Variability in donor organ offer acceptance and lung transplantation survival

doi:10.1016/j.healun.2019.12.010

The Journal of Heart and Lung Transplantation

Volume 39, Issue 4, April 2020, Pages 353-362

https://doi.org/10.1016/j.healun.2019.12.010 Get rights and content

BACKGROUND

Lung transplantation offers a survival benefit for patients with end-stage lung disease. When suitable donors are identified, centers must accept or decline the offer for a matched candidate on their waitlist. The degree to which variability in per-center offer acceptance practices impacts candidate survival is not established. The purpose of this study was to determine the degree of variability in per-center rates of lung transplantation offer acceptance and to ascertain the associated contribution to observed differences in per-center waitlist mortality.

METHODS

We performed a retrospective cohort study of candidates waitlisted for lung transplantation in the US using registry data. Logistic regression was fit to assess the relationship of offer acceptance with donor, candidate, and geographic factors. Listing center was evaluated as a fixed effect to determine the adjusted per-center acceptance rate. Competing risks analysis employing the Fine-Gray model was undertaken to establish the relationship between adjusted per-center acceptance and waitlist mortality.

RESULTS

Of 15,847 unique organ offers, 4,735 (29.9%) were accepted for first-ranked candidates. After adjustment for important covariates, transplant centers varied markedly in acceptance rate (9%–67%). Higher cumulative incidence of 1-year waitlist mortality was associated with lower acceptance rate. For every 10% increase in adjusted center acceptance rate, the risk of waitlist mortality decreased by 36.3% (sub-distribution hazard ratio 0.637; 95% confidence interval 0.592–0.685).

CONCLUSIONS

Variability in center-level behavior represents a modifiable risk factor for waitlist mortality in lung transplantation. Further intervention is needed to standardize center-level offer acceptance practices and minimize waitlist mortality.

Section snippets

Data source

This study was approved by our institution's Institutional Review Board before study initiation. We performed a retrospective cohort analysis using United Network of Organ Sharing (UNOS) Standard Analysis and Research data. These data were subsequently linked with information from the Potential Transplant Recipient file, which provides match run information for every offer made for each candidate donor lung allograft that is ultimately employed for use in transplantation. Further discussion of

Study population

Across 65 listing centers, a total of 8,193 candidates received first-ranked offers from 15,847 unique donors after application of our inclusion criteria (Figure 1 for patient selection). The overall acceptance rate for the first-ranked offer was 29.9% (4,735/15,847). Complete demographic information for candidates and donors is reported in Table 1. Candidates who accepted the first-ranked offer tended to have a lower LAS at the time of match (median 47.5 for accept vs 50.5 for decline) and

Discussion

Cardiothoracic transplantation is appropriately one of the most closely scrutinized disciplines in medicine. The combination of a scarce resource and a medically comorbid patient population demands that outcomes at both the local and national levels be closely measured. In this retrospective analysis of US-based registry data, we find that organ offer acceptance patterns vary significantly by transplant center, a variation that contributes significantly to observed per-center differences in

Disclosure statement

The authors report no relevant conflicts of interests as described by ICMJE.

MSM is supported by the National Heart, Lung, and Blood Institute F32HL132460-02.

This work was supported by the NIH funded Cardiothoracic Surgery Trials Network (MLC), 5U01HL088953-05 and the National Institutes of Health TL-1 clinical and translational science award, UL1TR0025531 (NCATS).

