Evidence for protective roles of polyethylene glycol plus high sodium solution and trimetazidine against consequences of renal medulla ischaemia during cold preservation and reperfusion in a pig kidney model.

BACKGROUND: The renal medulla is particularly sensitive to oxidant stress and to ischaemia-reperfusion injury (IRI). In organ transplantation, delayed graft function is an important problem and cold ischaemia is thought to be the most important factor in short- and long-term complications. Our aim was to study cold-induced damage in proximal tubular segments and renal medulla osmolite excretion during use of various preservation solutions, and to clarify the role of trimetazidine (TMZ) in limiting renal dysfunction. METHODS: Using an autotransplanted pig kidney model, we assessed renal tubule function, medullary osmolite excretion and renal damage between day 1 and week 2 after 24 or 48 h cold storage in University of Wisconsin solution (UW), Celsior and ECPEG (two new high Na(+) preservation solutions) or the Hopital Edouard Herriot solution (HEH; a high Na(+) version of UW). In additional groups, TMZ was added to these preservation solutions for 24 and 48 h cold storage. RESULTS: Renal function was reduced under these preservation conditions. Tubular injury was associated with aminoaciduria and with a limited Na(+) reabsorbtion. Medullary damage led to the early appearance of trimethylamine-N-oxide and dimethylamine in urine. However, renal damage was modulated by preservation conditions. In addition, TMZ added to each of the solutions efficiently protected against IRI even after prolonged preservation. CONCLUSION: TMZ efficiently protected kidneys against damage when added to the HEH and particularly ECPEG solutions, even after 24 h cold storage. These findings point to a role for drugs that target mitochondria, and demonstrate that TMZ may provide a valuable therapeutic tool against IRI and could be included in therapeutic protocols.     

Influence of cold-storage conditions on renal function of autotransplanted large pig kidneys

BACKGROUND: The consequences of ischemia/reperfusion injury (IRI) on delayed graft function (DGF) and graft survival for kidney recipients remain a matter of debate. Several strategies have been proposed to reduce IRI. We have shown that adding the anti-ischemic drug trimetazidine (TMZ) to different preservation solutions had beneficial effects on the function of reperfused rat and pig kidneys. METHODS: We analyzed the renal parameters of reperfused, autotransplanted large pigs following transplantation. The left kidneys were first removed and cold flushed with Euro-Collins (EC) and University of Wisconsin (UW) solutions (with or without 10-6 mol/L TMZ) and were stored for 48 hours at 4 degrees C. The kidney was then autotransplanted, and the contralateral kidneys were removed. Creatinine clearance, natriuresis, proteinuria, the degree of interstitial fibrosis, the number of CD4, CD8, and macrophage-positive cells, and the amount of vascular cell adhesion molecule-1 were analyzed on kidney biopsies taken at 2, 4 to 5, and 10 to 12 weeks after surgery. RESULTS: The functions of the transplanted kidneys were better preserved after cold flushing with TMZ-supplemented solutions than with TMZ-free solutions. Creatinine clearance was higher, and proteinuria was lower in animals transplanted with kidneys cold flushed with TMZ-supplemented solutions than with TMZ-free solutions. The cytoprotective action of TMZ also reduced interstitial fibrosis and the numbers of infiltrating CD4- and CD8-positive cells. CONCLUSION: These results indicate that the condition of cold preservation may influence long-term kidney graft functions and suggest that, to a certain extent, TMZ reduces the degree of interstitial fibrosis.     

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.     

Polyethylene glycol reduces the inflammatory injury due to cold ischemia/reperfusion in autotransplanted pig kidneys

