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O'Brien Laramy M, Robinson J, Venkatramani CJ, Horn S, Steiner C, Son YJ. Drug Development Considerations for Additives to Organ Preservation Solutions. Transplantation 2025; 109:764-773. [PMID: 39375888 DOI: 10.1097/tp.0000000000005221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/09/2024]
Abstract
The addition of a novel therapeutic agent to an organ preservation solution has the potential to address unmet needs in organ transplantation and enhance outcomes for transplant recipients. However, the development expectations for novel therapeutic agents in this context are unclear because of limited precedence and published regulatory guidance documents. To address these gaps, we have articulated a drug development strategy that leverages expectations for parenteral drug products administered via more conventional routes (eg, intravenous) and provided considerations for when deviations may be justified. We have supplemented this strategy with a comparison to available regulatory guidance from the US Food and Drug Administration to highlight potential areas for further clarification. The strategy articulated here is based on Genentech's internal experience for a program intended for use in kidney transplantation.
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Affiliation(s)
| | - Jamie Robinson
- Pharma Technical Regulatory, Genentech, Inc., South San Francisco, CA
| | - C J Venkatramani
- Synthetic Molecule Pharmaceutical Sciences, Genentech, Inc., South San Francisco, CA
| | - Stephanie Horn
- Pharma Technical Regulatory-Device and Combination Products, F. Hoffmann-La Roche Ltd, Basel, Switzerland
| | - Carine Steiner
- Analytical Research & Development, Pharma Technical Development, F. Hoffmann-La Roche, Basel, Switzerland
| | - Yoen-Ju Son
- Pharma Technical Development Project and Portfolio Development, South San Francisco, CA
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2
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Leber B, Stimmeder S, Briendl K, Weber J, Rohrhofer L, Aigelsreiter A, Niedrist T, Sucher R, Stiegler P. Equal performance of HTK-based and UW-based perfusion solutions in sub-normothermic liver machine perfusion. Sci Rep 2025; 15:7601. [PMID: 40038333 PMCID: PMC11880568 DOI: 10.1038/s41598-025-90799-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 02/17/2025] [Indexed: 03/06/2025] Open
Abstract
Machine perfusion (MP) is gaining importance in liver transplantation, the only cure for many end-stage liver diseases. Varieties of different MP protocols are available. Currently, various MP protocols are available, differing not only in perfusion temperature but also in the specific perfusion solution required. We aimed to investigate the performance of an HTK-based perfusate during sub-normothermic MP (SNMP) of discarded human liver grafts compared to that of a UW-based solution. Twenty discarded livers (rejected for transplantation by all centers) were subjected to ex-vivo SNMP at 21°C with either HTK- or UW-based solution for 12 h. Perfusate and tissue samples collected before the start, after 6 h, and at the end of SNMP were analyzed for liver enzymes, along with mRNA expression of perfusate and tissue markers associated with organ damage. Hepatocellular viability was assessed by measuring bile production, monitoring pH stability, and analyzing histological changes in HE stained tissue sections. After propensity score matching 16 livers were analyzed. Overall, no differences between HTK- and UW-based solution were detected, except for an increased MLKL mRNA expression and impaired pH stability during SNMP with HTK-based perfusate. No other investigated parameters of cell injury, inflammation or hepatocellular viability supported this finding. Bile production was higher in the 6 HTK-perfused livers compared to the three UW-perfused livers that produced bile. Overall, these findings suggest that HTK performs comparably to a UW-based solution during 12 h of liver SNMP.
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Affiliation(s)
- Bettina Leber
- General, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, Neue Stiftingtalstraße 6, 8010, Graz, Austria.
