of histidine-tryptophan-ketoglutarate solution and University of Wisconsin solution in adult liver transplantation

BACKGROUND: A safe and effective preservation solution is a precondition for successful orthotopic liver transplantation (OLT). This study compared University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions in OLT. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 137 primary cadaveric. OLT performed between January 2003 and December 2006 at our institution. Sixty-eight grafts were harvested using UW and 69 using HTK. Recipients were managed similarly in regard to operative techniques and immunosuppression. We collected donor data including serum transaminases, serum sodium, ICU stay and assessed macroscopic liver quality. Recipient serum transaminases were collected on postoperative days 1, 7, 14, and 30. We compared biliary and vascular complications, as well as patient and graft survivals. RESULTS: Mean serum bilirubin levels were slightly higher in the HTK group at 1,7,14, and 30 days after transplantation, whereas transaminases were higher in the UW group. Primary nonfunction occurred in 1 patient in each group. Retransplantation was performed in 5 patients in the UW and in 9 patients in the HTK group. Biliary complication rates were similar in the UW and HTK groups (22% and 17%, respectively). Six arterial complications occurred in the HTK (8.7%) and 2 in the UW group (2.9%; P < .05). Mean follow-up was 25 months. Graft survival at 1, 12, and 36 months was 90%, 78%, and 75% versus 90%, 71%, and 71% in the UW versus HTK groups, respectively. One-, 12-, and 36-month patient survival rates were 93%, 78%, and 75% versus 93%, 78%, and 78% in the UW versus HTK groups, respectively. CONCLUSIONS: There were no significant differences in graft and patient survivals between the 2 groups. Whereas the biliary complication rates were comparable in both groups, the arterial complications were clearly higher in the UW group (8.7% vs 2.9%; P < .05%). UW and HTK solutions seemed to be equally safe and effective in the preservation of liver grafts. The high incidence of arterial complications in the UW group requires further prospective studies.     

Histidine-tryptophan-ketoglutarate versus University of Wisconsin solution in living donor liver transplantation: Results of a prospective study

The grafts obtained from a living donor hepatectomy are perfused on the back table with either University of Wisconsin solution (UW) or histidine-tryptophan-ketoglutarate solution (HTK). The efficacy and safety of these solutions have been studied in cadaveric liver transplantation, however, there is no study comparing the two solutions in adult-to-adult living donor liver transplantation. In this study, UW and HTK were used in the perfusion of right living donor grafts. The grafts were perfused with a predetermined sequence and volume of one of the solutions. Liver biochemistries, complications, and graft and patient survival were analyzed. From January 2001 to September 2002, 30 grafts were alternately perfused with either UW (UW group) or HTK (HTK group). The perfusion was performed first via the artery and then via the portal vein with a predetermined volume. At a mean follow-up of 13 ± 7 months, no significant statistical difference between groups UW and HTK in posttransplantation liver biochemistries, complications, or patient and graft survival (84% and 80%, respectively) was observed. In conclusion, UW and HTK are equally effective and safe in the perfusion of the living donor liver grafts. HTK has a slight practical advantage over UW because it does not need to be flushed away before reperfusion of the graft and is less expensive. (Liver Transpl 2003;9:822-826.)     

Comparative evaluation of two perfusion solutions for liver preservation and transplantation

The University of Wisconsin solution (UW) and the Bretschneider solution (HTK) were used in 39 adult cadaveric donors: 22 perfused with UW (group 1) and 17 with HTK (group II). Donors were flushed through the aorta (UW, 5 to 6 L; HTK, 8 to 10 L) and through the portal vein (UW or HTK, 1 L). Grafts perfused with HTK showed lower levels of SGOT at postoperative day 7 than those transplanted with UW (38 +/- 19 vs 58 +/- 31, P < .05). No difference was observed in other functional and outcome parameters. No cases of primary dysfunction were observed. Six-month graft survival was 85.7% in HTK group and 80.9% in UW group (P = NS). Six unrelated deaths were observed. Five biliary complications were observed in five patients: three in the UW group and two in the HTK group. In conclusion, data fail to show major differences between the two solutions used.     

Comparison of histidine-tryptophan-ketoglutarate and University of Wisconsin in living-donor liver transplantation

For cadaveric transplantations, histidine-tryptophan-ketoglutarate (HTK) and University of Wisconsin (UW) solutions have been shown to engender similar outcomes. In September 2004, our institution changed from UW to HTK as the primary preservation solution for liver and kidney transplantations. We reviewed records of living-donor liver transplant recipients from September 2001 to December 2005. This study compared early postoperative outcomes of liver transplantation using the 2 solutions. Perfusion was performed first via the portal vein and then via the hepatic artery until the outflow became clear. Patients were compared based on the organ preservation solution. The analysis included patient demographics, early postoperative complication rates, mortality rates, number of acute rejection episodes, costs for preservation solutions, and results of 1-, 7-, 14-, and 30- day liver function tests. Patients in both groups were managed with similar operative techniques, immunosuppressive regimens, and donor liver criteria. Statistical analyses were performed with chi- square and Mann-Whitney U tests. Donor and patient demographics were similar. No statistically significant differences were observed between the groups with regard to posttransplantation liver biochemistry, complication rates, number of acute rejection episodes, and mortality rates. The mean infused volume of preservation solution was 1000 +/- 400 mL (range, 500-2000 mL) for all patients. These volumes corresponded to a cost savings of US 148 dollars/L when using HTK solution. In conclusion, UW and HTK were equally effective and safe for perfusion of living-donor liver grafts; however, the use of HTK solution provided significant cost savings.     

Histidine-tryptophan-ketoglutarate solution vs. University of Wisconsin solution for liver transplantation: a systematic review.

University of Wisconsin (UW) solution has been recognized as the gold standard in liver preservation, but its limitations are becoming obvious, such as risk of biliary complications and its high cost. Alternatively, the effects of histidine-tryptophan-ketoglutarate (HTK), such as improved biliary protection and low cost, have been observed. This systematic review is conducted to compare the efficacy and safety of these 2 solutions. Databases from 1966 to June 2006 were searched. Randomized clinical trials (RCTs) and cohort studies comparing HTK and UW solutions for liver transplantation were included. Ten articles including 11 comparisons (1,200 patients) met the inclusion criteria, containing 2 RCTs and 9 cohort studies. No marked differences existed between the 2 groups in patient and graft survival rates, acute rejection, primary nonfunction, primary dysfunction, delayed graft function, and ALT and AST levels after transplantation. The only positive result was observed in the bile production after deceased donor liver transplantation (DDLT), which was statistically significantly higher in HTK group than that of UW group (95% confidence interval, 18.65-57.47; P=0.0001). Although the difference in biliary complications between the 2 groups did not reach statistical significance, HTK was thought to be more effective for biliary tract flush and prevention of biliary complications in some studies. There was no statistically significant difference of effects (except bile production) between HTK and UW. But trends were documented in some studies for the superiority of HTK in biliary tract flush, prevention of biliary complications, and cost saving. Adequately powered RCTs with longer follow-up periods are required to evaluate the long-term effect of these 2 solutions.