Risk Factors for Loss of Varicella Immunity After Pediatric Kidney Transplantation

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Soni, Santhosh Nadipuram, James Mirocha, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6866072/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 13 Nov, 2025 Read the published version in Pediatric Nephrology → Version 1 posted 5 You are reading this latest preprint version Abstract Background: Varicella zoster (VZV) vaccination pre-kidney transplant (Tx) can help prevent severe disseminated VZV in immunosuppressed recipients, however, studies have shown loss of humoral immunity post-Tx. Methods: A retrospective analysis of 45 pediatric kidney Tx recipients with positive pre-Tx VZV IgG (>1.09 index). VZV IgG was assessed annually and compared with the induction agent used, number of VZV vaccines received, and the interval between the last dose of VZV vaccine and Tx. Results: Median age at Tx was 16.7 years (IQR 12.7-18.5). 11 of 45 (24.4%) patients lost immunity to VZV at a median of 12.6 months post-Tx. Those who lost VZV immunity were younger at the time of Tx, 12.4 years vs. 17.3 years (P=0.05) and more likely to be on steroid-based immunosuppression 81.8% vs. 32.4% (P=0.006). There were no differences between the induction agents used and the ability to maintain VZV IgG antibodies. Subjects who required ³3 doses of VZV vaccine to develop VZV IgG seropositivity were at a higher risk for losing their anti-varicella antibody post-Tx (HR 3.81, 95%CI 1.09-13.30, P=0.04). Receiving VZV vaccination <1 year prior to kidney Tx was associated with a higher risk for losing anti-varicella antibody after Tx (HR 6.97, 95%CI 2.08-23.34). Conclusion: In this small cohort, pediatric kidney Tx recipients are more likely to lose VZV IgG in those who were younger at the time of Tx, on steroid-based immunosuppression, required 3 or more doses of VZV vaccination to seroconvert, or received VZV vaccine <1 year before Tx. Infection Pediatric Seroconversion Transplant Varicella Zoster Immunosuppression Figures Figure 1 Introduction Guidelines for vaccination of solid organ transplant candidates advise every effort should be made to ensure completion of recommended pre-transplant vaccines prior to surgery, as immunosuppressed transplant recipients are at higher risk for invasive disease and are less likely to produce as robust immune response to vaccines compared to those who are not immunocompromised [ 1 – 3 ]. With gaps in herd immunity secondary to a lack of or incomplete vaccination in the community, the risk for exposure to vaccine-preventable pathogens increases [ 4 , 5 ]. In a multi-center retrospective study of pre-kidney transplant vaccination coverage among 254 European children, unvaccinated children were four-times more likely to acquire a vaccine-preventable illness post-transplant compared to those who were vaccinated [ 6 ]. Post-transplant vaccine-preventable infections have also shown to be associated with morbidity, mortality, and higher costs. A retrospective study of 6980 children across 45 pediatric transplant centers in the United States found more than 15% of solid organ transplant recipients were hospitalized with a vaccine-preventable illness in the first 5 years after transplant, with 1.7% mortality, and costing $ 120,498 more than transplant-related hospitalizations not associated with vaccine-preventable infections [ 7 ]. Furthermore, the authors of this study noted 2.1% of hospitalizations in the first 5 years after pediatric solid organ transplant were due to varicella zoster (VZV) infections – a rate similar to the cohort admitted for illnesses due to pneumococcus (2.0%) and respiratory syncytial virus (1.8%) [ 7 ]. The efficacy of the recommended 2-dose varicella vaccine among the general pediatric population ranges between 94–98% [ 8 , 9 ]. Vaccination against VZV and monitoring for antibody response among kidney transplant candidates can help prevent severe disseminated VZV disease after transplantation. Despite confirmation of serologic response to vaccinations pre-transplant, studies have shown loss of humoral immunity post-transplant, putting recipients at risk for VZV infection and its associated morbidity and mortality. In a retrospective single center study of 18 pediatric solid organ transplant recipients with confirmed VZV seropositivity prior to transplant, 11.1% of the cohort lost their anti-varicella antibody within 6 months following transplant [ 10 ]. Broyer et al. noted that among 97 children who received VZV vaccination prior to kidney transplantation, 7% had negative VZV immune globulin G (IgG) at 1-year; this number increased to 24% at 5-years post-transplant [ 11 ]. While some studies in adult kidney transplant recipients found 100% VZV IgG positivity up to 1080 days after transplant, some studies mirror the findings in pediatric research with declining rates of VZV IgG seropositivity [ 12 – 16 ]. Potential influences for losing VZV immunity include the age at the time of transplant, the number of VZV vaccines received prior to transplantation, and the time interval between VZV vaccination and transplant [ 17 – 20 ]. In this study, we assessed the potential risk factors that could contribute to the maintenance of or loss of VZV immunity after pediatric kidney transplantation: 1) Induction agent used. 2) Number of VZV vaccines received prior to transplant. 3) Interval between last dose of VZV vaccine and transplantation. Methods Patient Population This is a single center retrospective observational study of 45 pediatric patients aged 2–20 years who received a kidney transplant between April 2018 through September 2023. All recipients who received pre-transplant varicella vaccination with documentation of subsequent positive VZV IgG (> 1.09 index) and received post-transplant VZV IgG monitoring were included in the study. Patients received induction immunosuppression with a lymphocyte-depleting agent (LDA; anti-thymocyte globulin (ATG) or alemtuzumab) or a non-lymphocyte-depleting agent (NLDA; basiliximab) and were maintained on mycophenolate mofetil, tacrolimus, with or without steroids. No subjects had a history of natural VZV infection before or after kidney transplant. Median follow-up duration was 14.9 months post-transplant (IQR 11.9–32.0 months). VZV IgG Testing Pre-transplant VZV IgG, determined by enzyme immunoassay, was assessed at the initial pre-transplant evaluation and reassessed every 2 years until transplant. Those who were seronegative at any point prior to transplant received an additional VZV vaccine and VZV serology was repeated at least 4 weeks following vaccination; a maximum of 4 doses of VZV vaccine was given per patient. Post-transplant VZV IgG monitoring was performed every 6–12 months post-transplant. VZV IgG was considered positive when the value was > 1.09 index. Equivocal titers (0.91–1.09) were considered negative in our analysis. Statistical Analysis Numerical variables were summarized by median and interquartile range (IQR) and were compared across groups by the Wilcoxon rank sum test. Categorical variables were summarized by frequency