Predictors of Nonseroconversion to SARS-CoV-2 Vaccination in Kidney Transplant Recipients
Background. Kidney transplant recipients (KTRs) are still at risk of severe COVID-19 disease after SARS‑CoV‑2 vaccination, especially when they have limited antibody formation. Our aim was to understand the factors that may limit their humoral response. Methods. Our data are derived from KTRs who we...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer
2022-11-01
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| Series: | Transplantation Direct |
| Online Access: | http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001397 |
| _version_ | 1811212204843728896 |
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| author | Sophie C. Frölke, BSc Pim Bouwmans, MD A. Lianne Messchendorp, MD, PhD Suzanne E. Geerlings, MD, PhD Marc H. Hemmelder, MD, PhD Ron T. Gansevoort, MD, PhD Luuk B. Hilbrands, MD, PhD Marlies E.J. Reinders, MD, PhD Jan-Stephan F. Sanders, MD, PhD Frederike J. Bemelman, MD, PhD Hessel Peters-Sengers, PhD RECOVAC Collaborators* |
| author_facet | Sophie C. Frölke, BSc Pim Bouwmans, MD A. Lianne Messchendorp, MD, PhD Suzanne E. Geerlings, MD, PhD Marc H. Hemmelder, MD, PhD Ron T. Gansevoort, MD, PhD Luuk B. Hilbrands, MD, PhD Marlies E.J. Reinders, MD, PhD Jan-Stephan F. Sanders, MD, PhD Frederike J. Bemelman, MD, PhD Hessel Peters-Sengers, PhD RECOVAC Collaborators* |
| author_sort | Sophie C. Frölke, BSc |
| collection | DOAJ |
| description | Background. Kidney transplant recipients (KTRs) are still at risk of severe COVID-19 disease after SARS‑CoV‑2 vaccination, especially when they have limited antibody formation. Our aim was to understand the factors that may limit their humoral response.
Methods. Our data are derived from KTRs who were enrolled in the Dutch Renal Patients COVID-19 Vaccination consortium, using a discovery cohort and 2 external validation cohorts. Included in the discovery (N = 1804) and first validation (N = 288) cohorts were participants who received 2 doses of the mRNA-1273 vaccine. The second validation cohort consisted of KTRs who subsequently received a third dose of any SARS-CoV-2 vaccine (N = 1401). All participants had no history of SARS-CoV-2 infection. A multivariable logistic prediction model was built using stepwise backward regression analysis with nonseroconversion as the outcome.
Results. The discovery cohort comprised 836 (46.3%) KTRs, the first validation cohort 124 (43.1%) KTRs, and the second validation cohort 358 (25.6%) KTRs who did not seroconvert. In the final multivariable model‚ 12 factors remained predictive for nonseroconversion: use of mycophenolate mofetil/mycophenolic acid (MMF/MPA); chronic lung disease, heart failure, and diabetes; increased age; shorter time after transplantation; lower body mass index; lower kidney function; no alcohol consumption; ≥2 transplantations; and no use of mammalian target of rapamycin inhibitors or calcineurin inhibitors. The area under the curve was 0.77 (95% confidence interval [CI], 0.74-0.79) in the discovery cohort after adjustment for optimism, 0.81 (95% CI, 0.76-0.86) in the first validation cohort, and 0.67 (95% CI, 0.64-0.71) in the second validation cohort. The strongest predictor was the use of MMF/MPA, with a dose-dependent unfavorable effect, which remained after 3 vaccinations.
Conclusions. In a large sample of KTRs, we identify a selection of KTRs at high risk of nonseroconversion after SARS-CoV-2 vaccination. Modulation of MMF/MPA treatment before vaccination may help to optimize vaccine response in these KTRs. This model contributes to future considerations on alternative vaccination strategies. |
| first_indexed | 2024-04-12T05:25:14Z |
| format | Article |
| id | doaj.art-f032a5736f2e47ffac77c7826f209baf |
| institution | Directory Open Access Journal |
| issn | 2373-8731 |
| language | English |
| last_indexed | 2024-04-12T05:25:14Z |
| publishDate | 2022-11-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Transplantation Direct |
| spelling | doaj.art-f032a5736f2e47ffac77c7826f209baf2022-12-22T03:46:19ZengWolters KluwerTransplantation Direct2373-87312022-11-01811e139710.1097/TXD.0000000000001397202211000-00007Predictors of Nonseroconversion to SARS-CoV-2 Vaccination in Kidney Transplant RecipientsSophie C. Frölke, BSc0Pim Bouwmans, MD1A. Lianne Messchendorp, MD, PhD2Suzanne E. Geerlings, MD, PhD3Marc H. Hemmelder, MD, PhD4Ron T. Gansevoort, MD, PhD5Luuk B. Hilbrands, MD, PhD6Marlies E.J. Reinders, MD, PhD7Jan-Stephan F. Sanders, MD, PhD8Frederike J. Bemelman, MD, PhD9Hessel Peters-Sengers, PhD10RECOVAC Collaborators*1 Renal Transplant Unit, Department of Internal Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.2 Division of Nephrology, Department of Internal Medicine, Maastricht University Medical Center, and CARIM School for Cardiovascular Disease, University of Maastricht, Maastricht, The Netherlands.3 Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.4 Division of Infectious Diseases, Department of Internal Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.2 Division of Nephrology, Department of Internal Medicine, Maastricht University Medical Center, and CARIM School for Cardiovascular Disease, University of Maastricht, Maastricht, The Netherlands.3 Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.5 Department of Nephrology, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.6 Department of Internal Medicine, Nephrology, and Transplantation, Erasmus MC Transplant Institute, Erasmus Medical Center, Rotterdam, The Netherlands.3 Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.1 Renal Transplant Unit, Department of Internal Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.1 Renal Transplant Unit, Department of Internal Medicine, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands.Background. Kidney transplant recipients (KTRs) are still at risk of severe COVID-19 disease after SARS‑CoV‑2 vaccination, especially when they have limited antibody formation. Our aim was to understand the factors that may limit their humoral response. Methods. Our data are derived from KTRs who were enrolled in the Dutch Renal Patients COVID-19 Vaccination consortium, using a discovery cohort and 2 external validation cohorts. Included in the discovery (N = 1804) and first validation (N = 288) cohorts were participants who received 2 doses of the mRNA-1273 vaccine. The second validation cohort consisted of KTRs who subsequently received a third dose of any SARS-CoV-2 vaccine (N = 1401). All participants had no history of SARS-CoV-2 infection. A multivariable logistic prediction model was built using stepwise backward regression analysis with nonseroconversion as the outcome. Results. The discovery cohort comprised 836 (46.3%) KTRs, the first validation cohort 124 (43.1%) KTRs, and the second validation cohort 358 (25.6%) KTRs who did not seroconvert. In the final multivariable model‚ 12 factors remained predictive for nonseroconversion: use of mycophenolate mofetil/mycophenolic acid (MMF/MPA); chronic lung disease, heart failure, and diabetes; increased age; shorter time after transplantation; lower body mass index; lower kidney function; no alcohol consumption; ≥2 transplantations; and no use of mammalian target of rapamycin inhibitors or calcineurin inhibitors. The area under the curve was 0.77 (95% confidence interval [CI], 0.74-0.79) in the discovery cohort after adjustment for optimism, 0.81 (95% CI, 0.76-0.86) in the first validation cohort, and 0.67 (95% CI, 0.64-0.71) in the second validation cohort. The strongest predictor was the use of MMF/MPA, with a dose-dependent unfavorable effect, which remained after 3 vaccinations. Conclusions. In a large sample of KTRs, we identify a selection of KTRs at high risk of nonseroconversion after SARS-CoV-2 vaccination. Modulation of MMF/MPA treatment before vaccination may help to optimize vaccine response in these KTRs. This model contributes to future considerations on alternative vaccination strategies.http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001397 |
| spellingShingle | Sophie C. Frölke, BSc Pim Bouwmans, MD A. Lianne Messchendorp, MD, PhD Suzanne E. Geerlings, MD, PhD Marc H. Hemmelder, MD, PhD Ron T. Gansevoort, MD, PhD Luuk B. Hilbrands, MD, PhD Marlies E.J. Reinders, MD, PhD Jan-Stephan F. Sanders, MD, PhD Frederike J. Bemelman, MD, PhD Hessel Peters-Sengers, PhD RECOVAC Collaborators* Predictors of Nonseroconversion to SARS-CoV-2 Vaccination in Kidney Transplant Recipients Transplantation Direct |
| title | Predictors of Nonseroconversion to SARS-CoV-2 Vaccination in Kidney Transplant Recipients |
| title_full | Predictors of Nonseroconversion to SARS-CoV-2 Vaccination in Kidney Transplant Recipients |
| title_fullStr | Predictors of Nonseroconversion to SARS-CoV-2 Vaccination in Kidney Transplant Recipients |
| title_full_unstemmed | Predictors of Nonseroconversion to SARS-CoV-2 Vaccination in Kidney Transplant Recipients |
| title_short | Predictors of Nonseroconversion to SARS-CoV-2 Vaccination in Kidney Transplant Recipients |
| title_sort | predictors of nonseroconversion to sars cov 2 vaccination in kidney transplant recipients |
| url | http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001397 |
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