immunization in children with kidney disease

1. IMMUNIZATION in RENAL DISEASE
Mojtaba Fazel
Pediatric Nephrologist
TUMS
‫ماه‬ ‫دی‬
۱۴۰۰

2. INTRODUCTION
Kidney disease patients are at risk for many infections, some of which are vaccine
preventable. Knowledge of vaccination is imperative to treat CKD patients effectively
Patients with ESKD have a reduced response to vaccination because of the general
suppression of the immune system associated with uremia
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. HEPATITIS B VIRUS VACCINE
• Controversy exists concerning the overall effectiveness of HB Vaccinn.
• Negative points for vaccination :
• 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
• The low rate of hepatitis B infection
• Despite these data many clinicians recommend that chronic dialysis
patients receive vaccination against hepatitis B(hemodialysis patients
vaccinated against hepatitis B had a 70 percent lower risk for infection
compared with nonvaccinated patients).

4. Attempts for Enhanceing the immune
response to hepatitis B vaccine
• 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(beta-1,3 glucans, chitosan,
levamisole)
• Giving a combined hepatitis A and B vaccine

5. Dosage and schedule
• Higher vaccine dosages or an increased number of doses are recommended for
subjects with CKD (eGFR <30 ml/min).
• Patients should receive four doses of hepatitis B vaccine as early in the course of
disease as possible
• Use special formulations of vaccine (40 mcg/ml) or two 1 ml 20 mcg doses given
at one site. Dose schedule should be 0, 1, 2, and 6 months
• Vaccine should be given intramuscular in deltoid regions
• Assess antibody titer to hep B surface antigen (anti-HBs). First titer should be
done 1-2 months after the primary course is completed and annually thereafter
• Booster dose should be given if anti-HBs titer falls below 10 mU/ml
• Revaccination with full doses is recommended for persons who do not develop
protective antibody titer after primary course.

6. Pneumococcal vaccine
• Vaccination against pneumococcal disease is associated with decreased
mortality among ESKD patients. Despite these data, and other
recommendations, overall pneumococcal vaccination rates among ESKD
patients remain suboptimal.
• 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. 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

7. Tetanus vaccine
• The response to tetanus vaccine in patients with 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 .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. 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.

8. Influenza vaccine
• The antibody response to the standard-dose influenza vaccine in
chronic hemodialysis patients is lower than that in the general
population. 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.
Despite these data, it is recommended to vaccinate ESKD patients
against influenza to mitigate the potential morbidity and mortality
risk of an influenza infection.
• 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.

9. Live attenuated vaccines
• Live vaccines are contraindicated in immunocompromised patients
due to risk of vaccine-induced infections. Even though the limited
number of studies in CKD patients has not shown any adverse
reactions, these vaccines should be avoided.

10. Varicella Vaccine & MMR
• Children 1 year of age or older should receive 1 dose of subcutaneous
varicella vaccine as recommended for healthy children of 13 years of
age and younger who do not had chicken pox previously. Adolescents
and adults should receive 2 doses of 0.5 ml subcutaneously, with
second injection at least 4 weeks after the first.
• 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.

11. Cont
• There is high risk of complications and death associated with chicken
pox infection in adulthood. About 85% of children on dialysis develop
protective antibody levels within 6 months following single dose of
vaccine. Varicella vaccine has been reported to be safe for children on
dialysis.
• Seroconversion rate following MMR vaccine for all 3 antigens is
approximately 30%, for mumps alone 50%, and for measles and
rubella combined 80%. Patients on dialysis should be tested for
seroconversion

12. Hepatitis A Vaccine
• Hepatitis A vaccine is highly immunogenic in children, adolescents,
and adults, with up to 100% of recipients develop protective level of
antibodies > 20 mU/ml persisting for up 48 months. CKD patients at
increased risk of infections such as travelers to countries to
intermediate or high endemicity of infection, children 2 years of age
and older living in areas rate of hepatitis A are at least twice the
national average should receive the vaccine as recommended for
normal persons.

