Vaccinations in children on immunosuppressive medications for renal disease

Abstract

Renal diseases are often treated with immunosuppressive medications, placing patients at risk of infections, some of which are vaccine-preventable. However, in such patients vaccinations may be delayed or disregarded due to complications of the underlying disease process and challenges in its management. The decision to administer vaccines to immunosuppressed children is a risk-benefit balance as such children may have a qualitatively diminished immunological response or develop diseases caused by the vaccine pathogen. Vaccination may cause a flare-up of disease activity or provocation of graft rejection in renal transplant recipients. Moreover, it cannot be assumed that a given antibody level provides the same protection in immunosupressed children as in healthy ones. We have evaluated the safety and efficacy of licensed vaccines in children on immunosuppressive therapy and in renal transplant recipients. The limited evidence available suggests that vaccines are most effective if given early, ideally before the requirement for immunosuppressive therapy, which may require administration of accelerated vaccine courses. Once treatment with immunosuppressive drugs is started, inactivated vaccines are usually considered to be safe when the disease is quiescent, but supplemental doses may be required. In the majority of cases, live vaccines are to be avoided. All vaccines are generally contraindicated within 3-6 months of a renal transplant.

Minimal Change Disease

“…Of note, live vaccines are contraindicated in patients receiving steroid-sparing agents and in patients receiving high-dose steroids; inactivated vaccines should be administered, keeping in mind that suboptimal response requiring a repeated dose may be an issue (40,57).…”

Evaluation of Immune and Vaccine Competence in Steroid-Sensitive Nephrotic Syndrome Pediatric Patients

“…Many reports already investigated the response to previous and subsequent vaccination in INS children and found a reduction of seroprotection induced by previous immunization and an impaired immunogenicity of vaccines administered following the onset of the disease (15)(16)(17)(18)(19). However, most of these studies evaluated the levels of vaccine-specific antibodies of INS patients who were under an intense immunosuppression, which can strongly impact the immune response (10). As reported, high-dose prednisone or steroid-sparing agents administered at time of HBV vaccination impair the antibody response (16,17).…”

“…Several Tcell dysregulations have indeed been described both in relapse and in remission (7,8) and altered levels of memory B cells have been observed already at disease onset, before any immunosuppressive therapy (9). The reduction of protective antibodies observed in INS patients can also be dependent on the prolonged and intense immunosuppression administered in severe forms of the disease, increasing the risk for these patients to develop severe infections (10,11). At disease onset, patients are treated with a standardized protocol of oral prednisone therapy, to which most patients respond within 4-6 weeks (defined as "steroid-sensitive nephrotic syndrome" patients, SSNS).…”

“…Within the majority of pediatric patients affected by SSNS, clinical evolution can be extremely heterogeneous, ranging from non-relapsing to severely steroid-dependent forms, which require repeated cycles of steroid therapy and further immunosuppression with one or more steroid-sparing drugs, including anti-proliferative agents, calcineurin inhibitors and B-cell depleting drugs (1). This intense and prolonged immunosuppression can strongly impact immune and vaccine competence in severe forms of SSNS (10,11).Whether this competence of SSNS pediatric patients is impaired only by the intense and prolonged immunosuppression required to maintain the disease remission or whether the intrinsic immune dysregulation can contribute to this impairment is not clear. Whatever the mechanism behind the lowering of serum IgG titers, this reduction hampers the correct evaluation of the immune and vaccine competence which is usually based on the dosage of total and antigen-specific serum IgG titers.…”

Prevalence of Influenza and Pneumococcal-23 Vaccination in Pediatric Patients with Renal Disease: A Single Urban Center Experience

“…We attribute our low immunization rates to several factors: subspecialty clinics that do not routinely offer vaccines, hesitancy by primary care pediatricians to immunize immunocompromised patients, the lack of a unified and universally accessible vaccination record for every child, and insufficient parental understanding of the importance of immunization. Due to the complexity of managing children with renal disease and the modifications in the standard vaccination schedule they require, we believe that it is paramount that the pediatric nephrology team take the lead in recommending the required vaccines for children with renal disease [14].…”