Kidney preservation in pigs with University of Wisconsin and Celsior solution

BACKGROUND: Although University of Wisconsin (UW) solution continues to be the most commonly used for intra-abdominal organs a new solution, Celsior, already utilized for heart and lungs, has been proposed for kidney and liver preservation. The aim of this research was to assess the effect of Celsior compared to UW on the immediate graft function of pig autotransplanted kidneys. METHODS: We used an autotransplantation pig model to avoid immunological interferences. After harvesting the graft was immediately bench perfused through the renal artery with 200 cc of solution and preserved for 24, 32 and 48 hrs. After cold ischemia grafts were autotransplanted on cava vein and aorta and a ureteral-ureteral anastomosis was performed. Contralateral nephrectomy was carried out at the end of this procedure. Each experimental group was composed of 5 animals. All animals were sacrificed after 1 week. RESULTS: All animals with 24 hr and 32 hr preserved grafts survived up to sacrifice; kidney function was recovered in all animals of 24 hr groups and in most of the animals of 32 hr preserved grafts (4/5) without any differences between the 2 solutions. In Celsior and UW 48 hr groups only 5 animals survived (3 and 2, respectively) and in all these animals kidney function was not totally recovered. CONCLUSIONS: Our data show that preservation of kidneys with the Celsior solution in the experimental setting is equivalent to UW solution.     

Pancreas preservation with University of Wisconsin and Celsior solutions: a single-center, prospective, randomized pilot study

BACKGROUND: Celsior is an extracellular-type, low-viscosity, preservation solution already used for heart, lung, liver, and kidney transplantation. We report the results of a single-center, prospective, randomized pilot study specifically designed to compare the safety profile of Celsior solution with University of Wisconsin (UW) solution in clinical pancreas transplantation. METHODS: A total of 105 consecutive procurements were randomized to graft preservation with UW (n=53) solution or Celsior (n=52) solution. The groups were comparable with regard to all donor and recipient characteristics. RESULTS: Five grafts were discarded and 100 grafts (50 UW vs. 50 Celsior) were transplanted. Mean cold and warm ischemia times were 11.0 +/- 2.1 hr and 37.2 +/- 6.0 min for UW compared with 10.8 +/- 1.8 hr and 38.1 +/- 5.9 min for Celsior (P =not significant). Delayed endocrine pancreas function was recorded in one graft preserved with UW solution. Eleven recipients (UW 12% vs. Celsior 10%, P =not significant) required a relaparotomy. The mean serum levels of glucose, amylase, and lipase remained comparable between the study arms at equivalent intervals after transplantation. One recipient died with functioning grafts in each study arm; two further grafts were lost to arterial thrombosis (Celsior) and chronic rejection (UW), respectively. Actuarial 1-year patient and graft survival rates overlapped in the two study arms (98% and 96%, respectively). CONCLUSIONS: Within the range of cold ischemia time reported in this study, UW and Celsior solutions have similar safety profiles for pancreas preservation.     

Wisconsin and Celsior solutions in renal preservation: a comparative preliminary study

The aim of this study was to evaluate the efficacy of the Celsior (C) solution for flushing and cold storage of cadaveric renal allografts. Among 177 cadaveric renal allografts harvested and transplanted in our unit, 138 were preserved with the University of Wisconsin (W) solution and 39 with the C solution. The mean age of the recipients was 48.1 +/- 13.5 years, including 107 men and 70 women. The immunosuppressive regimens were tacrolimus-based (n = 118) or cyclosporine-based (n = 59). Grafts perfused with W solution were obtained from older donors than those perfused with C solution (42.3 +/- 16.9 vs 38.1 +/- 12.5 years; P = .017) and had been transplanted to older recipients (49.5 +/- 14.4 vs 43.3 +/- 13.0 years; P = .017). The prevalence of delayed graft function (DGF) was similar in the 2 groups (39.1% in the W group vs 23.7% in the C group; P = .097), as well as the incidence of primary nonfunction grafts (5.8% vs 2.7%; P = .427). The serum creatinine value at 1 month was significantly higher among grafts preserved with W versus solution (1.9 +/- 0.9 vs 1.5 +/- 0.5 mg/dL; P = .000) as well as at 12 months (1.63 +/- 0.5 vs 1.35 +/- 0.4 mg/dL; P = .003). There were no differences in graft survival at 12 months (97% C group vs 88% W group; P = .069). Our results showed that C solution was equivalent to W solution with respect to DGF and primary function of kidneys. The differences in renal function may have been due to differences in donor and recipient ages.     

