Results from the ERA-EDTA Registry indicate a high mortality due to COVID-19 in dialysis patients and kidney transplant recipients across Europe

The aim of this study was to investigate 28-day mortality after COVID-19 diagnosis in the European kidney replacement therapy population. In addition, we determined the role of patient characteristics, treatment factors, and country on mortality risk with the use of ERA-EDTA Registry data on patients receiving kidney replacement therapy in Europe from February 1, 2020, to April 30, 2020. Additional data on all patients with a diagnosis of COVID-19 were collected from 7 European countries encompassing 4298 patients. COVID-19–attributable mortality was calculated using propensity score–matched historic control data and after 28 days of follow-up was 20. 0% (95% confidence interval 18. 7%–21. 4%) in 3285 patients receiving dialysis and 19. 9% (17. 5%–22. 5%) in 1013 recipients of a transplant. We identified differences in COVID-19 mortality across countries, and an increased mortality risk in older patients receiving kidney replacement therapy and male patients receiving dialysis. In recipients of kidney transplants ≥75 years of age, 44. 3% (35. 7%–53. 9%) did not survive COVID-19. Mortality risk was 1. 28 (1. 02–1. 60) times higher in transplant recipients compared with matched dialysis patients. Thus, the pandemic has had a substantial effect on mortality in patients receiving kidney replacement therapy, a highly vulnerable population due to underlying chronic kidney disease and a high prevalence of multimorbidity. The aim of this study was to investigate 28-day mortality after COVID-19 diagnosis in the European kidney replacement therapy population. In addition, we determined the role of patient characteristics, treatment factors, and country on mortality risk with the use of ERA-EDTA Registry data on patients receiving kidney replacement therapy in Europe from February 1, 2020, to April 30, 2020. Additional data on all patients with a diagnosis of COVID-19 were collected from 7 European countries encompassing 4298 patients. COVID-19–attributable mortality was calculated using propensity score–matched historic control data and after 28 days of follow-up was 20. 0% (95% confidence interval 18. 7%–21. 4%) in 3285 patients receiving dialysis and 19. 9% (17. 5%–22. 5%) in 1013 recipients of a transplant. We identified differences in COVID-19 mortality across countries, and an increased mortality risk in older patients receiving kidney replacement therapy and male patients receiving dialysis. In recipients of kidney transplants ≥75 years of age, 44. 3% (35. 7%–53. 9%) did not survive COVID-19. Mortality risk was 1. 28 (1. 02–1. 60) times higher in transplant recipients compared with matched dialysis patients. Thus, the pandemic has had a substantial effect on mortality in patients receiving kidney replacement therapy, a highly vulnerable population due to underlying chronic kidney disease and a high prevalence of multimorbidity. Editor’s NoteThis is one of several articles we think you will find of interest that are part of our special issue of Kidney International addressing the challenges of dialysis and transplantation during the COVID-19 pandemic. Please also find additional material in our commentaries and letters to the editor sections. We hope these insights will help you in the daily care of your own patients. This is one of several articles we think you will find of interest that are part of our special issue of Kidney International addressing the challenges of dialysis and transplantation during the COVID-19 pandemic. Please also find additional material in our commentaries and letters to the editor sections. We hope these insights will help you in the daily care of your own patients. Since the initial outbreak in Wuhan, China, in December 2019, coronavirus disease 2019 (COVID-19) has spread rapidly across the world, prompting a global pandemic. The disease—caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus—causes pneumonia, but also affects other organs. According to the European Centre for Disease Prevention and Control, the number of reported COVID-19 cases in the European Union (EU) is 2783 (range 281–6648) per million general population (pmp), representing 0. 28% (range 0. 03%–0. 66%) of the EU population, with variation in numbers depending on governmental control measures, definition of cases, and testing capacity. 1European Centre for Disease Prevention and ControlCOVID-19 situation update for the EU/EEA and the UK. https: //www. ecdc. europa. eu/en/cases-2019-ncov-eueeaDate accessed: June 9, 2020Google Scholar Mortality due to the SARS-CoV-2 virus is high compared with most other viral infections. Although a case fatality rate of 2. 3% was reported from China, 2Wu Z. McGoogan J. M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020; 323: 1239-1242Crossref PubMed Scopus (12778) Google Scholar the average rate is 11. 