1. Patients with chronic kidney disease (CKD) have impaired immune responses that increase their risk of infections. Vaccinations are an important prevention strategy, though CKD patients typically have lower vaccine effectiveness compared to those with healthy kidneys. 2. Key recommended vaccinations for CKD patients include: hepatitis B vaccine (4 doses of 40 μg), influenza vaccine (annual 15 μg doses), and pneumococcal vaccine (single 0.5 mL dose). These vaccines have shown protective benefits, though antibody responses tend to be lower in CKD patients. 3. Additional strategies to improve vaccine responses include earlier vaccination as kidney function declines, intradermal administration, and booster doses for hepatitis B when antibody levels decline below

1. VaccinationinCKDpatients

2. Review Article
Vaccination in CKD patients
Ashwini Tayade, Venkatasubramanian Ramasubramanian*
Department of Infectious Diseases, Apollo Hospitals, Chennai 600006, India
a r t i c l e i n f o
Article history:
Received 2 January 2013
Accepted 3 January 2013
Available online 20 January 2013
Keywords:
Chronic kidney disease (CKD)
Hepatitis B
Varicella
Influenza
a b s t r a c t
Infectious diseases are the second most common cause of death in end-stage renal disease
(ESRD) patients. Patients with ESRD are at high risk for several infections, due to exposure
to blood products and frequent dialysis. The increased susceptibility to infections among
these patients is indicative of a complex and varied state of immunodeficiency manifested
by abnormal phagocytosis, T and B lymphocytes abnormalities and impaired response to
T cell dependent pathogens such as hepatitis B and influenza viruses. These immunologic
abnormalities are complicated by the use of immunosuppressive drugs used to treat and
control underlying disease and exacerbated by nutritional deficiency and the dialysis
procedure. Though many of these infections can be prevented by appropriate vaccination,
the usual schedules of vaccination may be less effective.
The aim of this paper is to review the studies on the use of vaccines in ESRD patients
and summarize the vaccines required in this population.
Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.
Chronic kidney disease (CKD) is a serious condition associated
with premature mortality, decreased quality of life, and
increased health-care expenditure. There is increasing trend
in CKD prevalence worldwide, likewise for end stage renal
disease (ESRD) as well. The most common causes of CKD
worldwide are hypertension and diabetes. Although the exact
reasons for increasing trend are unknown, changes in the
demographics of the population, differences in disease bur-
den among racial groups and under-recognition of earlier
stages of CKD and of risk factors for CKD, may partially
explain this growth.1
The currently reported incidence of CKD
in India is based on extrapolated data from the US. As yet, no
large-scale population studies are available. There are limited
studies stating the prevalence of CKD in India as nearly
w0.8%. A cross sectional study in India, reported diabetic
nephropathy as the commonest cause (31%), followed by CKD
of undetermined etiology (16%), chronic glomerulonephritis
(14%) and hypertensive nephrosclerosis (13%).2
The advanced stages of CKD and ESRD (requiring renal
replacement therapy) are associated with a marked increase
in the risk of all-cause morbidity and mortality, particularly
acute infections (bacterial, viral, and fungal) contributing
substantially to the high rates of hospitalization. CKD is
a complex and varied state of immunodeficiency manifested
by abnormal phagocytosis, T- and B-lymphocyte abnormal-
ities and impaired responses to T-cell-dependent pathogens
such as hepatitis B and influenza viruses increasing the risk of
infections. These immunologic abnormalities are complicated
by the use of immunosuppressive drugs to treat and control
the underlying CKD.
The limited existing data suggest that annual mortality rates
in the dialysis population are increased by 10-fold for pneu-
monia and 100-fold for sepsis compared with the general
population. Several studies have shown that bacterial and viral
infections contribute to 30e36% deaths in patients on long
term dialysis.3
There is less data on the role of infections among
* Corresponding author.
E-mail address: idisdoc@gmail.com (V. Ramasubramanian).