| | - Sabrina Stimmeder
- General, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, Neue Stiftingtalstraße 6, 8010, Graz, Austria
| | - Kathrin Briendl
- General, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, Neue Stiftingtalstraße 6, 8010, Graz, Austria
| | - Jennifer Weber
- General, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, Neue Stiftingtalstraße 6, 8010, Graz, Austria
| | - Lisa Rohrhofer
- General, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, Neue Stiftingtalstraße 6, 8010, Graz, Austria
| | - Ariane Aigelsreiter
- Diagnostic and Research Institute of Pathology, Medical University of Graz, Neue Stiftingtalstraße 6, 8010, Graz, Austria
| | - Tobias Niedrist
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Neue Stiftingtalstraße 6, 8010, Graz, Austria
| | - Robert Sucher
- General, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, Neue Stiftingtalstraße 6, 8010, Graz, Austria
| | - Philipp Stiegler
- General, Visceral and Transplant Surgery, Department of Surgery, Medical University of Graz, Neue Stiftingtalstraße 6, 8010, Graz, Austria
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Akdogan M, Demirbakan K, Baydilek Y, Yuksel Y. Lactated Ringer as Preservation Solution in Living Donor Renal Transplantation. Transplant Proc 2023:S0041-1345(23)00313-5. [PMID: 37202302 DOI: 10.1016/j.transproceed.2023.04.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Accepted: 04/25/2023] [Indexed: 05/20/2023]
Abstract
BACKGROUND Optimal organ preservation remains a critical hallmark event in renal transplantation as it is the supply line. Previous studies have shown that the choice of preservation solution may affect transplant outcomes. In this study, we aimed to present the early follow-up results of the graft and patients, using lactated Ringer to preserve kidney allografts with living donors. METHODS The results of 97 living donor transplant operations performed in Sanko University Hospital were evaluated retrospectively. The patient's evaluation included demographics, dialysis time duration, renal replacement method, primary disease, comorbidity, surgical and clinical complications in the acute period, graft functions, blood levels of calcineurin inhibitor drugs, anastomotic renal artery, warm ischemia, and cold ischemia times. RESULTS Donor (49 men, 50.5%) and recipient (58 men, 59.7%) demographics, HLA compatibility (mismatch), hospitalization days, and length of warm and cold ischemic time are summarized in Table 1. Primary nonfunction was not defined in any patients, but delayed graft function was observed during the follow-up of 3 patients (3.09%), who were all hypotensive in the post-transplantation period, and positive inotropic infusion was needed for hemodynamic stability. CONCLUSIONS Lactated Ringer demonstrated efficacy in terms of patient and graft survival, and its lower cost represents a financial advantage, so it can be used in living donor kidney transplantation because it is safe, effective, and inexpensive. Standard preservation solutions may still be recommended in cases with long cold ischemia times, such as paired exchange transplants and cadaveric transplants. Thus, randomized controlled studies are needed for further investigation.
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Affiliation(s)
- Mehtap Akdogan
- Department of Nephrology, Sanko University Medical School, Gaziantep, Turkey.
| | - Kenan Demirbakan
- Department of General Surgery, Sanko University Medical School, Gaziantep, Turkey
| | - Yunus Baydilek
- Department of Anesthesiology, Sanko University Medical School, Gaziantep, Turkey
| | - Yucel Yuksel
- Department of General Surgery, Sanko University Medical School, Gaziantep, Turkey
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De Beule J, Fieuws S, Monbaliu D, Naesens M, Sainz-Barriga M, Sprangers B, Kuypers D, Pirenne J, Jochmans I. The effect of IGL-1 preservation solution on outcome after kidney transplantation: A retrospective single-center analysis. Am J Transplant 2021; 21:830-837. [PMID: 32888364 DOI: 10.1111/ajt.16302] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 08/25/2020] [Accepted: 08/26/2020] [Indexed: 01/25/2023]
Abstract
Institut Georges Lopez-1 (IGL-1) solution is increasingly used for kidney preservation, although little information on outcomes is available. Outcomes of all deceased donor kidneys preserved by IGL-1, University of Wisconsin solution (UW), or histidine-tryptophan-ketoglutarate (HTK) and transplanted in our center (2000-2018) were analyzed. Multivariable analysis for delayed graft function (DGF), functional DGF, estimated glomerular filtration rate (eGFR, CKD-EPI equation), proteinuria, acute rejection, death-censored graft loss, and patient survival were performed. A double robust approach, consisting of propensity score weighting and correction for confounders, minimized the risk of bias. In total, 1943 transplants were included: 234 with IGL-1, 1046 with UW, and 663 with HTK. As IGL-1 was only introduced in 2014, a prespecified sensitivity analysis of 917 kidneys (2010-2018) was performed using the same statistical approach. After weighting, IGL-1 retained a higher proportion of kidneys donated after circulatory death (DCD). IGL-1 was not independently associated with any of the outcomes when compared to UW or HTK. Sensitivity analysis between 2010 and 2018 showed similar results. In this retrospective analysis, using robust methodology to reduce the risk of bias, IGL-1 preservation results in equal outcomes compared to UW or HTK, despite more DCD transplants in the IGL-1 group.