14. • 1746 participants were recruited: 1116 HD, 171 PD, 176 non-dialysis
CKD patients and 283 KT recipients. Most patients (98%) received
mRNA vaccines.
• patients. At 28 days, 95% of patients had developed antibodies: 79%
of KT, 98% of HD, 99% of PD and 100% of non-dialysis CKD patients
(p<0.001). In a multivariate adjusted analysis, absence of an antibody
response was independently associated to KT .

15. Cont
• Conclusion:
• The rate of anti-Spike antibody development after vaccination in KT
patients was low but in other CKD patients it approached 100%;
suggesting that KT patients require persistent isolation measures and
booster doses of a Covid-19 vaccine. Potential differences between
Covid-19 vaccines should be explored in prospective controlled
studies.
• Nephrology Dialysis Transplantation, gfab313, https://doi.org/10.1093/ndt/gfab313

16. Choice of COVID-19 vaccine
• Replication-defective viral-vectored vaccines such as ChAdOx1 nCoV-
19 (Oxford-AstraZeneca) and the mRNA vaccines BNT162b2 (Pfizer-
BioNTech) and mRNA-1273 (Moderna) are safe to use
• In phase 3 trials, BNT162b2, mRNA-1273 and ChAdOx1 nCoV-19
prevented COVID-19 in 95%, 94.1% and 70.4% of participants,
respectively, suggesting that the mRNA vaccines might induce
protective immunity more reliably than ChAdOx1 nCoV-19. Use of
these vaccines might therefore be preferable for patients who are
immune compromised.
• Nature Reviews Nephrology volume 17, pages 291–293 (2021)Cite this article

18. ‫سر‬ ‫داروهای‬ ‫کننده‬ ‫دریافت‬ ‫درکودکان‬ ‫واکسیناسیون‬
‫کوب‬
‫ایمنی‬ ‫کننده‬
•
‫سیسـتم‬ ‫مهارکننده‬ ‫هـای‬ ‫درمـان‬ ‫شـروع‬ ‫از‬ ‫قبـل‬ ‫شـود‬ ‫مـی‬ ‫توصیـه‬ ‫امـکان‬ ‫صـورت‬ ‫در‬
‫ایمنـی‬
(
‫ایمنـی‬ ‫سیسـتم‬ ‫مهارکننـده‬ ‫داروهـای‬ ‫و‬ ‫رادیوتراپـی‬ ،‫درمانـی‬ ‫شـیمی‬ ‫ماننـد‬
)
‫شـود‬ ‫کامـل‬ ‫کشـوری‬ ‫سـازی‬ ‫ایمن‬ ‫برنامـه‬ ‫طبـق‬ ‫کـودک‬ ‫واکسیناسـیون‬
.
‫هـای‬ ‫واکسـن‬
‫زنـده‬
‫حداقـل‬ ‫بایـد‬
4
‫فاصلـه‬ ‫در‬ ‫هـا‬ ‫آن‬ ‫تجویـز‬ ‫و‬ ‫شـوند‬ ‫تجویـز‬ ‫درمان‬ ‫شـروع‬ ‫از‬ ‫قبـل‬ ‫هفته‬
‫از‬ ‫کمتـر‬ ‫زمانـی‬
2
‫اسـت‬ ‫ممنوع‬ ‫ایمنی‬ ‫سیسـتم‬ ‫مهارکننده‬ ‫هـای‬ ‫درمـان‬ ‫شـروع‬ ‫از‬ ‫هفتـه‬
.
‫حداقـل‬ ‫بایـد‬ ‫فعال‬ ‫غیر‬ ‫هـای‬ ‫واکسـن‬
2
‫شـوند‬ ‫تجویز‬ ‫درمـان‬ ‫شـروع‬ ‫از‬ ‫قبـل‬ ‫هفتـه‬
.
•
‫بدخیمـ‬ ‫بـه‬ ‫مبتال‬ ‫کـودکان‬ ‫ماننـد‬ ‫ایمنـی‬ ‫سیسـتم‬ ‫نقایـص‬ ‫بـه‬ ‫مبتال‬ ‫کـودکان‬ ‫در‬
‫دریافـت‬ ،‫ی‬
‫ب‬ ‫های‬ ‫واکسـن‬ ‫دریافـت‬ ،‫ایمنی‬ ‫خـود‬ ‫های‬ ‫بیمـاری‬ ‫به‬ ‫مبتالیان‬ ‫و‬ ‫پیونـد‬ ‫کننـدگان‬
‫اکتریـال‬
‫زنده‬
(
‫ب‬
.
‫ث‬
.
‫ژ‬
)
‫زنده‬ ‫ویروسـی‬ ‫های‬ ‫واکسـن‬ ‫و‬
(
MMR
،
‫تـب‬ ‫و‬ ‫خوراکـی‬ ‫اطفـال‬ ‫فلـج‬
‫زرد‬
)
‫اسـت‬ ‫ممنـوع‬
.

