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Vaccination in ckd patients


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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.

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Vaccination in ckd patients

  1. 1. VaccinationinCKDpatients
  2. 2. Review ArticleVaccination in CKD patientsAshwini Tayade, Venkatasubramanian Ramasubramanian*Department of Infectious Diseases, Apollo Hospitals, Chennai 600006, Indiaa r t i c l e i n f oArticle history:Received 2 January 2013Accepted 3 January 2013Available online 20 January 2013Keywords:Chronic kidney disease (CKD)Hepatitis BVaricellaInfluenzaa b s t r a c tInfectious 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 exposureto blood products and frequent dialysis. The increased susceptibility to infections amongthese patients is indicative of a complex and varied state of immunodeficiency manifestedby abnormal phagocytosis, T and B lymphocytes abnormalities and impaired response toT cell dependent pathogens such as hepatitis B and influenza viruses. These immunologicabnormalities are complicated by the use of immunosuppressive drugs used to treat andcontrol underlying disease and exacerbated by nutritional deficiency and the dialysisprocedure. 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 patientsand 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 associatedwith premature mortality, decreased quality of life, andincreased health-care expenditure. There is increasing trendin CKD prevalence worldwide, likewise for end stage renaldisease (ESRD) as well. The most common causes of CKDworldwide are hypertension and diabetes. Although the exactreasons for increasing trend are unknown, changes in thedemographics of the population, differences in disease bur-den among racial groups and under-recognition of earlierstages of CKD and of risk factors for CKD, may partiallyexplain this growth.1The currently reported incidence of CKDin India is based on extrapolated data from the US. As yet, nolarge-scale population studies are available. There are limitedstudies stating the prevalence of CKD in India as nearlyw0.8%. A cross sectional study in India, reported diabeticnephropathy as the commonest cause (31%), followed by CKDof undetermined etiology (16%), chronic glomerulonephritis(14%) and hypertensive nephrosclerosis (13%).2The advanced stages of CKD and ESRD (requiring renalreplacement therapy) are associated with a marked increasein the risk of all-cause morbidity and mortality, particularlyacute infections (bacterial, viral, and fungal) contributingsubstantially to the high rates of hospitalization. CKD isa complex and varied state of immunodeficiency manifestedby abnormal phagocytosis, T- and B-lymphocyte abnormal-ities and impaired responses to T-cell-dependent pathogenssuch as hepatitis B and influenza viruses increasing the risk ofinfections. These immunologic abnormalities are complicatedby the use of immunosuppressive drugs to treat and controlthe underlying CKD.The limited existing data suggest that annual mortality ratesin the dialysis population are increased by 10-fold for pneu-monia and 100-fold for sepsis compared with the generalpopulation. Several studies have shown that bacterial and viralinfections contribute to 30e36% deaths in patients on longterm dialysis.3There is less data on the role of infections among* Corresponding author.E-mail address: (V. Ramasubramanian).Available online at www.sciencedirect.comjournal homepage: p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 2 9 e3 50976-0016/$ e see front matter Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.