References (28)

M Valapour et al.
OPTN/SRTR 2015 annual data report: lung
Am J Transplant
(2017)
JP Singer et al.
Effect of lung transplantation on health-related quality of life in the era of the lung allocation score: a U.S. prospective cohort study
Am J Transplant
(2017)
LC Pullen
Lung allocation sequence: the system evolves
Am J Transplant
(2018)
LJ Benvenuto et al.
Geographic disparities in donor lung supply and lung transplant waitlist outcomes: a cohort study
Am J Transplant
(2018)
TC Crawford et al.
Lung transplant mortality is improving in recipients with a lung allocation score in the upper quartile
Ann Thorac Surg
(2017)
D Weill et al.
A consensus document for the selection of lung transplant candidates: 2014—an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation
J Heart Lung Transplant
(2015)
DS Goldberg et al.
Liver transplant center variability in accepting organ offers and its impact on patient survival
J Hepatol
(2016)
A Wey et al.
Heart and lung organ offer acceptance practices of transplant programs are associated with waitlist mortality and organ yield
Am J Transplant
(2018)
AB Massie et al.
Big data in organ transplantation: registries and administrative claims
Am J Transplant
(2014)
TM Egan et al.
Effect of the lung allocation score on lung transplantation in the United States
J Heart Lung Transplant
(2016)

CA Merlo et al.

Impact of U.S. Lung Allocation Score on survival after lung transplantation

J Heart Lung Transplant

(2009)

MS Mulvihill et al.

Decline of increased risk donor offers on waitlist survival in heart transplantation

J Am Coll Cardiol

(2018)

ML Cox et al.

Implications of declining donor offers with increased risk of disease transmission on waiting list survival in lung transplantation

J Heart Lung Transplant

(2019)

DA Maldonado et al.

A novel patient-centered ”intention-to-treat” metric of U.S. lung transplant center performance

Am J Transplant

(2018)