Luminal preservation of rat small intestine with University of Wisconsin or Celsior solution

AIMS: Luminal administration of a preservation solution that prevents mucosal injury may decrease posttransplant complications. However, luminal administration of University of Wisconsin solution (UW) is controversial. In this study, we examined the potential of Celsior as a luminal small bowel preservation solution in comparison to UW or UW enriched with glutamine. METHODS: Small bowels of six normal WagRij rats were excised and divided into six equal segments. Each segment was luminally flushed with 10 mL ice-cold UW, UW with glutamine (20 g/L) or Celsior, and stored for 0, 2.5, and 24 hours at 4 degrees C. LDH, glucose, and lactate concentrations were determined in the preservation solutions. Histologic changes were determined using the Park score. RESULTS: Lactate dehydrogenase (LDH) was increased in all solutions after 2.5- and after 24-hour preservation. However, LDH was lower in Celsior than UW and UW with glutamine. Furthermore, higher glucose and lactate levels were found after 2.5- and 24-hour preservation in UW and UW with glutamine compared to Celsior. Histologically, jejunal segments were more susceptible to preservation than ileal segments, irrespective of the preservation solution used. Mucosal injury was evident after 2.5 hours (Park Scale 0-3) and increased significantly after 24 hours (park scale 3-6). CONCLUSIONS: Based on the lower glucose, lactate, and LDH levels in small intestines stored in Celsior, this study suggests that Celsior is a better luminal preservation solution than UW. Unfortunately, histological evaluations still show severe mucosal injury, indicating that there is a need for better luminal preservation solutions or for concomittant intravascular delivery of a preservation solution.     

Pancreas preservation with University of Wisconsin and Celsior solutions

BACKGROUND: Although the use of Celsior has been recently described for heart, lung, liver, and kidney transplantation, no data are available on its use for clinical pancreas preservation. METHODS: We herein describe the results of 112 pancreas transplants preserved with either University of Wisconsin (UW; (n = 56) or Celsior (n = 56) solution at two Italian transplant centers. The groups were comparable with regard to all donor and recipient characteristics. RESULTS: Mean cold and warm ischemia times were 10.1 +/- 2.2 hours and 37.2 +/- 8.2 minutes for UW compared to 10.8 +/- 2.4 hours and 38.3 +/- 6.7 minutes for Celsior (P = NS). Delayed endocrine pancreas function was recorded in two UW-preserved grafts (3.6%). Actuarial 1-year patient survival was 94.6% for UW as compared with 100% for Celsior (P = NS). Equivalent graft survival figures were 91.0% for UW as compared with 96.4% for Celsior (P = NS). CONCLUSIONS: Within the range of cold ischemia times reported in this study, UW and Celsior solutions have similar safety profiles for pancreas transplantation.     

Kidney transplantation with Belzer or Custodiol solution: a randomized prospective study