  3. 3. Decreased VaccineResponsivenessImpaired Immune Response• Polymorphonuclearleukocytes• T-Iymphocytes• MonocytesComorbid Conditions• Advanced Age• Diabetes mellitus• Other systemic illnesses• DisabilitiesLoss of Cutaneous Barriers• Edema• Dialysis catheters• Needle sticks in AVF/AVGsInfection-Related DeathInfection-RelatedHospitalization orProlonged Length of StayIncreased Exposure toInfectious Agents• Frequent Health-CareUtilization ACUTEINFECTIONImmunosuppressiveTherapy for KidneyDiseaseFig. 1 e Risk factors and outcomes of infection in kidney disease. AVF, arteriovenous fistula; AVG, arteriovenous graft.apollomedicine10(2013)29e3530
  4. 4. patients with mild to moderate CKD. In addition to an increasedincidence of being hospitalized with infections, patients withCKD have longer lengths of hospital stay during infection-related admissions compared with patients without CKD.Fig. 1.4Given 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 andpoor outcomes related to infections are not easily modified(e.g., demographic characteristics, causes of kidney disease)and despite improved infection control initiatives theprevalence continues to increase. Targeted interventions,including reducing unnecessary exposure to pathogens(hospitalizations) and preventive vaccinations can help.According to the Advisory Committee on ImmunizationPractices (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 allinactivated vaccines on the same schedule recommended forimmunocompetent persons (Fig. 2).51. Hepatitis BHemodialysis patients remain at increased risk of acquiringHBV because of increased exposure to blood products, sharedhemodialysis equipment, frequent breaching of skin, immu-nodeficiency, and continuing high prevalence rates of HBVinfection among hemodialysis populations. The prevalenceand incidence of the hepatitis B infections are very high about7.6% and 3.2% respectively among dialysis patients in India.The frequency of HBV seropositivity in renal replacementtherapy in India had been reported to vary from 4% to 44%.6When 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 morethan 90%. The use of HBV vaccine and preventive measureshave helped reduce the annual incidence of HBV infection inpatients on dialysis, from 3% to 0.05% between 1976 and1997 in the USA. Alternatively, among chronic kidney disease(CKD) populations, immune responses to HBV vaccinationare impaired, proportionally to the degree of kidney failure.Hence, CKD patients experience lower seroconversion rates(32e80%), lower peak antibody titers, and shorter durations ofseroprotection (protective antibody titers maintained in 50%of CKD patients compared with 85% of healthy individualsafter 1 year).7,8A reduced immunogenicity is also observed inthe elderly, smokers, males and diabetics.Various strategies have been attempted to improve sero-conversion and maintain protective antibody levels, including1) Adding one extra dose of vaccine, a four vaccine series2) Doubling the dose of vaccine to 40 mg/dose3) Repeating the vaccine at yearly intervals or when theantibody titer falls below 10 IU/L4) Starting vaccination at an earlier stage of CKD5) Intradermal injection at more frequent intervalsIn addition, the vaccine has been given in combination witha 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 ofthese 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 viaintradermal injection appears to be promising.In a study by Siddiqui et al, seroprotection after four dosesof 40 mg vaccine at zero, one, two, and six months was found tobe better and cost effective in chronic kidney disease patientscompared to three doses of 20 mg vaccine given to normalhealthy individuals with adequate renal function.9Another study compared intradermal versus intramus-cular route in hemodialysis patients nonresponsive to pri-mary HBV vaccination. They were revaccinated with either IDVaccineHepatitis B (Recombivax HB®)Hepatitis B (Engerix-B®)PneumococcalInfluenzaMeasles, mumps, rubella (MMR)VaricellaInactivated poliovirus (IPV)Diptheria and tetanus toxoids, andpertussis 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 mL0.5 mL0.5 mL0.5 mL0.5 mL0.5 mL0.5 mL0.5 mL0.5 mL0.5 mL0.25mLIM 333411 or 2§3 or 41 or 2§21125331–3**11IMIMIMIMIMIMIMSCSCSCSCSCIMIMIMIMIM or SC0.50 mL0.50 mL0.50 mL≥20 years<20 years≥20 years>2 years6–35 months2 months–7 years2 months–7 years2 months–5 years7 years3–8 years9–12 years1–12 years12 months–18years>12 years>18 years>12 years<18 yearsDosevolumeRoute ofadministration*Numberof dosesBoostersYes, when anti-HBsYes, when anti-HBsNo (revaccinationNoNoNoNoNoNoNoNoEvery 10 yearsOne at 15 monthsin 3–5 years)<10 mU/mL<10 mU/mLFig. 