Benefits of active oxygenation during hypothermic machine perfusion of kidneys in a preclinical model of deceased after cardiac death donors
In the first meta-analysis examining the role of HMPO2 in kidney transplantation finds it may lower adverse events, particularly in DCD cases.
By Raphaël Thuillier et al.
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Background
Deceased after cardiac death donors (DCDs) represent a valuable source of organs; however, preventing poor outcome is difficult, even with the use of machine perfusion (MP). It is of paramount importance to improve this method. We proposed to evaluate the benefits of active oxygenation during kidney graft hypothermic MP using a novel perfusion machine: Kidney Assist (KA).
Hypothermic Machine Perfusion Preservation of the DCD Kidney: Machine Effects
Kidneys from DCD donors represent a significant pool, but preservation problems exist. The study objective was to test the importance of machine type for hypothermic preservation of DCD kidneys.
By Susanne L. Lindell, et al.
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Abstract
Purpose. Kidneys from DCD donors represent a significant pool, but preservation problems exist.The study objective was to test the importance of machine type for hypothermic preservation of DCD kidneys. Methods. Adult Beagle dog kidneys underwent 45 minutes of warm in situ ischemia followed by hypothermic perfusion for 24 hours (Belzer-MPS Solution) on either anORS LifePort or a Waters RM3 using standard perfusion protocols. Kidneys were then autotransplanted, and renal function was assessed over 7 days following contralateral nephrectomy. Results. Renal vascular resistance was not different between the two pumps. After 24 hours, the oxygen partial pressure and oxygen delivery in the LifePort perfusate were significantly lower than those in the RM3 but not low enough to change lactate production. TheLifePort ran significantly colder than RM3 (2∘ versus 5∘C).The arterial pressure waveform of the RM3 was qualitatively different from the waveform of the LifePort. Preservation injury after transplantation was not different between the devices. When the LifePort was changed to nonpulsatile flow, kidneys displayed significantly greater preservation injury compared to RM3. Conclusions. Both LifePort and RM3 can be used for hypothermic machine perfusion preservation of DCD kidneys with equal outcomes as long as the duty cycle remains pulsatile.
Machine Measured Renal Resistance (MMRR) is the most sensitive tool for prediction of early renal allograft survival.
Studies have recognized the relationship among renal allograft resistance, graft function and survival. The relationship of MMRR and chronic allograft pathology remains unstudied.
By Y.Y. Yushkov et al.
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Method
Method: We performed a retrospective analysis of 1181 deceased donor kidneys transplanted in a large donor service area (DSA) from 2007-2009. All kidneys were evaluated using MMRR and Optimized Needle Biopsy Technique protocol. All biopsies were frozen section evaluations performed by a single transplant pathology laboratory for the DSA. The pathology report identified the following renal allograft parameters: 1. Total number of glomeruli/number of obsolete glomeruli (GS); 2. Tubular interstitial scarring (TIS); 3. Intimal fibrous narrowing of arteries (IFN). MMRR was measured after 3 hours of machine perfusion based on previous studies indicating this is the earliest time to predict a difference in graft survival by MMRR cohorts. Based upon MMRR, allografts were separated into three groups: < 0.2, 0.2-0.3, >0.3. Renal function at 1 year was measured using e-GFR (MDRD). ANOVA was used to correlate pre-transplant MMRR with GS, TIS, IFN and 1-year recipient e-GFR.
Machine perfusion following static cold storage preservation in kidney transplantation
Donor-matched pairanalysis of the prognostic impact of longer pump time
By Gaetano Ciancio et al.
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Summary
The impact of machine perfusion (MP) time on kidney transplant outcome is mixed in previous studies using multivariable analyses. In an analysis of 66 pairs of donor-matched adult, first transplant recipients (N = 132) with identical donor characteristics except for pump time, tests of association of shorter versus longer pump time (first versus second kidney removed) by delayed graft function(DGF), slow graft function(SGF), and biopsy proven acute rejection (BPAR) were performed using McNemar’s test. Freedom-from-BPAR, graft and patient survival, and renal function were also compared. Mean ± SD pump times for paired recipients with first and second kidneys were 22.7 ± 7.3 h and 31.2 ± 7.9 h, respectively (mean difference: 8.5 ± 4.5 h, P < .000001). There was no significant impact of pump time on DGF or SGF, with discordant pairs favoring less SGF with longer pump time (N.S.). The incidence of BPAR during the first 12 months post-transplant yielded a borderline difference favoring longer pump time (P = .09), and freedom-from-BPAR during the first 12 months was significantly more favorable for longer pump times (95% vs. 84%, P = 0.04). No differences were observed in graft and patient survival, and renal function. While offering significantly favorable protection from BPAR, this analysis of donor-matched recipient pairs corroborates longer MP (pump) times having no unfavorable effect on other clinical outcomes.