19. cont
•
‫باال‬ ‫دز‬ ‫با‬ ‫پردنیزون‬ ‫که‬ ‫کودکانی‬ ‫در‬
(
‫از‬ ‫بیش‬
2
‫یا‬ ‫وزن‬ ‫کیلوگرم‬ ‫هر‬ ‫ازای‬ ‫به‬ ‫گرم‬ ‫میلی‬
‫از‬ ‫بیش‬
20
‫از‬ ‫بیش‬ ‫وزن‬ ‫با‬ ‫کودکان‬ ‫برای‬ ‫روز‬ ‫در‬ ‫گرم‬ ‫میلی‬
10
‫کیلوگرم‬
)
‫آن‬ ‫معادل‬ ‫ویا‬
‫طوالنی‬ ‫مدت‬ ‫به‬ ‫و‬
(
14
‫بیشتر‬ ‫یا‬ ‫روز‬
)
‫حداق‬ ‫باید‬ ،‫کنند‬ ‫می‬ ‫مصرف‬ ‫روزانه‬ ‫صورت‬ ‫به‬
‫ل‬
‫زنده‬ ‫ویروسی‬ ‫های‬ ‫واکسن‬ ‫تجویز‬ ‫از‬ ‫درمان‬ ‫دوره‬ ‫اتمام‬ ‫از‬ ‫پس‬ ‫ماه‬ ‫یک‬ ‫تا‬
(
MMR
،
‫فلج‬
‫زرد‬ ‫تب‬ ‫و‬ ‫خوراکی‬ ‫اطفال‬
)
‫کرد‬ ‫اجتناب‬
.
•
•
‫بـاال‬ ‫دز‬ ‫بـا‬ ‫پردنیـزون‬ ‫مصـرف‬ ‫درمـوارد‬
(
‫از‬ ‫بیـش‬
2
‫کیلوگـرم‬ ‫هـر‬ ‫ازای‬ ‫بـه‬ ‫گـرم‬ ‫میلـی‬
‫از‬ ‫بیـش‬ ‫یـا‬ ‫بـدن‬ ‫وزن‬
20
‫از‬ ‫بیـش‬ ‫وزن‬ ‫با‬ ‫کـودکان‬ ‫بـرای‬ ‫روز‬ ‫در‬ ‫گـرم‬ ‫میلـی‬
10
‫کیلوگـرم‬
)
‫کمتـر‬ ‫مـدت‬ ‫بـرای‬ ‫درمیان‬ ‫روز‬ ‫یـک‬ ‫یـا‬ ‫روزانه‬ ‫صـورت‬ ‫بـه‬ ‫آن‬ ‫معـادل‬ ‫ویـا‬
‫از‬
14
‫را‬ ‫زنـده‬ ‫ویروسـی‬ ‫هـای‬ ‫واکسـن‬ ‫تـوان‬ ‫مـی‬ ‫درمـان‬ ‫خاتمـه‬ ‫از‬ ‫پـس‬ ‫بالفاصلـه‬ ، ‫روز‬
‫كرد‬ ‫تجویـز‬
.