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. (5 mg of vaccine every week for 8 weeks) or IM (40 mg of vaccineat weeks 1 and 8) HBV vaccine. The geometric mean peakantibody titer was significantly greater in the ID versus IMgroup: 239 IU/L (95% CI, 131e434) versus 78 IU/L (95% CI,36e168; P 0.001). There was a trend toward longer duration ofseroprotection with ID vaccination. ID vaccine was safe andwell tolerated.10The seroprotection rates vary in relation to the degree ofrenal failure and the amount of vaccine administered; whencompared, it was seen that in all three groups of patients,seroprotection was better when 40 mg of vaccine was used ascompared to 20 mg of vaccine. The Advisory Committee onImmunization Practices recommends a four dose schedule ofrecombinant Engerix B (40 mg) vaccine in renal patients over20 years of age.The current Center for Disease Control (CDC) recommen-dations for vaccination of renal patients over 20 years of agealso specifies a four dose recombinant vaccine schedule of40 mg Engerix B at 0, 1, 2, and 6 months.Anti-HBs titre titer should be checked 1e2 months afteradministration of the last dose of the vaccine series to confirma protective level of anti-HBs (>10 mIU/mL). Persons found tohave anti-HBs levels of <10 mIU/mL after the primary vaccineseries should be revaccinated.For hemodialysis patients, the need for booster dosesshould be assessed by annual antibody to hepatitis B surfaceantigen (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 kidneydisease remains highly recommendable. The sooner they arevaccinated, the better the response. Dose recommendation isfour 40 mg doses of Engerix B.2. InfluenzaInfluenza causes significant mortality and morbidity in thegeneral population, with 20,000 deaths annually. Comparedwith the general population, pulmonary infection kills morepatients on dialysis and mortality rates from sepsis are higher.Patients with ESRD have significantly lower response rates toinfluenza vaccine as compared with healthy control subjectsbut nonetheless have been shown to develop protectiveantibody 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 beenreported in some studies to vary from 7 to 44%, whereasprotection rates (defined as hemagglutination inhibitiontire > 40) in these same studies has ranged from 46 to 93%depending on the dialysis modality and specific strain titermeasured (e.g., H3N2, H1N1, type B).11Despite smaller proportions of patients with ESRD ach-ieving potential antibody levels compared to patients withoutkidney failure (and response varies depending on the partic-ular viral antigen and whether the patient is on peritonealdialysis or hemodialysis), there does appear to be a clinicalbenefit from vaccination.Influenza vaccine response was studied in the first yearafter renal transplantation. The results showed that influenzavaccination was associated with a lower risk of subsequentallograft loss and death. Although this study cannot commenton formation of protective antibodies after vaccination, thesedata do not support withholding vaccination on the basis ofconcerns of adversely affecting allograft function.12In conclusion, influenza vaccination is highly recom-mended among ESRD patients. Antibody titers can be lowerthan those in healthy subjects. However, satisfactory protec-tive rates can be reached by annual vaccination. It is thusrecommended to vaccinate adult ESRD patients against influ-enza each year, using a standard dose (15 mg annually).133. Pneumococcal vaccinationOverall, pulmonary infectious mortality rate is 14-folde16-fold higher in dialysis patients and approximately two-foldhigher in renal transplant recipients compared with the gen-eral population .CKD patients have more severe pneumoniaat admission compared with non-CKD patients. Duringobservational analysis of a prospective cohort of hospitalizedadults with pneumonia, in a tertiary teaching hospital, Strep-tococcus pneumoniae was found to be the most frequentpathogen (28.1 versus 34.7%; P ¼ 0.05). Mortality was higher inpatients with CKD (15.8 versus 8.3%; P < 0.001), while priorpneumococcal vaccination (adjusted odds ratio, 0.05; 95% CI0.005e0.69) and leukocytosis at