Waters Medical Systems

Meta-Analysis and Clinical Guidance of Oxygenated Hypothermic Machine Perfusion for Kidney Transplantation

In the first meta-analysis examining the role of HMPO2 in kidney transplantation finds it may lower adverse events, particularly in DCD cases.

By Degong Jia et al.

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Highlights

  • HMPO2 reduced the number of patients with adverse events and the proportion of severe adverse events.
  • HMPO2 performed better in donation after cardiac death, and continuous
  • HMPO2 was superior to end-HMPO2.

Background

It remains unclear whether oxygenated hypothermic machine perfusion (HMPO2) during kidney preservation is beneficial for prognosis.

Methods

A comprehensive search of databases and clinical trial registries was conducted to identify eligible studies on HMPO2 application during kidney transplantation. A multi-subgroup analysis was further conducted to explore the heterogeneity among studies.

Results

Compared to the control treatment, HMPO2 did not significantly alter the incidence of postoperative acute rejection, graft survival, patient mortality, delayed graft function (DGF), functional DGF, primary nonfunction, or estimated glomerular filtration rate, whereas the warm ischemia time appeared to be longer. However, the number of patients with adverse events and the proportion of severe adverse events were reduced in the HMPO2 group. Subgroup analysis indicated that HMPO2 performed better in donation after cardiac death (DCD), and continuous HMPO2 was superior to end-HMPO2.


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The Evolution of Kidney Graft Preservation Through the Years

By Andres Calva Lopez et al.

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Abstract

Chronic kidney disease (CKD) is a prevalent disease affecting almost 10% of the world’s population, with many cases progressing to end-stage kidney disease (ESKD). Kidney transplantation (KT) is the gold-standard treatment for ESKD. Due to growing KT waitlists, the deceased kidney donor (DKDs) criteria have expanded to increase the number of available kidney grafts. Kidney graft preservation ensures optimal graft function after KT. Static cold storage (SCS) as a preservation method is still widely used. Hypothermic machine perfusion (HMP) has proven to decrease delayed graft function (DGF) and increase graft survival. Most recent studies advocate for the use of HMP regardless of donor type. However, emerging technologies, such as hypothermic oxygenated machine perfusion (HOPE) and normothermic machine perfusion (NMP), have shown promising results in specific scenarios. This review aims to provide a summary of the well-established kidney graft preservation methods and their outcomes, as well as novel technological advances that allow for newer preservation strategies.

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The Role of Glutathione in Protecting against the Severe Inflammatory Response Triggered by COVID-19


We highlight the relevance of restoring GSH levels in the attempt to protect the most vulnerable subjects from severe symptoms of COVID-19.


By Francesca Silvagno et al.

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Summary

The novel COVID-19 pandemic is affecting the world’s population differently: mostly in the presence of conditions such as aging, diabetes and hypertension the virus triggers a lethal cytokinestorm and patients die from acute respiratory distress syndrome, whereas in many cases the dis‐ease has a mild or even asymptomatic progression. A common denominator in all conditions associated with COVID-19 appears to be the impaired redox homeostasis responsible for reactive oxygen species (ROS) accumulation; therefore, levels of glutathione (GSH), the key antioxidant guardian in all tissues, could be critical in extinguishing the exacerbated inflammation that triggers organ failure in COVID-19. The present review provides a biochemical investigation of the mechanisms leading to deadly inflammation in severe COVID-19, counterbalanced by GSH. The pathways competing for GSH are described to illustrate the events concurring to cause a depletion of endogenous GSH stocks. Drawing on evidence from literature that demonstrates the reduced levels of GSH in the main conditions clinically associated with severe disease, we highlight the relevance of restoring GSH levels in the attempt to protect the most vulnerable subjects from severe symptoms of COVID-19. Finally, we discuss the current data about the feasibility of increasing GSH levels, which could be used to prevent and subdue the disease.


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Original and generic preservation solutions in organ transplantation. A new paradigm?

As generics enter the organ preservation space, researchers question if they meet the same standards critical to transplant success.

By Joan Roselló-Catafau et al.

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Solid organ transplantation is a very complex process, in which the storage of the graft in a preservation solution is mandatory in order to extend ischemic times and contain further damage. The condition in which the organ is transplanted is critical for the outcome of the organ recipient. The recent emergence of generic versions of organ preservation solutions (solutions with the same composition and under the same legislation as the original versions, but with different brands) compelled us to study whether the standards are maintained when comparing the original and its generic counterpart. Along these lines, we discuss and comment on some aspects concerning this issue of general interest in the organ transplantation field.

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Delayed Kidney Transplantation After 83 Hours of Cold Ischemia Time In Combined Liver-Kidney Transplant

The field of kidney transplantation (KTx) has evolved with hypothermic machine perfusion (HMP) to extend the time between procurement and transplant expanding the shipping distance (e.g. East-to-West coast in the U.S.).

By Burein Ekser et al.

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Summary

The field of kidney transplantation (KTx) has evolved with hypothermic machine perfusion (HMP) to extend the time between procurement and transplant expanding the shipping distance (e.g. East-to-West coast in the U.S.). HMP also enabled to limit the harmful effect of cold ischemia time (CIT), therefore, decreased the rate of delayed graft function (DGF).1 Studies on long-term effects of CIT showed proportional increase in DGF and graft failure with each hour of CIT.2 In case of combined liver-kidney transplantation (CLKTx), the recipient is critically ill with coagulopathy, hyperbilirubinemia, and on pressor(s) support immediately after liver transplantation (LTx), creating an unfavorable hostile environment for the kidney allograft. Therefore, it is preferable that KTx is delayed with the support of HMP.3 We previously showed a novel approach of delaying the kidney portion of CLKTx in a cohort of 61 patients with a mean CIT of 50 hours (range 20-81 hours) with excellent outcomes in patient survival.3,4 Our studies confirmed that DGF is the most important negative predictor of patient survival in this complex group of patients.

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A Novel Approach in Combined Liver and Kidney Transplantation With Long-Term Outcomes

In the first meta-analysis examining the role of HMPO2 in kidney transplantation finds it may lower adverse events, particularly in DCD cases.

By Burcin Ekser et al.

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Background

The aim of this study was to compare the outcomes of simultaneous and delayed implantation of kidney grafts in combined liver-kidney transplantation (CLKT).

Liver allocation according to the model for end-stage liver disease (MELD) system was introduced in 2002. As a direct consequence, there was a rapid increase in the yearly number of combined liver-kidney transplants (CLKTs), as patients with renal failure had a consistently high MELD score.1 As many as 30% of liver transplant (LT) patients have renal insufficiency at the time of transplant, contributing significantly to their overall MELD score.1,2 The selection of candidates for CLKT, however, is complex because renal disease associated with liver failure may be acute or chronic in nature. As a consequence, there is no well-defined allocation policy for patients listed for CLKT.3,4 Despite ‘‘proposed’’ listing criteria for CLKT, several transplant centers use more liberal selection criteria to minimize post-LT kidney failure.5,6 Nadim et al7 conducted a survey of 88 transplant centers that perform CLKT in the United States to determine practice patterns. The majority of centers in this study (73%) used dialysis duration for acute renal failure as a cutoff for CLKT listing, with duration varying between >4 and >8 weeks. There were 30% of centers that used any acute kidney injury alone as adequate criterion for determining the need for CLKT.7

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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).

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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. 

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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.

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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.

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