Kidney CaseCJASN Conference: ePress. Published on July 1, 2019 as doi: 10.2215/CJN.02210219 How I Treat

Vaccinating the Patient with ESKD

Sana F. Khan and Brendan T. Bowman CJASN 14: ccc–ccc, 2019. doi: https://doi.org/10.2215/CJN.02210219

Introduction panel. The patient is irate about faulty vaccinations, Infections account for 8% of the total mortality in ESKD stating he was told his recent vaccination would help Division of patients (1). ESKD patients are at increased risk of prevent B infection, not cause it. Detailed Nephrology, infectious complications due to their immunosuppressed information from the patient’s dialysis unit revealed University of Virginia Health System, status. Metabolic complications of uremia cause ab- administration of booster dose 2 weeks Charlottesville, normalities in monocyte and neutrophil function, as prior to admission. Virginia well as antigen processing, formation and cell mediated immune responses (2). The effects on Correspondence: vaccine efficacy include lower seroconversion rate, Overview of Special Recommendations in the Dr. Sana F. Khan, lower peak antibody titers and faster decline in ESKD Population Division of Nephrology, antibody titers. Consequently, the Centers for Disease Current guidelines on vaccination practices recom- University of Virginia Control and Prevention (CDC) in the United States has mend annual vaccination with seasonal influenza vaccine, Health System, summarized recommendations from the Advisory unless contraindicated (prior history of Guillain–Barre Box 800133, Committee on Immunization Practices (ACIP), and syndrome within 6 weeks of prior dose of influenza Charlottesville, VA issued specific guidelines for vaccinations in ESKD vaccine) (4). Several formulations of the inactivated 22908. Email: sk4yp@ virginia.edu patients. Additionally, the CDC provides updated influenza virus are approved for use: standard dose recommendations via the Morbidity and Mortality (15 mg hemagglutinin) quadrivalent (four influenza Weekly Report. Besides age appropriate vaccine rec- strains) and trivalent (three influenza strains) inacti- ommendations, augmented vaccination regimens have vated influenza virus, high dose (60 mg hemagglutinin) been detailed for hepatitis B, pneumococcus and in- trivalent inactivated influenza virus and adjuvanted fluenza vaccines, in an effort to boost immune re- standard dose trivalent inactivated influenza virus. activity and prolong the vaccines’ protective effects (3). A vaccine containing recombinant hemagglutinin is We explain specific hepatitis B and influenza guide- also available. There are no official recommendations lines and gaps in knowledge around their application regarding choice of vaccine specific to ESKD patients. to patients with ESKD via the following cases. Box 1 Small studies have shown improved seroconversion summarizes the recommendations for these immuni- rates with adjuvanted vaccine use (5). There is cur- zation protocols (Figure 1). rently no data regarding recombinant influenza vac- cine in dialysis patients. Similarly, there are no head to head trials of standard dose inactivated influenza Patient 1 fl A 58-year-old female with ESKD contacts the dial- virus versus high dose inactivated in uenza virus. ysis unit to inform the staff she will not be attending However, a recent retrospective study suggested high fl treatment today. The patient reports she presented to dose trivalent inactivated in uenza virus was associ- the emergency department over the weekend with ated with a modest reduction in hospitalization rates fever, cough and cold symptoms 336 hours. The compared with standard dose trivalent and quadriva- patient is diagnosed with influenza A by rapid PCR lent vaccines (6). Unfortunately, studies of inactivated fl testing and was prescribed oseltamivir 30 mg post- in uenza virus are limited by either small samples dialysis for 5 days. You review the patient’s immu- evaluating only seroconversion or by retrospective nizations at dialysis and note she received the designs vulnerable to residual confounding. In addi- fl standard 15 mgtrivalentinfluenza vaccine 2 months tion, seasonal changes in the overall inactivated in u- fi prior as part of unit wide vaccination protocol. enza virus ef cacy due to antigenic drift make comparisons of vaccine types across various flu sea- sons challenging. Patient 2 Current ACIP guidelines recommend hepatitis B A 65-year-old male with ESKD is admitted to the vaccination series for all ESKD patients, preceded hospital for a diabetic foot ulcer. Routine hospital by serologic testing and followed by post vaccina- testing for hepatitis B surface antigen (HBsAg) is tion confirmation of immunity (7). Serologic testing positive, and the patient is dialyzed with isolation consists of hepatitis B surface antigen (HBsAg), anti- practices while awaiting results of an acute hepatitis B bodies to hepatitis B surface antigen (anti-HBs), and www.cjasn.org Vol 14 October, 2019 Copyright © 2019 by the American Society of Nephrology 1 2 CJASN

