Maria Jose Soler1, Marlies Noordzij2, Daniel Abramowicz3,4, Gabriel de Arriba5, Carlo Basile6, Marjolijn van Buren7,8, Adrian Covic9, Marta Crespo10, Raphaël Duivenvoorden11, Ziad A Massy12,13, Alberto Ortiz14, J Emilio Sanchez15, Emily Petridou16, Kate Stevens17, Colin White18, Priya Vart2,19, Ron T Gansevoort2. 1. Department of Nephrology, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Research, Vall d'Hebron Barcelona Hospital Campus, Red de Investigación Renal (REDINREN), Barcelona, Spain. 2. Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 3. Department of Nephrology, Antwerp University Hospital, Edegem, Belgium. 4. Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Antwerp, Belgium. 5. Department of Nephrology, University Hospital Guadalajara, University of Alcala, Guadalajara, Spain. 6. Division of Nephrology, Miulli General Hospital, Acquaviva delle Fonti, Italy. 7. Department of Nephrology, University Medical Center Leiden, University of Leiden, Leiden, The Netherlands. 8. Department of Internal Medicine, Haga Hospital, The Hague, The Netherlands. 9. Grigore T. Popa University of Medicine and Pharmacy, Dr. C.I. Parhon Hospital, Iasi, Romania. 10. Department of Nephrology, Hospital del Mar, Mar Institute for Medical Research, Red de Investigación Renal (REDINREN) (RD16/0009/0013), Barcelona, Spain. 11. Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands. 12. Department of Nephrology, Centre Hospitalier Universitaire (CHU) Ambroise Paré, Assistance Publique-Hôpitaux de Paris (AP-HP), Boulogne-Billancourt, France. 13. Centre for Research in Epidemiology and Population Health (CESP), Institut National de la Santé et de la Recherche Médicale (INSERM) UMRS 1018, Team 5, University Versailles-Saint Quentin, University of Paris Saclay, Villejuif, France. 14. Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz, Autonomous University of Madrid (UAM), Red de Investigación Renal (REDINREN), Madrid, Spain. 15. University Hospital of Cabuenes, Asturias, Spain. 16. Representative of the European Kidney Patients' Federation, Nicosia, Cyprus. 17. Glasgow Renal and Transplant Unit, Queen Elizabeth University Hospital, Glasgow, United Kingdom. 18. Representative of the European Kidney Patients' Federation, Dublin, Ireland. 19. Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, The Netherlands.
Abstract
BACKGROUND AND OBJECTIVES: There is concern about potential deleterious effects of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) in patients with coronavirus disease 2019 (COVID-19). Patients with kidney failure, who often use ACEis/ARBs, are at higher risk of more severe COVID-19. However, there are no data available on the association of ACEi/ARB use with COVID-19 severity in this population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: From the European Renal Association COVID-19 database (ERACODA), we retrieved data on kidney transplant recipients and patients on dialysis who were affected by COVID-19, between February 1 and October 1, 2020, and had information on 28-day mortality. We used Cox proportional-hazards regression to calculate hazard ratios for the association between ACEi/ARB use and 28-day mortality risk. Additionally, we studied the association of discontinuation of these agents with 28-day mortality. RESULTS: We evaluated 1511 patients: 459 kidney transplant recipients and 1052 patients on dialysis. At diagnosis of COVID-19, 189 (41%) of the transplant recipients and 288 (27%) of the patients on dialysis were on ACEis/ARBs. A total of 88 (19%) transplant recipients and 244 (23%) patients on dialysis died within 28 days of initial presentation. In both groups of patients, there was no association between ACEi/ARB use and 28-day mortality in both crude and adjusted models (in transplant recipients, adjusted hazard ratio, 1.12; 95% confidence interval [95% CI], 0.69 to 1.83; in patients on dialysis, adjusted hazard ratio, 1.04; 95% CI, 0.73 to 1.47). Among transplant recipients, ACEi/ARB discontinuation was associated with a higher mortality risk after adjustment for demographics and comorbidities, but the association was no longer statistically significant after adjustment for severity of COVID-19 (adjusted hazard ratio, 1.36; 95% CI, 0.40 to 4.58). Among patients on dialysis, ACEi/ARB discontinuation was not associated with mortality in any model. We obtained similar results across subgroups when ACEis and ARBs were studied separately, and when other outcomes for severity of COVID-19 were studied, e.g., hospital admission, admission to the intensive care unit, or need for ventilator support. CONCLUSIONS: Among kidney transplant recipients and patients on dialysis with COVID-19, there was no significant association of ACEi/ARB use or discontinuation with mortality.
BACKGROUND AND OBJECTIVES: There is concern about potential deleterious effects of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) in patients with coronavirus disease 2019 (COVID-19). Patients with kidney failure, who often use ACEis/ARBs, are at higher risk of more severe COVID-19. However, there are no data available on the association of ACEi/ARB use with COVID-19 severity in this population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: From the European Renal Association COVID-19 database (ERACODA), we retrieved data on kidney transplant recipients and patients on dialysis who were affected by COVID-19, between February 1 and October 1, 2020, and had information on 28-day mortality. We used Cox proportional-hazards regression to calculate hazard ratios for the association between ACEi/ARB use and 28-day mortality risk. Additionally, we studied the association of discontinuation of these agents with 28-day mortality. RESULTS: We evaluated 1511 patients: 459 kidney transplant recipients and 1052 patients on dialysis. At diagnosis of COVID-19, 189 (41%) of the transplant recipients and 288 (27%) of the patients on dialysis were on ACEis/ARBs. A total of 88 (19%) transplant recipients and 244 (23%) patients on dialysis died within 28 days of initial presentation. In both groups of patients, there was no association between ACEi/ARB use and 28-day mortality in both crude and adjusted models (in transplant recipients, adjusted hazard ratio, 1.12; 95% confidence interval [95% CI], 0.69 to 1.83; in patients on dialysis, adjusted hazard ratio, 1.04; 95% CI, 0.73 to 1.47). Among transplant recipients, ACEi/ARB discontinuation was associated with a higher mortality risk after adjustment for demographics and comorbidities, but the association was no longer statistically significant after adjustment for severity of COVID-19 (adjusted hazard ratio, 1.36; 95% CI, 0.40 to 4.58). Among patients on dialysis, ACEi/ARB discontinuation was not associated with mortality in any model. We obtained similar results across subgroups when ACEis and ARBs were studied separately, and when other outcomes for severity of COVID-19 were studied, e.g., hospital admission, admission to the intensive care unit, or need for ventilator support. CONCLUSIONS: Among kidney transplant recipients and patients on dialysis with COVID-19, there was no significant association of ACEi/ARB use or discontinuation with mortality.