7% (range 0. 6%–18. 9%) in the EU general population. 1European Centre for Disease Prevention and ControlCOVID-19 situation update for the EU/EEA and the UK. https: //www. ecdc. europa. eu/en/cases-2019-ncov-eueeaDate accessed: June 9, 2020Google Scholar Among hospitalized patients in United Kingdom suffering from severe COVID-19, the case fatality rate reaches 26%. 3Docherty A. B. Harrison E. M. Green C. A. et al. Features of 16, 749 hospitalised UK patients with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol. medRxiv. 2020; 04: 20076042Google Scholar Patients treated with kidney replacement therapy (KRT; either dialysis or kidney transplantation) represent a vulnerable population. Under normal circumstances, age-standardized cardiovascular and noncardiovascular mortality rates in dialysis patients are already 8. 8 and 8. 1 times higher than in the general population, respectively, 4de Jager D. J. Grootendorst D. C. Jager K. J. et al. Cardiovascular and noncardiovascular mortality among patients starting dialysis. JAMA. 2009; 302: 1782-1789Crossref PubMed Scopus (593) Google Scholar and compared with their age- and sex-matched counterparts in the general population, kidney transplant recipients experience a 30%–50% reduced life expectancy. 5ERA-EDTA RegistryERA-EDTA Registry Annual Report 2017. 2019. https: //www. era-edta. org/en/registry/publications/annual-reports/#2017Google Scholar It may be expected that COVID-19 causes substantial mortality in both dialysis and kidney transplant populations due to their underlying chronic kidney disease and a high prevalence of comorbid conditions such as diabetes mellitus and cardiovascular disease. In transplant recipients, the potential effect of their long-term use of immunosuppression is a matter of debate. Some argue they may be at greater risk of severe infection because of their impaired immune system, 6Coates P. T. Wong G. Drueke T. et al. Early experience with COVID-19 in kidney transplantation. Kidney Int. 2020; 97: 1074-1075Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar whereas others speculate that immunosuppressive therapy may be protective as it might address the COVID-19–induced cytokine storm. 7Tay M. Z. Poh C. M. Rénia L. et al. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020; 20: 363-374Crossref PubMed Scopus (2942) Google Scholar Although no deaths were reported among 5 COVID-19 cases on hemodialysis in a single Chinese center, 8Wang R. Liao C. He H. et al. COVID-19 in hemodialysis patients: a report of 5 cases. Am J Kidney Dis. 2020; 76: 141-143Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar several case series from Italy (n = 41, n = 94), 9Scarpioni R. Manini A. Valsania T. et al. Covid-19 and its impact on nephropathic patients: the experience at Ospedale “Guglielmo da Saliceto” in Piacenza. G Ital Nefrol. 2020; 37: 4Google Scholar, 10Alberici F. Delbarba E. Manenti C. et al. A report from the Brescia Renal COVID Task Force on the clinical characteristics and short-term outcome of hemodialysis patients with SARS-CoV-2 infection. Kidney Int. 2020; 98: 20-26Abstract Full Text Full Text PDF PubMed Scopus (191) Google Scholar Spain (n = 36), 11Goicoechea M. Sánchez Cámara L. A. Macías N. et al. COVID-19: clinical course and outcomes of 36 maintenance hemodialysis patients from a single center in Spain. Kidney Int. 2020; 98: 27-34Abstract Full Text Full Text PDF PubMed Scopus (241) Google Scholar and the United States (n = 59) 12Valeri A. M. Robbins-Juarez S. Y. Stevens J. S. et al. Presentation and outcomes of patients with ESKD and COVID-19. J Am Soc Nephrol. 2020; 31: 1409-1415Crossref PubMed Scopus (258) Google Scholar with varying follow-up suggest a high mortality in the dialysis population with rates ranging from 29% to 41%. Preliminary reports in transplant recipients seem to suggest a somewhat lower mortality, with estimates ranging from 13% (n = 15) in the United States to 25% in Italy (n = 20). 13Mohan S. Early description of coronavirus 2019 disease in kidney transplant recipients in New York. J Am Soc Nephrol. 2020; 31: 1150-1156Crossref PubMed Scopus (191) Google Scholar, 14Banerjee D. Popoola J. Shah S. et al. COVID-19 infection in kidney transplant recipients. Kidney Int. 2020; 97: 1076-1082Abstract Full Text Full Text PDF PubMed Scopus (295) Google Scholar, 15Alberici F. Delbarba E. Manenti C. et al. A single center observational study of the clinical characteristics and short-term outcome of 20 kidney transplant patients admitted for SARS-CoV2 pneumonia. Kidney Int. 2020; 97: 1083-1088Abstract Full Text Full Text PDF PubMed Scopus (286) Google Scholar The largest study to date is from Spain, reporting on a group of 868 KRT patients (67% dialysis patients and 33% transplant patients) with a mortality rate of 23%. 