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/apme
a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 2 9 e3 5
0976-0016/$ e see front matter Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.apme.2013.01.007

3. Decreased Vaccine
Responsiveness
Impaired Immune Response
• Polymorphonuclear
leukocytes
• T-Iymphocytes
• Monocytes
Comorbid Conditions
• Advanced Age
• Diabetes mellitus
• Other systemic illnesses
• Disabilities
Loss of Cutaneous Barriers
• Edema
• Dialysis catheters
• Needle sticks in AVF/AVGs
Infection-Related Death
Infection-Related
Hospitalization or
Prolonged Length of Stay
Increased Exposure to
Infectious Agents
• Frequent Health-Care
Utilization ACUTE
INFECTION
Immunosuppressive
Therapy for Kidney
Disease
Fig. 1 e Risk factors and outcomes of infection in kidney disease. AVF, arteriovenous fistula; AVG, arteriovenous graft.
apollomedicine10(2013)29e3530

4. patients with mild to moderate CKD. In addition to an increased
incidence of being hospitalized with infections, patients with
CKD have longer lengths of hospital stay during infection-
related admissions compared with patients without CKD.
Fig. 1.4
Given the risks and associated complications of in-
fections in patients with CKD and ESRD, strategies to pre-
vent infections effectively are of paramount importance.
Unfortunately many of the risk factors for infection and
poor outcomes related to infections are not easily modified
(e.g., demographic characteristics, causes of kidney disease)
and despite improved infection control initiatives the
prevalence continues to increase. Targeted interventions,
including reducing unnecessary exposure to pathogens
(hospitalizations) and preventive vaccinations can help.
According to the Advisory Committee on Immunization
Practices (ACIP) and the American Academy of Pediatrics
(AAP), patients on dialysis can safely receive all live attenu-
ated vaccines, except the oral polio vaccine, as well as all
inactivated vaccines on the same schedule recommended for
immunocompetent persons (Fig. 2).5
1. Hepatitis B
Hemodialysis patients remain at increased risk of acquiring
HBV because of increased exposure to blood products, shared
hemodialysis equipment, frequent breaching of skin, immu-
nodeficiency, and continuing high prevalence rates of HBV
infection among hemodialysis populations. The prevalence
and incidence of the hepatitis B infections are very high about
7.6% and 3.2% respectively among dialysis patients in India.
The frequency of HBV seropositivity in renal replacement
therapy in India had been reported to vary from 4% to 44%.6
When administered to healthy individuals, HBV vacci-
nation is an extremely effective means of disease prevention.
Administration of three doses of 20 mg of HBV surface antigen
(HBsAg) over 6 months achieves seroprotection rates of more
than 90%. The use of HBV vaccine and preventive measures
have helped reduce the annual incidence of HBV infection in
patients on dialysis, from 3% to 0.05% between 1976 and
1997 in the USA. Alternatively, among chronic kidney disease
(CKD) populations, immune responses to HBV vaccination
are impaired, proportionally to the degree of kidney failure.
Hence, CKD patients experience lower seroconversion rates
(32e80%), lower peak antibody titers, and shorter durations of
seroprotection (protective antibody titers maintained in 50%
of CKD patients compared with 85% of healthy individuals
after 1 year).7,8
A reduced immunogenicity is also observed in
the elderly, smokers, males and diabetics.
Various strategies have been attempted to improve sero-
conversion and maintain protective antibody levels, including
1) Adding one extra dose of vaccine, a four vaccine series
2) Doubling the dose of vaccine to 40 mg/dose
3) Repeating the vaccine at yearly intervals or when the
antibody titer falls below 10 IU/L
4) Starting vaccination at an earlier stage of CKD
5) Intradermal injection at more frequent intervals
In addition, the vaccine has been given in combination with
a number of substances such as erythropoietin, granulocyte-
macrophage colony-stimulating factor (GM-CSF), IL-2, inter-
feron (IFN)-a, IFN-g and thymopentin. The rationale for use of
these factors is that increased mobilization of the mono-
cyteemacrophage system will result in better antigen pro-
cessing. Of all the factors, GM-CSF as adjuvant therapy via
intradermal injection appears to be promising.
