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Less-than-perfect kidneys can be successfully used for transplants

Based on findings from researchers at Johns Hopkins Medicine it has been strongly recommended that harvested kidneys with acute kidney injury (AKI) no longer be rejected outright, in order to bolster efforts to reduce the drastic shortage of organs available for transplant in the US. Currently, the national discard or rejection rate for all potential donor kidneys is approximately 18%, but for AKI kidneys, it jumps to about 30%.

According to October 2019 statistics from the US Department of Health and Human Services, some 95,000 Americans with kidney failure – also known as end-stage renal disease, or ESRD – are awaiting donor organs. Unfortunately, as reported by the US Centres for Disease Control and Prevention, nearly 9,000 of these patients drop off the waiting list each year because they cannot get a kidney in time, succumbing to death or deteriorating health that makes transplantation no longer possible.

Making matters worse, says the National Institute of Diabetes and Digestive and Kidney Diseases, the need for donor kidneys is rising at 8% per year, yet their availability has not grown to match.

The latest research confirms on a larger scale the results of an earlier study by Johns Hopkins Medicine-led researchers showing that acutely injured deceased-donor kidneys do not fail or get rejected after transplantation at any greater rate than non-injured kidneys from similar deceased donors.

"We estimate there may hundreds of kidneys with AKI each year that are going unused but could be transplanted," says Dr Chirag Parikh, director of the division of nephrology at the Johns Hopkins University School of Medicine senior author of the study. "Therefore, we are urging the transplant community to bring AKI kidneys into the donor pool with more confidence."

AKI, as described by the National Kidney Foundation, is a "sudden episode of kidney failure or kidney damage that happens within a few hours or a few days." This causes waste products to build up in the blood, making it hard for kidneys to maintain the correct balance of fluids in the body.

AKI symptoms differ depending on the cause and may include: too little urine leaving the body; swelling in the legs and ankles, and around the eyes; fatigue; shortness of breath; confusion; nausea; chest pain; and in severe cases, seizures or coma. The disorder is most commonly seen in hospitalized patients whose kidneys are affected by medical and surgical stress and complications.

In 2018, a team led by Parikh reviewed the medical records documenting approximately 2,500 kidneys transplanted from nearly 1,300 deceased donors – of which 24% (about 600) had AKI at the time of donation. The researchers reported no significant differences in the rates of organ rejection among kidneys from deceased donors with or without AKI.

For the latest study, the researchers greatly expanded the number of transplanted kidneys analysed to validate or refute the 2018 results. Organs from 13,444 deceased donors were transplanted into 25,323 ESRD patients in the United States between 1 January, 2010 and 31 December, 2013. Of this number, 12,810 received kidneys with AKI and 12,513 were given kidneys without any signs of acute injury and that had been matched to the AKI kidneys on other criteria.

For this matching, each AKI kidney was paired at the beginning of the study with a non-AKI kidney using a statistical method that mathematically linked as many donor characteristics as possible, including age, sex, ethnicity and medical conditions other than AKI. This allowed the investigators to more accurately measure the impact, if any, of just AKI on transplant success.

The transplant recipients were followed for four to six years after their surgery.
"We found that deceased-donor AKI had no association with either short-term or long-term survival of the organ, strongly supporting our idea that kidneys with AKI should be actively harvested and transplanted," Parikh says.

To determine how many potentially viable kidneys with AKI were lost during the study period (2010 to 2013), the researchers looked at how many deceased donor kidneys with AKI were recovered, then either transplanted or discarded.

"We found that although nearly 17,500, or 85%, of the more than 20,500 available AKI kidneys were harvested over the three years, only slightly more than 12,700 were transplanted," Parikh says. "This means almost 8,000 organs were either rejected after procurement or never obtained at all simply because the donors had acute kidney injury."

Increasing the donor pool to include AKI kidneys, Parikh adds, would help achieve the goal of the Advancing American Kidney Health initiative, a 2019 presidential directive that aims to double the number of kidneys available for transplant by 2030.

Abstract
Importance: The shortage of deceased donor kidneys for transplants is an ongoing concern. Prior studies support transplanting kidneys from deceased donors with acute kidney injury (AKI), but those investigations have been subject to selection bias and small sample sizes. Current allocation practices of AKI kidneys in the United States are not well characterized.
Objectives: To evaluate the association of deceased donor AKI with recipient graft survival and to characterize recovery and discard practices for AKI kidneys by organ procurement organizations.

Design, Setting, and Participants: Registry-based, propensity score–matched cohort study from January 1, 2010, to December 31, 2013, in the United States. The dates of analysis were March 1 to November 1, 2019. From 2010 to 2013, a total of 6832 deceased donors with AKI and 15 310 deceased donors without AKI had at least 1 kidney transplanted. This study used a 1:1, propensity score–matched analysis to match deceased donors with AKI to deceased donors without AKI and investigated outcomes in their corresponding kidney recipients.
Exposure: Deceased donor AKI, defined as at least 50% or 0.3-mg/dL increase in terminal serum creatinine level from admission.

Main Outcomes and Measures: Recipients were assessed for the time to death-censored graft failure and the following secondary outcomes: delayed graft function, primary nonfunction, and the time to all-cause graft failure.
Results: Ninety-eight percent (6722 of 6832) of deceased donors with AKI were matched to deceased donors without AKI. The mean (SD) age of the 13 444 deceased donors was 40.4 (14.4) years, and 63% (8529 of 13 444) were male. A total of 25 323 recipients were analyzed (15 485 [61%] were male), and their mean (SD) age was 52.0 (14.7) years. Recipients were followed up for a median of 5 (interquartile range, 4-6) years. Deceased donor AKI status had no association with death-censored graft failure (hazard ratio, 1.01; 95% CI, 0.95-1.08) or all-cause graft failure (hazard ratio, 0.97; 95% CI, 0.93-1.02). The results were consistent after examining by AKI stage and adjusting for recipient and transplant characteristics. More recipients of AKI kidneys developed delayed graft function (29% vs 22%, P < .001). Few recipients (120 of 25 323 [0.5%]) developed primary nonfunction regardless of deceased donor AKI status. Recovery and transplantation of AKI kidneys varied by organ procurement organization; most (39 of 58) had high recovery and high discard of AKI kidneys.

Conclusions and Relevance: Deceased donor AKI kidneys transplanted in the study period had recipient graft survival comparable to that of non-AKI kidneys. This study’s findings suggest that the transplant community should evaluate whether currently discarded AKI kidneys from donors without substantial comorbidities can be used more effectively.

Authors
Caroline Liu, Isaac E Hall, Sherry Mansour, Heather R Thiessen Philbrook, Yaqi Jia, Chirag R Parikh

[link url="https://www.hopkinsmedicine.org/news/newsroom/news-releases/less-than-perfect-kidneys-can-be-successfully-used-for-transplants-study-shows"]Johns Hopkins Medicine material[/link]

[link url="https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2758404"]JAMA Network Open abstract[/link]

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