PURPOSE: The purpose of this study was to compare the Belzer vs Custodiol solutions for cadaveric kidney perfusion in relation to delayed graft function, renal function, acute rejection episodes, and patient and graft survivals. METHODS: This randomized prospective study included 42 kidneys and 9 simultaneous kidney and pancreas recipients from December 2002 to February 2004, namely 24 in the Custodiol arm and 27 in the Belzer arm. We analyzed delayed graft function frequency, acute rejection episodes (biopsy proven), renal function (creatinine at 1, 6, and 12 months), as well as graft and patient survivals. Categorical and continuous variables were evaluated as appropriate. RESULTS: We failed to observe a difference in the immunosuppressant drug protocol, cold ischemia time, or mean recipient or donor age. The prevalence of delayed graft function was 63% among the Belzer arm, and 50% among the Custodiol arm (P = NS). The renal function was the same in both arms at 1, 6, and 12 months. The graft survival after 3 months was 94% among the Belzer group (death from sepsis), and 95% among the Custodiol group (nonfunctioning graft). At 1 year, the results were 78% among the Belzer group (4 deaths from cardiovascular or infectious complications and 2 graft losses), and 79% among the Custodiol group (3 deaths, 1 primary nonfunctioning graft, and 1 graft loss; P = NS). After 12 months follow-up, patient survival was 84% among the Belzer group, and 86% among the Custodiol group. In the first year, the incidences of biopsy-proven acute rejection episodes were 37% among the Belzer group, and 33% among the Custodiol group. CONCLUSION: Custodiol solution achieved similar results compared with Belzer solution.     

Myocardial preservation using Celsior solution in cardiac transplantation: early results and 5-year follow-up of a multicenter prospective study of 70 cardiac transplantations

BACKGROUND: Several storage methods using a wide variety of extracellular or intracellular solutions applied either as continuous perfusion, intermittent perfusion, or simple immersion of the heart have been commonly used. We have performed a prospective randomized multicenter study of 70 cardiac transplantation recipients to evaluate the Celsior solution for cardiac preservation. METHODS: Seventy consecutive patients were included in this trial and received a cardiac graft arrested and preserved with Celsior. The first follow-up period was 1 month. The mean age of the recipients was 49 years (range, 28 to 66 years), and 81.7% were male. The main disease was nonobstructive cardiomyopathy (64.3%). The age range of donors was between 14 and 56 years with a mean of 33 years. The majority of grafts (73%) were stored in 1 L of Celsior. A midterm follow-up at 5 years was performed and was 100% complete. RESULTS: The operative mortality (<30-day) rate was 6 of 70 (8.6%). Sixty-three patients (90%) had at least satisfactory hemodynamic measurements on day 2. The first postoperative echocardiograms showed good myocardial performance for 90% of the grafts. Actuarial survival rate at 5 years was 75% +/- 5.1%. CONCLUSIONS: The use of Celsior in cardiac transplantation was safe and very effective. This solution proved very valuable in at-risk patients.     

The effect of Celsior solution on 12-hour cardiac preservation in comparison with University of Wisconsin solution

BACKGROUND: Celsior is a new extracellular-type preservation solution which has been developed to act not only as a storage medium but also as a perfusion fluid during initial donor heart arrest, poststorage graft reimplantation and early reperfusion. We designed this experimental study to evaluate the effect of the Celsior solution in comparison with the University of Wisconsin solution from the viewpoint of energy depletion. METHODS: Adult mongrel dogs weighing 9 to 13 kg were divided into two groups. In the UW group (n=7), a 4 degrees C University of Wisconsin solution was used for coronary vascular washout and storage following cardiac arrest using a glucose-insulin-potassium solution. In the Celsior group (n=7), the Celsior solution was used to obtain cardiac arrest, coronary vascular washout and storage. High energy phosphate levels and myocardial pH were measured using (31)P-nuclear magnetic resonance spectroscopy immediately after preservation and at 3, 6 and 12 hours after preservation. After 12-hour cold storage, left ventricular free wall tissues were harvested for histological examination. RESULTS: High energy phosphate levels and myocardial pH were significantly better preserved in the Celsior group than in the UW group. In the histological findings, glycogen granules were preserved well in the Celsior group. CONCLUSIONS: We conclude from our study that the Celsior solution is comparable to the University of Wisconsin solution for use in 12-hour heart preservation in canine models.     