In a study by Siddiqui et al, seroprotection after four doses
of 40 mg vaccine at zero, one, two, and six months was found to
be better and cost effective in chronic kidney disease patients
compared to three doses of 20 mg vaccine given to normal
healthy individuals with adequate renal function.9
Another study compared intradermal versus intramus-
cular route in hemodialysis patients nonresponsive to pri-
mary HBV vaccination. They were revaccinated with either ID
Vaccine
Hepatitis B (Recombivax HB®)
Hepatitis B (Engerix-B®)
Pneumococcal
Influenza
Measles, mumps, rubella (MMR)
Varicella
Inactivated poliovirus (IPV)
Diptheria and tetanus toxoids, and
pertussis vaccine (DTP/DTaP)
Tetanus and diphtheria toxoids (Td)
Haemophilus influenzae type B (HbOC)
Diptheria and tetanus toxoids (DT)
Age group
<20 years 5 µg (0.5 mL)
40 µg (1.0 mL)†
10 µg (0.5 mL)
40 µg (2.0 mL)‡
0.5 mL
0.5 mL
0.5 mL
0.5 mL
0.5 mL
0.5 mL
0.5 mL
0.5 mL
0.5 mL
0.5 mL
0.25mL
IM 3
3
3
4
1
1 or 2§
3 or 4
1 or 2§
2
1
1
2
5
3
3
1–3**
1
1
IM
IM
IM
IM
IM
IM
IM
SC
SC
SC
SC
SC
IM
IM
IM
IM
IM or SC
0.50 mL
0.50 mL
0.50 mL
≥20 years
<20 years
≥20 years
>2 years
6–35 months
2 months–7 years
2 months–7 years
2 months–5 years
7 years
3–8 years
9–12 years
1–12 years
12 months–18years
>12 years
>18 years
>12 years
<18 years
Dose
volume
Route of
administration*
Number
of doses
Boosters
Yes, when anti-HBs
Yes, when anti-HBs
No (revaccination
No
No
No
No
No
No
No
No
Every 10 years
One at 15 months
in 3–5 years)
<10 mU/mL
<10 mU/mL
Fig. 2 e ACIP recommended vaccines for patients on chronic dialysis.
a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 2 9 e3 5 31

5. (5 mg of vaccine every week for 8 weeks) or IM (40 mg of vaccine
at weeks 1 and 8) HBV vaccine. The geometric mean peak
antibody titer was significantly greater in the ID versus IM
group: 239 IU/L (95% CI, 131e434) versus 78 IU/L (95% CI,
36e168; P 0.001). There was a trend toward longer duration of
seroprotection with ID vaccination. ID vaccine was safe and
well tolerated.10
The seroprotection rates vary in relation to the degree of
renal failure and the amount of vaccine administered; when
compared, it was seen that in all three groups of patients,
seroprotection was better when 40 mg of vaccine was used as
compared to 20 mg of vaccine. The Advisory Committee on
Immunization Practices recommends a four dose schedule of
recombinant Engerix B (40 mg) vaccine in renal patients over
20 years of age.
The current Center for Disease Control (CDC) recommen-
dations for vaccination of renal patients over 20 years of age
also specifies a four dose recombinant vaccine schedule of
40 mg Engerix B at 0, 1, 2, and 6 months.
Anti-HBs titre titer should be checked 1e2 months after
administration of the last dose of the vaccine series to confirm
a protective level of anti-HBs (>10 mIU/mL). Persons found to
have anti-HBs levels of <10 mIU/mL after the primary vaccine
series should be revaccinated.
For hemodialysis patients, the need for booster doses
should be assessed by annual antibody to hepatitis B surface
antigen (anti-HBs) testing. A booster dose should be admin-
istered when anti-HBs levels decline to <10 mIU/ml.
In conclusion, HBV vaccination in patients with kidney
disease remains highly recommendable. The sooner they are
vaccinated, the better the response. Dose recommendation is
four 40 mg doses of Engerix B.