20. cont
•
‫پایین‬ ‫دز‬ ‫با‬ ‫پردنیزون‬ ‫با‬ ‫درمان‬ ‫موارد‬ ‫در‬
(
‫كمتراز‬
2
‫وزن‬ ‫کیلوگرم‬ ‫هر‬ ‫ازای‬ ‫به‬ ‫گرم‬ ‫میلی‬
‫از‬ ‫کمتر‬ ‫یا‬ ‫بدن‬
20
‫از‬ ‫بیش‬ ‫وزن‬ ‫با‬ ‫کودکان‬ ‫برای‬ ‫گرم‬ ‫میلی‬
10
‫کیلوگرم‬
)
‫آن‬ ‫معادل‬ ‫یا‬ ‫و‬
‫اس‬ ‫بالمانع‬ ‫زنده‬ ‫ویروسی‬ ‫های‬ ‫واکسن‬ ‫دریافت‬ ،‫درمیان‬ ‫روز‬ ‫یک‬ ‫یا‬ ‫روزانه‬ ‫صورت‬ ‫به‬
‫ت‬
.
•
•
،‫فیزیولوژیــک‬ ‫نگهدارنــده‬ ‫دز‬ ‫بــا‬ ‫هــا‬ ‫کورتیکوســتروئید‬ ‫مصــرف‬ ‫درصــورت‬
‫اســت‬ ‫بالمانــع‬ ‫زنــده‬ ‫ویروســی‬ ‫هــای‬ ‫واکســن‬ ‫دریافــت‬
.
•
‫نقایص‬ ‫دارای‬ ‫بیماران‬ ‫با‬ ‫نزدیک‬ ‫تماس‬ ‫در‬ ‫که‬ ‫افرادی‬ ‫و‬ ‫خانواده‬ ‫افراد‬ ‫واکسیناسیون‬
‫سیستم‬
‫بود‬ ‫خواهد‬ ‫کشوری‬ ‫واکسیناسیون‬ ‫جاری‬ ‫برنامه‬ ‫با‬ ‫مطابق‬ ،‫هستند‬ ‫ایمنی‬
.
‫ت‬ ‫این‬ ‫با‬
‫که‬ ‫فاوت‬
‫وا‬ ،‫اطفال‬ ‫فلج‬ ‫خوراکی‬ ‫واکسن‬ ‫جای‬ ‫به‬ ‫باید‬ ‫بودن‬ ‫شرایط‬ ‫واجد‬ ‫درصورت‬ ‫افراد‬ ‫این‬
‫کسن‬
‫کنند‬ ‫دریافت‬ ‫اطفال‬ ‫فلج‬ ‫تزریقی‬
.

21. ‫اعضا‬ ‫پیوند‬ ‫کنندگان‬ ‫دریافت‬
•
‫هس‬ ‫اعضـا‬ ‫پیونـد‬ ‫دریافـت‬ ‫کاندیـد‬ ‫کـه‬ ‫بزرگسـاالنی‬ ‫و‬ ‫کـودکان‬ ‫شـود‬ ‫مـی‬ ‫توصیـه‬
،‫ـتند‬
‫تـا‬ ‫حداقـل‬
2
‫زیـرا‬ ،‫کننـد‬ ‫دریافت‬ ‫را‬ ‫نیـاز‬ ‫مـورد‬ ‫های‬ ‫واکسـن‬ ،‫پیوند‬ ‫از‬ ‫قبـل‬ ‫هفته‬
‫ب‬ ‫پیونـدی‬ ‫عضـو‬ ‫دریافت‬ ‫از‬ ‫پـس‬ ‫که‬ ‫پیوند‬ ‫زدن‬ ‫پـس‬ ‫از‬ ‫کننـده‬ ‫جلوگیـری‬ ‫داروهـای‬
‫ـه‬
‫ش‬ ‫می‬ ‫ها‬ ‫واکسـن‬ ‫بـه‬ ‫بـدن‬ ‫ایمنی‬ ‫سیسـتم‬ ‫پاسـخ‬ ‫کاهش‬ ‫باعـث‬ ،‫شـود‬ ‫مـی‬ ‫داده‬ ‫بیمـار‬
‫ـود‬
.
•
‫زنـده‬ ‫ویروسـی‬ ‫هـای‬ ‫واکسـن‬
(
‫ماننـد‬
MMR
‫مرغـان‬ ‫آبلـه‬ ‫و‬
)
‫قبـل‬ ‫ماه‬ ‫یـک‬ ‫تا‬ ‫حداقل‬ ‫بایـد‬
‫شـوند‬ ‫تجویز‬ ،‫پیونـد‬ ‫از‬
.