Efficacy of renal preservation: comparative study of Celsior and University of Wisconsin solutions

OBJECTIVE: We sought to compare the efficacy of Celsior and University of Wisconsin (UW) solutions on the perfusion and cold storage of renal grafts for human transplantation. PATIENTS AND METHODS: Retrospective analyses of 313 kidney transplants were performed between 2002 and 2005; group A (n = 160), UW solution and group B (n = 153), Celsior solution were used in the preservation of the organs. The mean donor age was lower in group B (group A = 42.67 years vs group B = 38.96 years; P < .05), living donors were more frequent in the UW group (group A = 10% vs group B = 0.9%; P < .001). Multiorgan procurement procedures were more common in the Celsior group (group A = 75% vs group B = 81.7%; P < .001). Recipients with no associated comorbidities were more frequent in the UW group (group A = 50% vs group B = 36%; P < .001). Recipient mean age, cold ischemia time, and HLA matches were comparable. RESULTS: Delayed graft function (group A = 22.7% vs group B = 20.6%), acute rejections (group A = 21.4% vs group B = 18.4%), and serum creatinine at 6 months (group A = 1.75 vs group B = 1.67 mg/dL), 1 year (group A = 1.47 vs group B = 1.74 mg/dL), and 2 years (group A = 1.43 vs group B = 1.58 mg/dL) showed no differences (P = NS). Graft (group A = 82.23% vs group B = 84.11%) and patient (group A = 93% vs group B = 93.69%) survivals at 3 years were similar (P = NS). There were no differences in the causes of graft loss. CONCLUSION: The efficacy of UW and Celsior solutions is equivalent in the cold storage and renal preservation for transplantation.     

Pancreas preservation with the University of Wisconsin versus Celsior solutions

INTRODUCTION: The use of Celsior solution for organ preservation has not been thoroughly studied in pancreas transplantation. The aim of this study was to compare University of Wisconsin and Celsior solutions for preservation of pancreas grafts. PATIENTS AND METHODS: From March 1995 to December 2005, 72 patients with type 1 diabetes underwent pancreas transplantation. There were 42 men and 30 women, with a mean age at transplantation of 38.1 +/- 7.5 years (range: 27 to 55 years), and a mean duration of diabetes of 22.5 +/- 6.6 years. Recipients were classified into two groups according to the preservation solution: (A) Celsior (n = 28, 38.9%) and (B) Wisconsin (n = 44, 61.1%). RESULTS: The donor and recipient characteristics were similar in both groups. There were five cases of venous thrombosis in the Wisconsin group and two in the Celsior group (P = NS). The venous drainage technique in the former group was portocaval in 19 patients and portoiliac in 25; in the Celsior group, portocaval in 23 patients and portoiliac in five (P = .001). Enteric drainage was used in 19 patients from the Celsior group and 17 patients from the Wisconsin group (P = .01). Actuarial 2-year graft survival was 74.6% in the Wisconsin group and 77.4% in the Celsior group (P = NS). CONCLUSIONS: No differences were observed in venous thrombosis between the two groups. The lower rate of venous thrombosis with the portocaval technique was related to the type of venous drainage rather than the type of preservation solution. Celsior solution may be considered as good as Wisconsin solution for pancreas transplantation.     

A multicenter pilot prospective study comparing Celsior and University of Wisconsin preserving solutions for use in liver transplantation

Primary dysfunction (PDF) still occurs after orthotopic liver transplantation (OLT). Celsior solution (CS) might offer some advantages over the conventional University of Wisconsin (UW) solution for organ preservation, but to date, this has not been prospectively evaluated in the context of OLT. In this prospective, randomized, multicenter, pilot study, 215 potential liver donors were enrolled and randomized. In 42 cases, the livers were unsuitable for transplantation; therefore, 173 randomized livers ultimately were implanted after perfusion and cold preservation with CS (n = 83) or UW solution (n = 90). In accord with the indications of the CS manufacturing company, total CS infusion volume was 90 mL/kg, greater than that of UW solution (60 mL/kg). The main aim of the study is to compare the prevalence of PDF between the two groups. Donor and recipient variables were similar in the two groups. Episodes of PDF were numerically lower in the CS (2.4%) than UW group (7.8%), but the difference was not statistically significant. There was a trend toward a lesser need for early re-OLT (<30 days) in the CS group (P = .0507), but again, no statistically significant difference emerged. Overall and time-differentiated postoperative deaths also were similar. One-year actuarial patient (UW, 89% v CS, 87%) and graft (UW, 83% v CS, 85%) survival rates were similar. In conclusion, CS was similar to UW solution as a preservation solution in the clinical setting of OLT at the infusion volumes described, although some theoretical advantages of CS composition suggest that CS might prove a valid alternative to UW preservation solution in multiorgan harvesting, including the liver. A study on a larger patient basis is needed. (Liver Transpl 2003;9:814-821.)     

