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Kidney Transplant Outcomes in Recipients With Cognitive Impairment

A National Registry and Prospective Cohort Study

Thomas, Alvin G.1,2; Ruck, Jessica M. MD2; Shaffer, Ashton A.2,3; Haugen, Christine E. MD2; Ying, Hao2; Warsame, Fatima2; Chu, Nadia PhD3; Carlson, Michelle C. PhD4,5; Gross, Alden L. PhD3,5; Norman, Silas P. MD6; Segev, Dorry L. MD, PhD2,3; McAdams-DeMarco, Mara PhD2,3

doi: 10.1097/TP.0000000000002431
Original Clinical Science—General

Background. Cognitive impairment is common in patients with end-stage renal disease and is associated with poor outcomes on dialysis. We hypothesized that cognitive impairment might be associated with an increased risk of all-cause graft loss (ACGL) in kidney transplant (KT) recipients.

Methods. Using the Modified Mini-Mental State (3MS) examination, we measured global cognitive function at KT hospital admission in a prospective, 2-center cohort of 864 KT candidates (August 2009 to July 2016). We estimated the association between pre-KT cognitive impairment and ACGL using Cox regression, adjusting for recipient, donor, and transplant factors.

Results. In living donor KT (LDKT) recipients, the prevalence was 3.3% for mild impairment (60 ≤ 3MS < 80) and 3.3% for severe impairment (3MS < 60). In deceased donor KT (DDKT) recipients, the prevalence was 9.8% for mild impairment and 2.6% for severe impairment. The LDKT recipients with cognitive impairment had substantially higher ACGL risk than unimpaired recipients (5-year ACGL: 45.5% vs 10.6%; P < 0.01; adjusted hazard ratio [aHR] any impairment, 5.40 (95% confidence interval [CI], 1.78-16.34; P < 0.01); aHR severe impairment, 5.57 (95% CI, 1.29-24.00; P = 0.02). Similarly, DDKT recipients with severe impairment had higher ACGL risk than recipients without severe impairment (5-year ACGL, 53.0% vs 24.2%; P = 0.04); aHR severe impairment, 2.92 (95% CI, 1.13-7.50; P = 0.03).

Conclusions. Given the elevated risk of ACGL among KT recipients with cognitive impairment observed in this 2-center cohort, research efforts should explore the mechanisms of graft loss and mortality associated with cognitive impairment and identify potential interventions to improve posttransplant survival.

1 Department of Epidemiology, University of North Carolina, Chapel Hill, NC.

2 Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.

3 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

4 Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

5 Johns Hopkins University Center on Aging and Health, Baltimore, MD.

6 Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI.

Received 28 March 2018. Revision received 7 August 2018.

Accepted 10 August 2018.

A.G.T. and J.M.R. contributed equally to this article.

Funding for this study was provided in part by the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK); National Heart, Lung, and Blood Institute (NHBLI); and the National Institute on Aging (NIA); grant numbers T32HL007055 (A.T.), K01AG043501 (PI: M.M.-D.), R01AG055781 (PI: M.M.-D.), R01DK114074 (PI: M.M.-D.), F30DK116658 (PI: A.S.), F32AG053025 (PI: C.H.), K01AG050699 (PI: A.G.), K24DK101828 (PI: D.S.), and R01DK096008 (PI: D.S.). Additionally, J.R. and D.S. are supported by a Doris Duke Charitable Foundation Clinical Research Mentorship grant.

The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Mr. Thomas, Dr. Ruck, Ms. Shaffer, Dr. Haugen, Dr. Segev, and Dr. McAdams-DeMarco reported institutional grant support from the National Institutes of Health. Dr. Ruck and Dr. Segev also report institutional grant support from the Doris Duke Charitable Foundation. No other disclosures were reported.

The analyses described here are the responsibility of the authors alone and do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the U.S. Government. The data reported here have been supplied by the Minneapolis Medical Research Foundation (MMRF) as the contractor for the Scientific Registry of Transplant Recipients (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 the SRTR or the U.S. Government.

M.M.-D. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

A.G.T., J.M.R., A.A.S., M.M.-D. participated in the study concept and design. A.G.T., H.Y., S.P.N., D.L.S., M.M.-D. participated in the acquisition of data. A.G.T., D.L.S., M.M.-D. participated in the analysis and interpretation of data. A.G.T., J.M.R., A.A.S., C.E.H., M.M.-D. participated in the drafting of the article. A.G.T., J.M.R., A.A.S., C.E.H., H.Y., F.W., M.C.C., A.L.G., S.P.N., D.L.S., M.M.-D. participated in the critical revision of the article for important intellectual content. A.G.T., M.M.-D. participated in the statistical analysis. A.G.T., J.M.R., A.A.S., C.E.H., D.L.S., M.M.-D. obtained funding. N.C., M.C.C., A.L.G., D.L.S., M.M.-D. participated in the administrative, technical, and material support. M.M.-D. participated in the study supervision.

SRTR Registry staff performed all Social Security number linkages to Social Security Death Master File and Centers for Medicare & Medicaid Services data to ensure confidentiality of Social Security number data provided to the Organ Procurement and Transplantation Network.

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (

Correspondence: Mara McAdams-DeMarco, PhD, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Rm W6033, 615 N Wolfe St, Baltimore, MD 21205. (

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