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.

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.

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.).

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.

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.

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.

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. 

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. 

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.

Preservation Methods for Kidney and Liver

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 1^_1/2 hour.

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.

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.