Sex differences in COVID-19 mortality risk in patients on kidney function replacement therapy

Priya Vart; Raphaël Duivenvoorden; Aaltje Adema; Adrian Covic; Patrik Finne; Nicole Heijtink ter Braak; Kaisa Laine; Marlies Noordzij; Marcel Schouten; Kitty J. Jager; Ron T. Gansevoort; Jeroen B. van der Net; Marie Essig; Peggy W.G. du Buf-Vereijken; Betty van Ginneken; Nanda Maas; Brigit C. van Jaarsveld; Frederike J. Bemelman; Farah Klingenberg-Salahova; Frederiek Heenan-Vos; Marc G. Vervloet; Azam Nurmohamed; Liffert Vogt; Daniel Abramowicz; Sabine Verhofstede; Omar Maoujoud; Thomas Malfait; Jana Fialova; Edoardo Melilli; Alexandre Favà; Josep M. Cruzado; Nuria Montero Perez; Joy Lips; Harmen Krepel; Harun Adilovic; Daniela Radulescu; Maaike Hengst; Constantijn Konings; Andrzej Rydzewski; Philippe Braconnier; Daniel Weis; Ryszard Gellert; João Oliveira; Daniela G. Alferes; Elena V. Zakharova; Patrice Max Ambühl; Rebecca Guidotti; Andrea Walker; Fanny Lepeytre; Clémentine Rabaté; Frank van der Sande; Martinus Christiaans; Marc Hemmelder; ERACODA Collaborators

doi:10.1038/s41598-022-22657-4

Sex differences in COVID-19 mortality risk in patients on kidney function replacement therapy

Priya Vart^*, Raphaël Duivenvoorden, Aaltje Adema, Adrian Covic, Patrik Finne, Nicole Heijtink ter Braak, Kaisa Laine, Marlies Noordzij, Marcel Schouten, Kitty J. Jager, Ron T. Gansevoort, Jeroen B. van der Net, Marie Essig, Peggy W.G. du Buf-Vereijken, Betty van Ginneken, Nanda Maas, Brigit C. van Jaarsveld, Frederike J. Bemelman, Farah Klingenberg-Salahova, Frederiek Heenan-VosMarc G. Vervloet, Azam Nurmohamed, Liffert Vogt, Daniel Abramowicz, Sabine Verhofstede, Omar Maoujoud, Thomas Malfait, Jana Fialova, Edoardo Melilli, Alexandre Favà, Josep M. Cruzado, Nuria Montero Perez, Joy Lips, Harmen Krepel, Harun Adilovic, Daniela Radulescu, Maaike Hengst, Constantijn Konings, Andrzej Rydzewski, Philippe Braconnier, Daniel Weis, Ryszard Gellert, João Oliveira, Daniela G. Alferes, Elena V. Zakharova, Patrice Max Ambühl, Rebecca Guidotti, Andrea Walker, Fanny Lepeytre, Clémentine Rabaté, Frank van der Sande, Martinus Christiaans, Marc Hemmelder, ERACODA Collaborators

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

In the general population with COVID-19, the male sex is an established risk factor for mortality, in part due to a more robust immune response to COVID-19 in women. Because patients on kidney function replacement therapy (KFRT) have an impaired immune response, especially kidney transplant recipients due to their use of immunosuppressants, we examined whether the male sex is still a risk factor for mortality among patients on KFRT with COVID-19. From the European Renal Association COVID-19 Database (ERACODA), we examined patients on KFRT with COVID-19 who presented between February 1st, 2020, and April 30th, 2021. 1204 kidney transplant recipients (male 62.0%, mean age 56.4 years) and 3206 dialysis patients (male 61.8%, mean age 67.7 years) were examined. Three-month mortality in kidney transplant recipients was 16.9% in males and 18.6% in females (p = 0.31) and in dialysis patients 27.1% in males and 21.9% in females (p = 0.001). The adjusted HR for the risk of 3-month mortality in males (vs females) was 0.89 (95% CI 65, 1.23, p = 0.49) in kidney transplant recipients and 1.33 (95% CI 1.13, 1.56, p = 0.001) in dialysis patients (pinteraction = 0.02). In a fully adjusted model, the aHR for the risk of 3-month mortality in kidney transplant recipients (vs. dialysis patients) was 1.39 (95% CI 1.02, 1.89, p = 0.04) in males and 2.04 (95% CI 1.40, 2.97, p < 0.001) in females (pinteraction = 0.02). In patients on KFRT with COVID-19, the male sex is not a risk factor for mortality among kidney transplant recipients but remains a risk factor among dialysis patients. The use of immunosuppressants in kidney transplant recipients, among other factors, may have narrowed the difference in the immune response to COVID-19 between men and women, and therefore reduced the sex difference in COVID-19 mortality risk.

