INTRODUCTION — The general health care of patients with end-stage kidney disease (ESKD) is often provided by nephrologists. A principal feature of such care is the implementation of preventive measures, including immunizations.

Patients with ESKD have a reduced response to vaccination because of the general suppression of the immune system associated with uremia. Compared with vaccination in patients without ESKD, for example, dialysis patients have a lower antibody titer and an inability to maintain adequate antibody titers over time [1,2]. The relatively low antibody response to a vaccine also appears to correlate with the degree of renal failure but not with the specific mode of dialysis [3]. It appears that disturbances in T lymphocytes and antigen-presenting cells may be responsible for the altered acquired immunity in ESKD patients, but additional studies are required [4-6].

Little information exists concerning the effects of dialysis adequacy on the antibody response to vaccination. There is, however, indirect evidence that increasing dialysis may be associated with an enhanced response. In a study of 32 nutritionally replete peritoneal dialysis patients immunized with the hepatitis B vaccine, the initial weekly Kt/V was 2.37 and 2.01 in converters and nonconverters, respectively [7].

Despite the evidence of decreased efficacy, recommendations are to vaccinate patients with ESKD [1,8-10]. Immunization recommendations in the United States are developed by the Advisory Committee on Immunization Practices (ACIP) of Centers for Disease Control and Prevention (CDC) and are presented in the figures (figure 1 and figure 2). A review of vaccination strategies in patients with ESKD is presented here. The discussion will center upon the vaccines of most importance for the dialysis population. These include hepatitis B virus (HBV), tetanus, pneumococcal, influenza, and varicella-zoster virus (VZV) vaccines.

HEPATITIS B VIRUS VACCINE — Controversy exists concerning the overall effectiveness, including the cost/benefit ratio, of hepatitis B virus (HBV) vaccination in patients with ESKD. The primary arguments against routine HBV vaccination in this patient population are based upon the following observations:

●Reduced efficacy of the vaccine – Compared with a response rate of >90 percent in patients without renal failure, only 50 to 60 percent of those with ESKD develop antibodies following HBV vaccination [11,12]. Patients with chronic kidney disease (CKD) not requiring dialysis have a higher antibody response, suggesting that the immune response correlates with the degree of renal failure [3,13-15].

●The low rate of hepatitis B infection – The incidence of hepatitis B infection is only approximately 0.12 percent among hemodialysis patients [16].

Despite these data, we and many clinicians recommend that chronic dialysis patients receive vaccination against hepatitis B [3,17,18]. Support for this recommendation is provided by a case-control study that found that hemodialysis patients vaccinated against hepatitis B had a 70 percent lower risk for infection compared with nonvaccinated patients [19].

Cases of HBV infection in hemodialysis units have also prompted the Centers for Disease Control (CDC) to reiterate its recommendation that all dialysis patients receive hepatitis B vaccination [20,21]. 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 [20].

The number of dialysis patients who have received hepatitis B vaccination has increased significantly over the last several decades. As an example, the percentage of dialysis patients who had received at least three doses of hepatitis B vaccine had increased from 5.4 percent in 1983 to 56 percent in 2002 [16]. A review of ESKD Medicare beneficiaries found that, among incident hemodialysis patients, there was a 77 percent likelihood of receiving the hepatitis vaccine within three years of beginning dialysis [22]. Dialysis facility or preprinted chart orders for vaccination may improve vaccination rates for hepatitis, as well as pneumococcus, in dialysis patients [23].

Because of the generally low response rate among patients with ESKD, multiple attempts have been made to enhance the immune response to hepatitis B vaccine. These include [3,24-33]:

●Doubling the dose of vaccine.

●Giving booster doses of vaccine in response to a fall in antibody titer.

●Attempting to increase the immune response either by changing the mode of injection (intradermal versus intramuscular) or by adding immunostimulants or adjuvants [34-37]. As an example, one multicenter study randomly assigned 300 patients with CKD to four doses of hepatitis B ASO4 vaccine (zero, one, two, and six months) or three doses of hepatitis B ASO2V vaccine (zero, one, and six months) [36]. The two vaccines are associated with different adjuvants. At 12 months, the ASO2V vaccine, compared with the ASO4 vaccine, was associated with a significantly more rapid and robust response, with seroconversion rates of 77 and 39 percent at two months and 94 and 79 percent at 12 months, respectively. Thus, three doses of the hepatitis B ASO2V vaccine provide rapid and persistent protection against HBV among patients with CKD. This vaccine is not available in the United States.