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Affiliation(s)
- Julie De Beule
- Laboratory of Abdominal Transplantation, Transplantation Research Group, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium.,Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Steffen Fieuws
- Interuniversity Centre for Biostatistics and Statistical Bioinformatics, Department of Public Health, KU Leuven, Leuven, Belgium
| | - Diethard Monbaliu
- Laboratory of Abdominal Transplantation, Transplantation Research Group, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium.,Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Maarten Naesens
- Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium.,Department of Nephrology, University Hospitals Leuven, Leuven, Belgium
| | - Mauricio Sainz-Barriga
- Laboratory of Abdominal Transplantation, Transplantation Research Group, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium.,Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Ben Sprangers
- Department of Nephrology, University Hospitals Leuven, Leuven, Belgium.,Laboratory of Molecular Immunology (Rega Institute), Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium
| | - Dirk Kuypers
- Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium.,Department of Nephrology, University Hospitals Leuven, Leuven, Belgium
| | - Jacques Pirenne
- Laboratory of Abdominal Transplantation, Transplantation Research Group, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium.,Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Ina Jochmans
- Laboratory of Abdominal Transplantation, Transplantation Research Group, Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium.,Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
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5
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Ischémie–reperfusion. Liquides de conservation et machines de perfusion en transplantation rénale. Prog Urol 2016; 26:964-976. [DOI: 10.1016/j.purol.2016.08.007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2016] [Revised: 08/20/2016] [Accepted: 08/22/2016] [Indexed: 12/12/2022]
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Latchana N, Peck JR, Whitson BA, Henry ML, Elkhammas EA, Black SM. Preservation solutions used during abdominal transplantation: Current status and outcomes. World J Transplant 2015; 5:154-164. [PMID: 26722644 PMCID: PMC4689927 DOI: 10.5500/wjt.v5.i4.154] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Revised: 09/01/2015] [Accepted: 11/11/2015] [Indexed: 02/05/2023] Open
Abstract
Organ preservation remains an important contributing factor to graft and patient outcomes. During donor organ procurement and transportation, cellular injury is mitigated through the use of preservation solutions in conjunction with hypothermia. Various preservation solutions and protocols exist with widespread variability among transplant centers. In this review of abdominal organ preservation solutions, evolution of transplantation and graft preservation are discussed followed by classification of preservation solutions according to the composition of electrolytes, impermeants, buffers, antioxidants, and energy precursors. Lastly, pertinent clinical studies in the setting of hepatic, renal, pancreas, and intestinal transplantation are reviewed for patient and graft survival as well as financial considerations. In liver transplants there may be some benefit with the use of histidine-tryptophan-ketoglutarate (HTK) over University of Wisconsin solution in terms of biliary complications and potential cost savings. Renal grafts may experience increased initial graft dysfunction with the use of Euro-Collins thereby dissuading its use in support of HTK which can lead to substantial cost savings. University of Wisconsin solution and Celsior are favored in pancreas transplants given the concern for pancreatitis and graft thrombosis associated with HTK. No difference was observed with preservation solutions with respect to graft and patient survival in liver, renal, and pancreas transplants. Studies involving intestinal transplants are sparse but University of Wisconsin solution infused intraluminally in combination with an intra-vascular washout is a reasonable option until further evidence can be generated. Available literature can be used to ameliorate extensive variation across centers while potentially minimizing graft dysfunction and improving associated costs.
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Abstract
PURPOSE OF REVIEW To summarize the history of organ preservation and place into this context the current trends in preservation. RECENT FINDINGS Multiple large retrospective studies have analyzed cold preservation solutions in an attempt to determine superiority with largely negative results. Experimental and some clinical studies have examined machine perfusion of procured grafts, in both hypothermic and normothermic contexts with variable, but promising, results. Lastly, there are experimental efforts to evaluate mesenchymal stem cell therapy on rehabilitation of marginal donor organs. SUMMARY New trends in organ preservation may soon translate into more efficient use of the limited donor pool.