Efficacy and safety of Celsior preservation fluid in liver transplantation: one-year follow up of a prospective, multicenter, non-randomized study

The purpose of this prospective, nine-center, non-randomized study was to assess the efficacy and safety of Celsior preservation fluid in liver transplantation using unselected donors. As data comparing allograft outcomes following liver transplantation using Celsior and University of Wisconsin (UW) preservation fluids are limited, we also compared our cohort with matched controls selected from the European Liver Transplant Registry (ELTR) who received total liver grafts preserved with UW solution during the same period. One hundred and forty patients who received livers preserved with Celsior were included. The primary endpoint, graft loss at one-yr post-transplantation, was observed in 24 patients (17.1%) which was not significantly different from the 20.0% pre-defined threshold rate (95% confidence interval [CI] 10.9, 23.4; p=0.398). Predictive factors for graft loss on univariate analysis were moderate-to-severe steatosis on the donor graft (5/22 patients with graft loss vs. 8/107 patients without, p=0.046) and duration of warm ischemia (1.4±1.1 h in patients with graft loss vs. 0.9±0.5 h in patients without, p=0.034). Hepatic artery thrombosis and stenosis occurred in seven (5.0%) and six (4.3%) patients, respectively. The comparison of our patients to 420 ELTR controls showed that one-yr graft survival rates (Celsior: 82.9%, 95% CI 75.8, 88.2; UW: 78.6%, 95% CI 74.4, 82.2) and Kaplan-Meier one-yr graft survival distributions (p=0.285) were similar. Within the cold ischemia time achieved in our study, liver preservation with Celsior appeared efficient and safe. Comparison with ELTR patients suggested that liver allograft survival was similar using Celsior or UW solution for preservation of unselected donor grafts.     

University of Wisconsin solution versus Celsior solution in clinical pancreas transplantation

INTRODUCTION: This study compared the safety and efficacy of University of Wisconsin solution (UW) and Celsior solution (C) in pancreas transplantation (PTx). METHODS: A retrospective review of 154 PTx performed over a 61-month period included 77 grafts preserved with UW and 77 with C. The two groups were comparable for both donor and recipient characteristics. RESULTS: After a mean cold ischemia time of 624 minutes (range 360 to 945 minutes) for UW versus 672 minutes (range 415 to 1005 minutes) for C (P = NS), no primary endocrine nonfunction occurred. Delayed endocrine function was diagnosed in two grafts in the UW group (2.6%) versus none in the C group (P = NS). After a minimum follow-up of 4 months (mean 26.5 +/- 15.2 months), 22 recipients (UW = 11 vs C = 11; P = NS) required relaparotomy. Overall, 18 pancreata were lost due to either patient death with functioning graft (UW = 4 vs C = 1; P = NS) or graft loss due to other reasons (UW = 8 vs C = 5; P = NS). Actuarial 1- and 5-year patient survival rates were 93.5% and 86.8% for UW compared with 98.7% and 98.7% for C (P = .04). Actuarial graft survival rates at the same times were 88.3% and 75.0% for UW compared with 90.4% and 90.4% for C (P = NS). CONCLUSIONS: Within the range of cold ischemia times reported in this study, UW and C show similar safety and efficacy profiles for PTx.     

