Sherry G Mansour1,2, Pavan K Bhatraju3,4, Steven G Coca5, Wassim Obeid6, Francis P Wilson1,2, Ian B Stanaway4, Yaqi Jia6, Heather Thiessen-Philbrook6, Alan S Go7,8,9,10,11, T Alp Ikizler12, Edward D Siew13, Vernon M Chinchilli14, Chi-Yuan Hsu7,11, Amit X Garg15,16,17, W Brian Reeves18, Kathleen D Liu7,19, Paul L Kimmel20, James S Kaufman21, Mark M Wurfel3,4, Jonathan Himmelfarb4, Samir M Parikh22, Chirag R Parikh23. 1. Clinical Translational Research Accelerator, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut. 2. Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut. 3. Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, Seattle, Washington. 4. Kidney Research Institute, Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington. 5. Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. 6. Division of Nephrology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland. 7. Division of Nephrology, Department of Medicine, University of California, San Francisco, San Francisco, California. 8. Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California. 9. Division of Nephrology, Department of Medicine, Stanford University, Palo Alto, California. 10. Department of Health Research and Policy, Stanford University, Palo Alto, California. 11. Division of Research, Kaiser Permanente Northern California, Oakland, California. 12. Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. 13. Division of Nephrology and Hypertension, Vanderbilt University School of Medicine, Nashville, Tennessee. 14. Department of Public Health Sciences, Penn State College of Medicine, Hershey, Pennsylvania. 15. Division of Nephrology, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. 16. Department of Epidemiology and Biostatistics, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada. 17. ICES, Ontario, Canada. 18. Division of Nephrology, Department of Medicine, University of Texas Joe and Teresa Long School of Medicine, San Antonio, Texas. 19. Department of Anesthesia, Division of Critical Care Medicine, University of California, San Francisco, San Francisco, California. 20. Division of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland. 21. Division of Nephrology, Veterans Affairs New York Harbor Healthcare System and New York University School of Medicine, New York, New York. 22. Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. 23. Division of Nephrology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland chirag.parikh@jhmi.edu.
Abstract
BACKGROUND: The mechanisms underlying long-term sequelae after AKI remain unclear. Vessel instability, an early response to endothelial injury, may reflect a shared mechanism and early trigger for CKD and heart failure. METHODS: To investigate whether plasma angiopoietins, markers of vessel homeostasis, are associated with CKD progression and heart failure admissions after hospitalization in patients with and without AKI, we conducted a prospective cohort study to analyze the balance between angiopoietin-1 (Angpt-1), which maintains vessel stability, and angiopoietin-2 (Angpt-2), which increases vessel destabilization. Three months after discharge, we evaluated the associations between angiopoietins and development of the primary outcomes of CKD progression and heart failure and the secondary outcome of all-cause mortality 3 months after discharge or later. RESULTS: Median age for the 1503 participants was 65.8 years; 746 (50%) had AKI. Compared with the lowest quartile, the highest quartile of the Angpt-1:Angpt-2 ratio was associated with 72% lower risk of CKD progression (adjusted hazard ratio [aHR], 0.28; 95% confidence interval [CI], 0.15 to 0.51), 94% lower risk of heart failure (aHR, 0.06; 95% CI, 0.02 to 0.15), and 82% lower risk of mortality (aHR, 0.18; 95% CI, 0.09 to 0.35) for those with AKI. Among those without AKI, the highest quartile of Angpt-1:Angpt-2 ratio was associated with 71% lower risk of heart failure (aHR, 0.29; 95% CI, 0.12 to 0.69) and 68% less mortality (aHR, 0.32; 95% CI, 0.15 to 0.68). There were no associations with CKD progression. CONCLUSIONS: A higher Angpt-1:Angpt-2 ratio was strongly associated with less CKD progression, heart failure, and mortality in the setting of AKI.
