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Cardiovascular Disease Outcomes Related to Early Stage Renal Impairment After Liver Transplantation

VanWagner, Lisa B., MD1,2,3; Montag, Samantha, MS2; Zhao, Lihui, PhD2; Allen, Norrina B., PhD2; Lloyd-Jones, Donald M., MD2,4; Das, Arighno, BA1; Skaro, Anton I., MD, PhD5; Hohmann, Samuel, PhD6; Friedewald, John J., MD3,7; Levitsky, Josh, MD, MSc1,3

doi: 10.1097/TP.0000000000002175
Original Clinical Science—Liver

Background In the general population, even mild renal disease is associated with increased cardiovascular (CV) complications. Whether this is true in liver transplant recipients (LTR) is unknown.

Methods This was a retrospective cohort study of 671 LTR (2002-2012) from a large urban tertiary care center and 37 322 LTR using Vizient hospitalization data linked to the United Network for Organ Sharing. The 4-variable Modification of Diet in Renal Disease equation estimated glomerular filtration rate (eGFR). Outcomes were 1-year CV complications (death/hospitalization from myocardial infarction, heart failure, atrial fibrillation, cardiac arrest, pulmonary embolism, or stroke) and mortality. Latent mixture modeling identified trajectories in eGFR in the first liver transplantation (LT) year in the 671 patients.

Results Mean (SD) eGFR was 72.1 (45.7) mL/min per 1.73 m2. Six distinct eGFR trajectories were identified in the local cohort (n = 671): qualitatively normal-slow decrease (4% of cohort), normal-rapid decrease (4%), mild-stable (18%), mild-slow decrease (35%), moderate-stable (30%), and severe-stable (9%). In multivariable analyses adjusted for confounders and baseline eGFR, the greatest odds of 1-year CV complications were in the normal-rapid decrease group (odds ratio, 10.6; 95% confidence interval, 3.0-36.9). Among the national cohort, each 5-unit lower eGFR at LT was associated with a 2% and 5% higher hazard of all-cause and CV-mortality, respectively (P < 0.0001), independent of multiple confounders.

Conclusions Even mild renal disease at the time of LT is a risk factor for posttransplant all-cause and CV mortality. More rapid declines in eGFR soon after LT correlate with risk of adverse CV outcomes, highlighting the need to study whether early renal preservation interventions also reduce CV complications.

The authors identify renal impairment as a predictor of both all-cause and cardiovascular mortality after liver transplantation.

1 Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.

2 Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.

3 Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL.

4 Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.

5 Division of General Surgery and Multi-Organ Transplant, Department of Surgery, University of Western Ontario Schulich School of Medicine and Dentistry, Ontario, Canada.

6 Center for Advanced Analytics, Vizient, Chicago, IL.

7 Division of Nephrology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.

Received 4 September 2017. Revision received 10 January 2018.

Accepted 17 January 2018.

This work was supported by an investigator-initiated grant from Novartis (J.L., CRAD001HUS188T). This work was also supported by the National Institutes of Health (L.V., 1 F32 HL116151-01), the American Liver Foundation (L.V., New York, NY), and an Alpha Omega Alpha Postgraduate Award (L.V.). L.V. is currently supported by the National Institutes of Health's National Center for Advancing Translational Sciences, grant number KL2TR001424. The Northwestern Medicine Enterprise Data Warehouse (NMEDW) is funded, in part, by the National Center for Advancing Translational Sciences (NCATS) of the NIH research grant UL1TR001422 to the Northwestern University Clinical and Translational Sciences (NUCATS) Institute. The data reported here have been supplied by the United Network for Organ Sharing as the contractor for the Organ Procurement and Transplantation Network (OPTN) and by Vizient (formally University HealthSystem Consortium (UHC)). The interpretation of this data and the views expressed in this manuscript are those of the authors and do not necessarily represent the views of Novartis, Vizient, the National Institutes of Health, or the U.S. Department of Health and Human Services.

The authors of this manuscript have conflicts of interest to disclose as described by Transplantation. This work was supported by Novartis (CRAD001HUS188T). J.L. is a speaker and advisor for Novartis. L.V. is a speaker for Salix outside the current work.

L.B.VW. participated in research design, data acquisition, obtaining funding, interpretation of results and article drafting. S.M. participated in data analysis and article editing L.Z. participated in research design, data analysis and article editing. N.B.A. participated in research design, interpretation of results and article editing D.M.L.-J. participated in research design, obtaining funding, interpretation of results and article editing A.D. participated in data acquisition, interpretation of results, and article editing. A.I.S. participated in data acquisition, interpretation of results, and article editing. S.H. participated in data acquisition, interpretation of results, and article editing. J.J.F. participated in interpretation of results and article editing. J.L. participated in research design, obtaining funding, interpretation of results and article editing.

Correspondence: Josh Levitsky, MD, MSc, Northwestern University Feinberg School of Medicine, Suite 1900, 676, N. St Clair St, Chicago, IL 60611. (j-levitsky@northwestern.edu).

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 (www.transplantjournal.com).

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