and percentage and were compared across groups by the Fisher exact test. Freedom from loss of VZV IgG was estimated by the Kaplan-Meier method and group differences were assessed by the log-rank test. Hazard ratios (HR) and their 95% confidence intervals (CI) were obtained from Cox proportional hazards models. A two-sided 0.05 significance level was used throughout. SAS version 9.4 (SAS Institute, Cary, North Carolina) was used for statistical calculations. This study was approved by the Cedars-Sinai Medical Center Institutional Review Board (STUDY00000398). This study was conducted in accordance with ethical guidelines based on federal regulations and the common rule. Cedars-Sinai Medical Center also has a Federal Wide Assurance. Results A total of 45 subjects received pre-transplant varicella vaccination with confirmation of seroconversion prior to kidney transplantation and received post-transplant VZV IgG monitoring starting at 6–12 months following surgery – this represented 100% of pediatric renal transplants performed at our center during the study’s inclusion period. Median age at transplant was 16.7 years (IQR 12.7–18.5), 64.4% were males, 64.4% were Hispanic, 88.9% received a deceased-donor renal transplant, and 13.3% were highly sensitized (PRA > 30%). Comparison of patient characteristics among those who maintained post-transplant VZV immunity (n = 34) vs. those who lost immunity (n = 11) is highlighted in Table 1. Notably, those who lost VZV immunity were younger at the time of transplant, 12.4 years (IQR 3.9–17.4) vs. 17.3 years (IQR 13.4–19.0) (P = 0.05), and more likely to be on steroid-based immunosuppression, 9 (81.8%) vs. 11 (32.4%) (Table 1, P = 0.006). Median time between confirmation of positive pre-transplant VZV IgG testing and transplant was 8.8 months (IQR 4.8–13.6), and there was no difference between the pre-transplant VZV IgG titers between the group who lost immunity vs. those who maintained their VZV IgG after transplantation, 1.7 index (IQR 1.3–3.4) vs. 1.9 index (IQR 1.6–2.6), respectively (Table 2, P = 0.99). Median time to negative post-transplant VZV IgG was 12.6 months (IQR 8.8–14.9) compared to last VZV serological testing in those that maintained immunity was 22.8 months (IQR 12.0-33.9) (Table 2, P = 0.07). There were no differences in the WBC count at the time of last post-transplant VZV IgG testing (Table 2, P = 0.92). Induction Agent Used There were no differences between the induction agents used among those who maintained vs. lost post-transplant VZV IgG immunity (Table 1). Nine of 11 subjects (81.8%) who developed negative VZV IgG post-transplants received a lymphocyte-depleting agent compared to 29 of 34 patients (85.3%) among those whose immunity persisted (P > 0.99). Number of VZV Vaccines Received Prior to Transplant A majority of the patients received two doses of VZV vaccine prior to transplantation (75.6%); 2 subjects (4.4%) received only one dose of VZV vaccine, while 7 (15.6%) and 2 (4.4%) received three and four doses, respectively (Table 2). There is an increased risk for losing VZV seropositivity after transplant among those who required 3 or more doses of VZV vaccine in order to seroconvert prior to transplantation (HR 3.81, 95%CI 1.09–13.30, P = 0.04). Interval Between Last Dose of VZV Vaccine and Transplant Time interval between last VZV vaccine dose and transplant was shorter among those who lost VZV immunity compared to those who maintained positive VZV IgG levels, 10.7 months (IQR 4.4–98.2) vs. 103.9 months (IQR 42.6-151.5) (Table 2, P = 0.02). Freedom from loss of VZV IgG up to 83 months following transplantation was compared based on the time interval between the last VZV vaccination and transplant (< 1 year vs. ≥1 year) (Fig. 1 ). Six of 10 (60%) of those who received their last VZV vaccine < 1 year before transplantation lost their post-transplant VZV IgG seropositivity compared to 5 of 35 (14.3%) of those who were vaccinated ≥1 year prior (Table 2). Receiving VZV vaccination < 1 year prior to kidney transplantation was associated with a higher risk for losing VZV immunity post-transplant (Fig. 1 ; HR 6.97, 95% CI 2.08–23.34). Furthermore, over a follow-up time of 3 years, 70.4% develop negative VZV IgG when vaccinated < 1-year preceding transplantation compared to 20.0% in the cohort vaccinated ≥1 year earlier (Fig. 1 , P = 0.0003). Post-Transplant Varicella Infection: Despite 24.4% of our post-transplant patients losing immunity to VZV, none of these patients developed VZV infection during the median follow-up period of 14.9 months (IQR 11.9–32.0 months). Discussion Among our pediatric kidney transplant cohort with serologic response to VZV vaccination and no history of natural VZV infection before transplantation, 24.4% recipients lost humoral immunity at a median time of 12.6 months post-transplant. Similar findings on the risk for loss of VZV IgG seropositivity are highlighted in several studies. Broyer et al. noted among 94 pediatric patients who received VZV immunization prior to kidney transplantation, 7% and 24% had negative VZV IgG antibodies at 1- and 5-years post-transplant, respectively [ 11 ]. A meta-analysis on the seroprevalence of VZV IgG antibody in kidney transplant recipients illustrated varying VZV IgG durability post-transplant, ranging from 23%-100% VZV IgG positivity between 657–2130 days following transplantation [ 12 ]. In a study of 18 pediatric solid organ transplant patients (8 liver, 6, kidney, 4 heart) with seropositivity of VZV IgG antibodies pre-transplant, 11% had undetectable VZV antibody titers within 6-months post-transplant [ 10 ]. Among pediatric liver transplant recipients, 42 of 67 (63%) who received VZV vaccine prior to transplantation were non-immune to VZV at a median time of 3.3 years after transplantation [ 17 ]. We found no differences in the induction immunosuppression received between those who maintained or lost VZV IgG following transplant. Patients who were maintained on steroid-based immunosuppression, however, were more likely to lose anti-varicella antibody at a median time of 13.0 months (IQR 10.3–20.1) post-transplant. In contrast, highly sensitized recipients (panel of reactive antibodies > 30%) all of whom received desensitization with a combination of plasmapheresis, IVIg, rituximab, and/or tociluzimab no more than 6 months prior to transplantation, did not appear to be at higher risk for losing VZV IgG antibody despite intensified immunosuppression going into transplant. It is important to note, however, that the highly sensitized patients do receive IVIg the day of and within a week following transplant, which could have provided additional VZV IgG. Although our cohort only had two patients who were treated for rejection before the loss of VZV IgG antibody, we could not statistically assess the correlation between treatment for rejection and risk for loss of VZV IgG seropositivity. The findings in our highly sensitized cohort could suggest the risk following intensified immunosuppression for allograft rejection is low. In a multicenter prospective study involving pediatric liver and kidney transplants, Barton et