BACKGROUND: The conditions of storage of donor kidney may influence the deleterious consequences of ischemia/reperfusion injury (IRI) on delayed graft function. Since polyethylene glycol (PEG) can protect renal tubule cells against cold injury, we tested the effects of adding PEG 20 kD to ice-cold preservation solutions on the IRI of autotransplanted pig kidneys. METHODS: The pigs' left kidneys were removed, cold-flushed with University of Wisconsin (UW) or simplified high K+ or high Na+ solutions with or without 30 g/L PEG 20M and stored for 48 hours at 4 degrees C. The kidneys were then autotransplanted and the contralateral kidneys were removed. Kidney biopsies were then performed and renal function parameters were analyzed over 8 to 12 weeks following surgery. RESULTS: The kidneys cold-flushed with PEG-supplemented solutions on day 7 post-transplantation were better preserved and exhibited less marked nuclear tubular cell damage than the kidneys cold-flushed with the UW solution alone. PEG also almost completely inhibited the overexpression of major histocompatibility complex class II that was detected in epithelial tubule cells from kidneys cold-flushed with the UW solution. PEG also significantly reduced the number of CD4+ T lymphocytes and limited the infiltration of macrophages/monocytes and the progression of interstitial fibrosis in the 8- to 12-week post-transplanted kidneys. Moreover, pigs autotransplanted with kidneys flushed with PEG-supplemented solutions had the best renal function and the lowest levels of proteinuria. CONCLUSIONS: These findings indicate that PEG inhibits the early inflammatory response due to IRI, improves renal function, and may prevent the progression of interstitial fibrosis in the long-term autotransplanted pig kidney.     

Protection of autotransplanted pig kidneys from ischemia-reperfusion injury by polyethylene glycol

BACKGROUND: Ischemia-reperfusion injury (IRI) is often responsible for graft rejection and leads to delayed graft function of cadaveric kidneys. We have shown that adding polyethylene glycol (PEG 20M) to the preservation solutions helps protect isolated perfused pig kidneys against cold ischemia and reperfusion injury. METHODS: We compared the effects of adding PEG to a simplified high-K+ perfusion solution of cold-stored kidneys to Euro-Collins or University of Wisconsin solutions on the function of reperfused autotransplanted pig kidneys. The left kidney was cold-flushed with the preservation solutions and stored for 48 hr at 4 degrees C before reimplantation. Creatinine clearance and fractional excretion of sodium were analyzed 2 days before surgery and over 7 days after transplantation. Histological sections were obtained 40 min after reperfusion and on day 7 after surgery. RESULTS: Adding PEG to the perfusate significantly reduced IRI from autotransplanted pig kidneys. Creatinine clearance was significantly higher and fractional excretion of sodium was significantly lower in pigs transplanted with kidneys cold-flushed with PEG-supplemented perfusate than in those flushed with Euro-Collins or University of Wisconsin solutions. PEG supplementation also better preserved the integrity of kidney cells and markedly reduced interstitial cell infiltrates. CONCLUSION: PEG protects against IRI and reduces early cellular inflammation. PEG may impair the recruitment and migration of leukocytes into retransplanted pig kidneys. Cold preservation of donor organs with PEG-supplemented solutions may therefore help limit IRI in human renal transplantation.     

Kidney transplantation from elderly donors: a prospective randomized study comparing celsior and UW solutions

AIM: The aim of present study was to assess the effect of Celsior as compared with University of Wisconsin (UW) solution on immediate and long-term function of kidney transplants harvested from elderly donors. METHODS: A prospective multicenter randomized study was designed to evaluate the efficacy of Celsior versus UW solution for the clinical preservation of the kidney. Fifty renal transplants were performed from donors over 60 years old. Twenty-five kidneys were stored in Celsior and 25 in UW solution. The groups were comparable with regard to donor and recipient characteristics. Renal function outcomes were compared by evaluating delayed graft function rates, daily urinary output, as well as the evolution of mean serum creatinine at 1, 3, 5, 7, and 15 days. RESULTS: The warm ischemia time was 42.4 +/- 11 minutes among Celsior vs 46.9 +/- 17.9 minutes in the UW cohort (P = NS). The cold ischemia time was 18 +/- 4.5 hours in Celsior and 19 +/- 6.5 hours in UW (P = NS). Delayed graft function occurred in 48% of the Celsior group and in 52% of the UW group (P = NS). Mean serum creatinine levels and mean daily urinary output were also similar. One- and 5-year graft survivals of kidneys preserved with Celsior were 91.8% and 79.3% compared with 96% and 87.4% for UW without any significant statistical difference. CONCLUSIONS: Our data show that the preservation of kidneys from elderly donors in Celsior solution is equivalent to that of UW solution.     