16Sánchez-Álvarez J. E. Fontán M. P. Martín C. J. et al. Status of SARS-CoV-2 infection in patients on renal replacement therapy. Report of the COVID-19 Registry of the Spanish Society of Nephrology (SEN). Nefrologia. 2020; 40: 272-278PubMed Google Scholar Risk estimates from studies with small sample sizes are known to suffer from inaccuracy due to random variation. In addition, because some of the above-mentioned samples were derived from in-hospital populations, the estimates reflect risk in a selected group of more severely ill patients and may not be generalizable to the broader KRT patient population. Moreover, most of these studies, including the largest one, used the case fatality rate as a measure of mortality, which is often calculated while the individual outcome (recovery or death) is known only for a proportion of infected patients. 17Natale F. Ghio D. Tarchi D. Goujon A. Conte A. COVID-19 cases and case fatality rate by age. https: //ec. europa. eu/knowledge4policy/publication/covid-19-cases-case-fatality-rate-ageₑnDate accessed: June 9, 2020Google Scholar To date, large population-based studies on mortality in the KRT population with complete follow-up information are lacking. Therefore, the first aim of the present study was to investigate the COVID-19 attributable mortality 28 days after diagnosis in European dialysis and kidney transplant recipients with the use of historic cohorts of prevalent dialysis and transplant patients without COVID-19. The second aim was to compare mortality between dialysis and transplant patients with COVID-19. Finally, we aimed to determine the role of patient characteristics, KRT treatment-related factors, and country as risk factors for death in both groups. From February 1, 2020, to April 30, 2020, a total of 4298 KRT patients were diagnosed with COVID-19, of which 3285 (76. 4%) were on dialysis—3160 on hemodialysis and 125 on peritoneal dialysis—and 1013 (23. 6%) were living with a functioning transplant (Table 1). The majority of dialysis patients diagnosed with COVID-19 originated from France (49. 6%) and Spain (29. 7%). In dialysis patients, the median age at COVID-19 diagnosis was 71. 7 years (interquartile range IQR 60. 6–80. 5), ranging from 63. 2 years in Romania to 74. 0 years in Spain. Two-thirds were ≥65 years of age, almost two-thirds were male, almost half suffered from either diabetes mellitus (25. 5%) or hypertension/renovascular disease (RVD) (21. 2%) as primary renal disease (PRD), and 96. 2% were on hemodialysis. Sufficient numbers of transplant patients with COVID-19 were available from France (50. 5%) and Spain (49. 5%). Transplant recipients were younger than those on dialysis (P < 0. 001), with a median age of 60. 9 years (IQR 51. 1–69. 4) and 37. 3% being ≥65 years. Similarly to dialysis patients, 65. 4% were male (P = 0. 23), however, the share of patients with diabetes mellitus (12. 8%) and hypertension/RVD (10. 6%) as PRD was lower. Table 1Characteristics of KRT patients diagnosed with COVID-19, by treatment modality and countryDialysisTransplantAllHDPDAustriaFrench-speaking part of BelgiumaData on patients younger than 20 years were not included. FranceRomaniaSpainSwitzerlandThe NetherlandsAllFranceSpainNo. of patients32853160125441401631270976871371013512501Age at diagnosis, yr, median (IQR) 71. 7 (60. 6–80. 5) 71. 8 (60. 8–80. 6) 70. 2 (59. 4–78. 5) 71. 8 (62. 8–81. 3) 71. 2 (57. 9–78. 5) 72 (60. 8–81. 2) 63. 2 (52. 7–70. 2) 74 (63–81. 2) 73. 7 (59. 6–81. 9) 73. 4 (61–81. 5) 60. 9 (51. 1–69. 4) 59. 6 (49. 9–67. 9) 62. 5 (52. 3–70. 9) 0–199 (0. 3) 8 (0. 3) 1 (0. 8) 0 (0) NA3 (0. 2) 1 (0. 4) 5 (0. 5) 0 (0) 0 (0) 8 (0. 8) 4 (0. 8) 4 (0. 8) 20–44225 (6. 8) 215 (6. 8) 10 (8. 0) 2 (4. 5) 11 (7. 9) 127 (7. 8) 26 (9. 6) 46 (4. 7) 7 (8. 0) 6 (4. 4) 128 (12. 6) 80 (15. 6) 48 (9. 6) 45–64854 (26. 0) 817 (25. 9) 37 (29. 6) 10 (22. 7) 41 (29. 3) 401 (24. 6) 123 (45. 6) 222 (22. 7) 22 (25. 3) 35 (25. 5) 499 (49. 3) 263 (51. 4) 236 (47. 1) 65–74857 (26. 1) 823 (26. 0) 34 (27. 2) 15 (34. 1) 34 (24. 3) 429 (26. 3) 82 (30. 4) 245 (25. 1) 16 (18. 4) 36 (26. 3) 260 (25. 7) 115 (22. 5) 145 (28. 9) ≥751340 (40. 8) 1297 (41. 0) 43 (34. 4) 17 (38. 6) 54 (38. 6) 671 (41. 1) 38 (14. 1) 458 (46. 9) 42 (48. 3) 60 (43. 8) 118 (11. 6) 50 (9. 8) 68 (13. 6) Sex Male2077 (63. 2) 1993 (63. 1) 84 renal disease modality of KRT median of starting treatment of starting treatment coronavirus disease kidney replacement not peritoneal are as n or median are country was only it had dialysis or transplant patients with on patients younger than 20 years were not of starting treatment in a COVID-19, coronavirus disease kidney replacement not peritoneal disease. are as n or median are country was only it had dialysis or transplant patients with COVID-19. 