Underlying medical conditions, graft failure, and immunosuppression place solid organ transplant recipients (recipients) at heighten risk of death. We report the underlying causes of death among adult US recipients and compare their mortality to the US general population. We obtained causes of death by linking a sample of deaths from the US organ transplant registry to the National Death Index and weighted the linked deaths to represent all deaths among recipients aged 18 years or older during 1999-2019. To compare mortality to the US general population, we calculated standardized mortality ratios (SMRs). Among 496,467 recipients, 153,491 deaths occurred, of which 99,373 were NDI-linked. Leading causes of death were heart disease (16.9% of deaths), graft failure (14.9%), and cancer (14.4%). Compared to the US general population, recipients had 4.02 times the risk of death, and mortality was elevated for all 16 causes analyzed (e.g., 3.32-fold for heart disease and 2.08-fold for cancer) except dementia/Alzheimers disease. During 2015-2019, overall mortality was elevated 3.08-fold, with lung recipients experiencing the highest elevation (SMR=7.91), followed by heart (3.20), liver (2.86), and kidney (2.81) recipients. Although mortality improved over time, US recipients continue to face substantially elevated mortality, both overall and for common causes of death.

A.K.I received consulting fees from Vera Pharmaceuticals.

Intramural Research Program of the National Cancer Institute. This work was conducted partially under the auspices of the Hennepin Healthcare Research Institute (HHRI), contractor for the Scientific Registry of Transplant Recipients (SRTR), under contract no. 75R60220C00011 (US Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation). The US Government (and others acting on its behalf) retains a paid-up, nonexclusive, irrevocable, worldwide license for all works produced under the SRTR contract, and to reproduce them, prepare derivative works, distribute copies to the public, and perform publicly and display publicly, by or on behalf of the Government. The data reported here have been supplied by HHRI as the contractor for SRTR. The interpretation and reporting of these data are the responsibility of the author(s) and in no way should be seen as an official policy of or interpretation by SRTR or the US Government.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study was exempt from research ethics board review because the National Cancer Institute deemed it not human subjects research.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data use agreement restrictions preclude sharing National Death Index data with external researchers; however, with the proper approvals, Scientific Registry of Transplant Recipient data are publicly available.

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