●Giving a combined hepatitis A and B vaccine [38].

Data exist to support the following strategies to improve antibody production to hepatitis B vaccine in patients with ESKD [21]:

●Double the vaccine dose suggested for patients without ESKD (ie, 40 mcg/dose in patients with ESKD).

●Administer the vaccine in the deltoid muscle.

●Give additional doses to patients with ESKD (eg, Heptavax 40 mcg intramuscular [IM] at zero, one, and six months or Engerix 40 mcg IM at zero, one, two, and six months).

●Begin the vaccination series as soon as 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 [3].

●Since spurious seropositivity for HBsAg may occur shortly after vaccination, it has been recommended that testing of serum for HBsAg be avoided within three weeks of vaccination [39].

●Administer an additional three-dose series to dialysis patients who failed to respond to the initial series, which is defined as antibody titers ≤10 int. units/L one to two months after completion of the first series [2].

●Administer a single booster dose of 40 mcg if the antibody titer falls to ≤10 int. units/L in the patient who initially developed an antibody response to vaccination or after natural infection [40,41]. There appears to be no benefit to repeated boosters in those whose antibody titers remain ≤10 int. units/L.

Despite the availability of the hepatitis B vaccine, the most important factor in preventing the spread of hepatitis B 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 dialysis patients [17].

Human immunodeficiency virus infection — Human immunodeficiency virus (HIV) infection does not appear to decrease the effectiveness of the hepatitis B vaccine in dialysis patients, suggesting that this vaccine should be offered to these patients. In a retrospective cohort study, protective antibody titers developed in 62 of 116 HIV-infected patients (54 percent) who received three doses of the vaccine [42]; this rate was comparable with that observed among 220 randomly selected non-HIV-infected dialysis patients (50 percent) [42]. Nearly 70 percent of the HIV-infected responders maintained protective antibody titers at six months. Among those in whom titers remain <10 int. units/L after the standard three doses, the Infectious Disease Society of America (IDSA) recommends the administration of a fourth injection [43].

OTHER VACCINATIONS — Compared with the data available concerning hepatitis B vaccine, there is less information concerning the response of patients ESKD to tetanus, pneumococcus, influenza, varicella-zoster virus (VZV), H1N1, human papillomavirus (HPV), and Staphylococcus aureus vaccines. The antibody response to these vaccines is generally less than in patients without renal failure, mirroring the experience with hepatitis B vaccination.

Tetanus vaccine — The few data available concerning tetanus vaccine suggest that the response in patients with chronic kidney disease (CKD) is less than in patients with normal kidney function. A prospective, controlled study evaluated the response to tetanus and hepatitis B vaccines among 23 patients with CKD, 27 dialysis patients, 7 transplant recipients, and 15 healthy controls [44]. 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 renal failure than in controls without kidney disease. Patients who had previously responded to hepatitis B 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 dialysis patients develop antibodies, thereby making vaccination effective for most patients [3].

Pneumococcal vaccine — We vaccinate patients who have ESKD with the pneumococcal vaccine in accordance with the recommendations of the Advisory Committee on Immunization Practices (ACIP) (figure 2) [45]. The dose, route, 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 ESKD patients [46]. Despite these data, and the recommendations of the ACIP, overall pneumococcal vaccination rates among ESKD patients remain suboptimal [22].

The antibody response to the pneumococcal vaccine can be variable among patients with CKD and ESKD. As an example, in a study of 155 chronic hemodialysis patients over 50 years of age who received pneumococcal vaccination, significant immunity was maintained for one year following vaccination [47]. 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 [48].

Influenza vaccine — We vaccinate all patients with ESKD with the yearly influenza vaccine (figure 2) [1,3,8,21]. Additional details regarding available vaccine formulations, schedule, and administration are discussed at length elsewhere. (See "Seasonal influenza vaccination in adults", section on 'Available formulations'.)

The antibody response to the standard-dose influenza vaccine in chronic hemodialysis patients is lower than that in the general population [49-52]. 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 [46,53,54]. Despite these data, we continue to vaccinate ESKD patients against influenza to mitigate the potential morbidity and mortality risk of an influenza infection [45]. Compared with the standard dose vaccine, a high-dose influenza vaccine has not been associated with a lower rate of influenza-related hospitalizations or mortality among patients with ESKD [55,56].