Favorable Outcomes With Machine Perfusion and Longer Pump Times in Kidney Transplantation
A Single-Center, Observational Study.
By Gaetano Ciancio et al
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Hypothermic machine perfusion (MP) preservation is used for all deceased donor kidney transplants at our center. Kidneys are placed in cold storage at retrieval, then transferred to MP on arrival. Because a lack of consensus regarding optimal use of MP still exists, we evaluated the overall impact of using MP at our center and the prognostic value of MP (Pump) time. Methods. We retrospectively analyzed 339 adult, primary deceased donor kidney transplant recipients who were pooled across three prospective, randomized immunosuppression trials (since 2000) at our center. In addition to providing overall results for delayed graft function (DGF) (requirement for dialysis in the first week), slow graft function (SGF), first biopsy-proven acute rejection (BPAR), and graft failure, stepwise logistic and Cox regression analyses were used to determine the prognostic value of pump time, particularly after controlling for other significant prognosticators.
Current State of Hypothermic Machine Perfusion Preservation of Organs: The Clinical Perspective
Focusing on the application of hypothermic perfusion technology as a topic of current interest with the potential to improve the quantity and quality of donor organs and the outcome of transplantation.
By Michael J. Taylor
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Abstract
This review focuses on the application of hypothermic perfusion technology as a topic of current interest with the potential to have a salutary impact on the mounting clinical challenges to improve the quantity and quality of donor organs and the outcome of transplantation. The ex vivo perfusion of donor organs on a machine prior to transplant, as opposed to static cold storage on ice, is not a new idea but is being re-visited because of the prospects of making available more and better organs for transplantation. The rationale for pursuing perfusion technology will be discussed in relation to emerging data on clinical outcomes and economic benefits for kidney transplantation. Reference will also be made to on-going research using other organs with special emphasis on the pancreas for both segmental pancreas and isolated islet transplantation. Anticipated and emerging benefits of hypothermic machine perfusion of organs are: (i) maintaining the patency of the vascular bed, (ii) providing nutrients and low demand oxygen to support reduced energy demands, (iii) removal of metabolic by-products and toxins, (iv) provision of access for administration of cytoprotective agents and/or immunomodulatory drugs, (v) increase of available assays for organ viability assessment and tissue matching, (vi) facilitation of a change from emergency to elective scheduled surgery with reduced costs and improved outcomes, (vii) improved clinical outcomes as demonstrated by reduced PNF and DGF parameters, (viii) improved stabilization or rescue of ECD kidneys or organs from NHBD that increase the size of the donor pool, (ix) significant economic benefit for the transplant centers and reduced health care costs, and (x) provision of a technology for ex vivo use of non-transplanted human organs for pharmaceutical development research.
For every patient that receives a transplanted organ, there are four more on the waiting list. In addition, a patient dies from the lack of a transplant almost every 11/2 hour.
By Charles Y. Lee et al.
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Summary
With the successful testing of the immunosuppressive effects of cyclosporine in transplant patients in 1978, the field of organ transplants began an exponential growth. With that, the field of organ preservation became increasingly important as the need to increase preservation time and improve graft function became paramount. However, for every patient that receives a transplanted organ, there are four more on the waiting list. In addition, a patient dies from the lack of a transplant almost every 1½ hour. To alleviate this donor crisis, there is a need to expand the donor pool to marginal donor organs. The main reason these organs are underutilized is because the current method of static preservation, simple cold storage, is ineffective. This article will provide a general review of the methods of preservation including simple cold storage, hypothermic machine perfusion, normothermic machine perfusion, and oxygen persufflation. In addition, the article will provide a review of how these dynamic preservation methods have improved the recovery and preservation of marginal donor organs including Donation after Cardiac Death and Fatty livers.
Influence of Pulsatile Perfusion Preservation on Outcomes in Kidney Transplantation from Expanded Criteria Donors
Retrospective analysis of intermediate-term outcomes in ECD kidney transplantations according to method of preservation at a single center using a standardized approach.
By Robert J Stratta et al.
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Background
Expanded criteria donors (ECDs) increase the donor organ pool, but the value of transplanting these kidneys has been questioned because of concerns about diminished survival, poorer renal function, and higher rates of delayed graft function.
Improved Immediate Renal Allograft Function After Initial Simple Cold Storage
Immediate renal allograft function has been identified as being an important variable in ultimate graft survival.
By M. L. Henry
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Summary
Immediate renal allograft function has been identified as being an important variable in ultimate graft survival.1 Simple cold storage, particularly if preserved for longer than 24 hours, can chave a high incidence of early dysfunction (ED) when cylosporine is used as immediate post transplant immunotherapy.2 Because of the importance of immediate function (IF) and our prejudice toward pulsatile perfusion (PP), we began to place all imported kidnesy previously preserved by simple cold storage onto the PP machine for preservation before transplantation at our center. The following is a description of the outcomes of this trial.