hospital admission (adjustedodds ratio, 0.10; 95% CI 0.01e0.64) were protective.14The ACIP currently recommends that a single 0.5 mL doseof the 23-valent pneumococcal polysaccharide vaccine beadministered intramuscularly or subcutaneously to all dialy-sis patients 2 years of age or older. More than 75% of dialysispatients have an adequate response to the vaccine, measuredby a two-fold or greater increase in post vaccination antibodytiter and/or a geometric mean greater than 200 ng/mL, buttheir antibody levels are considerably lower than those ofhealthy vaccinated adults.15As compared with healthy adults, patients with advancedCKD and ESRD seem to have reduced responsiveness topneumococcal vaccination, although findings have beeninconsistent across studies. Patients who have kidney diseaseand are vaccinated with the pneumococcal vaccine seem todevelop different serotype-specific titers, develop lower levelsof antibody titers, and have a more rapid loss of antibody titersas compared with healthy control subjects. During a study ofCKD 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 bya rapid decline in antibody level within 6 months.16Pneumococcal conjugate vaccine is immunogenic in renaltransplant recipients and, for certain serotypes, demonstratesa trend toward greater immunogenicity by quantitative anti-body measurements, compared with polysaccharide vaccine.However, when assessed using functional antibody responseby OPA, there does not appear to be a substantial differencebetween the two vaccines. Overall response rates were gen-erally suboptimal for both groups, but this could potentially beovercome with repeat dosing schedules or, perhaps, higherdoses of vaccine.17Another strategy would be to use conjugatevaccine to prime the immune system and then give a boostera p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 2 9 e3 532
  6. 6. dose of the polysaccharide vaccine. This may result in an evengreater response than a single vaccine dose and has shownpromise in other groups of immunocompromised patients.Further studies of transplant recipients are required todetermine an optimal vaccination strategy. In conclusion,pneumococcal vaccine is recommended for all patients withCKD, but the role of polysaccharide and conjugate vaccinesneed to be better defined for optimal protection.4. Diphtheria and tetanus vaccination(tetanus and diphtheria toxoids)Children on dialysis should receive the diphtheria and tetanustoxoids and pertussis (DTaP) vaccine as recommended forhealthy children. Booster doses of tetanus-diphtheria toxoids(Td) should follow every 10 years after completing the primaryseries. Like other vaccines even after diphtheria and tetanusvaccination, seroconversion rate has been shown to be lower indialysis patients than in healthy subjects.5A short-term studyshowed that tetanus vaccination (with booster injection) in HDpatients led to 96.5% of seroconversion rate (>0.06 HU/ml), butantibodies rapidly declined after 6 months. In one study, theimmunological status after tetanus (40 UI) and diphtheria (4 UI)toxoid vaccination was tested among 21HD patients withoutprotection before vaccination. Five years after the vaccination,15 patients (71%) had a protective antibody level for tetanusand 7 (33%) for diphtheria. In conclusion, diphtheria and teta-nus infections can be prevented by using vaccines in ESRDpatients. However, because of impaired seroconversion rates,monitoring of antibody levels is recommended and a boostermay be used in non-responding patients.185. Measles, mumps, and rubella vaccineThe measles, mumps, and rubella (MMR) vaccine should begiven to all children, including those on dialysis, between12 and 15 months of age, with a booster dose between 4 and6 years of age. Among healthy children, the seroconversionrate for one dose of MMR vaccine is more than 90%. For chil-dren on dialysis, the seroconversion rate for all three antigensis approximately 30%, for mumps alone 50%, and for measlesand rubella combined 80%. Therefore some have suggestedchildren on dialysis may benefit from post vaccination testingto assess seroconversion.19It is recommended to assess the seroconversion aftervaccination (standard doses) among these patients. For adultpatients, one single dose should be used.6. Haemophilus influenza type B conjugatevaccineThere is limited information on the use of Haemophilus influ-enza type B (Hib) vaccine in children on chronic