Varicella-zoster virus vaccine — We vaccinate all patients with ESKD ≥50 years of age using the recombinant zoster vaccine rather than the live attenuated vaccine (figure 2). Additional detail regarding types of vaccines and vaccine administration is presented elsewhere. (See "Vaccination for the prevention of shingles (herpes zoster)" and "Vaccination for the prevention of shingles (herpes zoster)", section on 'Available vaccines'.)

Among dialysis patients, a zoster infection is associated with a higher mortality [57], 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 vintage-matched controls [58]. There are no data looking at efficacy of the recombinant vaccine among patients with ESKD. However, our preferential use of the recombinant vaccine is based upon its greater efficacy and sustained immunity against zoster in other populations. Additional data regarding comparative efficacy of the recombinant vaccine versus the live attenuated vaccine is presented elsewhere. (See "Vaccination for the prevention of shingles (herpes zoster)", section on 'Available vaccines'.)

Staphylococcus aureus vaccine — Given the high morbidity and mortality due to S. aureus infection and bacteremia among patients with ESKD, a S. aureus vaccine was developed [59]. However, a phase-III, placebo-controlled trial found no reduction in S. aureus types 5 and 8 infection with the vaccine [60]. As a result, the company discontinued development of this vaccine [61].

The failure of staphylococcal vaccines suggests that an effective vaccine will have to be multicomponent, incorporating several surface proteins, toxoids, and surface polysaccharides in order to overcome S. aureus's multiple and redundant virulence factors [62].

Human papillomavirus vaccine — An HPV vaccine is recommended in both female and male children and young adults. 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.

Little is known about the vaccine's efficacy in CKD, but it appears to be safe and to have short-term efficacy [63]. Female children and young women, especially those anticipating kidney transplantation, should probably be offered this vaccine. As young men are also now eligible for this vaccine, they should also be considered for and probably offered this vaccine. The CDC recommends this vaccine for women with ESKD through age 26 years and for men with ESKD through age 21 years (figure 2). (See "Human papillomavirus vaccination".)

A study of 57 girls aged 9 to 21 years with CKD (n = 25), on dialysis (n = 9), and post-kidney transplantation (n = 23) who received the standard three-dose HPV vaccine found 100 percent antibody response at <12 months and ≥12 months post-three doses in girls with CKD and on dialysis [63]. The maintenance of the antibody response was significantly less in the transplanted girls, prompting the authors to call for additional study in this population [63].

Rabies vaccine — If indicated, dialysis patients should also be vaccinated for rabies. One study demonstrated the effectiveness of the immunological response of well-dialyzed hemodialysis patients who received intradermal rabies vaccination [64]. (See "When to use rabies prophylaxis".)

KIDNEY TRANSPLANT RECIPIENTS — Recipients of kidney transplants respond to vaccines in a manner similar to chronic dialysis patients: The antibody response is often less than in patients without kidney disease, and protective antibody titers fall rapidly. Immunizations in renal and nonrenal solid organ transplant patients are discussed separately. (See "Immunizations in solid organ transplant candidates and recipients".)

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

●Patients with end-stage kidney disease (ESKD) have a reduced response to vaccination because of the general suppression of the immune system associated with uremia. Compared with vaccination in patients without ESKD, dialysis patients have a lower antibody titer and an inability to maintain adequate antibody titers over time. (See 'Introduction' above.)

●Although the development and, especially, the duration of protective antibody titers in response to vaccine administration in dialysis patients are often suboptimal, recommendations are to vaccinate ESKD patients against hepatitis B. The antibody response to hepatitis B may be improved by vaccinating early in the course of chronic kidney disease (CKD), doubling the dose of vaccine administered, giving an additional dose, and giving an early booster dose with a fall in antibody titer. Adjuvants to boost the immune response may prove useful but are not yet widely available or used. (See 'Hepatitis B virus vaccine' above.)

●The response to pneumococcal vaccine is diminished among patients with CKD, particularly maintenance of adequate antibody titers. Despite this, pneumococcal vaccination is recommended in patients with ESKD. (See 'Pneumococcal vaccine' above.)

●We vaccinate all patients with ESKD with the yearly influenza vaccine. Additional details regarding available vaccine formulations, schedule, and administration are discussed at length elsewhere. (See 'Influenza vaccine' above and "Seasonal influenza vaccination in adults", section on 'Available formulations'.)

●There is little information about other vaccines in the dialysis population, but vaccinations for human papilloma virus (HPV) and herpes zoster should be considered, especially in patients on transplant waiting lists. (See 'Human papillomavirus vaccine' above and 'Varicella-zoster virus vaccine' above.)