al. noted that while VZV IgG antibodies tended to be lower during periods of higher immunosuppression, the antibody levels remained protective [ 18 ]. Furthermore, one patient received a steroid pulse for treatment of acute rejection without subsequent decline in their VZV IgG titer [ 18 ]. While a majority (75.6%) of our cohort received 2 doses of VZV vaccine prior to transplantation, 4.4% received only 1 dose and 20.0% received 3 or more doses. Interestingly, those that received more doses than the standard childhood 2-dose VZV series, were more likely to lose their VZV seropositivity following transplantation. Current recommendation from the Advisory Committee on Immunization Practices and Centers for Disease Control is a 2-dose VZV vaccine series due to that finding that a second dose of VZV vaccine produced a more robust antibody level compared to 1-dose, and decreased the rate of breakthrough varicella infection by 3.3-fold [ 21 ]. Nonetheless, primary vaccine failure after the 2-dose series is possible, necessitating an additional booster dose [ 22 ]. While the most likely cause of primary vaccine failure in our population are factors inherent to the immune response of the recipient, this could potentially also translate to a reason for the less durable VZV seroprotection in those requiring additional booster dose(s) [ 23 ]. The interval between the last dose of VZV vaccine and transplantation appears to influence the durability of VZV IgG following transplant. Our cohort revealed the threshold of 1 year from last vaccine to transplant was independently and significantly associated with maintenance of immunity against VZV [ 17 ]. The authors hypothesized that the intensified immunosuppression immediately post-transplant could hinder the development of VZV immunity for those who had not yet mounted a full immune response following vaccination, potentially due to the short time interval between vaccination and transplantation [ 17 ]. Interestingly, a meta-analysis of adult transplant studies noted some cohorts had 100% seropositivity even up to 1080 days post-transplant [ 12 ]. This raises the question of whether natural infection provides better VZV IgG durability compared to vaccination, as the adult cohorts are more likely to have had natural infection due to the lack of VZV vaccine during their childhood. There are several limitations in our study, with one attributed to the small cohort of 45 patients, which raises the possibility for type 2 error. Post-transplant VZV IgG were checked at approximate defined timepoints, which may not accurately reflect the exact timing to loss of VZV IgG following transplantation. While none of our patients who lost their VZV immunity developed VZV infection despite being on immunosuppression, loss of VZV IgG may not lead to complete loss of VZV immunity, as viral-specific T-cell (Tc) responses could still be intact and provide some degree of immune protection [ 15 , 24 – 27 ]. Future studies should evaluate VZV Tc and the clinical course in those who have and have not maintained post-transplant VZV IgG following pre-transplant VZV vaccination. Conclusions Pediatric kidney transplant recipients are at risk for losing VZV IgG seropositivity after transplantation. Post-transplant VZV serologies should be serially monitored to identify patients at high risk for disseminated VZV. Identifying these patients is important to counsel families on post-exposure prophylaxis or need for immediate treatment should any symptoms arise. Given the risk for losing VZV IgG, close contacts should make sure they are up to date on vaccines to help provide herd immunity. Despite strategies for post-exposure prophylaxis and treatment of VZV infection in solid organ transplant recipients, it does not offer complete protection against the morbidity and mortality associated with VZV disease in the immunocompromised. Further research should be directed at evaluating VZV cellular immunity and determining strategies to provide protection against VZV among pediatric kidney transplant recipients who lose their pre-transplant vaccine-induced humoral immunity. Abbreviations ATG: anti-thymocyte globulin IgG: immune globulin G LDA: lymphocyte depleting agent NLDA: non-lymphocyte depleting agent Tc: T-cell VZV: Varicella zoster WBC: white blood cell Declarations The authors confirm contribution to the paper as follows: study conception and design: HP, JM, JG, SH, PRS, SN, DP; data collection: HP, JG, SH, DP; analysis and interpretation of results: HP, JM, JG, SH, PRS, SN, DP; draft manuscript preparation: HP, JM, JG, SH, PRS, SN, DP. All authors reviewed the results and approved the final version of the manuscript. The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. References Kao CM, Michaels MG. Approach to vaccinating the pediatric solid organ transplant candidate and recipient. Front Pediatr. 2023;11:1271065. Epub 20231108. doi: 10.3389/fped.2023.1271065. PubMed PMID: 38027303; PubMed Central PMCID: PMCPMC10663229. Danziger-Isakov L, Kumar D, Practice AICo. Vaccination of solid organ transplant candidates and recipients: Guidelines from the American society of transplantation infectious diseases community of practice. Clinical transplantation. 2019;33(9):e13563. Epub 20190605. doi: 10.1111/ctr.13563. PubMed PMID: 31002409. Rubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58(3):309-18. doi: 10.1093/cid/cit816. PubMed PMID: 24421306. Fox TG, Nailescu C. Vaccinations in pediatric kidney transplant recipients. Pediatric nephrology (Berlin, Germany). 2019;34(4):579-91. Epub 20180418. doi: 10.1007/s00467-018-3953-z. PubMed PMID: 29671067. Hill HA, Elam-Evans LD, Yankey D, Singleton JA, Kang Y. Vaccination Coverage Among Children Aged 19-35 Months - United States, 2017. MMWR Morb Mortal Wkly Rep. 2018;67(40):1123-8. Epub 20181012. doi: 10.15585/mmwr.mm6740a4. PubMed PMID: 30307907; PubMed Central PMCID: PMCPMC6181261. Hocker B, Aguilar M, Schnitzler P, Pape L, Dello Strologo L, Webb NJA, et al. Incomplete vaccination coverage in European children with end-stage kidney disease prior to renal transplantation. Pediatric nephrology (Berlin, Germany). 2018;33(2):341-50. Epub 20171005. doi: 10.1007/s00467-017-3776-3. PubMed PMID: 28983694. Feldman AG, Beaty BL, Curtis D, Juarez-Colunga E, Kempe A. Incidence of Hospitalization for Vaccine-Preventable Infections in Children Following Solid Organ Transplant and Associated Morbidity, Mortality, and Costs. JAMA Pediatr. 2019;173(3):260-8. doi: 10.1001/jamapediatrics.2018.4954. PubMed PMID: 30640369; PubMed Central PMCID: PMCPMC6439884. Kuter B, Matthews H, Shinefield H, Black S, Dennehy P, Watson B, et al. Ten year follow-up of healthy children who received one or two injections of varicella vaccine. Pediatr Infect Dis J. 2004;23(2):132-7. doi: 10.1097/01.inf.0000109287.97518.67. PubMed PMID: 14872179. Shapiro ED, Vazquez M, Esposito D, Holabird N, Steinberg SP, Dziura J, et al. Effectiveness of 2 doses of varicella vaccine in children. J Infect Dis. 2011;203(3):312-5. doi: 10.1093/infdis/jiq052. PubMed PMID: 21208922; PubMed Central PMCID: PMCPMC3071110. Warmington L, Lee BE, Robinson JL. Loss of antibodies to measles and varicella following solid organ transplantation in children. Pediatr Transplant. 