Original language	English
Article number	17978
Number of pages	13
Journal	Scientific Reports
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41598-022-22657-4
Publication status	Published - 26 Oct 2022

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Vart, P., Duivenvoorden, R., Adema, A., Covic, A., Finne, P., Braak, N. H. T., Laine, K., Noordzij, M., Schouten, M., Jager, K. J., Gansevoort, R. T., van der Net, J. B., Essig, M., du Buf-Vereijken, P. W. G., van Ginneken, B., Maas, N., van Jaarsveld, B. C., Bemelman, F. J., Klingenberg-Salahova, F., ... ERACODA Collaborators (2022). Sex differences in COVID-19 mortality risk in patients on kidney function replacement therapy. Scientific Reports, 12(1), Article 17978. https://doi.org/10.1038/s41598-022-22657-4

@article{52dad859613e415ea5d47ef3c46c329c,

title = "Sex differences in COVID-19 mortality risk in patients on kidney function replacement therapy",

abstract = "In the general population with COVID-19, the male sex is an established risk factor for mortality, in part due to a more robust immune response to COVID-19 in women. Because patients on kidney function replacement therapy (KFRT) have an impaired immune response, especially kidney transplant recipients due to their use of immunosuppressants, we examined whether the male sex is still a risk factor for mortality among patients on KFRT with COVID-19. From the European Renal Association COVID-19 Database (ERACODA), we examined patients on KFRT with COVID-19 who presented between February 1st, 2020, and April 30th, 2021. 1204 kidney transplant recipients (male 62.0%, mean age 56.4 years) and 3206 dialysis patients (male 61.8%, mean age 67.7 years) were examined. Three-month mortality in kidney transplant recipients was 16.9% in males and 18.6% in females (p = 0.31) and in dialysis patients 27.1% in males and 21.9% in females (p = 0.001). The adjusted HR for the risk of 3-month mortality in males (vs females) was 0.89 (95% CI 65, 1.23, p = 0.49) in kidney transplant recipients and 1.33 (95% CI 1.13, 1.56, p = 0.001) in dialysis patients (pinteraction = 0.02). In a fully adjusted model, the aHR for the risk of 3-month mortality in kidney transplant recipients (vs. dialysis patients) was 1.39 (95% CI 1.02, 1.89, p = 0.04) in males and 2.04 (95% CI 1.40, 2.97, p < 0.001) in females (pinteraction = 0.02). In patients on KFRT with COVID-19, the male sex is not a risk factor for mortality among kidney transplant recipients but remains a risk factor among dialysis patients. The use of immunosuppressants in kidney transplant recipients, among other factors, may have narrowed the difference in the immune response to COVID-19 between men and women, and therefore reduced the sex difference in COVID-19 mortality risk.",

author = "Priya Vart and Rapha{\"e}l Duivenvoorden and Aaltje Adema and Adrian Covic and Patrik Finne and Braak, {Nicole Heijtink ter} and Kaisa Laine and Marlies Noordzij and Marcel Schouten and Jager, {Kitty J.} and Gansevoort, {Ron T.} and {van der Net}, {Jeroen B.} and Marie Essig and {du Buf-Vereijken}, {Peggy W.G.} and {van Ginneken}, Betty and Nanda Maas and {van Jaarsveld}, {Brigit C.} and Bemelman, {Frederike J.} and Farah Klingenberg-Salahova and Frederiek Heenan-Vos and Vervloet, {Marc G.} and Azam Nurmohamed and Liffert Vogt and Daniel Abramowicz and Sabine Verhofstede and Omar Maoujoud and Thomas Malfait and Jana Fialova and Edoardo Melilli and Alexandre Fav{\`a} and Cruzado, {Josep M.} and Perez, {Nuria Montero} and Joy Lips and Harmen Krepel and Harun Adilovic and Daniela Radulescu and Maaike Hengst and Constantijn Konings and Andrzej Rydzewski and Philippe Braconnier and Daniel Weis and Ryszard Gellert and Jo{\~a}o Oliveira and Alferes, {Daniela G.} and Zakharova, {Elena V.} and Amb{\"u}hl, {Patrice Max} and Rebecca Guidotti and Andrea Walker and Fanny Lepeytre and Cl{\'e}mentine Rabat{\'e} and {van der Sande}, Frank and Martinus Christiaans and Marc Hemmelder and {ERACODA Collaborators}",