2. Influenza
Influenza causes significant mortality and morbidity in the
general population, with 20,000 deaths annually. Compared
with the general population, pulmonary infection kills more
patients on dialysis and mortality rates from sepsis are higher.
Patients with ESRD have significantly lower response rates to
influenza vaccine as compared with healthy control subjects
but nonetheless have been shown to develop protective
antibody levels to the majority of influenza strains examined.
Among patients with ESRD, response rates to influenza vac-
cination (defined as a four-fold increase in titers) have been
reported in some studies to vary from 7 to 44%, whereas
protection rates (defined as hemagglutination inhibition
tire > 40) in these same studies has ranged from 46 to 93%
depending on the dialysis modality and specific strain titer
measured (e.g., H3N2, H1N1, type B).11
Despite smaller proportions of patients with ESRD ach-
ieving potential antibody levels compared to patients without
kidney failure (and response varies depending on the partic-
ular viral antigen and whether the patient is on peritoneal
dialysis or hemodialysis), there does appear to be a clinical
benefit from vaccination.
Influenza vaccine response was studied in the first year
after renal transplantation. The results showed that influenza
vaccination was associated with a lower risk of subsequent
allograft loss and death. Although this study cannot comment
on formation of protective antibodies after vaccination, these
data do not support withholding vaccination on the basis of
concerns of adversely affecting allograft function.12
In conclusion, influenza vaccination is highly recom-
mended among ESRD patients. Antibody titers can be lower
than those in healthy subjects. However, satisfactory protec-
tive rates can be reached by annual vaccination. It is thus
recommended to vaccinate adult ESRD patients against influ-
enza each year, using a standard dose (15 mg annually).13
3. Pneumococcal vaccination
Overall, pulmonary infectious mortality rate is 14-folde16-
fold higher in dialysis patients and approximately two-fold
higher in renal transplant recipients compared with the gen-
eral population .CKD patients have more severe pneumonia
at admission compared with non-CKD patients. During
observational analysis of a prospective cohort of hospitalized
adults with pneumonia, in a tertiary teaching hospital, Strep-
tococcus pneumoniae was found to be the most frequent
pathogen (28.1 versus 34.7%; P ¼ 0.05). Mortality was higher in
patients with CKD (15.8 versus 8.3%; P < 0.001), while prior
pneumococcal vaccination (adjusted odds ratio, 0.05; 95% CI
0.005e0.69) and leukocytosis at hospital admission (adjusted
odds ratio, 0.10; 95% CI 0.01e0.64) were protective.14
The ACIP currently recommends that a single 0.5 mL dose
of the 23-valent pneumococcal polysaccharide vaccine be
administered intramuscularly or subcutaneously to all dialy-
sis patients 2 years of age or older. More than 75% of dialysis
patients have an adequate response to the vaccine, measured
by a two-fold or greater increase in post vaccination antibody
titer and/or a geometric mean greater than 200 ng/mL, but
their antibody levels are considerably lower than those of
healthy vaccinated adults.15
As compared with healthy adults, patients with advanced
CKD and ESRD seem to have reduced responsiveness to
pneumococcal vaccination, although findings have been
inconsistent across studies. Patients who have kidney disease
and are vaccinated with the pneumococcal vaccine seem to
develop different serotype-specific titers, develop lower levels
of antibody titers, and have a more rapid loss of antibody titers
as compared with healthy control subjects. During a study of
CKD patients not on dialysis, significant antibody titers
(antibody titer > 200 ng/L) were observed in only 68% of pa-
tients at 6 months and 48% at 1 year, and revaccination pro-
duced a significant immune response in only 50%, followed by
a rapid decline in antibody level within 6 months.16
Pneumococcal conjugate vaccine is immunogenic in renal
transplant recipients and, for certain serotypes, demonstrates
a trend toward greater immunogenicity by quantitative anti-
body measurements, compared with polysaccharide vaccine.