Trimetazidine reduces renal dysfunction by limiting the cold ischemia/reperfusion injury in autotransplanted pig kidneys

Ischemia/reperfusion injury leads to delayed graft function, which is a major problem in kidney transplantation. This study investigated the effects of adding trimetazidine (TMZ) to the perfusate of cold-stored kidneys on the function of reperfused autotransplanted pig kidney. The left kidney was removed and cold-flushed with Euro-Collins (EC), or University of Wisconsin (UW) solutions with or without 10(-6)M TMZ and stored for 48 h at 4 degrees C. The kidneys were then autotransplanted and the contralateral kidneys were removed. Several parameters were analyzed over the 14 d after transplantation. The survival rate was 57% in pigs transplanted with kidneys cold-flushed with UW and 43% for those flushed with EC solution; it was 100% for pigs having kidneys cold-flushed with TMZ-supplemented UW and EC solutions. The functions of the transplanted kidneys were also better preserved after cold flush with TMZ-supplemented solutions than with TMZ-free solutions. Creatinine clearance was higher and the urinary excretion of trimethylamine-N-oxide and dimethylamine, used as markers of renal medulla injury, were lower in animals transplanted with kidneys cold-flushed with TMZ-supplemented solutions than with TMZ-free solutions. The cytoprotective action of TMZ also reduced interstitial and peritubular inflammation and the numbers of infiltrating mononuclear CD45+and CD3+ T cells. These results indicate that the tissue damage due to ischemia/reperfusion injury may be prevented, at least in part, by adding TMZ to preservation solutions.     

Kidney preservation with university of Wisconsin and Celsior solution: a prospective multicenter randomized study

BACKGROUND: Although the University of Wisconsin (U.W.) solution continues to be the most commonly used for intra-abdominal organs, a new solution, Celsior, already used for heart and lungs, has been proposed for kidney and liver preservation. The aim of this research was to assess the effect of Celsior as compared with U.W. on immediate graft function and a 2-year follow-up of kidney transplants. METHODS: A prospective multicenter randomized study was designed to evaluate the efficacy of the Celsior solution in the clinical preservation of the kidney. In this report, we present the data collected as of September 2000. One hundred donors were included in the trial resulting in 187 renal transplants. Ninety-nine kidneys were stored in Celsior solution and 88 in U.W. solution. The groups were comparable with regard to donor and recipient characteristics. RESULTS: Delayed graft function occurred in 31.3% of the Celsior group and in 33.9% of the U.W. group (P=n.s.). Mean serum creatinine levels and mean daily urinary output were also comparable. Two year graft survival in kidneys preserved with Celsior was 84% as compared with 75% for U.W.-preserved kidneys without any significant statistical difference. CONCLUSIONS: Our data show that the preservation of kidneys in Celsior solution in a clinical setting is equivalent to that of U.W. solution. When using Celsior during multiple-organ donor harvesting it would be possible to perform an in situ flush of all intra-abdominal and intrathoracic organs with a single cold storage 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.     

An automated and portable low-flow pulsatile perfusion system for organ preservation

While machine preservation reduces the incidence of delayed graft function in renal transplant recipients, it is only used in 10% of kidney transplantations. The performance of our portable, lowflow-pulsatile organ perfusion system was examined in a canine kidney autotransplantation model. Grafts were stored for 72 h by simple cold preservation in University of Wisconsin (UW) solution, or by high or low-flow machine preservation. After preservation, the grafts were autotransplanted and the animals were followed for 15 days. Graft function was better in machine-preserved kidneys. Tissue biochemistry indicated that machine preservation resulted in higher levels of adenine nucleotides and better histological integrity than the cold storage. While histology and biochemistry of machine-preserved groups were similar, electromicroscopy of high-flow grafts showed mild accumulation of intravenous debris and endothelial swelling. This study shows that a simplified machine perfusion technique is effective for organ preservation.     