note = "Funding Information: Unrestricted research grants were obtained from the European Renal Association, The Dutch Kidney Foundation, Baxter, and Sandoz. Neither organization had any role in the design of the study, interpretation of results, nor in writing of the article. Funding Information: The ERACODA collaboration is an initiative to study prognosis and risk factors for mortality due to COVID-19 in patients with a kidney transplant or on dialysis that is endorsed by the ERA-EDTA. ERACODA is an acronym for European Renal Association COVID-19 Database. The organizational structure contains a Working Group assisted by a Management Team and an Advisory Board. The ERACODA Working Group members: Franssen CFM, Gansevoort RT (coordinator), Hemmelder MH, Hilbrands LB and Jager KJ. The ERACODA Management Team members: Duivenvoorden R, Noordzij M and Vart P. The ERACODA Advisory Board members: Abramowicz D, Basile C, Covic A, Crespo M, Massy ZA, Mitra S, Petridou E, Sanchez JE, White C. We thank all people that entered information in the ERACODA database for their participation, and especially all healthcare workers that have taken care of the included COVID-19 patients. The abstract of this manuscript was presented at the European Renal Association Conference 2022 and has been published in the Nephrology, Dialysis, and Transplantation journal (https://doi.org/10.1093/ndt/gfac095.003). The manuscript has not been submitted for consideration elsewhere. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = oct,

day = "26",

doi = "10.1038/s41598-022-22657-4",

language = "English",

volume = "12",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

}

Vart, P, Duivenvoorden, R, Adema, A, Covic, A, Finne, P, Braak, NHT, Laine, K, Noordzij, M, Schouten, M, Jager, KJ, Gansevoort, RT, van der Net, JB, Essig, M, du Buf-Vereijken, PWG, van Ginneken, B, Maas, N, van Jaarsveld, BC, Bemelman, FJ, Klingenberg-Salahova, F, Heenan-Vos, F, Vervloet, MG, Nurmohamed, A, Vogt, L, Abramowicz, D, Verhofstede, S, Maoujoud, O, Malfait, T, Fialova, J, Melilli, E, Favà, A, Cruzado, JM, Perez, NM, Lips, J, Krepel, H, Adilovic, H, Radulescu, D, Hengst, M, Konings, C, Rydzewski, A, Braconnier, P, Weis, D, Gellert, R, Oliveira, J, Alferes, DG, Zakharova, EV, Ambühl, PM, Guidotti, R, Walker, A, Lepeytre, F, Rabaté, C, van der Sande, F , Christiaans, M , Hemmelder, M & ERACODA Collaborators 2022, 'Sex differences in COVID-19 mortality risk in patients on kidney function replacement therapy', Scientific Reports, vol. 12, no. 1, 17978. https://doi.org/10.1038/s41598-022-22657-4

TY - JOUR

T1 - Sex differences in COVID-19 mortality risk in patients on kidney function replacement therapy

AU - Vart, Priya

AU - Duivenvoorden, Raphaël

AU - Adema, Aaltje

AU - Covic, Adrian

AU - Finne, Patrik

AU - Braak, Nicole Heijtink ter

AU - Laine, Kaisa

AU - Noordzij, Marlies

AU - Schouten, Marcel

AU - Jager, Kitty J.

AU - Gansevoort, Ron T.

AU - van der Net, Jeroen B.

AU - Essig, Marie

AU - du Buf-Vereijken, Peggy W.G.

AU - van Ginneken, Betty

AU - Maas, Nanda

AU - van Jaarsveld, Brigit C.

AU - Bemelman, Frederike J.

AU - Klingenberg-Salahova, Farah

AU - Heenan-Vos, Frederiek

AU - Vervloet, Marc G.

AU - Nurmohamed, Azam

AU - Vogt, Liffert

AU - Abramowicz, Daniel

AU - Verhofstede, Sabine

AU - Maoujoud, Omar

AU - Malfait, Thomas

AU - Fialova, Jana

AU - Melilli, Edoardo

AU - Favà, Alexandre

AU - Cruzado, Josep M.

AU - Perez, Nuria Montero

AU - Lips, Joy

AU - Krepel, Harmen

AU - Adilovic, Harun

AU - Radulescu, Daniela

AU - Hengst, Maaike

AU - Konings, Constantijn

AU - Rydzewski, Andrzej

AU - Braconnier, Philippe

AU - Weis, Daniel

AU - Gellert, Ryszard

AU - Oliveira, João

AU - Alferes, Daniela G.

AU - Zakharova, Elena V.