However, when assessed using functional antibody response
by OPA, there does not appear to be a substantial difference
between the two vaccines. Overall response rates were gen-
erally suboptimal for both groups, but this could potentially be
overcome with repeat dosing schedules or, perhaps, higher
doses of vaccine.17
Another strategy would be to use conjugate
vaccine to prime the immune system and then give a booster
a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 2 9 e3 532

6. dose of the polysaccharide vaccine. This may result in an even
greater response than a single vaccine dose and has shown
promise in other groups of immunocompromised patients.
Further studies of transplant recipients are required to
determine an optimal vaccination strategy. In conclusion,
pneumococcal vaccine is recommended for all patients with
CKD, but the role of polysaccharide and conjugate vaccines
need to be better defined for optimal protection.
4. Diphtheria and tetanus vaccination
(tetanus and diphtheria toxoids)
Children on dialysis should receive the diphtheria and tetanus
toxoids and pertussis (DTaP) vaccine as recommended for
healthy children. Booster doses of tetanus-diphtheria toxoids
(Td) should follow every 10 years after completing the primary
series. Like other vaccines even after diphtheria and tetanus
vaccination, seroconversion rate has been shown to be lower in
dialysis patients than in healthy subjects.5
A short-term study
showed that tetanus vaccination (with booster injection) in HD
patients led to 96.5% of seroconversion rate (>0.06 HU/ml), but
antibodies rapidly declined after 6 months. In one study, the
immunological status after tetanus (40 UI) and diphtheria (4 UI)
toxoid vaccination was tested among 21HD patients without
protection before vaccination. Five years after the vaccination,
15 patients (71%) had a protective antibody level for tetanus
and 7 (33%) for diphtheria. In conclusion, diphtheria and teta-
nus infections can be prevented by using vaccines in ESRD
patients. However, because of impaired seroconversion rates,
monitoring of antibody levels is recommended and a booster
may be used in non-responding patients.18
5. Measles, mumps, and rubella vaccine
The measles, mumps, and rubella (MMR) vaccine should be
given to all children, including those on dialysis, between
12 and 15 months of age, with a booster dose between 4 and
6 years of age. Among healthy children, the seroconversion
rate for one dose of MMR vaccine is more than 90%. For chil-
dren on dialysis, the seroconversion rate for all three antigens
is approximately 30%, for mumps alone 50%, and for measles
and rubella combined 80%. Therefore some have suggested
children on dialysis may benefit from post vaccination testing
to assess seroconversion.19
It is recommended to assess the seroconversion after
vaccination (standard doses) among these patients. For adult
patients, one single dose should be used.
6. Haemophilus influenza type B conjugate
vaccine
There is limited information on the use of Haemophilus influ-
enza type B (Hib) vaccine in children on chronic dialysis. The
ACIP recommends the vaccine for these patients beginning at
2 months of age using the same dosage and schedules used for
healthy children and adults.5
The vaccine is safe: a study of
children on continuous ambulatory peritoneal dialysis has
shown seroconversion rates of 90%, with a persistence of
immunity for 22 months after vaccination.20
7. Oral poliovirus vaccine
There are no data discussing the use of oral poliovirus vaccine
(OPV) in children undergoing dialysis. However, because of
a theoretical risk that they will not be able to effectively limit
the replication of the vaccine virus, OPV should not be used to
immunize immunocompromised children, including children
on dialysis. Also OPV should not be used on household mem-
bers or health care staff in close contact with these patients.5
8. Inactivated poliovirus vaccine
Inactivated poliovirus vaccine is only recommended for specific
groups of persons, including ESRD patients. The efficiency and
safety of inactivated poliovirus vaccine was assessed in 49
chronic dialysis patients, resulting in 86% of patients having
sufficient antibody levels.21
9. Varicella vaccine
Children 1 year or older on dialysis who have not had chick-
enpox previously should receive one subcutaneous dose of the
varicella vaccine as recommended by the ACIP for healthy
children 13 years of age or younger.5
Due to the high risk of complications and death associated