1, 2020, COVID-19 cases of all prevalent patients on dialysis range and of those living with a functioning range with dialysis and transplant patients without COVID-19, those with COVID-19 were years The proportion of male patients was with more among dialysis patients, and more among transplant recipients In both dialysis and transplant patients with COVID-19 were more patients with diabetes mellitus as PRD and days after COVID-19 diagnosis, of hemodialysis patients and of 125 patients on peritoneal dialysis had that in the dialysis group as a had 28 days after diagnosis, with of deaths on the of In transplant recipients, of 1013 had after 28 28-day of death of was to that in the dialysis with of deaths on the of 28 the to that most of the deaths due to COVID-19 had this with the expected mortality in the matched control group of dialysis patients without COVID-19, the COVID-19 attributable mortality was 20. 0% and mortality risk was (95% confidence interval times higher in dialysis patients diagnosed with COVID-19 In transplant recipients diagnosed with COVID-19, the attributable mortality was 19. 9% the expected mortality in the matched control mortality is lower in transplant patients compared with dialysis patients, their mortality risk was (95% times higher compared with their matched control patients 1). that the mortality risk in transplant recipients with COVID-19 was higher compared with the selected group of dialysis patients that be matched In dialysis patients, the of mortality by age substantial differences across age with 28-day mortality in patients ≥75 years of age as high as (Table The risk of death in was in patients with hypertension/RVD as PRD had the of death by diabetes mellitus and The 28-day of death was in those treated with peritoneal dialysis and in hemodialysis patients. were substantial differences in mortality across the 7 it was in the and in Romania identified higher age and male as risk factors for 28-day mortality in COVID-19 dialysis patients (Table for all available dialysis patients in Romania and France had a lower mortality risk than those in The of death by age and PRD is in and the COVID-19–attributable mortality is in of death in and risk factors in dialysis patients with of death 28 days (95% (95% for age was for and the for was for age and the for primary renal disease was for age, and the for of KRT was for age, and the for treatment modality was for age, of KRT and and the for country was for age, and of KRT for age was for and the for was for age and the for primary renal disease was for age, and the for of KRT was for age, and the for treatment modality was for age, of KRT and and the for country was for age, and of KRT at COVID-19 diagnosis, renal disease of KRT Spain this was of dialysis modality The confidence COVID-19, coronavirus disease kidney replacement peritoneal The for age was for and the for was for age and the for primary renal disease was for age, and the for of KRT was for age, and the for treatment modality was for age, of KRT and and the for country was for age, and of KRT Spain this was of dialysis in a of death among dialysis patients and transplant patients with coronavirus disease 2019 by confidence confidence COVID-19, coronavirus disease kidney replacement peritoneal disease. In kidney transplant recipients, the of mortality by age group a high 44. 3% of death in those ≥75 years of age, which for almost half of the patients (Table The of death was in and in and in patients suffering from diabetes mellitus as PRD by hypertension/RVD and in those with The of death was higher in Spain than in France In only higher age was identified as a risk for 28-day mortality (Table The of death by age and PRD is in and the COVID-19–attributable mortality is in of death in and risk factors in transplant patients with of death 28 days (95% (95% for age was for and the for was for age and the for primary renal disease was for age, and the for of KRT and of transplant was for age, and and the for country was for age, and of KRT transplantation in for age was for and the for was for age and the for primary renal disease was for age, and the for of KRT and of transplant was for age, and and the for country was for age, and of KRT transplantation in at COVID-19 diagnosis, renal disease of KRT of transplantation confidence COVID-19, coronavirus disease kidney replacement peritoneal The for age was for and the for was for age and the for primary renal disease was for age, and the for of KRT and of transplant was for age, and and the for country was for age, and of KRT transplantation in in a confidence COVID-19, coronavirus disease kidney replacement peritoneal disease. In this we present complete population-based data on more than KRT patients by COVID-19 collected and renal in We report the of death at 28 days after diagnosis and risk factors in dialysis patients from 7 European countries and in transplant recipients from 2 European In both the dialysis and the transplant of patients had by 28 days after matched that transplant recipients had a higher risk of death compared with their dialysis in dialysis patients higher