Modulation of peripheral-type benzodiazepine receptor levels in a reperfusion injury pig kidney-graft model

BACKGROUND: Ischemia-reperfusion injury is associated with an increased risk of acute rejection, delayed graft function, or chronic graft dysfunction. Mitochondria play a central role in this process. METHODS: Using an autotransplantation pig kidney model, both early (40 min and 7 days) and late (2-16 weeks) changes in renal function and morphology were determined after different periods of cold ischemia in University of Wisconsin or Euro-Collins solutions. We have also investigated the expression of the peripheral-type benzodiazepine receptor (PBR), which is also critical in maintaining outer mitochondrial membrane stability. RESULTS: Function of the kidneys was better preserved after 1 hr and 24 hr than after 48 hr and 72 hr in Euro-Collins and University of Wisconsin solutions. Medulla injury was reduced in 1 hr-preserved and 24 hr-preserved groups. PBR was found to be present in epithelial cells of the deep cortical and outer medulla in both normal human and well-preserved pig kidneys. PBR expression was modulated by ischemia-reperfusion injury and the concurrent tubular injury and repair processes. CONCLUSION: This study indicates that PBR expression correlates with the quality of kidney preservation and might serve as an index of kidney and mitochondria viability. Moreover, these data suggest that PBR might be involved in membrane biogenesis during reperfusion. In addition, considering the identical localization of PBR in human and pig kidneys, these findings could have a direct application in human clinical settings of kidney pathology.     

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.     

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.     

Effect of IGL-1, a new preservation solution, on kidney grafts (a pre-clinical study)

Abstract Ischemia-reperfusion injury conditions short-term and long-term graft function. The effects of the inversion of K⁺ and Na⁺ concentrations and substitution with polyethylene glycol for hydroxyethyl starch in University of Wisconsin (K-UW) solution were evaluated in isolated perfused rat kidneys and in autotransplanted pig kidneys. In the rat model kidneys were cold-stored for 24 h in K-UW or Na-UW or Na-PEG UW solutions (IGL-1 solution). Fractional sodium reabsorption and glomerular filtration rate was better in kidneys preserved in Na-UW and IGL-1 solution than those preserved in K-UW solution. In the pig model the left kidney was harvested and preserved in K-UW or IGL-1 solution for 24 h and then transplanted. In the autotransplanted pig model, kidneys preserved in IGL-1 solution showed a better function and a significant reduction of MHC class II expression, cellular apoptosis and interstitial fibrosis. In conclusion, kidneys preserved in IGL-1 solution tolerated ischemia/ reperfusion injury better than those preserved in K-UW solution.     

Anti-thrombin Therapy During Warm Ischemia and Cold Preservation Prevents Chronic Kidney Graft Fibrosis in a DCD Model

Ischemia reperfusion injury (IRI) is pivotal for renal fibrosis development via peritubular capillaries injury. Coagulation represents a key mechanism involved in this process. Melagatran® (M), a thrombin inhibitor, was evaluated in an autotransplanted kidney model, using Large White pigs. To mimic deceased after cardiac death donor conditions, kidneys underwent warm ischemia (WI) for 60 min before cold preservation for 24 h in University of Wisconsin solution. Treatment with M before WI and/or in the preservation solution drastically improved survival at 3 months, reduced renal dysfunction related to a critical reduction in interstitial fibrosis, measured by Sirius Red staining. Tissue analysis revealed reduced expression of transforming growth factor-β (TGF-β) and activation level of its effectors phospho-Smad3, Smad4 and connective tissue growth factor (CTGF) after M treatment. Fibrinolysis activation was also observed, evidenced by downregulation of PAI-1 protein and gene expression. In addition, M reduced S100A4 expression and vimentin staining, which are markers for epithelial mesenchymal transition, a major pathway to chronic kidney fibrosis. Finally, expression of oxidative stress markers Nox2 and iNOS was reduced. We conclude that inhibition of thrombin is an effective therapy against IRI that reduces chronic graft fibrosis, with a significantly positive effect on survival.     

Evaluation of a new preservative solution for cardiac graft during hypothermia.

