Long-term efficacy and safety of SARS-CoV-2 vaccination in patients with chronic kidney disease, on dialysis or after kidney transplantation: a national prospective observational cohort study

Pim Bouwmans ,Carla C Baan ,Marlies E.j Reinders ,Debbie Van Baarle ,Theo Rispens ,Marinus A Van Den Dorpel ,Ester Ten Hoope ,Sophie C Frölke ,Nynke Y Rots ,A Lianne Messchendorp ,Ester B M Remmerswaal ,Johanna P M Vervoort ,Renate G Van Der Molen ,Alferso C Abrahams ,Céline Imhof ,Dimitri A Diavatopoulos ,Maurice Steenhuis ,Marc H Hemmelder ,Fréderike J Bemelman ,Aiko P.j De Vries ,Ron T Gansevoort ,Priya Vart ,Luuk B Hilbrands ,Reshwan S R K Malahe ,Marc A Ten Dam ,Tony De Ronde ,Fiona Van Der Klis ,Marcia M L Kho ,Wanda S Konijn ,Jan-Stephan Sanders ,Marion Braks

doi:10.1186/s12882-022-02680-3

Abstract

BackgroundCOVID-19 is associated with increased morbidity and mortality in patients with chronic kidney disease (CKD) stages G4-G5, on dialysis or after kidney transplantation (kidney replacement therapy, KRT). SARS-CoV-2 vaccine trials do not elucidate if SARS-CoV-2 vaccination is effective in these patients. Vaccination against other viruses is known to be less effective in kidney patients. Our objective is to assess the efficacy and safety of various types of SARS-CoV-2 vaccinations in patients with CKD stages G4-G5 or on KRT.MethodsIn this national prospective observational cohort study we will follow patients with CKD stages G4-G5 or on KRT (n = 12,000) after SARS-CoV-2 vaccination according to the Dutch vaccination program. Blood will be drawn for antibody response measurements at day 28 and month 6 after completion of vaccination. Patient characteristics and outcomes will be extracted from registration data and questionnaires during 2 years of follow-up. Results will be compared with a control group of non-vaccinated patients. The level of antibody response to vaccination will be assessed in subgroups to predict protection against COVID-19 breakthrough infection.ResultsThe primary endpoint is efficacy of SARS-CoV-2 vaccination determined as the incidence of COVID-19 after vaccination. Secondary endpoints are the antibody based immune response at 28 days after vaccination, the durability of this response at 6 months after vaccination, mortality and (serious) adverse events.ConclusionThis study will fulfil the lack of knowledge on efficacy and safety of SARS-CoV-2 vaccination in patients with CKD stages G4-G5 or on KRT.Trial registrationThe study protocol has been registered in clinicaltrials.gov(NCT04841785).Current knowledge about this subjectCOVID-19 has devastating impact on patients with CKD stages G4-G5, on dialysis or after kidney transplantation.Effective SARS-CoV-2 vaccination is very important in these vulnerable patient groups.Recent studies on vaccination in these patient groups are small short-term studies with surrogate endpoints.Contribution of this studyAssessment of incidence and course of COVID-19 after various types of SARS-CoV-2 vaccination during a two-year follow-up period in not only patients on dialysis or kidney transplant recipients, but also in patients with CKD stages G4-G5.Quantitative analysis of antibody response after SARS-CoV-2 vaccination and its relationship with incidence and course of COVID-19 in patients with CKD stages G4-G5, on dialysis or after kidney transplantation compared with a control group.Monitoring of (serious) adverse events and development of anti-HLA antibodies.Impact on practice or policyPublication of the study design contributes to harmonization of SARS-CoV-2 vaccine studymethodology in kidney patients at high-risk for severe COVID-19.Data on efficacy of SARS-CoV-2 vaccination in patients with CKD will provide guidance for future vaccination policy.

Highlights

COVID-19 is associated with increased morbidity and mortality in patients with chronic kidney disease (CKD) stages G4-G5, on dialysis or after kidney transplantation
The COVID-19 associated mortality risk in these patient groups was reported to be 3- to 4-fold increased as compared to the general healthy population [1], which is considerably higher than the 1.5-to-2-fold increase that was described in patients with obesity, hypertension or diabetes [2]
A recent Call to Action by the ERAEDTA Council and European Renal Association COVID-19 Database (ERACODA) Working Group included the advice to perform dedicated vaccination studies to address this important knowledge gap regarding the efficacy of SARS-CoV-2 vaccination [11]

Summary

Introduction

COVID-19 is associated with increased morbidity and mortality in patients with chronic kidney disease (CKD) stages G4-G5, on dialysis or after kidney transplantation (kidney replacement therapy, KRT). Our objective is to assess the efficacy and safety of various types of SARS-CoV-2 vaccinations in patients with CKD stages G4-G5 or on KRT. It is well known that vaccination efficacy against other viruses such as hepatitis B and influenza is considerably lower in patients with severely impaired kidney function, due to the immunosuppressive effect of uremic waste products [10]. One study showed a robust humoral response in the majority of haemodialysis patients after SARS-CoV-2 vaccination [12], but in a different study when compared to a control group, antibody titres were significantly lower [13]. Current data on SARS-CoV-2 vaccination efficacy in kidney patients report on surrogate endpoints, such as antibody titres

Objectives

Methods

Conclusion