age, male and country as risk factors, whereas in transplant recipients only higher age was with an increased risk of The data suggest that the of diagnosed COVID-19 in the KRT population was as of the prevalent dialysis population and of those living on a functioning were by COVID-19, this disease to had a greater impact on the KRT population compared to the general Centre for Disease Prevention and ControlCOVID-19 situation update for the EU/EEA and the UK. https: //www. ecdc. europa. eu/en/cases-2019-ncov-eueeaDate accessed: June 9, 2020Google Scholar which may be due to their older age, or the of more our COVID-19 patients were from population-based they may not represent all KRT patients with COVID-19. The majority of are or and not not of a general or a patients may not and may testing in dialysis more during the of the this is the case for hemodialysis patients their dialysis center a times a The of patients with COVID-19 were lower in patients on peritoneal dialysis and in transplant We speculate that in these testing may to the and more severe cases, and our data for these populations represent a group of patients. This is by the high number of transplant recipients on the of diagnosis This may our that transplant patients are at higher risk of death than dialysis patients of propensity the other being may more of a while the infection than an the cytokine P. T. Wong G. Drueke T. et al. Early experience with COVID-19 in kidney transplantation. Kidney Int. 2020; 97: 1074-1075Abstract Full Text Full Text PDF PubMed Scopus (44) Google M. Z. Poh C. M. Rénia L. et al. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020; 20: 363-374Crossref PubMed Scopus (2942) Google Scholar Although the risk of COVID-19 was in KRT patients, 28-day mortality in COVID-19 patients the mortality that may be expected for KRT patients of propensity on the historic control on the 28-day of death due to COVID-19 by age in the general population is lacking. data on the rate in the general population to in and to for those years of G. G. S. rate and characteristics of patients in to COVID-19 in 2020; 323: Google Scholar data from Spain higher and COVID-19, no COVID-19 a accessed: June 9, 2020Google Scholar This may suggest that mortality from COVID-19 in the dialysis population age 71. 7 is times higher and in transplant patients age 60. 9 times compared with patients with COVID-19 of in dialysis and transplant patients will an important role in this substantial mortality, but our data did not on this We however, in that in both the dialysis and the transplant almost of patients COVID-19 at to 28 days after diagnosis, the that a substantial number of may not admitted to the care to their high risk of In both dialysis and transplant patients with COVID-19, higher age the most important risk for mortality in our The that male was a risk in dialysis patients with COVID-19 is of It in the general population and also the increased cardiovascular mortality in compared with on dialysis without Jager D. J. M. et al. Cardiovascular and noncardiovascular mortality among and starting J Am Soc Nephrol. PubMed Scopus Google Scholar studies disease to be a risk in dialysis F. Delbarba E. Manenti C. et al. A report from the Brescia Renal COVID Task Force on the clinical characteristics and short-term outcome of hemodialysis patients with SARS-CoV-2 infection. Kidney Int. 2020; 98: 20-26Abstract Full Text Full Text PDF PubMed Scopus (191) Google Scholar We did not to but PRD be as a for In our the estimates of the additional risk by diabetes mellitus and hypertension/RVD did suggest a in an additional effect of PRD on of age not be as a of In dialysis patients with COVID-19, we that the of death across Although it is we not to from that because of the variation may be to in the of COVID-19 cases a of varying testing differences in the of and the to for and This study reports data from renal that aim to complete data with the in and this it to reporting on patient populations with COVID-19, renal the of impaired testing from of cases, of the of care of or not reporting to the KRT treatment will to an of This is to be small for hemodialysis patients, but it may be more important for peritoneal dialysis patients and transplant recipients, more severe cases were The of this by varying testing may across countries and using data as a we had no to additional information on patient and treatment characteristics that be important to the outcome of COVID-19 patients on Finally, this study the number of COVID-19 patients on KRT to date, it may suffer from of in an to The COVID-19 pandemic has had a substantial effect on mortality in all of KRT patients by the in KRT patients and in transplant It is that in the hemodialysis may as important of It is of that in the and control in and be to to the of their patients and the to their as as in this and studies on of COVID-19 in KRT patients are