Andrew Bostom1, Dominik Steubl2, Pranav S Garimella3, Nora Franceschini4, Mary B Roberts1, Andreas Pasch5, Joachim H Ix3, Katherine R Tuttle6, Anastasia Ivanova4, Theresa Shireman7, S Joseph Kim8, Reginald Gohh9, Daniel E Weiner10, Andrew S Levey10, Chi-Yuan Hsu11, John W Kusek12, Charles B Eaton13,14. 1. Center For Primary Care and Prevention, Memorial Hospital of Rhode Island, Pawtucket, Rhode Island, USA. 2. Klinikum rechts der Isar, Technische Universität, München, Germany. 3. Division of Nephrology-Hypertension, Department of Medicine, University of California, San Diego, California, USA. 4. Department of Epidemiology, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. 5. University of Bern, Bern, Switzerland. 6. Providence Medical Research Center, University of Washington, Spokane, Washington, USA. 7. Center for Gerontology and Healthcare Research, Brown University, Providence, Rhode Island, USA. 8. Division of Nephrology and the Kidney Transplant Program, Toronto General Hospital, Toronto, Ontario, Canada. 9. Division of Hypertension and Kidney Diseases, Department of Medicine, Rhode Island Hospital, Providence, Rhode Island, USA. 10. Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, Massachusetts, USA. 11. Division of Nephrology, University of California-San Francisco, San Francisco, California, USA. 12. National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. 13. Department of Family Medicine, Warren Alpert Medical School, Brown University, Providence, Rhode Island, USA. 14. Department of Epidemiology, School of Public Health, Brown University, Providence, Rhode Island, USA.
Abstract
BACKGROUND: Uromodulin is a kidney-derived glycoprotein and putative tubular function index. Lower serum uromodulin was recently associated with increased risk for kidney allograft failure in a preliminary, longitudinal single-center -European study involving 91 kidney transplant recipients (KTRs). METHODS: The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial is a completed, large, multiethnic controlled clinical trial cohort, which studied chronic, stable KTRs. We conducted a case cohort analysis using a randomly selected subset of patients (random subcohort, n = 433), and all individuals who developed kidney allograft failure (cases, n = 226) during follow-up. Serum uromodulin was determined in this total of n = 613 FAVORIT trial participants at randomization. Death-censored kidney allograft failure was the study outcome. RESULTS: The 226 kidney allograft failures occurred during a median surveillance of 3.2 years. Unadjusted, weighted Cox proportional hazards modeling revealed that lower serum uromodulin, tertile 1 vs. tertile 3, was associated with a threefold greater risk for kidney allograft failure (hazards ratio [HR], 95% CI 3.20 [2.05-5.01]). This association was attenuated but persisted at twofold greater risk for allograft failure, after adjustment for age, sex, smoking, allograft type and vintage, prevalent diabetes mellitus and cardiovascular disease (CVD), total/high-density lipoprotein cholesterol ratio, systolic blood pressure, estimated glomerular filtration rate, and natural log urinary albumin/creatinine: HR 2.00, 95% CI (1.06-3.77). CONCLUSIONS: Lower serum uromodulin, a possible indicator of less well-preserved renal tubular function, remained associated with greater risk for kidney allograft failure, after adjustment for major, established clinical kidney allograft failure and CVD risk factors, in a large, multiethnic cohort of long-term, stable KTRs.
BACKGROUND:Uromodulin is a kidney-derived glycoprotein and putative tubular function index. Lower serum uromodulin was recently associated with increased risk for kidney allograft failure in a preliminary, longitudinal single-center -European study involving 91 kidney transplant recipients (KTRs). METHODS: The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial is a completed, large, multiethnic controlled clinical trial cohort, which studied chronic, stable KTRs. We conducted a case cohort analysis using a randomly selected subset of patients (random subcohort, n = 433), and all individuals who developed kidney allograft failure (cases, n = 226) during follow-up. Serum uromodulin was determined in this total of n = 613 FAVORIT trial participants at randomization. Death-censored kidney allograft failure was the study outcome. RESULTS: The 226 kidney allograft failures occurred during a median surveillance of 3.2 years. Unadjusted, weighted Cox proportional hazards modeling revealed that lower serum uromodulin, tertile 1 vs. tertile 3, was associated with a threefold greater risk for kidney allograft failure (hazards ratio [HR], 95% CI 3.20 [2.05-5.01]). This association was attenuated but persisted at twofold greater risk for allograft failure, after adjustment for age, sex, smoking, allograft type and vintage, prevalent diabetes mellitus and cardiovascular disease (CVD), total/high-density lipoprotein cholesterol ratio, systolic blood pressure, estimated glomerular filtration rate, and natural log urinary albumin/creatinine: HR 2.00, 95% CI (1.06-3.77). CONCLUSIONS: Lower serum uromodulin, a possible indicator of less well-preserved renal tubular function, remained associated with greater risk for kidney allograft failure, after adjustment for major, established clinical kidney allograft failure and CVD risk factors, in a large, multiethnic cohort of long-term, stable KTRs.
Authors: Dominik Steubl; Petra Buzkova; Pranav S Garimella; Joachim H Ix; Prasad Devarajan; Michael R Bennett; Paolo H M Chaves; Michael G Shlipak; Nisha Bansal; Mark J Sarnak Journal: Am J Kidney Dis Date: 2019-05-22 Impact factor: 8.860
Authors: Kavish R Patidar; Pranav S Garimella; Etienne Macedo; James E Slaven; Marwan S Ghabril; Regina E Weber; Melissa Anderson; Eric S Orman; Lauren D Nephew; Archita P Desai; Naga P Chalasani; Tarek M El-Achkar Journal: Am J Physiol Gastrointest Liver Physiol Date: 2019-08-14 Impact factor: 4.052
Authors: Joe Chan; My Svensson; Tone M Tannæs; Bard Waldum-Grevbo; Trond Jenssen; Ivar A Eide Journal: Am J Nephrol Date: 2022-02-01 Impact factor: 4.605
Authors: Sherry G Mansour; Caroline Liu; Yaqi Jia; Peter P Reese; Isaac E Hall; Tarek M El-Achkar; Kaice A LaFavers; Wassim Obeid; Avi Z Rosenberg; Parnaz Daneshpajouhnejad; Mona D Doshi; Enver Akalin; Jonathan S Bromberg; Meera N Harhay; Sumit Mohan; Thangamani Muthukumar; Bernd Schröppel; Pooja Singh; Joe M El-Khoury; Francis L Weng; Heather R Thiessen-Philbrook; Chirag R Parikh Journal: Transplantation Date: 2021-04-01 Impact factor: 4.939
Authors: Stephan Kemmner; Christopher Holzmann-Littig; Helene Sandberger; Quirin Bachmann; Flora Haberfellner; Carlos Torrez; Christoph Schmaderer; Uwe Heemann; Lutz Renders; Volker Assfalg; Tarek M El-Achkar; Pranav S Garimella; Jürgen Scherberich; Dominik Steubl Journal: J Clin Med Date: 2021-06-11 Impact factor: 4.241