dialysis. TheACIP recommends the vaccine for these patients beginning at2 months of age using the same dosage and schedules used forhealthy children and adults.5The vaccine is safe: a study ofchildren on continuous ambulatory peritoneal dialysis hasshown seroconversion rates of 90%, with a persistence ofimmunity for 22 months after vaccination.207. Oral poliovirus vaccineThere are no data discussing the use of oral poliovirus vaccine(OPV) in children undergoing dialysis. However, because ofa theoretical risk that they will not be able to effectively limitthe replication of the vaccine virus, OPV should not be used toimmunize immunocompromised children, including childrenon dialysis. Also OPV should not be used on household mem-bers or health care staff in close contact with these patients.58. Inactivated poliovirus vaccineInactivated poliovirus vaccine is only recommended for specificgroups of persons, including ESRD patients. The efficiency andsafety of inactivated poliovirus vaccine was assessed in 49chronic dialysis patients, resulting in 86% of patients havingsufficient antibody levels.219. Varicella vaccineChildren 1 year or older on dialysis who have not had chick-enpox previously should receive one subcutaneous dose of thevaricella vaccine as recommended by the ACIP for healthychildren 13 years of age or younger.5Due to the high risk of complications and death associatedwith chickenpox infection in adulthood, susceptible adoles-cents and adults should receive two doses of the varicellavaccine subcutaneously, with the second injection at least4 weeks after the first. Among patients undergoing dialysis,data on the immunogenicity of the varicella vaccine arelimited. A recent report, however, showed that up to 85% ofchildren 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 theseroconversion rate among healthy children. The varicellavaccine has been reported to be safe for children on dialysis,with no systemic adverse reactions reported.2210. Hepatitis A vaccineData on hepatitis A vaccination in hemodialysis patients islimited. Hepatitis A virus (HAV) vaccination in ESRD patientsis well tolerated and immunogenic .The Advisory Committeeon Immunization Practices (ACIP) recommends using thestandard dose and schedule in adult ESRD patients of Havrixat 0 and between 6 and 12 months.23For ESRD patients older than 12 years, available guidelinesrecommend two doses of 0.5 ml with no booster doses. Weberet 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 thoseobserved in healthy subjects. There was a tendency to higherGMT in the group who received the vaccine subcutaneously.24a 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. 7. Another study showed that this HA vaccine has goodimmunogenicity compared with the HB vaccine and that thestandard three doses of HA vaccine given at 0, 1 and 6 monthsare safe and effective even in HD patients.11. Inactivated vaccines and toxoidsAll inactivated vaccines and toxoids are safe and effectivewhen used in dialysis patients, and should be administeredto children and adults on chronic dialysis using the samedoses and schedules recommended for immunocompetentpersons.512. Contraindicated vaccinesMany vaccines have been used for years in ESRD populations.However, some vaccines are still contraindicated in thesepatients. Live vaccines (yellow fever, polio, varicella and MMRvaccines) are generally avoided because they present a theo-retical risk of vaccine-induced infection. However, severalstudies investigated the efficacy and safety profiles for some ofthese vaccines (varicella and MMR vaccines) in ESRD patients,with success. In contrast, oral poliovirus should not be used inESRD and RT patients. ESRD patients who need polio vacci-nation should receive the inactivated poliovirus vaccine.1313. SummaryIn summary, patients with CKD, on dialysis, or followinga kidney transplant are immunocompromised, and infectionis a major concern. It appears that there are no added risks toimmunization with non-live vaccines, and there is the po-tential for deriving benefit in terms of reductions in cost andhospitalizations.Pediatric patients on dialysis should receive all the vac-cines currently recommended by the ACIP and the AAP forhealthy children, except the oral polio vaccine. Adult patientsshould receive the hepatitis B vaccine series, pneumococcalvaccine, yearly influenza vaccinations, tetanus-diphtheriatoxoids, and varicella vaccine, if