Figure 1. | Recommended ESKD specific influenza and hepatitis B immunization guidelines. IIV, inactivated influenza vaccine; IM, intramuscular; RIV, recombinant influenza vaccine. to hepatitis B core antigen (anti-HBc). Currently, high dose versus adjuvanted type are sorely needed to one of two single recombinant antigen vaccines are admin- optimize care for this most vulnerable population. We istered intramuscularly in ESKD patients, with a three or recommend continued encouragement for patients regard- four dose series of double antigen dose (40 mg) depending ing adherence to vaccination schedules and counseling that on the formulation. Alternatively, an adjuvanted recombi- vaccine efficacy varies from year to year. For patient 1, in nant can administered in a two-dose addition to oseltamivir, we require flu-positive patients to series. Current recommendations are for postvaccination wear a droplet mask for 7 to 10 days post diagnosis—the serologic testing at 1–2 months after completion of the approximate duration of viral shedding, in hopes of re- primary series. Anti-HBs levels .10 mIU/ml are noted to ducing intra-facility transmission. be protective per CDC guidelines. A second hepatitis B Turning to hepatitis B vaccinations, patient 2 illustrates a vaccination series should be administered in patients with familiar scenario in which a patient receives hepatitis B anti-HBs ,10 mIU/ml after the primary vaccine series. serologic testing in close temporal proximity to vaccination Patients without protective levels of anti-HBs are screened resulting in a positive HBsAg test. Most often this occurs in for HBsAg monthly. Responders to the vaccine series have admitted patients where protocols dictate routine hepatitis anti-HBs levels monitored annually with one booster dose B screening, or in outpatient dialysis clinics due to mis- (40 mg recombinant hepatitis B) administered if anti-HBs is timed lab draws. Transient HBsAg positivity is a known ,10 mIU/ml (7). There are currently no recommendations consequence of vaccination and resolves in approximately regarding monitoring HBsAg in vaccine responders, and 20 days (10). In this situation, we obtain a rapid hepatitis B there have been reports of false negative HBsAg, as well as viral load test to confirm the likely false positive result, as reverse seroconversion (8,9). was the situation with patient 2. While awaiting testing results, patients are dialyzed on a dedicated machine, which is terminally cleaned following use. Most inpatient Our Practice laboratories provide hepatitis B viral load testing knowing Since 2015, our program has provided high dose influ- this is required for discharge placement in a dialysis unit. enza vaccine in all adult patients with ESKD, regardless of In outpatient units, there are no guidelines as to whether age. This policy is informed by the concept of ESKD as an these patients should be dialyzed in hepatitis B isolation immune-suppressed state and high rates of confirmed or among the unit population, especially given the high influenza within our centers during the 2013–2014 flu likelihood of a false positive result. Pending a negative viral season despite 90% of patients receiving standard dose load test, we dialyze these patients in hepatitis B isolation vaccine (national average 71.3% (1)). As with many topics rooms; however, the room is thoroughly disinfected, the in ESKD, data providing clear direction for medical patient has a dedicated machine and no other known directors remains elusive. Trials illustrating the relative hepatitis B confirmed patients are run concurrently. We feel efficacy of standard dose inactivated influenza virus versus this approach best balances the risk of exposing the general CJASN 14: ccc–ccc, October, 2019 Vaccinating the Patient with ESKD, Khan and Bowman 3

population to a potential true infection while protecting the influenza vaccines in patients with chronic kidney affected patient from infection from known hepatitis B disease undergoing hemodialysis: MF59-adjuvanted versus non-adjuvanted vaccines. Hum Vaccin Immunother infected patients. 12: 2902–2908, 2016 6. Miskulin DC, Weiner DE, Tighiouart H, Lacson EK Jr, Meyer KB, Disclosures Dad T, Manley HJ: High-Dose seasonal influenza vaccine in Dr. Bowman and Dr. Khan have nothing to disclose. patients undergoing dialysis. Clin J Am Soc Nephrol 13: 1703–1711, 2018 References 7. Schillie S, Vellozzi C, Reingold A, Harris A, Haber P,Ward JW, 1. United States renal data system. 2018 Annual Report. Available Nelson NP: Prevention of infection in the at: https://www.usrds.org/2018/view/v2_05.aspx. Accessed United States: Recommendations of the advisory MMWR Recomm February 17, 2019 committee on immunization practices. Rep 2. Hauser AB, Stinghen AE, Kato S, Bucharles S, Aita C, Yuzawa 67: 1–31, 2018 Y, Pecoits-Filho R: Characteristics and causes of immune 8. Foy MC, Thio CL, Hwang HS, Saulynas M, Hamilton JP, Fine DM, dysfunction related to uremia and dialysis. PeritDialInt28 Atta MG: False-negative hepatitis B virus (HBV) surface antigen [Suppl 3]: S183–S187, 2008 in a vaccinated dialysis patient with a high level of HBV DNA in Clin Vaccine Immunol 3. Guidelines for vaccinating kidney dialysis patients and the United States. 19: 820–822, 2012 patients with chronic kidney disease. Recommendations of 9. Rhea S, Moorman A, Pace R, Mobley V, MacFarquhar J, Robinson the Advisory Committee on Immunization Practices E, Hayden T, Thai H, Drobeniuc J, Brooks JT, Moore Z, Patel PR: (ACIP).Available at: https://www.cdc.gov/dialysis/pdfs/vacci- Hepatitis B reverse seroconversion and transmission in a hemo- nating_dialysis_patients_and_patients_dec2012.pdf. Accessed dialysis center: A public health investigation and case report. Am J Kidney Dis February 17, 2019 68: 292–295, 2016 4. Grohskopf LA, Sokolow LZ, Broder KR, Walter EB, Fry AM, 10. Lacson E, Teng M, Ong J, Vienneau L, Ofsthun N, Lazarus JM: Jernigan DB: Prevention and control of seasonal influenza Antibody response to Engerix-B and Recombivax-HB hepatitis B Hemodial Int with vaccines: Recommendations of the Advisory Committee vaccination in end-stage renal disease. 9: 367–375, on Immunization Practices-United States, 2018-19 Influenza 2005 season. MMWR Recomm Rep 67: 1–20, 2018 5. Noh JY,Song JY,Choi WS, Lee J, Seo YB, Kwon YJ, Ko GJ, Cha DR, Published online ahead of print. Publication date available at Kang YS, Lee YK, Cheong HJ, Kim WJ: Immunogenicity of trivalent www.cjasn.org.