AU - Ambühl, Patrice Max

AU - Guidotti, Rebecca

AU - Walker, Andrea

AU - Lepeytre, Fanny

AU - Rabaté, Clémentine

AU - van der Sande, Frank

AU - Christiaans, Martinus

AU - Hemmelder, Marc

AU - ERACODA Collaborators

N1 - Funding Information: Unrestricted research grants were obtained from the European Renal Association, The Dutch Kidney Foundation, Baxter, and Sandoz. Neither organization had any role in the design of the study, interpretation of results, nor in writing of the article. Funding Information: The ERACODA collaboration is an initiative to study prognosis and risk factors for mortality due to COVID-19 in patients with a kidney transplant or on dialysis that is endorsed by the ERA-EDTA. ERACODA is an acronym for European Renal Association COVID-19 Database. The organizational structure contains a Working Group assisted by a Management Team and an Advisory Board. The ERACODA Working Group members: Franssen CFM, Gansevoort RT (coordinator), Hemmelder MH, Hilbrands LB and Jager KJ. The ERACODA Management Team members: Duivenvoorden R, Noordzij M and Vart P. The ERACODA Advisory Board members: Abramowicz D, Basile C, Covic A, Crespo M, Massy ZA, Mitra S, Petridou E, Sanchez JE, White C. We thank all people that entered information in the ERACODA database for their participation, and especially all healthcare workers that have taken care of the included COVID-19 patients. The abstract of this manuscript was presented at the European Renal Association Conference 2022 and has been published in the Nephrology, Dialysis, and Transplantation journal (https://doi.org/10.1093/ndt/gfac095.003). The manuscript has not been submitted for consideration elsewhere. Publisher Copyright: © 2022, The Author(s).

PY - 2022/10/26

Y1 - 2022/10/26

N2 - In the general population with COVID-19, the male sex is an established risk factor for mortality, in part due to a more robust immune response to COVID-19 in women. Because patients on kidney function replacement therapy (KFRT) have an impaired immune response, especially kidney transplant recipients due to their use of immunosuppressants, we examined whether the male sex is still a risk factor for mortality among patients on KFRT with COVID-19. From the European Renal Association COVID-19 Database (ERACODA), we examined patients on KFRT with COVID-19 who presented between February 1st, 2020, and April 30th, 2021. 1204 kidney transplant recipients (male 62.0%, mean age 56.4 years) and 3206 dialysis patients (male 61.8%, mean age 67.7 years) were examined. Three-month mortality in kidney transplant recipients was 16.9% in males and 18.6% in females (p = 0.31) and in dialysis patients 27.1% in males and 21.9% in females (p = 0.001). The adjusted HR for the risk of 3-month mortality in males (vs females) was 0.89 (95% CI 65, 1.23, p = 0.49) in kidney transplant recipients and 1.33 (95% CI 1.13, 1.56, p = 0.001) in dialysis patients (pinteraction = 0.02). In a fully adjusted model, the aHR for the risk of 3-month mortality in kidney transplant recipients (vs. dialysis patients) was 1.39 (95% CI 1.02, 1.89, p = 0.04) in males and 2.04 (95% CI 1.40, 2.97, p < 0.001) in females (pinteraction = 0.02). In patients on KFRT with COVID-19, the male sex is not a risk factor for mortality among kidney transplant recipients but remains a risk factor among dialysis patients. The use of immunosuppressants in kidney transplant recipients, among other factors, may have narrowed the difference in the immune response to COVID-19 between men and women, and therefore reduced the sex difference in COVID-19 mortality risk.

AB - In the general population with COVID-19, the male sex is an established risk factor for mortality, in part due to a more robust immune response to COVID-19 in women. Because patients on kidney function replacement therapy (KFRT) have an impaired immune response, especially kidney transplant recipients due to their use of immunosuppressants, we examined whether the male sex is still a risk factor for mortality among patients on KFRT with COVID-19. From the European Renal Association COVID-19 Database (ERACODA), we examined patients on KFRT with COVID-19 who presented between February 1st, 2020, and April 30th, 2021. 1204 kidney transplant recipients (male 62.0%, mean age 56.4 years) and 3206 dialysis patients (male 61.8%, mean age 67.7 years) were examined. Three-month mortality in kidney transplant recipients was 16.9% in males and 18.6% in females (p = 0.31) and in dialysis patients 27.1% in males and 21.9% in females (p = 0.001). The adjusted HR for the risk of 3-month mortality in males (vs females) was 0.89 (95% CI 65, 1.23, p = 0.49) in kidney transplant recipients and 1.33 (95% CI 1.13, 1.56, p = 0.001) in dialysis patients (pinteraction = 0.02). In a fully adjusted model, the aHR for the risk of 3-month mortality in kidney transplant recipients (vs. dialysis patients) was 1.39 (95% CI 1.02, 1.89, p = 0.04) in males and 2.04 (95% CI 1.40, 2.97, p < 0.001) in females (pinteraction = 0.02). In patients on KFRT with COVID-19, the male sex is not a risk factor for mortality among kidney transplant recipients but remains a risk factor among dialysis patients. The use of immunosuppressants in kidney transplant recipients, among other factors, may have narrowed the difference in the immune response to COVID-19 between men and women, and therefore reduced the sex difference in COVID-19 mortality risk.

U2 - 10.1038/s41598-022-22657-4

DO - 10.1038/s41598-022-22657-4

M3 - Article

C2 - 36289317

SN - 2045-2322

VL - 12

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 17978

ER -