BACKGROUND: The mechanisms underlying long-term sequelae after AKI remain unclear. Vessel instability, an early response to endothelial injury, may reflect a shared mechanism and early trigger for CKD and heart failure. METHODS: To investigate whether plasma angiopoietins, markers of vessel homeostasis, are associated with CKD progression and heart failure admissions after hospitalization in patients with and without AKI, we conducted a prospective cohort study to analyze the balance between angiopoietin-1 (Angpt-1), which maintains vessel stability, and angiopoietin-2 (Angpt-2), which increases vessel destabilization. Three months after discharge, we evaluated the associations between angiopoietins and development of the primary outcomes of CKD progression and heart failure and the secondary outcome of all-cause mortality 3 months after discharge or later. RESULTS: Median age for the 1503 participants was 65.8 years; 746 (50%) had AKI. Compared with the lowest quartile, the highest quartile of the Angpt-1:Angpt-2 ratio was associated with 72% lower risk of CKD progression (adjusted hazard ratio [aHR], 0.28; 95% confidence interval [CI], 0.15 to 0.51), 94% lower risk of heart failure (aHR, 0.06; 95% CI, 0.02 to 0.15), and 82% lower risk of mortality (aHR, 0.18; 95% CI, 0.09 to 0.35) for those with AKI. Among those without AKI, the highest quartile of Angpt-1:Angpt-2 ratio was associated with 71% lower risk of heart failure (aHR, 0.29; 95% CI, 0.12 to 0.69) and 68% less mortality (aHR, 0.32; 95% CI, 0.15 to 0.68). There were no associations with CKD progression. CONCLUSIONS: A higher Angpt-1:Angpt-2 ratio was strongly associated with less CKD progression, heart failure, and mortality in the setting of AKI.
Authors: P C Maisonpierre; C Suri; P F Jones; S Bartunkova; S J Wiegand; C Radziejewski; D Compton; J McClain; T H Aldrich; N Papadopoulos; T J Daly; S Davis; T N Sato; G D Yancopoulos Journal: Science Date: 1997-07-04 Impact factor: 47.728
Authors: S O Syrjälä; R Tuuminen; A I Nykänen; A Raissadati; A Dashkevich; M A I Keränen; R Arnaudova; R Krebs; C C Leow; P Saharinen; K Alitalo; K B Lemström Journal: Am J Transplant Date: 2014-04-07 Impact factor: 8.086
Authors: Shane McCarthy; Sayantan Das; Warren Kretzschmar; Olivier Delaneau; Andrew R Wood; Alexander Teumer; Hyun Min Kang; Christian Fuchsberger; Petr Danecek; Kevin Sharp; Yang Luo; Carlo Sidore; Alan Kwong; Nicholas Timpson; Seppo Koskinen; Scott Vrieze; Laura J Scott; He Zhang; Anubha Mahajan; Jan Veldink; Ulrike Peters; Carlos Pato; Cornelia M van Duijn; Christopher E Gillies; Ilaria Gandin; Massimo Mezzavilla; Arthur Gilly; Massimiliano Cocca; Michela Traglia; Andrea Angius; Jeffrey C Barrett; Dorrett Boomsma; Kari Branham; Gerome Breen; Chad M Brummett; Fabio Busonero; Harry Campbell; Andrew Chan; Sai Chen; Emily Chew; Francis S Collins; Laura J Corbin; George Davey Smith; George Dedoussis; Marcus Dorr; Aliki-Eleni Farmaki; Luigi Ferrucci; Lukas Forer; Ross M Fraser; Stacey Gabriel; Shawn Levy; Leif Groop; Tabitha Harrison; Andrew Hattersley; Oddgeir L Holmen; Kristian Hveem; Matthias Kretzler; James C Lee; Matt McGue; Thomas Meitinger; David Melzer; Josine L Min; Karen L Mohlke; John B Vincent; Matthias Nauck; Deborah Nickerson; Aarno Palotie; Michele Pato; Nicola Pirastu; Melvin McInnis; J Brent Richards; Cinzia Sala; Veikko Salomaa; David Schlessinger; Sebastian Schoenherr; P Eline Slagboom; Kerrin Small; Timothy Spector; Dwight Stambolian; Marcus Tuke; Jaakko Tuomilehto; Leonard H Van den Berg; Wouter Van Rheenen; Uwe Volker; Cisca Wijmenga; Daniela Toniolo; Eleftheria Zeggini; Paolo Gasparini; Matthew G Sampson; James F Wilson; Timothy Frayling; Paul I W de Bakker; Morris A Swertz; Steven McCarroll; Charles Kooperberg; Annelot Dekker; David Altshuler; Cristen Willer; William Iacono; Samuli Ripatti; Nicole Soranzo; Klaudia Walter; Anand Swaroop; Francesco Cucca; Carl A Anderson; Richard M Myers; Michael Boehnke; Mark I McCarthy; Richard Durbin Journal: Nat Genet Date: 2016-08-22 Impact factor: 38.330