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8
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Preservation solutions for static cold storage of abdominal allografts: which is best? Curr Opin Organ Transplant 2014; 19:100-7. [PMID: 24553501 DOI: 10.1097/mot.0000000000000063] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
PURPOSE OF REVIEW To update the reader on the recent literature in liver, kidney, pancreas, and intestine static cold preservation, and to identify which solutions are most advantageous for each organ. RECENT FINDINGS The comparison of randomized trials of histidine-tryptophan-ketoglutarate (HTK), Celsior, and University of Wisconsin solutions has shown equivalent risk of delayed graft function after kidney transplantation. Similar outcomes have been observed after pancreas preservation with University of Wisconsin, HTK, and Celsior solution. In live-donor liver transplantation, University of Wisconsin and HTK solution have shown equivalent results, whereas in the recent trials of deceased-donor liver transplantation, University of Wisconsin, HTK, and Celsior solutions have shown equivalence. Contrary to the most clinical trials, national registry data in kidney, pancreas, and liver transplantation demonstrate more detrimental effects and earlier graft loss after preservation with HTK versus University of Wisconsin solution. Early outcomes after intestinal transplantation with University of Wisconsin or HTK solution have shown no significant difference and animal studies indicate intraluminal preservation may be beneficial. SUMMARY The University of Wisconsin solution is the standard criterion static cold preservation for the procurement of liver, kidney, pancreas, and intestine. University of Wisconsin, HTK, and Celsior solutions all provide similar allograft outcomes in most clinical trials, but subtle differences have become more apparent in the recent studies and registry reports.
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9
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Cavaillé-Coll M, Bala S, Velidedeoglu E, Hernandez A, Archdeacon P, Gonzalez G, Neuland C, Meyer J, Albrecht R. Summary of FDA workshop on ischemia reperfusion injury in kidney transplantation. Am J Transplant 2013; 13:1134-48. [PMID: 23566221 DOI: 10.1111/ajt.12210] [Citation(s) in RCA: 112] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2012] [Revised: 01/24/2013] [Accepted: 01/31/2013] [Indexed: 01/25/2023]
Abstract
The Food and Drug Administration (FDA) held an open public workshop in September 2011 to discuss the current state of science related to the effects of ischemia reperfusion injury (IRI) on outcomes in kidney transplantation. Topics included the development of IRI and delayed graft function (DGF), histology and biomarkers, donor factors, recipient factors, organ quality and organ preservation by means of cold storage solutions or machine perfusion. Various mechanisms of injury and maladaptive response to IRI were discussed as potential targets of intervention. Animal models evaluating specific pathophysiological pathways were presented, as were the limitations of extrapolating animal results to humans. Clinical trials of various drug products administered in the peri-transplant period were summarized; a few demonstrated early improvements in DGF, but none demonstrated an improvement in late graft function. Clinical trial design for IRI and DGF were also discussed.
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Affiliation(s)
- M Cavaillé-Coll
- Division of Transplant and Ophthalmology Products, Office of Antimicrobial Products, Office of New Drugs, Center for Drug Evaluation and Research, FDA, Silver Spring, MD, USA
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10
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Review of Randomized Clinical Trials of Donor Management and Organ Preservation in Deceased Donors. Transplantation 2012; 94:425-41. [DOI: 10.1097/tp.0b013e3182547537] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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11
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Grossini E, Molinari C, Pollesello P, Bellomo G, Valente G, Mary D, Vacca G, Caimmi P. Levosimendan protection against kidney ischemia/reperfusion injuries in anesthetized pigs. J Pharmacol Exp Ther 2012; 342:376-88. [PMID: 22566668 DOI: 10.1124/jpet.112.193961] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/08/2025] Open
Abstract
Ischemia/reperfusion (I/R) injury is an important cause of acute renal failure because of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine any possible protective effects of levosimendan in an in vivo pig model of renal I/R injury. In 40 anesthetized pigs (eight groups of five pigs each), I/R was induced by clamping-reopening the left renal artery. During ischemia, in three groups of pigs, levosimendan and the multiorgan preservation solution Custodiol, alone or in combination with levosimendan, were infused in the renal artery. In two other groups of animals, levosimendan in combination with Custodiol was administered after the intrarenal nitric-oxide (NO) synthase blocker N(ω)-nitro-L-arginine methyl ester (L-NAME) or the mitochondrial ATP-sensitive K(+) channel (K(ATP) channel) inhibitor 5-hydroxydecanoate (5-HD). In the other animals, saline, L-NAME, or 5-HD were administered alone. Throughout the experiments, urinary N-acetyl-β-glucosaminidase (NAG) release was measured, and renal function was assessed. Moreover, renal biopsy samples were taken for the detection of apoptosis and tissue peroxidation. In pigs treated with levosimendan or the combination of levosimendan and Custodiol, NAG, peroxidation, and apoptotic markers were lower than in animals treated with Custodiol alone. In addition, renal function was better preserved, and cell survival and antioxidant systems were more activated. All beneficial effects were prevented by L-NAME and 5-HD. In conclusion, levosimendan alone or in combination with Custodiol exerted better protection against renal I/R injuries than Custodiol alone through antioxidant, antiapoptotic, and prosurvival actions depending on mitochondrial K(ATP) channels and NO-related mechanisms.