BACKGROUND: Reports conflict on the beneficial effects of several cardioplegic solutions such as University of Wisconsin and St. Thomas' Hospital solutions. Therefore our objective was to assess the efficacy of several cardioplegic solutions for cardiac preservation by comparing University of Wisconsin modified solution (UW-1 and UW-1 + calcium = UW-2), St. Thomas' Hospital solution N degrees 1 (STH-1), Celsior solution, and a solution from our laboratory, Lyon preservation solution (LYPS). METHODS: We randomized male rats (n = 70) to 7 groups: LYPS, Celsior, STH-1, UW-1, UW-2, normal saline solution, and control. All hearts, except control hearts were preserved by cold storage (8 hours, 4 degrees C) in the various solutions. We used isolated non-working-heart preparations (left ventricular function evaluation, n = 5/group) or biopsy specimens (energetic store evaluation, n = 5/group) to assess quality of heart preservation. RESULTS: Hearts stored with the saline solution had a mean left ventricular developed pressure (LVDP) of 3.6 +/- 1.3 mm Hg. In contrast, LYPS and Celsior hearts had mean LVDP close to that of the control hearts (97 +/- 2.6, 92.1 +/- 2.2, and 122 +/- 1.9 mm Hg, respectively), whereas STH-1, UW-1, and UW-2 hearts presented an intermediate functional response (48 +/- 4, 39.9 +/- 4.1, and 69 +/- 1.8 mm Hg, respectively). The STH-1 and saline hearts showed increased release of creatine kinase (541.9 +/- 168 and 1,080.8 +/- 126.2 UI/liter, respectively). The energetic charge (EC = [(0.5 ADP + ATP)/ATP + ADP + AMP]) in Celsior, UW-2, and saline was significantly lower (p < 0.001) than in the other groups. CONCLUSION: The composition of the preservation solutions had a notable effect on myocardial viability. Our results indicated that LYPS and Celsior solutions had comparable efficacy for left ventricular function. However these solutions may offer better preservation than do UW-1, UW-2, or STH-1 solutions.     

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.     

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.     

Protective Roles of Polyethylene Glycol and Trimetazidine against Cold Ischemia and Reperfusion Injuries of Pig Kidney Graft

Ischemia‐reperfusion injury (IRI) represents an allo‐independent risk factor which favors chronic allograft nephropathy (CAN). Here we analyzed the influence of preservation solutions on the function of autotransplanted pig kidneys over 1–16 weeks after surgery. Kidneys were cold‐flushed and cold‐stored for 24 or 48 h either in University of Wisconsin (UW), modified‐UW Hôpital Edouard Herriot, polyethylene glycol 20 kDa (PEG)‐supplemented preservation solutions with low K⁺ (ECPEG) or high K⁺ (ICPEG) content. Animals autotransplanted with kidneys cold‐stored for 24 h in ECPEG exhibited the greatest levels of creatinine clearance (C_cr: 161 ± 12 mL/min, n = 10) and the lowest levels of proteinuria (0.5 ± 0.03 mg/mL) 16 weeks after surgery as compared with pigs autotransplanted with kidneys cold‐stored in the other solutions tested (C_cr ranging from 80 and 140 mL/min). Similar differences, but with lower C_cr levels, were achieved after a prolonged period of cold‐storage(48 h). ECPEG better preserved the kidneys from monocytes/macrophages and CD4⁺ T cells infiltrations, VCAM‐1 and MHC class II overexpressions and occurrence of renal interstitial fibrosis (2%) as compared with the other preservation solutions (5%–20%). Adding the anti‐ischemic drug trimetazidine (TMZ) to the preservation solutions, particularly ECPEG, further improved the quality of the week‐16 post‐transplanted kidneys (C_cr: 182 ± 12 mL/min, n = 10). These findings demonstrated that adding PEG to extracellular‐like (with low K⁺ content) preservation solutions in combination with TMZ significantly improved the long‐term outcome of kidney grafts in this model of autotransplanted pig kidney.     

Effect of IGL-1, a new preservation solution, on kidney grafts (a pre-clinical study)

Ischemia-reperfusion injury conditions short-term and long-term graft function. The effects of the inversion of K⁺ and Na⁺ concentrations and substitution with polyethylene glycol for hydroxyethyl starch in University of Wisconsin (K-UW) solution were evaluated in isolated perfused rat kidneys and in autotransplanted pig kidneys. In the rat model kidneys were cold-stored for 24 h in K-UW or Na-UW or Na-PEG UW solutions (IGL-1 solution). Fractional sodium reabsorption and glomerular filtration rate was better in kidneys preserved in Na-UW and IGL-1 solution than those preserved in K-UW solution. In the pig model the left kidney was harvested and preserved in K-UW or IGL-1 solution for 24 h and then transplanted. In the autotransplanted pig model, kidneys preserved in IGL-1 solution showed a better function and a significant reduction of MHC class II expression, cellular apoptosis and interstitial fibrosis. In conclusion, kidneys preserved in IGL-1 solution tolerated ischemia/reperfusion injury better than those preserved in K-UW solution.