Pulmonary preservation with Bretscheider''s HTK and Celsior solution in minipigs

Background: Pulmonary preservation with high potassium/low oncotic pressure Euro-Collins (EC) solution is associated with endothelial dysfunction and reduced surfactant function. We compared two low potassium solutions, histidine-tryptophane-ketoglutarate (HTK) and Celsior, to EC in lung ischemia-reperfusion injury. Methods: In 19 minipigs, the left lung was perfused in situ with cold preservation solution (EC, n=6; HTK, n=6; Celsior, n=7). Reperfusion was started after 90 min of warm ischemia. The right pulmonary artery and main bronchus were clamped. Bronchoalveolar lavage (BAL) was obtained before ischemia and after 2 h of reperfusion. Surfactant activity was determined from the BAL in a pulsating bubble surfactometer. Results: Animals in the EC group survived 3.7±1.4 h. Six Celsior and five HTK treated animals survived the observation period of 7 h (P<0.001). Compliance of the reperfused lung deteriorated less in both Celsior and HTK groups (P<0.001). In EC and HTK animals, the pO₂/FiO₂ ratio was lower (P=0.002), and pulmonary vascular resistance was higher (P=0.02) than in Celsior animals. Surfactant function was impaired after reperfusion in all groups. Conclusions: Compared to EC, HTK solution showed moderate and Celsior distinct improvement of post-ischemic pulmonary function. However, surfactant function was not well preserved in any group.     

A new model for human intestinal preservation: comparison of University of Wisconsin and Celsior preservation solutions

AIM: We compared University of Wisconsin (UW) and Celsior preservation solutions using a new model of human intestinal preservation that mimics the clinical conditions of small bowel procurement. METHODS: Intestinal grafts were harvested from four multiorgan donors. After classic warm dissection for organ procurement, an ileal segment of 50 cm was immediately flushed with Celsior. After the perfusion of the abdominal organs with UW, a second segment of adjacent ileum was harvested. The two intestinal grafts were then divided into segments by stapling, before immersion into the corresponding preservation solution (Celsior or UW) for 0-, 6-, 12-, or 24-hour incubation at 4 degrees C. A histological score was graded after blinded examination of three random specimens within each ileal graft for each duration of preservation. RESULTS: Control specimens showed normal histology. After 6 hours of preservation, most villi showed complete epithelial detachment although the crypts appeared intact. After 12 hours of preservation, a larger proportion of the villi showed extensive epithelial sloughing. After 24 hours, the damage involved the entire mucosa with the crypt epithelium largely detached from the basal membrane. No statistical difference in histological score was observed between the two preservation solutions. CONCLUSION: This study showed severe histological alterations of graft mucosa after short periods of preservation by UW or Celsior solutions. This model may be useful to evaluate improvements in the quality of preservation of human intestinal transplants.     

Effects of Celsior and University of Wisconsin preservation solutions on hemodynamics and endothelial function after cardiac transplantation in humans: a single‐center,prospective, randomized trial

Abstract Optimal preservation of the myocardium remains a major concern in clinical and experimental heart transplantation. The present study compared the efficacy of University of Wisconsin (UW) and Celsior preservation solution with respect to myocardial performance, epicardial and microvascular endothelial vasomotor function and myocardial expression of endothelin and nitric oxide synthases in humans. Forty‐one cardiac transplant recipients received either UW (n = 20) or Celsior (n = 21) preserved hearts. Catecholamine and vasodilator requirements were assessed within the first 5 postoperative days. Left ventricular performance and endothelial function was assessed 1 month after transplantation. Endothelin and nitric oxide synthase gene expression were detected in myocardial biopsy samples. Celsior preserved hearts required significantly more catecholamines and vasodilators within the first 5 postoperative days. Myocardial performance and endothelial function were comparable 1 month after transplantation. Total ischemic time correlated with impaired endothelial function in the Celsior but not in the UW group. Endothelin and inducible nitric oxide synthase gene expression were significantly higher in the Celsior group. The results of the study show that both solutions provide myocardial protection with regard to left ventricular performance and endothelial function 1 month after cardiac transplantation. The necessity for higher vasodilator and catecholamine therapy in Celsior preserved hearts suggests post‐ischemic myocardial stunning within the first 5 postoperative days. The positive correlation between impaired endothelial function and total ischemic time in the Celsior group requires longitudinal investigation in particular with regard to the development of allograft vasculopathy.