2005;9(3):311-4. doi: 10.1111/j.1399-3046.2005.00313.x. PubMed PMID: 15910386. Broyer M, Tete MJ, Guest G, Gagnadoux MF, Rouzioux C. Varicella and zoster in children after kidney transplantation: long-term results of vaccination. Pediatrics. 1997;99(1):35-9. doi: 10.1542/peds.99.1.35. PubMed PMID: 8989334. Alimohammadi M, Moosazadeh M, Mardomi A, Mousavi T. Seroprevalence of VZV IgG antibody in kidney transplant recipients: A systematic and meta-analysis review. Transplant immunology. 2022;75:101730. Epub 20221102. doi: 10.1016/j.trim.2022.101730. PubMed PMID: 36341911. Rondaan C, de Joode AAE, van Assen S, Bos NA, Westerhuis R, Westra J. Increased incidence of herpes zoster in patients on renal replacement therapy cannot be explained by intrinsic defects of cellular or humoral immunity to varicella-zoster virus. Antiviral Res. 2018;158:206-12. Epub 20180810. doi: 10.1016/j.antiviral.2018.08.006. PubMed PMID: 30102958. Rondaan C, de Joode AAE, Wang L, Siderius M, Raveling-Eelsing E, van Leer-Buter C, et al. Immune response to varicella-zoster virus before and after renal transplantation. Antiviral Res. 2020;183:104938. Epub 20201006. doi: 10.1016/j.antiviral.2020.104938. PubMed PMID: 32979400. van Besouw NM, Verjans GM, Zuijderwijk JM, Litjens NH, Osterhaus AD, Weimar W. Systemic varicella zoster virus reactive effector memory T-cells impaired in the elderly and in kidney transplant recipients. J Med Virol. 2012;84(12):2018-25. doi: 10.1002/jmv.23427. PubMed PMID: 23080511. Chaves Tdo S, Lopes MH, de Souza VA, Dos Santos Sde S, Pereira LM, Reis AD, et al. Seroprevalence of antibodies against varicella-zoster virus and response to the varicella vaccine in pediatric renal transplant patients. Pediatr Transplant. 2005;9(2):192-6. doi: 10.1111/j.1399-3046.2005.00279.x. PubMed PMID: 15787792. Yoeli JK, Yoeli D, Miloh TA, Rana A, Goss JA, Munoz-Rivas F. Measles, mumps, rubella (vaccine) and varicella vaccines in pediatric liver transplant: An initial analysis of post-transplant immunity. Pediatr Transplant. 2019;23(5):e13490. Epub 20190620. doi: 10.1111/petr.13490. PubMed PMID: 31219224. Barton M, Wasfy S, Melbourne T, Hebert D, Moore D, Robinson J, et al. Sustainability of humoral responses to varicella vaccine in pediatric transplant recipients following a pretransplantation immunization strategy. Pediatr Transplant. 2009;13(8):1007-13. Epub 20081215. doi: 10.1111/j.1399-3046.2008.01113.x. PubMed PMID: 19207222. Liman AYJ, Wozniak LJ, de St Maurice A, Dunkel GL, Wanlass EM, Venick RS, et al. Low post-transplant measles and varicella titers among pediatric liver transplant recipients: A 10-year single-center study. Pediatr Transplant. 2022;26(6):e14322. Epub 20220517. doi: 10.1111/petr.14322. PubMed PMID: 35582739. Webb NJ, Fitzpatrick MM, Hughes DA, Brocklebank TJ, Judd BA, Lewis MA, et al. Immunisation against varicella in end stage and pre-end stage renal failure. Trans-Pennine Paediatric Nephrology Study Group. Arch Dis Child. 2000;82(2):141-3. doi: 10.1136/adc.82.2.141. PubMed PMID: 10648369; PubMed Central PMCID: PMCPMC1718197. Prevention CfDCa. Varicella Vaccine Recommendations. 2025. Bianchi FP, Tafuri S, Larocca AMV, Germinario CA, Stefanizzi P. Long -term persistence of antibodies against varicella in fully immunized healthcare workers: an Italian retrospective cohort study. BMC Infect Dis. 2021;21(1):475. Epub 20210525. doi: 10.1186/s12879-021-06180-x. PubMed PMID: 34034659; PubMed Central PMCID: PMCPMC8152326. Hinman AR, Orenstein WA, Mortimer EA, Jr. When, where, and how do immunizations fail? Ann Epidemiol. 1992;2(6):805-12. doi: 10.1016/1047-2797(92)90074-z. PubMed PMID: 1342333. Eberhardt CS, Wieland A, Nasti TH, Grifoni A, Wilson E, Schmid DS, et al. Persistence of Varicella-Zoster Virus-Specific Plasma Cells in Adult Human Bone Marrow following Childhood Vaccination. J Virol. 2020;94(13). Epub 20200616. doi: 10.1128/JVI.02127-19. PubMed PMID: 32321817; PubMed Central PMCID: PMCPMC7307153. Levin MJ, Weinberg A. Immune Responses to Varicella-Zoster Virus Vaccines. Curr Top Microbiol Immunol. 2023;438:223-46. doi: 10.1007/82_2021_245. PubMed PMID: 35102438. Murata K, Hoshina T, Onoyama S, Tanaka T, Kanno S, Ishimura M, et al. Reduction in the Number of Varicella-Zoster Virus-Specific T-Cells in Immunocompromised Children with Varicella. Tohoku J Exp Med. 2020;250(3):181-90. doi: 10.1620/tjem.250.181. PubMed PMID: 32213753. Jiang W, Withers B, Sutrave G, Clancy LE, Yong MI, Blyth E. Pathogen-Specific T Cells Beyond CMV, EBV and Adenovirus. Curr Hematol Malig Rep. 2019;14(4):247-60. doi: 10.1007/s11899-019-00521-z. PubMed PMID: 31228095. Tables Table 1. Patient demographics. Total (n=45) Maintained Immunity (n=34) Lost Immunity (n=11) P Age at transplant, years 16.7 (12.7-18.5) 17.3 (13.4-19.0) 12.4 (3.9-17.4) 0.05 Sex 0.28 Male 29 (64.4) 20 (58.8) 9 (81.8) Female 16 (35.6) 14 (41.2) 2 (18.2) Race/Ethnicity 0.7 Hispanic 29 (64.4) 23 (67.6) 6 (54.5) Non-Hispanic White 9 (20.0) 6 (17.6) 3 (27.3) Non-Hispanic Black 5 (11.1) 4 (11.8) 1 (9.1) Asian 2 (4.4) 1 (2.9) 1 (9.1) Original disease 0.35 CAKUT 21 (46.7) 14 (41.2) 7 (63.6) FSGS 5 (11.1) 3 (8.8) 2 (18.2) Glomerulonephritis 10 (22.2) 9 (26.5) 1 (9.1) Other 9 (20.0) 8 (23.5) 1 (9.1) Deceased-donor renal transplant 40 (88.9) 31 (91.2) 9 (81.8) 0.58 Repeat transplant 2 (4.4) 1 (2.9) 1 (9.1) 0.43 Highly sensitized (PRA > 30%) 6 (13.3) 3 (8.8) 3 (27.3) 0.15 Induction agent >0.99 Lymphocyte depleting agent 38 (84.4) 29 (85.3) 9 (81.8) Non-lymphocyte depleting agent 7 (15.6) 5 (14.7) 2 (18.2) Steroid-based immunosuppression 20 (44.4) 11 (32.4) 9 (81.8) 0.006 Follow-up time, months 14.9 (11.9-32.0) 22.8 (12.0-33.9) 12.6 (8.8-14.9) 0.07 Values are expressed as n (%) or median (interquartile range). CAKUT, congenital anomalies of the kidney and urinary tract; FSGS, focal segmental glomerulosclerosis; PRA, panel of reactive antibodies. Table 2. Varicella zoster vaccination and IgG titer pre- and post-transplant. Total (n=45) Maintained Immunity (n=34) Lost Immunity (n=11) P Number of pre-transplant VZV doses 0.35 1 2 (4.4) 2 (5.9) 0 (0) 2 34 (75.6) 27 (79.4) 7 (63.6) 3 7 (15.6) 4 (11.8) 3 (27.3) 4 2 (4.4) 1 (2.9) 1 (9.1) Time between last VZV vaccine and transplant, months 98.1 (15.2-146.4) 103.9 (42.6-151.5) 10.7 (4.4-98.2) 0.02 Time between last VZV vaccine and transplant 0.01 ≤ 12 months 10 (22.2) 4 (11.8) 6 (54.5) 12-24 months 4 (8.9) 3 (8.8) 1 (9.1) > 24 months 31 (68.9) 27 (79.4) 4 (36.4) Time between pre-transplant VZV IgG and transplant, months 8.8 (4.8-13.6) 10.5 (5.1-13.7) 5.1 (3.3-15.3) 0.38 Pre-transplant VZV IgG, index 1.9 (1.3-2.57) 1.9 (1.6-2.6) 1.7 (1.3-3.4) 0.99 Time from transplant to post-transplant VZV IgG, months * 14.9 (11.9-32.0) 22.8 (12.0-33.9) 12.6 (8.8-14.9) 0.07 Post-transplant VZV IgG, index * 1.49 (1.1-2.3) 1.8 (1.3-2.5) 0.8 (0.6-1.0) 0.0001 WBC count, 1000/uL ** 5.9 (4.6-7.4) 5.8 (4.6-7.2) 5.9 (3.0-7.4) 0.92 Values are expressed as n (%) or median (interquartile range). VZV, varicella zoster virus; IgG, immunoglobulin G; WBC, white blood cell. * The most recent VZV IgG or the first negative VZV IgG post-transplant. ** WBC count at the time of post-transplant VZV IgG titer. Cite Share Download PDF Status: Published Journal Publication published 13 Nov, 2025 Read the published version in Pediatric Nephrology → Version 1 posted Editorial decision: Major Revisions Needed 29 Jul, 2025 Reviewers agreed at journal 07 Jul, 2025 Reviewers invited by journal 11 Jun, 2025 Editor assigned by journal 10 Jun, 2025 First submitted to journal 10 Jun, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6866072","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":469950783,"identity":"a1fe349e-8d28-4e94-b577-e4c78eba5ab8","order_by":0,"name":"Helen Pizzo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA50lEQVRIie3RMQrCMBSA4RcC6fLAtVLBKwSEqlOvYhE6Cy6OESEuFleP0xKoiweoWFARiqPgIuhgi6C4xLoJ5oeQZPhISABMph+MAxXljMUgO4CoCiFPQvlXpIzZlUjbGo8PA8gazblKRpdb5oEVHo460p3Fk9YCciQiCdahzH2BS7ejvVjqSwdBISUzd0OE6oEdMK4l2/30WhJG0R3CTXmfSUokLQkydCkwRYQd0J2WrPyJgzxHG1m/HkrlS0yYTgBfqviMo8wrXiw+XYqL1SxJT1rzgNFrzR4f9LHobVflFJPJZPqj7p+hRph0s30qAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0003-2997-7483","institution":"Cedars-Sinai Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Helen","middleName":"","lastName":"Pizzo","suffix":""},{"id":469950784,"identity":"d7a32d5f-d2e2-460c-9afb-b7b986b44af3","order_by":1,"name":"Priya R. Soni","email":"","orcid":"","institution":"Cedars-Sinai Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Priya","middleName":"R.","lastName":"Soni","suffix":""},{"id":469950785,"identity":"d2fd8b56-7f2e-423e-a3b0-4c6f21862a56","order_by":2,"name":"Santhosh Nadipuram","email":"","orcid":"","institution":"Cedars-Sinai Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Santhosh","middleName":"","lastName":"Nadipuram","suffix":""},{"id":469950786,"identity":"f5eac12b-aa6a-4db9-93c8-43cf3748cdb7","order_by":3,"name":"James Mirocha","email":"","orcid":"","institution":"Cedars-Sinai Medical Center","correspondingAuthor":false,"prefix":"","firstName":"James","middleName":"","lastName":"Mirocha","suffix":""},{"id":469950787,"identity":"360c1604-0700-4fca-beee-0ce93abf45cf","order_by":4,"name":"Jonathan Garrison","email":"","orcid":"","institution":"Cedars-Sinai Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Jonathan","middleName":"","lastName":"Garrison","suffix":""},{"id":469950788,"identity":"60d3d3db-799b-44f4-926d-419fdf0b0b11","order_by":5,"name":"Sherlyn Hilario","email":"","orcid":"","institution":"Cedars-Sinai Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Sherlyn","middleName":"","lastName":"Hilario","suffix":""},{"id":469950789,"identity":"8e898969-da83-48ee-abcd-64946bd1f207","order_by":6,"name":"Dechu Puliyanda","email":"","orcid":"","institution":"Cedars-Sinai Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Dechu","middleName":"","lastName":"Puliyanda","suffix":""}],"badges":[],"createdAt":"2025-06-10 20:24:53","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6866072/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6866072/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00467-025-07022-7","type":"published","date":"2025-11-13T15:58:12+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":84776110,"identity":"f61dc2b6-acb7-4367-b920-bee2c2b900d2","added_by":"auto","created_at":"2025-06-17 08:57:38","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":50619,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-6866072/v1/507a513070f9c7ee745ee323.png"},{"id":96105066,"identity":"55b0b3fe-f5af-4205-82ea-9b40892a911c","added_by":"auto","created_at":"2025-11-17 16:08:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":545470,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6866072/v1/e1bae00b-0812-45b5-a56f-963a1c62b7d4.pdf"}],"financialInterests":"","formattedTitle":"Risk Factors for Loss of Varicella Immunity After Pediatric Kidney Transplantation","fulltext":[{"header":"Introduction","content":"\u003cp\u003e Guidelines for vaccination of solid organ transplant candidates advise every effort should be made to ensure completion of recommended pre-transplant vaccines prior to surgery, as immunosuppressed transplant recipients are at higher risk for invasive disease and are less likely to produce as robust immune response to vaccines compared to those who are not immunocompromised [ \u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e \u0026ndash; \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e ]. With gaps in herd immunity secondary to a lack of or incomplete vaccination in the community, the risk for exposure to vaccine-preventable pathogens increases [ \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e , \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e ]. In a multi-center retrospective study of pre-kidney transplant vaccination coverage among 254 European children, unvaccinated children were four-times more likely to acquire a vaccine-preventable illness post-transplant compared to those who were vaccinated [ \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e ]. Post-transplant vaccine-preventable infections have also shown to be associated with morbidity, mortality, and higher costs. A retrospective study of 6980 children across 45 pediatric transplant centers in the United States found more than 15% of solid organ transplant recipients were hospitalized with a vaccine-preventable illness in the first 5 years after transplant, with 1.7% mortality, and costing \u003cspan\u003e$\u003c/span\u003e120,498 more than transplant-related hospitalizations not associated with vaccine-preventable infections [ \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e ]. Furthermore, the authors of this study noted 2.1% of hospitalizations in the first 5 years after pediatric solid organ transplant were due to varicella zoster (VZV) infections \u0026ndash; a rate similar to the cohort admitted for illnesses due to pneumococcus (2.0%) and respiratory syncytial virus (1.8%) [ \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e ]. \u003c/p\u003e \u003cp\u003eThe efficacy of the recommended 2-dose varicella vaccine among the general pediatric population ranges between 94\u0026ndash;98% [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Vaccination against VZV and monitoring for antibody response among kidney transplant candidates can help prevent severe disseminated VZV disease after transplantation. Despite confirmation of serologic response to vaccinations pre-transplant, studies have shown loss of humoral immunity post-transplant, putting recipients at risk for VZV infection and its associated morbidity and mortality. In a retrospective single center study of 18 pediatric solid organ transplant recipients with confirmed VZV seropositivity prior to transplant, 11.1% of the cohort lost their anti-varicella antibody within 6 months following transplant [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Broyer et al. noted that among 97 children who received VZV vaccination prior to kidney transplantation, 7% had negative VZV immune globulin G (IgG) at 1-year; this number increased to 24% at 5-years post-transplant [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. While some studies in adult kidney transplant recipients found 100% VZV IgG positivity up to 1080 days after transplant, some studies mirror the findings in pediatric research with declining rates of VZV IgG seropositivity [\u003cspan additionalcitationids=\"CR13 CR14 CR15\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Potential influences for losing VZV immunity include the age at the time of transplant, the number of VZV vaccines received prior to transplantation, and the time interval between VZV vaccination and transplant [\u003cspan additionalcitationids=\"CR18 CR19\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In this study, we assessed the potential risk factors that could contribute to the maintenance of or loss of VZV immunity after pediatric kidney transplantation: 1) Induction agent used. 2) Number of VZV vaccines received prior to transplant. 3) Interval between last dose of VZV vaccine and transplantation.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient Population\u003c/h2\u003e \u003cp\u003eThis is a single center retrospective observational study of 45 pediatric patients aged 2\u0026ndash;20 years who received a kidney transplant between April 2018 through September 2023. All recipients who received pre-transplant varicella vaccination with documentation of subsequent positive VZV IgG (\u0026gt;\u0026thinsp;1.09 index) and received post-transplant VZV IgG monitoring were included in the study. Patients received induction immunosuppression with a lymphocyte-depleting agent (LDA; anti-thymocyte globulin (ATG) or alemtuzumab) or a non-lymphocyte-depleting agent (NLDA; basiliximab) and were maintained on mycophenolate mofetil, tacrolimus, with or without steroids. No subjects had a history of natural VZV infection before or after kidney transplant. Median follow-up duration was 14.9 months post-transplant (IQR 11.9\u0026ndash;32.0 months).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eVZV IgG Testing\u003c/h3\u003e\n\u003cp\u003ePre-transplant VZV IgG, determined by enzyme immunoassay, was assessed at the initial pre-transplant evaluation and reassessed every 2 years until transplant. Those who were seronegative at any point prior to transplant received an additional VZV vaccine and VZV serology was repeated at least 4 weeks following vaccination; a maximum of 4 doses of VZV vaccine was given per patient. Post-transplant VZV IgG monitoring was performed every 6\u0026ndash;12 months post-transplant. VZV IgG was considered positive when the value was \u0026gt;\u0026thinsp;1.09 index. Equivocal titers (0.91\u0026ndash;1.09) were considered negative in our analysis.\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eNumerical variables were summarized by median and interquartile range (IQR) and were compared across groups by the Wilcoxon rank sum test. Categorical variables were summarized by frequency and percentage and were compared across groups by the Fisher exact test. Freedom from loss of VZV IgG was estimated by the Kaplan-Meier method and group differences were assessed by the log-rank test. Hazard ratios (HR) and their 95% confidence intervals (CI) were obtained from Cox proportional hazards models. A two-sided 0.05 significance level was used throughout. SAS version 9.4 (SAS Institute, Cary, North Carolina) was used for statistical calculations.\u003c/p\u003e \u003cp\u003e This study was approved by the Cedars-Sinai Medical Center Institutional Review Board (STUDY00000398). This study was conducted in accordance with ethical guidelines based on federal regulations and the common rule. Cedars-Sinai Medical Center also has a Federal Wide Assurance.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 45 subjects received pre-transplant varicella vaccination with confirmation of seroconversion prior to kidney transplantation and received post-transplant VZV IgG monitoring starting at 6\u0026ndash;12 months following surgery \u0026ndash; this represented 100% of pediatric renal transplants performed at our center during the study\u0026rsquo;s inclusion period. Median age at transplant was 16.7 years (IQR 12.7\u0026ndash;18.5), 64.4% were males, 64.4% were Hispanic, 88.9% received a deceased-donor renal transplant, and 13.3% were highly sensitized (PRA\u0026thinsp;\u0026gt;\u0026thinsp;30%). Comparison of patient characteristics among those who maintained post-transplant VZV immunity (n\u0026thinsp;=\u0026thinsp;34) vs. those who lost immunity (n\u0026thinsp;=\u0026thinsp;11) is highlighted in Table\u0026nbsp;1. Notably, those who lost VZV immunity were younger at the time of transplant, 12.4 years (IQR 3.9\u0026ndash;17.4) vs. 17.3 years (IQR 13.4\u0026ndash;19.0) (P\u0026thinsp;=\u0026thinsp;0.05), and more likely to be on steroid-based immunosuppression, 9 (81.8%) vs. 11 (32.4%) (Table\u0026nbsp;1, P\u0026thinsp;=\u0026thinsp;0.006).\u003c/p\u003e \u003cp\u003eMedian time between confirmation of positive pre-transplant VZV IgG testing and transplant was 8.8 months (IQR 4.8\u0026ndash;13.6), and there was no difference between the pre-transplant VZV IgG titers between the group who lost immunity vs. those who maintained their VZV IgG after transplantation, 1.7 index (IQR 1.3\u0026ndash;3.4) vs. 1.9 index (IQR 1.6\u0026ndash;2.6), respectively (Table\u0026nbsp;2, P\u0026thinsp;=\u0026thinsp;0.99). Median time to negative post-transplant VZV IgG was 12.6 months (IQR 8.8\u0026ndash;14.9) compared to last VZV serological testing in those that maintained immunity was 22.8 months (IQR 12.0-33.9) (Table\u0026nbsp;2, P\u0026thinsp;=\u0026thinsp;0.07). There were no differences in the WBC count at the time of last post-transplant VZV IgG testing (Table\u0026nbsp;2, P\u0026thinsp;=\u0026thinsp;0.92).\u003c/p\u003e\n\u003ch3\u003eInduction Agent Used\u003c/h3\u003e\n\u003cp\u003eThere were no differences between the induction agents used among those who maintained vs. lost post-transplant VZV IgG immunity (Table\u0026nbsp;1). Nine of 11 subjects (81.8%) who developed negative VZV IgG post-transplants received a lymphocyte-depleting agent compared to 29 of 34 patients (85.3%) among those whose immunity persisted (P\u0026thinsp;\u0026gt;\u0026thinsp;0.99).\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eNumber of VZV Vaccines Received Prior to Transplant\u003c/h2\u003e \u003cp\u003eA majority of the patients received two doses of VZV vaccine prior to transplantation (75.6%); 2 subjects (4.4%) received only one dose of VZV vaccine, while 7 (15.6%) and 2 (4.4%) received three and four doses, respectively (Table\u0026nbsp;2). There is an increased risk for losing VZV seropositivity after transplant among those who required 3 or more doses of VZV vaccine in order to seroconvert prior to transplantation (HR 3.81, 95%CI 1.09\u0026ndash;13.30, P\u0026thinsp;=\u0026thinsp;0.04).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eInterval Between Last Dose of VZV Vaccine and Transplant\u003c/h3\u003e\n\u003cp\u003eTime interval between last VZV vaccine dose and transplant was shorter among those who lost VZV immunity compared to those who maintained positive VZV IgG levels, 10.7 months (IQR 4.4\u0026ndash;98.2) vs. 103.9 months (IQR 42.6-151.5) (Table\u0026nbsp;2, P\u0026thinsp;=\u0026thinsp;0.02). Freedom from loss of VZV IgG up to 83 months following transplantation was compared based on the time interval between the last VZV vaccination and transplant (\u0026lt;\u0026thinsp;1 year vs. \u0026ge;1 year) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Six of 10 (60%) of those who received their last VZV vaccine\u0026thinsp;\u0026lt;\u0026thinsp;1 year before transplantation lost their post-transplant VZV IgG seropositivity compared to 5 of 35 (14.3%) of those who were vaccinated \u0026ge;1 year prior (Table\u0026nbsp;2). Receiving VZV vaccination\u0026thinsp;\u0026lt;\u0026thinsp;1 year prior to kidney transplantation was associated with a higher risk for losing VZV immunity post-transplant (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e; HR 6.97, 95% CI 2.08\u0026ndash;23.34). Furthermore, over a follow-up time of 3 years, 70.4% develop negative VZV IgG when vaccinated\u0026thinsp;\u0026lt;\u0026thinsp;1-year preceding transplantation compared to 20.0% in the cohort vaccinated \u0026ge;1 year earlier (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, P\u0026thinsp;=\u0026thinsp;0.0003).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003ePost-Transplant Varicella Infection:\u003c/h3\u003e\n\u003cp\u003eDespite 24.4% of our post-transplant patients losing immunity to VZV, none of these patients developed VZV infection during the median follow-up period of 14.9 months (IQR 11.9\u0026ndash;32.0 months).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAmong our pediatric kidney transplant cohort with serologic response to VZV vaccination and no history of natural VZV infection before transplantation, 24.4% recipients lost humoral immunity at a median time of 12.6 months post-transplant. Similar findings on the risk for loss of VZV IgG seropositivity are highlighted in several studies. Broyer et al. noted among 94 pediatric patients who received VZV immunization prior to kidney transplantation, 7% and 24% had negative VZV IgG antibodies at 1- and 5-years post-transplant, respectively [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. A meta-analysis on the seroprevalence of VZV IgG antibody in kidney transplant recipients illustrated varying VZV IgG durability post-transplant, ranging from 23%-100% VZV IgG positivity between 657\u0026ndash;2130 days following transplantation [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In a study of 18 pediatric solid organ transplant patients (8 liver, 6, kidney, 4 heart) with seropositivity of VZV IgG antibodies pre-transplant, 11% had undetectable VZV antibody titers within 6-months post-transplant [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Among pediatric liver transplant recipients, 42 of 67 (63%) who received VZV vaccine prior to transplantation were non-immune to VZV at a median time of 3.3 years after transplantation [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe found no differences in the induction immunosuppression received between those who maintained or lost VZV IgG following transplant. Patients who were maintained on steroid-based immunosuppression, however, were more likely to lose anti-varicella antibody at a median time of 13.0 months (IQR 10.3\u0026ndash;20.1) post-transplant. In contrast, highly sensitized recipients (panel of reactive antibodies\u0026thinsp;\u0026gt;\u0026thinsp;30%) all of whom received desensitization with a combination of plasmapheresis, IVIg, rituximab, and/or tociluzimab no more than 6 months prior to transplantation, did not appear to be at higher risk for losing VZV IgG antibody despite intensified immunosuppression going into transplant. It is important to note, however, that the highly sensitized patients do receive IVIg the day of and within a week following transplant, which could have provided additional VZV IgG. Although our cohort only had two patients who were treated for rejection before the loss of VZV IgG antibody, we could not statistically assess the correlation between treatment for rejection and risk for loss of VZV IgG seropositivity. The findings in our highly sensitized cohort could suggest the risk following intensified immunosuppression for allograft rejection is low. In a multicenter prospective study involving pediatric liver and kidney transplants, Barton et al. noted that while VZV IgG antibodies tended to be lower during periods of higher immunosuppression, the antibody levels remained protective [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Furthermore, one patient received a steroid pulse for treatment of acute rejection without subsequent decline in their VZV IgG titer [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile a majority (75.6%) of our cohort received 2 doses of VZV vaccine prior to transplantation, 4.4% received only 1 dose and 20.0% received 3 or more doses. Interestingly, those that received more doses than the standard childhood 2-dose VZV series, were more likely to lose their VZV seropositivity following transplantation. Current recommendation from the Advisory Committee on Immunization Practices and Centers for Disease Control is a 2-dose VZV vaccine series due to that finding that a second dose of VZV vaccine produced a more robust antibody level compared to 1-dose, and decreased the rate of breakthrough varicella infection by 3.3-fold [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Nonetheless, primary vaccine failure after the 2-dose series is possible, necessitating an additional booster dose [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. While the most likely cause of primary vaccine failure in our population are factors inherent to the immune response of the recipient, this could potentially also translate to a reason for the less durable VZV seroprotection in those requiring additional booster dose(s) [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe interval between the last dose of VZV vaccine and transplantation appears to influence the durability of VZV IgG following transplant. Our cohort revealed the threshold of \u0026lt;\u0026thinsp;1 year best predicted a heightened risk for loss of anti-varicella antibody after transplantation. Similarly, in a multivariate analysis, Yoeli et al. also noted that a time interval of \u0026gt;\u0026thinsp;1 year from last vaccine to transplant was independently and significantly associated with maintenance of immunity against VZV [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The authors hypothesized that the intensified immunosuppression immediately post-transplant could hinder the development of VZV immunity for those who had not yet mounted a full immune response following vaccination, potentially due to the short time interval between vaccination and transplantation [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Interestingly, a meta-analysis of adult transplant studies noted some cohorts had 100% seropositivity even up to 1080 days post-transplant [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. This raises the question of whether natural infection provides better VZV IgG durability compared to vaccination, as the adult cohorts are more likely to have had natural infection due to the lack of VZV vaccine during their childhood.