22. cont
•
‫اطفال‬ ‫فلج‬ ‫خوراکی‬ ‫واکسن‬ ‫تجویز‬
OPV)
)
‫افراد‬ ‫و‬ ‫پیوندی‬ ‫عضو‬ ‫کنندگان‬ ‫دریافت‬ ‫برای‬
‫دارد‬ ‫ممنوعیت‬ ‫ایشان‬ ‫خانگی‬ ‫درتماس‬
.
‫خوراک‬ ‫واکسن‬ ‫جای‬ ‫به‬ ‫توان‬ ‫می‬ ‫نیاز‬ ‫درصورت‬
‫ی‬
‫اطفال‬ ‫فلج‬
OPV)
)
‫اطفال‬ ‫فلج‬ ‫تزریقی‬ ‫واکسن‬ ‫از‬
IPV)
)
‫نمود‬ ‫استفاده‬
.
•
،‫گانه‬ ‫سه‬ ‫های‬ ‫واکسن‬ ،‫پیوند‬ ‫از‬ ‫بعد‬ ‫توان‬ ‫می‬ ‫شرایط‬ ‫به‬ ‫توجه‬ ‫با‬ ‫و‬ ‫نیاز‬ ‫صورت‬ ‫در‬
‫م‬ ‫و‬ ‫پنوموکوک‬ ،‫آنفلوانزا‬ ،‫ب‬ ‫هپاتیت‬ ،‫گانه‬ ‫پنج‬ ،‫ب‬ ‫تیپ‬ ‫آنفلوانزای‬ ‫هموفیلوس‬
‫ننگوکوک‬
‫کرد‬ ‫تجویز‬ ‫بیمار‬ ‫برای‬ ‫را‬
.
‫نخس‬ ‫های‬ ‫ماه‬ ‫در‬ ‫بدن‬ ‫ایمنی‬ ‫پاسخ‬ ‫کاهش‬ ‫به‬ ‫توجه‬ ‫با‬ ‫ولی‬
‫بعد‬ ‫ت‬
‫تا‬ ‫ها‬ ‫واکسن‬ ‫این‬ ‫تجویز‬ ‫شود‬ ‫می‬ ‫توصیه‬ ،‫پیوند‬ ‫از‬
6
‫بیفتد‬ ‫تعویق‬ ‫به‬ ‫پیوند‬ ‫از‬ ‫بعد‬ ‫ماه‬
.
‫تض‬ ‫داروهای‬ ‫دز‬ ‫و‬ ‫بیمار‬ ‫شرایط‬ ‫براساس‬ ‫زنده‬ ‫ویروسی‬ ‫های‬ ‫واکسن‬ ‫مورد‬ ‫در‬ ‫تصمیم‬
‫عیف‬
‫فاصله‬ ‫حداقل‬ ‫رعایت‬ ‫با‬ ‫ایمنی‬ ‫سیستم‬ ‫کننده‬
۶
‫باشد‬ ‫می‬ ‫معالج‬ ‫پزشک‬ ‫برعهده‬ ‫ماه‬
.

23. References:
• UpToDate- Immunizations in patients with end-stage kidney disease
• Indian Journal of Nephrology (IJN)- 2016 Apr; 26(Suppl 1): S15–S18.
• Nephrology Dialysis Transplantation, gfab313, https://doi.org/10.1093/ndt/gfab313, Published:12 November
2021
• COVID-19 vaccines and kidney disease Nature Reviews Nephrology volume 17, pages 291–293 (2021)
• ‫سازی‬ ‫ایمن‬ ‫کشوری‬ ‫کمیته‬ ‫مصوب‬ ‫سازی‬ ‫ایمن‬ ‫راهنمای‬ ‫و‬ ‫برنامه‬
1394