Research output: Contribution to journal › Article › Academic › peer-review
Predictors of nonseroconversion to SARS-COV-2 vaccination in kidney transplant recipients. / Frölke, Sophie C.; Bouwmans, Pim; Messchendorp, A. Lianne et al.
In: Transplantation direct, Vol. 8, No. 11, 07.10.2022, p. E1397.Research output: Contribution to journal › Article › Academic › peer-review
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TY - JOUR
T1 - Predictors of nonseroconversion to SARS-COV-2 vaccination in kidney transplant recipients
AU - Frölke, Sophie C.
AU - Bouwmans, Pim
AU - Messchendorp, A. Lianne
AU - Geerlings, Suzanne E.
AU - Hemmelder, Marc H.
AU - Gansevoort, Ron T.
AU - Hilbrands, Luuk B.
AU - Reinders, Marlies E. J.
AU - Sanders, Jan-Stephan F.
AU - Bemelman, Frederike J.
AU - Peters-Sengers, Hessel
AU - Abrahams, A.
AU - Baas, M.
AU - ten Dam, M.
AU - Gommers, L.
AU - Imhof, C.
AU - Malahe, S.
AU - Mattheussens, W.
AU - Moerman, I.
AU - Standaar, T.
AU - Remmerswaal, E. B. M.
AU - RECOVAC Collaborators
AU - Vegting, Y.
AU - de Vries, A.
N1 - Funding Information: The RECOVAC consortium received funding by The Netherlands Organisation for Health Research and Development (ZonMw) and the Dutch Kidney Foundation. Publisher Copyright: Copyright © 2022 The Author(s).
PY - 2022/10/7
Y1 - 2022/10/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85140921207&partnerID=8YFLogxK
U2 - 10.1097/TXD.0000000000001397
DO - 10.1097/TXD.0000000000001397
M3 - Article
C2 - 36245996
VL - 8
SP - E1397
JO - Transplantation direct
JF - Transplantation direct
SN - 2373-8731
IS - 11
ER -
ID: 26636977