they are susceptible.Vaccines are well tolerated by these patients, but higherdoses and/or additional boosters may be required periodicallyto adequately protect dialysis patients from vaccine-pre-ventable diseases.Although both children and adults on dialysis may show animpaired 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 seriouscomplications from vaccine-preventable diseases. Because theprotection these vaccines provide may be incomplete or tran-sient, infection control strategies at hospitals and other healthcare facilities should be implemented simultaneously. Healthcare providers are encouraged to assess each patients need forvaccinations individually and formulate immunization strat-egies early in the course of progressive renal disease, ideallybefore the patient requires dialysis.Conflicts of interestAll authors have none to declare.r e f e r e n c e s1. National Kidney Foundation. K/DOQI clinical practiceguidelines for chronic kidney disease: evaluation, classification,and stratification. Am J Kidney Dis. 2002;39(2 suppl 1).2. Rajapurkar MM, John GT, Kirpalani AL, et al. What do weknow about chronic kidney disease in India: first report of theIndian CKD registry. BMC Nephrol. 2012;13:10.3. Sarnak MJ, Jaber BL. Mortality caused by sepsis in patientswith end-stage renal disease compared with the generalpopulation. Kidney Int. 2000;58:1758e1764.4. Dalrymple Lorien S, Go Alan S. Epidemiology of acuteinfections among patients with chronic kidney disease. Clin JAm Soc Nephrol. 2008;3:1487e1493.5. 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Intradermal versus intramuscular hepatitis B vaccinationin hemodialysis patients: a prospective open-labelrandomized controlled trial in nonresponders to primaryvaccination. Am J Kidney Dis. 2009;54:95e103.11. Vogtlander NP, Brown A, Valentijn RM, et al. Impairedresponse rates, but satisfying protection rates to influenzavaccination in dialysis patients. Vaccine.2004;22:2199e2201.12. Hurst Frank P, Lee Jessica J, Jindal Rahul M. Outcomesassociated with influenza vaccination in the first yearafter kidney transplantation. Clin J Am Soc Nephrol.2011;6:1192e1197.13. Rangel, Coronado VG, Euler GL, et al. Vaccinerecommendations for patients on chronic dialysis. TheAdvisory Committee on Immunization Practices and theAmerican Academy of Paediatrics. Semin Dial.2000;13:101e107.14. Viasus Diego, Garcia-Vidal Carolina, Josep M, et al.Epidemiology, clinical features and outcomes of pneumoniain patients with chronic kidney disease. Nephrol DialTransplant. 2011;26(9):2899e2906.15. Kytel MW, Dailey MP, Schiffman G, et al. Pneumococcalvaccine immunization of patients with renal impairment.Proc Soc Exp Biol Med. 1986;182:468e473.16. Fuchshuber A, Kuhnemund, Keuth B. Pneumococcal vaccinein children and young adults with chronic renal disease.Nephrol Dial Transplant. 1996;11:468e473.a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 2 9 e3 534
  8. 8. 17. Chan CY, Molrine DC, George S, et al. Pneumococcalconjugate vaccine primes for antibody responses topolysaccharide pneumococcal vaccine after treatment ofHodgkin’s disease. J Infect Dis. 1996;173:256e258.18. Kruger S, Muller-Steinhardt M, Kirchner H, et al. A 5-year follow-uponantibodyresponseafterdiphtheriaandtetanusvaccinationin hemodialysis patients. Am J Kidney Dis. 2001;38:1264e1270.19. Schulman SL, Deforest A, Kaiser BA, Polinsky MS, Baluarte HJ.Response to measles-mumps-rubella vaccine in children ondialysis. Pediatr Nephrol. 1992;6:187e189.20. Neu AM, Lederman HM, Warady BA, Fivush BA. Haemophilusinfluenza type b immunization in infants on peritonealdialysis. Pediatr Nephrol. 1996;10:84e85.21. Sipila R, Hortling L, Hovi T. Good seroresponse to enhanced-potency inactivated poliovirus vaccine in patients on chronicdialysis. Nephrol Dial Transplant. 1990;5:352e355.22. Zamora I, Simon JM, Da Silva ME, Piqueras AI. Attenuatedvaricella virus vaccine in children with renal transplants.Pediatr Nephrol. 1994;8:190e192. 199.23. Fleischmann EH, Kruppenbacher J, Bock HL, et al. Activeimmunization against hepatitis A in dialysis patients. NephrolDial Transplant. 2002;17:1825e1828.24. Kuramoto I, Fujiyama S, Matsushita K. Immune responseafter hepatitis A vaccination in haemodialysis patients:comparison with hepatitis B vaccination. J GastroenterolHepatol. June 1994;9(3):228e231.a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 2 9 e3 5 35
  9. 9. Apollohospital: