Predictors of Nonseroconversion to SARS-CoV-2 Vaccination in Kidney Transplant Recipients

Sophie C Frölke; Pim Bouwmans; A Lianne Messchendorp; Suzanne E Geerlings; Marc H Hemmelder; Ron T Gansevoort; Luuk B Hilbrands; Marlies E J Reinders; Jan-Stephan F Sanders; Frederike J Bemelman; Hessel Peters-Sengers

doi:10.1097/TXD.0000000000001397

Predictors of Nonseroconversion to SARS-CoV-2 Vaccination in Kidney Transplant Recipients

Transplant Direct. 2022 Oct 7;8(11):e1397. doi: 10.1097/TXD.0000000000001397. eCollection 2022 Nov.

Affiliations

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.
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.
⁷ Center for Experimental and Molecular Medicine, Department of Nephrology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.

Abstract

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.