Immunizations in patients with end-stage kidney disease

INTRODUCTION — Infections are a leading cause of morbidity and mortality among patients with end-stage kidney disease (ESKD) [1]. Although vaccines can help prevent many of the most common infections to which these patients are exposed, patients with ESKD have a reduced response to vaccination.

Immunization recommendations in the United States are developed by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) and are shown in the figures (figure 1 and figure 2). This topic will review vaccination strategies and efficacy in patients with ESKD, focusing upon the vaccines of most importance for this population.

Immunizations in kidney and non-kidney solid organ transplant patients are presented separately. (See "Immunizations in solid organ transplant candidates and recipients".)

APPROACH TO VACCINATION

Recommended vaccines — Patients with ESKD who are not up to date on other routinely recommended vaccines (based on age and other risk factors) should receive any needed vaccines (figure 1 and figure 2). If patients with ESKD are traveling, they should undergo evaluation for additional vaccination based on their travel destination and potential exposures. (See "Standard immunizations for children and adolescents: Overview" and "Standard immunizations for nonpregnant adults".)

In addition to routine vaccines recommended for the general population, patients with ESKD should receive the following vaccines:

●Hepatitis B virus (HBV) vaccine (see 'Hepatitis B virus vaccine' below)

●Pneumococcal vaccine (see 'Pneumococcal vaccine' below)

This approach to vaccination is generally consistent with the Advisory Committee on Immunization Practices (ACIP) in the United States [2].

Timing of vaccination — In patients with ESKD who are kidney transplant candidates, any needed vaccines should be administered as early as possible and at least four weeks prior to transplant in immunocompetent patients. Although vaccine responses may be diminished in some patients during the pretransplant period, vaccine responses are even more attenuated posttransplantation, when the patient is immunosuppressed. (See "Immunizations in solid organ transplant candidates and recipients", section on 'Timing of immunizations'.)

Similarly, in patients with ESKD who are not transplant candidates, any needed vaccines should also be administered at the earliest opportunity.

VACCINE EFFICACY IN END-STAGE KIDNEY DISEASE — Patients with ESKD have a reduced response to vaccination due to immune dysregulation [3]. Compared with vaccinated patients without ESKD, for example, patients on dialysis have a lower antibody titer and an inability to maintain adequate antibody titers over time [4,5]. The relatively low antibody response to vaccination also appears to correlate with the degree of kidney failure but not with the specific mode of dialysis [6]. It appears that disturbances in T lymphocytes and antigen-presenting cells may be responsible for the altered acquired immunity in this population [7-9].

Despite the decreased antibody response, vaccination remains an important preventative measure for patients with ESKD. The efficacy of specific vaccines in this patient population is presented below.

Hepatitis B virus vaccine — All patients with ESKD should receive hepatitis B virus (HBV) vaccination [2]. The dose, route, and vaccine types are discussed in detail separately. (See "Hepatitis B virus immunization in adults", section on 'Indications' and "Hepatitis B virus immunization in adults", section on 'Patients on dialysis and immunocompromised hosts'.)

Cases of HBV infection in hemodialysis units prompted the Centers for Disease Control (CDC) to recommend that all patients with ESKD, on dialysis or predialysis, receive HBV vaccination [10,11]. Support for the recommendation is provided by a case-control study that found that patients on hemodialysis vaccinated against HBV had a 70 percent lower risk for infection compared with nonvaccinated patients [12]. The CDC suggested that the cost of vaccinating patients is mitigated by the reduced need for monthly surveillance of antigen and antibody status in those who develop specific antibodies [10].

Patients with ESKD have a reduced response to HBV vaccination. Compared with a response rate of >90 percent in patients without kidney failure, only 50 to 60 percent of those with ESKD develop antibodies following HBV vaccination [13,14].

Although HIV infection decreases the effectiveness of the HBV vaccine, this risk does not appear to be greater among patients on dialysis [15]. (See "Prevention of hepatitis B virus infection in adults with HIV", section on 'Vaccination'.)

Because of the generally low response rate among patients with ESKD, the following strategies have been used to improve antibody production to HBV vaccine in this population:

●Doubling the dose of vaccine (ie, 40 mcg/dose in patients with ESKD) [16]. (See "Hepatitis B virus immunization in adults", section on 'Patients on dialysis and immunocompromised hosts'.)

●Giving an HBV vaccine that uses a novel immunostimulatory adjuvant [17,18]. (See "Hepatitis B virus immunization in adults", section on 'Yeast-derived'.)

●Beginning the vaccination series as soon as chronic kidney disease (CKD) is recognized and the patient is known to be hepatitis B surface antigen (HBsAg) and antibody negative; the clinician should not wait until the patient is dialysis dependent to begin the vaccination protocol [6].

●Administering an additional vaccine series to patients on dialysis who failed to respond to the initial series, which is defined as antibody titers ≤10 international units/L one to two months after completion of the first series [5].

●Administering a single booster dose if the antibody titer falls to ≤10 international units/L in the patient who initially developed an antibody response to vaccination or after natural infection [19,20]. There appears to be no benefit to repeated boosters in those whose antibody titers remain ≤10 international units/L. (See "Hepatitis B virus immunization in adults", section on 'When a booster dose should be administered'.)

●Giving a combined hepatitis A and B vaccine [21]. (See "Hepatitis B virus immunization in adults", section on 'Combination vaccines'.)

Additional investigational approaches are discussed elsewhere. (See "Hepatitis B virus immunization in adults", section on 'New developments'.)

Clinicians should be aware that HBsAg may be detected up to 18 days following HBV vaccination and up to 52 days in patients on hemodialysis [22,23]. This result is clinically insignificant, and it has been recommended that testing for HBsAg be avoided within three weeks of vaccination [24] and potentially longer in patients on hemodialysis.

Despite the availability of the HBV vaccine, the most important factor in preventing the spread of HBV in a hemodialysis unit is the maintenance of universal precautions. The CDC also recommends isolating antigen-positive patients and prohibiting the use of shared medications (eg, common heparin vials) among patients on dialysis [12].

Pneumococcal vaccine — All patients with ESKD should receive pneumococcal vaccination (algorithm 1 and table 1). This approach is consistent with the recommendations of the Advisory Committee on Immunization Practices (ACIP) [2]. The dose, route, and vaccine types and intervals are discussed at length elsewhere. (See "Pneumococcal vaccination in adults", section on 'Vaccine administration'.)

Vaccination against pneumococcal disease is associated with decreased mortality among patients with ESKD [25]. Despite these data, and the recommendations of the ACIP, overall pneumococcal vaccination rates among patients ESKD remain suboptimal [26].

The antibody response to the pneumococcal vaccine can be variable among patients with CKD and ESKD. As an example, in a study of 155 patients on chronic hemodialysis over 50 years of age who received pneumococcal vaccination, significant immunity was maintained for one year following vaccination [27]. However, in another study of 44 children and young adults with CKD, only approximately one-half of the patients maintained sufficient immunity at one year [28].

Influenza vaccine — All patients with ESKD should receive an influenza vaccine annually as per the general population [2]. Additional details regarding available vaccine formulations, schedule, and administration are discussed at length elsewhere. (See "Seasonal influenza vaccination in adults", section on 'Formulations'.)

The antibody response to the standard-dose influenza vaccine in patients on chronic hemodialysis is lower than that in the general population [29-32]. In addition, a clear advantage of influenza vaccination on the rates of influenza infection, pneumonia, hospitalization, and mortality has not been demonstrated among patients with ESKD [25,33,34]. Despite these data, we continue to vaccinate patients with ESKD against influenza to mitigate the potential morbidity and mortality risk of an influenza infection [35].

It is uncertain whether the use of a high-dose vaccine may improve influenza vaccine efficacy in patients on dialysis. Observational studies of patients on dialysis have reported that a high-dose influenza vaccine is associated with a more sustained antibody response [36] and a lower hospitalization rate [37] compared with a standard-dose vaccine. However, another study did not observe an association between a high-dose vaccine and lower risk of hospitalization [38], and no study to date of patients on dialysis has reported a mortality benefit of a high-dose compared with a standard-dose influenza vaccine [37,38].

Varicella-zoster virus vaccine — Patients with ESKD who are ≥50 years old should receive the recombinant (non-live) zoster vaccine (RZV). This approach is consistent with recommendations of the ACIP [2]. In patients between 19 and 50 years old who are receiving immunosuppressive therapy, vaccination with RZV may also be indicated. Additional detail regarding types of vaccines and vaccine administration is presented elsewhere. (See "Vaccination for the prevention of shingles (herpes zoster)".)

Among patients on dialysis, a zoster infection is associated with a higher mortality [39], and administration of the live attenuated zoster vaccine is associated with a lower risk of developing zoster when compared with unvaccinated age-, sex-, and dialysis duration-matched controls [40]. However, the preferential use of the recombinant vaccine is based upon its greater efficacy and sustained immunity against zoster in other populations. Additional data regarding the comparative efficacy of the recombinant vaccine versus the live attenuated vaccine are presented elsewhere. (See "Vaccination for the prevention of shingles (herpes zoster)", section on 'Available vaccines'.)

Tetanus, diphtheria, and pertussis vaccine — Patients with ESKD should receive vaccination with the tetanus, diphtheria, and pertussis (Tdap) vaccine as recommended for the general population. (See "Diphtheria, tetanus, and pertussis immunization in children 7 through 18 years of age" and "Diphtheria, tetanus, and pertussis immunization in children 6 weeks through 6 years of age" and "Tetanus-diphtheria toxoid vaccination in adults" and "Pertussis infection in adolescents and adults: Treatment and prevention".)

Data on the efficacy of the tetanus vaccine in patients with CKD are limited but suggest that the response is less than in patients with normal kidney function. A prospective, controlled study evaluated the response to tetanus and HBV vaccines among 23 patients with nondialysis CKD, 27 patients on dialysis, 7 transplant recipients, and 15 healthy controls [41]. All healthy individuals and six of seven transplant recipients seroconverted after three doses of tetanus toxoid vaccine; by comparison, antibodies developed in only 69 and 55 percent of patients on dialysis and those with CKD, respectively. If present, antibody titers were lower in the groups with kidney function impairment than in those without kidney disease. Patients who had previously responded to HBV vaccine were more likely to respond to tetanus vaccine, implying that a subset of patients has a more intact immune system. Despite the reduced response to tetanus vaccine, most patients on dialysis develop antibodies, thereby making vaccination effective for most patients [6].

There are no published data describing the vaccine response among patients with ESKD to the diphtheria or pertussis components of the Tdap vaccine.

Human papillomavirus vaccine — Vaccination against human papillomavirus (HPV) is appropriate for patients with ESKD who have an indication based upon recommendations for the general population (figure 1) [42]. This vaccine protects against HPV types that are responsible for most cervical cancers and genital warts and is most effective when administered before the onset of sexual activity. (See "Human papillomavirus vaccination".)

Studies examining the efficacy of the HPV vaccine among patients with CKD have shown that the vaccine appears to be safe and has short-term efficacy [43,44]. As examples:

●A study of 57 females aged 9 to 21 years with CKD (n = 25), on dialysis (n = 9), or post-kidney transplantation (n = 23) who received the standard three-dose HPV vaccine found 100 percent antibody response at <12 months and ≥12 months in those with CKD and on dialysis [43]. Maintenance of the antibody response was significantly less among transplanted patients, prompting the authors to call for additional study in this population [43].

●In another study of 65 patients aged 9 to 18 years with CKD, on dialysis, or post-kidney transplantation who received the HPV vaccine, geometric mean antibody titers were higher among patients with CKD than among patients on dialysis, and both were higher than those in kidney transplant recipients [44]. Across all three groups, patients receiving immunosuppressive medications had a lower antibody response compared with those not receiving these medications.

COVID-19 vaccine — All patients with ESKD should be offered COVID-19 vaccination to prevent severe outcomes related to COVID-19. Data on the efficacy of COVID-19 vaccines among patients with ESKD are presented separately. (See "COVID-19: Issues related to end-stage kidney disease", section on 'Vaccination in dialysis patients and providers'.)

Rabies vaccine — If indicated, dialysis patients should also be vaccinated for rabies. One study demonstrated the effectiveness of the immunological response of well-dialyzed patients on hemodialysis who received intradermal rabies vaccination [45]. (See "Indications for post-exposure rabies prophylaxis".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Dialysis".)

SUMMARY AND RECOMMENDATIONS

●General principles – Infections are a leading cause of morbidity and mortality among patients with end-stage kidney disease (ESKD). Although vaccines can help prevent many of the most common infections to which these patients are exposed, patients with ESKD have a reduced response to vaccination. (See 'Vaccine efficacy in end-stage kidney disease' above.)

●Recommended vaccines – Patients with ESKD who are not up to date on other routinely recommended vaccines (based on age and other risk factors) should receive any needed vaccines (figure 1 and figure 2). If patients with ESKD are traveling, they should undergo evaluation for additional vaccination based on their travel destination and potential exposures. In addition to routine vaccines recommended for the general population, patients with ESKD should receive the hepatitis B virus (HBV) and pneumococcal vaccines. This approach to vaccination is generally consistent with the Advisory Committee on Immunization Practices (ACIP) in the United States. (See 'Recommended vaccines' above.)

●Timing of vaccination – In patients with ESKD who are kidney transplant candidates, any needed vaccines should be administered as early as possible and at least four weeks prior to transplant in immunocompetent patients. Although vaccine responses may be diminished in some patients during the pretransplant period, vaccine responses are even more attenuated posttransplantation, when the patient is immunosuppressed. Similarly, in patients with ESKD who are not transplant candidates, vaccines should also be administered as early as possible in their clinical course. (See 'Timing of vaccination' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledges Jean Holley, MD, FACP, who contributed to earlier versions of this topic review.