with chickenpox infection in adulthood, susceptible adoles-
cents and adults should receive two doses of the varicella
vaccine subcutaneously, with the second injection at least
4 weeks after the first. Among patients undergoing dialysis,
data on the immunogenicity of the varicella vaccine are
limited. A recent report, however, showed that up to 85% of
children on dialysis developed protective antibody levels
(geometric mean titer 1:640) within the first 6 months fol-
lowing a single dose of the vaccine, which is comparable to the
seroconversion rate among healthy children. The varicella
vaccine has been reported to be safe for children on dialysis,
with no systemic adverse reactions reported.22
10. Hepatitis A vaccine
Data on hepatitis A vaccination in hemodialysis patients is
limited. Hepatitis A virus (HAV) vaccination in ESRD patients
is well tolerated and immunogenic .The Advisory Committee
on Immunization Practices (ACIP) recommends using the
standard dose and schedule in adult ESRD patients of Havrix
at 0 and between 6 and 12 months.23
For ESRD patients older than 12 years, available guidelines
recommend two doses of 0.5 ml with no booster doses. Weber
et al compared hepatitis A vaccine response in dialysis pa-
tients with subcutaneous and intramuscular route. The geo-
metric mean titers (GMT) were high and similar to those
observed in healthy subjects. There was a tendency to higher
GMT in the group who received the vaccine subcutaneously.24
a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 2 9 e3 5 33

7. Another study showed that this HA vaccine has good
immunogenicity compared with the HB vaccine and that the
standard three doses of HA vaccine given at 0, 1 and 6 months
are safe and effective even in HD patients.
11. Inactivated vaccines and toxoids
All inactivated vaccines and toxoids are safe and effective
when used in dialysis patients, and should be administered
to children and adults on chronic dialysis using the same
doses and schedules recommended for immunocompetent
persons.5
12. Contraindicated vaccines
Many vaccines have been used for years in ESRD populations.
However, some vaccines are still contraindicated in these
patients. Live vaccines (yellow fever, polio, varicella and MMR
vaccines) are generally avoided because they present a theo-
retical risk of vaccine-induced infection. However, several
studies investigated the efficacy and safety profiles for some of
these vaccines (varicella and MMR vaccines) in ESRD patients,
with success. In contrast, oral poliovirus should not be used in
ESRD and RT patients. ESRD patients who need polio vacci-
nation should receive the inactivated poliovirus vaccine.13
13. Summary
In summary, patients with CKD, on dialysis, or following
a kidney transplant are immunocompromised, and infection
is a major concern. It appears that there are no added risks to
immunization with non-live vaccines, and there is the po-
tential for deriving benefit in terms of reductions in cost and
hospitalizations.
Pediatric patients on dialysis should receive all the vac-
cines currently recommended by the ACIP and the AAP for
healthy children, except the oral polio vaccine. Adult patients
should receive the hepatitis B vaccine series, pneumococcal
vaccine, yearly influenza vaccinations, tetanus-diphtheria
toxoids, and varicella vaccine, if they are susceptible.
Vaccines are well tolerated by these patients, but higher
doses and/or additional boosters may be required periodically
to adequately protect dialysis patients from vaccine-pre-
ventable diseases.
Although both children and adults on dialysis may show an
impaired and/or delayed immunologic response to certain an-
tigens, particularly hepatitis B virus and S. pneumoniae, appro-
priate immunizations can significantly reduce the risk of serious
complications from vaccine-preventable diseases. Because the
protection these vaccines provide may be incomplete or tran-
sient, infection control strategies at hospitals and other health
care facilities should be implemented simultaneously. Health
care providers are encouraged to assess each patients need for
vaccinations individually and formulate immunization strat-
egies early in the course of progressive renal disease, ideally
before the patient requires dialysis.
Conflicts of interest
All authors have none to declare.
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Linkedin:http://www.linkedin.com/company/apollo-hospitals
Blog:Blog:http://www.letstalkhealth.in/