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Affiliation(s)
- Elena Grossini
- Department of Translational Medicine, University East Piedmont, via Solaroli 17, I-28100 Novara, Italy.
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O'Callaghan JM, Knight SR, Morgan RD, Morris PJ. Preservation solutions for static cold storage of kidney allografts: a systematic review and meta-analysis. Am J Transplant 2012; 12:896-906. [PMID: 22221739 DOI: 10.1111/j.1600-6143.2011.03908.x] [Citation(s) in RCA: 81] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
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.
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Affiliation(s)
- J M O'Callaghan
- Centre for Evidence in Transplantation, Royal College of Surgeons of England and London School of Hygiene and Tropical Medicine, University of London, London, UK.
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Worku D, Laluf S, McGee J, Goswami M, VanMeter K, Slakey DP. P-selectin expression in cold preserved kidneys in University of Wisconsin and histidine-tryptophan-ketoglutarate solutions. J Surg Res 2009; 169:125-31. [PMID: 20036384 DOI: 10.1016/j.jss.2009.09.021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2009] [Revised: 08/15/2009] [Accepted: 09/09/2009] [Indexed: 01/08/2023]
Abstract
The differences and efficacy of standard preservation solutions in kidney transplantation, University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK), remain a topic of debate in recent clinical studies. P-selectins represent glycoproteins expressed on endothelial cells and platelets responsible for the earliest events in ischemia/reperfusion injury in kidney transplantation. This study aimed to compare the levels of P-selectin expression between cold preserved kidney tissues in UW and HTK solutions. Thirty kidneys were procured from male Lewis rats and stored in cold (4°C) solutions for periods of 4, 12, 16, 20, and 24h. Group 1 (n=15) kidneys were stored in UW solutions, and group 2 (n=15) kidneys were submerged in HTK solutions. At the end of each time point, the kidneys underwent preparation and levels of P-selectin expression in the tissues were measured using Immunoblot analyses and adjusted volumetric quantification of Western blot signals. For all periods of cold preservation, P-selectin expression was significantly down-regulated in kidney tissues stored in UW compared with HTK solutions (P<0.001). In summary, UW demonstrated a significant benefit over HTK solution in down-regulating P-selectin expression in cold preserved kidney grafts.
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Affiliation(s)
- Dawit Worku
- Department of Surgery, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
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Bellamy CA, Nicely B, Mattice BJ, Teaster R. Comparative Analysis of Clinical Efficacy and Cost between University of Wisconsin Solution and Histidine-Tryptophan-Ketoglutarate. Prog Transplant 2008; 18:166-71; quiz 172. [DOI: 10.1177/152692480801800304] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Objective To compare University of Wisconsin solution (Viaspan), the universal standard for organ preservation, with histidine-tryptophan-ketoglutarate solution. An analysis of each solution, in reference to clinical trials with specific organs, is presented and assessed to find the efficacy of each in a clinical environment. Also to view each solution from an economical standpoint, and in the end develop an overall understanding of the key similarities and differences between each solution in order to assess appropriate use of each in a clinical setting. Data Sources A literature search was conducted by using PubMed, MEDLINE, BIOSIS, Embase, and other online data bases to find the most recent studies of University of Wisconsin and histidine-tryptophan-ketoglutarate solutions. Search terms included University of Wisconsin solution, histidine-tryptophan-ketoglutarate, preservation solution, cost analysis, biliary complication, and other related subjects. Study Selection Previous research was selected from the literature search to provide basic information on the 2 solutions and also to provide clinical examples of each solution and the efficacy of each with specific organs. Data Synthesis Information and published articles on the 2 solutions were gathered for descriptive and comparative purposes. Conclusions The 2 solutions appear equally effective in organ preservation. Each solution has its own organ-specific qualities, and each has different complications. The studies reviewed here indicate that the differences are minor and thus suggest that the 2 solutions are equally acceptable for clinical use. Of the 2 solutions, histidine-tryptophan-ketoglutarate costs less than University of Wisconsin solution.
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Bellamy C, Nicely B, Mattice B, Teaster R. Comparative analysis of clinical efficacy and cost between University of Wisconsin solution and histidine-tryptophan-ketoglutarate. Prog Transplant 2008. [DOI: 10.7182/prtr.18.3.668321g5v172325j] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
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