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Lung transplant warm ischemia–reperfusion injury (IRI) results in cellular injury, inflammation, and poor graft function. Mitsugumin 53 (MG53) is an endogenous protein with cell membrane repair properties and the ability to modulate the inflammasome. We hypothesize that the absence of circulating MG53 protein in the recipient increases IRI, and higher levels of circulating MG53 protein mitigate IRI associated with lung transplantation.
To demonstrate protection, wild-type (wt) lung donor allografts were transplanted into a wt background, a MG53 knockout (mg53−/−), or a constitutively overexpressed MG53 (tissue plasminogen activator-MG53) recipient mouse after 1 hour of warm ischemic injury. Mice survived for 5 days after transplantation. Bronchioalveolar lavage, serum, and tissue were collected at sacrifice. Bronchioalveolar lavage, serum, and tissue markers of apoptosis and a biometric profile of lung health were analyzed.
mg53−/− mice had significantly greater levels of markers of overall cell lysis and endothelial cell injury. Overexpression of MG53 resulted in a signature similar to that of wt controls. At the time of explant, tissue plasminogen activator-MG53 recipient tissue expressed significantly greater levels of MG53, measured by immunohistochemistry, compared with mg53−/−, demonstrating uptake of endogenous overexpressed MG53 into donor tissue.
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Outcomes of lung transplantation at a Canadian center using donors declined in the United States
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Donor lungs from the United States can be offered by US organ procurement organizations to Canada if no American centers accept them. The purpose of this study is to evaluate outcomes of patients undergoing transplant at a single center in Canada using declined lungs from the United States and to compare these outcomes to patients receiving lungs from Canadian donors.
A single-center retrospective review of recipients receiving lung transplantation between January 2009 and October 2019 was performed. An Organ Procurement and Transplantation Network standard transplant analysis and research-limited dataset as of August 17, 2021, was provided by the United Network for Organ Sharing. De-identified patient-level data were extracted from the standard transplant analysis and research file to identify lung offers made by US organ procurement organizations, declined by US lung centers, and transplanted by the University Health Network within the study time frame. We divided the analysis into 2 groups: recipients receiving donor lungs from Canada and recipients receiving donor lungs from the United States. Donor and recipient characteristics between the 2 groups were compared. Primary end point was proportional survival over a 10-year period. Secondary end points included 30-day mortality, intensive care unit and hospital length of stay, severe primary graft dysfunction, and incidence of chronic lung allograft dysfunction.
During the study period, 1424 lung transplants were performed at our center. Of these, 124 (8.7%) were performed using donors from the United States. The incidence of transplants using US donors increased from 5% (5 out of 102) in 2009 to 15% (30 out of 200) in 2018. US donors were younger (aged 41 vs 47 years; P = .004), less likely to be from donors after cardiac death (9.6% vs 20%; P = .008), had higher use of ex vivo lung perfusion (EVLP, 46% vs 27%; P = .0002), and higher incidence of positive nucleic acid test for hepatitis C (16% vs 0.7%; P = .0001). Although the incidence of EVLP utilization was higher in the US lungs versus Canada lungs, more than half of US lungs (54%) proceeded directly to transplantation. Similar short- and long-term outcomes were observed between the 2 groups, including overall survival (hazard ratio, 1.12; 95% CI, 0.85-1.47; P = .40)
Lung transplantation using donor lungs declined by multiple centers in the United States resulted in similar short- and long-term outcomes compared with donor lungs offered in Canada.
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Citation Excerpt :
These findings are in line with a prior study using UNOS, which found that even among patients receiving first-ranked offers (those for which they are the first candidate to receive the donor offer and therefore supposedly the “best match”), the rejection rate is over 75%.14 The same study also reported the sobering fact that nearly half of patients for whom the first, first-ranked offer is declined will not receive another first-ranked offer, with 2% never receiving another offer at all and 25% subsequently dying while awaiting transplant.14 In the present analysis, the first acceptable offer (most often occurring as the first or second offer received) was declined for 78% of patients with LAS >80 and 88% of patients with LAS 61–80.
The demand for organs for lung transplantation (LTx) continues to outweigh supply. However, nearly 75% of donor lungs are never transplanted. LTx offer acceptance practices and the effects on waitlist/post-transplant outcomes by candidate clinical acuity are understudied. UNOS was used to identify all LTx candidates, donors, and offers from 2005 to 2019. Candidates were grouped by Lung Allocation Score (LAS; applicable post-2005, ages ≥12 years): LAS<40, 40–60, 61–80, and >80. Offer acceptance patterns, waitlist death/decompensation, and post-transplant survival (PTS) were compared. “Acceptable organ offers” were those from donors whose organs were accepted for transplantation. Approximately 3 million offers to 34,531 candidates were reviewed. Median waitlist durations were: 9 days-(LAS>80), 17 days-(LAS 61–80), 42 days-(LAS 40–60), 125 days-(LAS<40) (P < 0.001 between all). Per waitlist-day, offer rates were: total offers – 0.8/day-(LAS>80), 0.7/day-(LAS 61–80), 0.6/day-(LAS 40–60), 0.4/day-(LAS<40); acceptable offers – 0.34/day-(LAS>80), 0.32/day-(LAS 61–80), 0.24/day-(LAS 40–60), 0.15/day-(LAS<40) (both P < 0.001 between all LAS). Among patients who experienced waitlist mortality/decompensation, ≥1 acceptable offer was declined in 92% (3939/4270) of patients – 78% for LAS >80, 88% for LAS 61–80, 93% for LAS 40–60, and 96% for LAS <40. Thirty-day waitlist mortality/decompensation rates were: 46%-(LAS>80), 24%-(LAS 61–80), 5%-(LAS 40–60), <1%-(LAS<40) (P < 0.001 between all). PTS was equivalent between patients for whom the first/second offer vs later offers were accepted (all LAS P > 0.4). The first offers that LTx candidates receive (including acceptable organs) are declined for nearly all candidates. Healthier candidates can afford offer selectivity but more ill patients (LAS>60) cannot, experiencing exceedingly high 30-day waitlist mortality.

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Variability in donor organ offer acceptance and lung transplantation survival

BACKGROUND

METHODS

RESULTS

CONCLUSIONS

Section snippets

Data source

Study population

Discussion

Disclosure statement

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