Elsevier

The Lancet

Volume 381, Issue 9868, 2–8 March 2013, Pages 727-734
The Lancet

Articles
Effect of donor age and cold storage time on outcome in recipients of kidneys donated after circulatory death in the UK: a cohort study

https://doi.org/10.1016/S0140-6736(12)61685-7Get rights and content

Summary

Background

Use of kidneys donated after controlled circulatory death has increased the number of transplants undertaken in the UK but there remains reluctance to use kidneys from older circulatory-death donors and concern that kidneys from circulatory-death donors are particularly susceptible to cold ischaemic injury. We aimed to compare the effect of donor age and cold ischaemic time on transplant outcome in kidneys donated after circulatory death versus brain death.

Methods

We used the UK transplant registry to select a cohort of first-time recipients (aged ≥18 years) of deceased-donor kidneys for transplantations done between Jan 1, 2005, and Nov 1, 2010. We did univariate comparisons of transplants from brain-death donors versus circulatory-death donors with χ2 tests for categorical data and Wilcoxon tests for non-parametric continuous data. We used Kaplan-Meier curves to show graft survival. We used Cox proportional hazards regression to adjust for donor and recipient factors associated with graft-survival with tests for interaction effects to establish the relative effect of donor age and cold ischaemia on kidneys from circulatory-death and brain-death donors.

Findings

6490 deceased-donor kidney transplants were done at 23 centres. 3 year graft survival showed no difference between circulatory-death (n=1768) and brain-death (n=4127) groups (HR 1·14, 95% CI 0·95–1·36, p=0·16). Donor age older than 60 years (compared with <40 years) was associated with an increased risk of graft loss for all deceased-donor kidneys (2·35, 1·85–3·00, p<0·0001) but there was no increased risk of graft loss for circulatory-death donors older than 60 years compared with brain-death donors in the same age group (p=0·30). Prolonged cold ischaemic time (>24 h vs <12 h) was not associated with decreased graft survival for all deceased-donor kidneys but was associated with poorer graft survival for kidneys from circulatory-death donors than for those from brain-death donors (2·36, 1·39–4·02, p for interaction=0·004).

Interpretation

Kidneys from older circulatory-death donors have equivalent graft survival to kidneys from brain-death donors in the same age group, and are acceptable for transplantation. However, circulatory-death donor kidneys tolerate cold storage less well than do brain-death donor kidneys and this finding should be considered when developing organ allocation policy.

Funding

UK National Health Service Blood and Transplant; Cambridge National Institute for Health Research Biomedical Research Centre.

Introduction

Transplantation is the preferred treatment for end-stage kidney disease but there is a severe shortage of deceased-donor kidneys.1, 2 In the UK, the number of deceased-donor kidney transplants undertaken has risen by 20% during the past 5 years.1 This increase is largely attributable to the substantial increase in the number of kidneys transplanted from circulatory-death donors, which have increased more than two and a half times and now provide more than a third of all deceased-donor kidneys.1, 2 Nearly all kidneys donated after circulatory death in the UK are from donors who have massive irreversible brain injury and death is certified following cessation of cardiopulmonary function after withdrawal of life-supporting treatment (Maastricht category 33). Kidneys from circulatory-death donors, unlike those donated after brain death, incur substantial warm ischaemic injury before and during procurement, which results in poor function immediately after transplantation.4, 5 Emerging evidence shows, however, that in the medium term (up to 5 years) kidneys from circulatory-death donors provide satisfactory graft function and these findings have helped overcome initial reluctance by many clinicians to accept such kidneys for their patients, at least when they are from circulatory-death donors who are younger than 60 years.6

In view of the increasingly important contribution of circulatory-death donors to kidney transplantation in the UK, two key issues need to be addressed to maximise use of kidneys from such donors and ensure that access to them by potential recipients is equitable. First, there is a need to know whether kidneys from circulatory-death donors aged older than 60 years fare any worse than kidneys from brain-death donors in the same age group. This point is particularly important because 29% of deceased donor kidneys used in the UK are from donors aged older than 60 years.1 Although further scope exists to increase the use of kidneys from older circulatory-death donors, widespread concern remains that such kidneys fare more poorly than do those from older brain-death donors and some transplant centres are reluctant to transplant them.7 Second, there is a need to allocate kidneys from circulatory-death donors as fairly as possible. In the UK, and many other countries, kidneys from brain-death donors (including those from older donors) are allocated through a national sharing scheme to ensure equity of access to kidney transplantation.8 By contrast, kidneys from circulatory-death donors are mostly used in the regional transplant centre associated with the donor hospital. Although national allocation is desirable, especially in view of the very wide regional variations in rates of donation after circulatory death, transporting kidneys between centres adds to the duration of cold storage that organs undergo before transplantation. Although for kidneys from brain-death donors the increased duration of cold ischaemia needed for national allocation does not adversely affect long-term transplantation outcome, concern remains that kidneys donated after circulatory death might be less tolerant of cold storage.9, 10

The UK is especially well-placed to address these issues, since it has one of the highest number of circulatory-death organ donors per head of population in the world and a well-established, comprehensive, and high-quality national transplant registry.11 In this Article we report the results of a UK-wide cohort analysis of the outcome of kidney transplants, comparing kidneys from controlled circulatory-death donors with those from brain-death donors. Our specific aim was to establish the effect of donor age and cold ischaemic time on transplant outcome.

Section snippets

Study population

We analysed data submitted to the UK transplant registry held by National Health Service (NHS) Blood and Transplant that records mandatory data for kidney transplants done by all 23 adult kidney transplant centres in the UK. We identified all recipients of deceased-donor renal transplants undertaken between Jan 1, 2005, and Nov 1, 2010. We excluded paediatric recipients (≤18 years) but we placed no age restrictions on donors. We also excluded transplants of kidneys from uncontrolled

Results

We identified 9169 recipients of deceased-donor renal transplants undertaken during the 5 year study period. We excluded 452 paediatric recipients, 158 patients who received transplants of kidneys from uncontrolled circulatory-death donors of Maastricht category 1 and 2, and 1277 patients who had received a previous renal transplant. We also excluded 990 recipients of non-renal organ transplants. This enabled analysis of 1827 recipients of circulatory-death kidneys and 4663 recipients of

Discussion

For first-time adult kidney transplant recipients in the UK between 2005 and 2010, increasing donor age was associated with inferior graft survival in recipients of all deceased-donor kidneys, but importantly we identified no difference in the effect of donor age between kidneys from circulatory-death and brain-death donors. By contrast, duration of cold storage had no effect on graft survival in recipients of kidneys from brain-death donors, but increasing length of cold ischaemic time was

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