\u003c/p\u003e \u003cp\u003eThere are several limitations in our study, with one attributed to the small cohort of 45 patients, which raises the possibility for type 2 error. Post-transplant VZV IgG were checked at approximate defined timepoints, which may not accurately reflect the exact timing to loss of VZV IgG following transplantation. While none of our patients who lost their VZV immunity developed VZV infection despite being on immunosuppression, loss of VZV IgG may not lead to complete loss of VZV immunity, as viral-specific T-cell (Tc) responses could still be intact and provide some degree of immune protection [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan additionalcitationids=\"CR25 CR26\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Future studies should evaluate VZV Tc and the clinical course in those who have and have not maintained post-transplant VZV IgG following pre-transplant VZV vaccination.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003ePediatric kidney transplant recipients are at risk for losing VZV IgG seropositivity after transplantation. Post-transplant VZV serologies should be serially monitored to identify patients at high risk for disseminated VZV. Identifying these patients is important to counsel families on post-exposure prophylaxis or need for immediate treatment should any symptoms arise. Given the risk for losing VZV IgG, close contacts should make sure they are up to date on vaccines to help provide herd immunity. Despite strategies for post-exposure prophylaxis and treatment of VZV infection in solid organ transplant recipients, it does not offer complete protection against the morbidity and mortality associated with VZV disease in the immunocompromised. Further research should be directed at evaluating VZV cellular immunity and determining strategies to provide protection against VZV among pediatric kidney transplant recipients who lose their pre-transplant vaccine-induced humoral immunity.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eATG: anti-thymocyte globulin\u003c/p\u003e\n\u003cp\u003eIgG: immune globulin G\u003c/p\u003e\n\u003cp\u003eLDA: lymphocyte depleting agent\u003c/p\u003e\n\u003cp\u003eNLDA: non-lymphocyte depleting agent\u003c/p\u003e\n\u003cp\u003eTc: T-cell\u003c/p\u003e\n\u003cp\u003eVZV: Varicella zoster\u003c/p\u003e\n\u003cp\u003eWBC: white blood cell\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThe authors confirm contribution to the paper as follows: study conception and design: HP, JM, JG, SH, PRS, SN, DP; data collection: HP, JG, SH, DP; analysis and interpretation of results: HP, JM, JG, SH, PRS, SN, DP; draft manuscript preparation: HP, JM, JG, SH, PRS, SN, DP. All authors reviewed the results and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eKao CM, Michaels MG. Approach to vaccinating the pediatric solid organ transplant candidate and recipient. Front Pediatr. 2023;11:1271065. Epub 20231108. doi: 10.3389/fped.2023.1271065. PubMed PMID: 38027303; PubMed Central PMCID: PMCPMC10663229.\u003c/li\u003e\n \u003cli\u003eDanziger-Isakov L, Kumar D, Practice AICo. Vaccination of solid organ transplant candidates and recipients: Guidelines from the American society of transplantation infectious diseases community of practice. Clinical transplantation. 2019;33(9):e13563. Epub 20190605. doi: 10.1111/ctr.13563. PubMed PMID: 31002409.\u003c/li\u003e\n \u003cli\u003eRubin LG, Levin MJ, Ljungman P, Davies EG, Avery R, Tomblyn M, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58(3):309-18. doi: 10.1093/cid/cit816. PubMed PMID: 24421306.\u003c/li\u003e\n \u003cli\u003eFox TG, Nailescu C. Vaccinations in pediatric kidney transplant recipients. Pediatric nephrology (Berlin, Germany). 2019;34(4):579-91. Epub 20180418. doi: 10.1007/s00467-018-3953-z. PubMed PMID: 29671067.\u003c/li\u003e\n \u003cli\u003eHill HA, Elam-Evans LD, Yankey D, Singleton JA, Kang Y. Vaccination Coverage Among Children Aged 19-35 Months - United States, 2017. MMWR Morb Mortal Wkly Rep. 2018;67(40):1123-8. Epub 20181012. doi: 10.15585/mmwr.mm6740a4. PubMed PMID: 30307907; PubMed Central PMCID: PMCPMC6181261.\u003c/li\u003e\n \u003cli\u003eHocker B, Aguilar M, Schnitzler P, Pape L, Dello Strologo L, Webb NJA, et al. Incomplete vaccination coverage in European children with end-stage kidney disease prior to renal transplantation. Pediatric nephrology (Berlin, Germany). 2018;33(2):341-50. Epub 20171005. doi: 10.1007/s00467-017-3776-3. PubMed PMID: 28983694.\u003c/li\u003e\n \u003cli\u003eFeldman AG, Beaty BL, Curtis D, Juarez-Colunga E, Kempe A. Incidence of Hospitalization for Vaccine-Preventable Infections in Children Following Solid Organ Transplant and Associated Morbidity, Mortality, and Costs. JAMA Pediatr. 2019;173(3):260-8. doi: 10.1001/jamapediatrics.2018.4954. PubMed PMID: 30640369; PubMed Central PMCID: PMCPMC6439884.\u003c/li\u003e\n \u003cli\u003eKuter B, Matthews H, Shinefield H, Black S, Dennehy P, Watson B, et al. Ten year follow-up of healthy children who received one or two injections of varicella vaccine. Pediatr Infect Dis J. 2004;23(2):132-7. doi: 10.1097/01.inf.0000109287.97518.67. PubMed PMID: 14872179.\u003c/li\u003e\n \u003cli\u003eShapiro ED, Vazquez M, Esposito D, Holabird N, Steinberg SP, Dziura J, et al. Effectiveness of 2 doses of varicella vaccine in children. J Infect Dis. 2011;203(3):312-5. doi: 10.1093/infdis/jiq052. PubMed PMID: 21208922; PubMed Central PMCID: PMCPMC3071110.\u003c/li\u003e\n \u003cli\u003eWarmington L, Lee BE, Robinson JL. Loss of antibodies to measles and varicella following solid organ transplantation in children. Pediatr Transplant. 2005;9(3):311-4. doi: 10.1111/j.1399-3046.2005.00313.x. PubMed PMID: 15910386.\u003c/li\u003e\n \u003cli\u003eBroyer M, Tete MJ, Guest G, Gagnadoux MF, Rouzioux C. Varicella and zoster in children after kidney transplantation: long-term results of vaccination. Pediatrics. 1997;99(1):35-9. doi: 10.1542/peds.99.1.35. PubMed PMID: 8989334.\u003c/li\u003e\n \u003cli\u003eAlimohammadi M, Moosazadeh M, Mardomi A, Mousavi T. Seroprevalence of VZV IgG antibody in kidney transplant recipients: A systematic and meta-analysis review. Transplant immunology. 2022;75:101730. Epub 20221102. doi: 10.1016/j.trim.2022.101730. PubMed PMID: 36341911.\u003c/li\u003e\n \u003cli\u003eRondaan C, de Joode AAE, van Assen S, Bos NA, Westerhuis R, Westra J. Increased incidence of herpes zoster in patients on renal replacement therapy cannot be explained by intrinsic defects of cellular or humoral immunity to varicella-zoster virus. Antiviral Res. 2018;158:206-12. Epub 20180810. doi: 10.1016/j.antiviral.2018.08.006. PubMed PMID: 30102958.\u003c/li\u003e\n \u003cli\u003eRondaan C, de Joode AAE, Wang L, Siderius M, Raveling-Eelsing E, van Leer-Buter C, et al. Immune response to varicella-zoster virus before and after renal transplantation. Antiviral Res. 2020;183:104938. Epub 20201006. doi: 10.1016/j.antiviral.2020.104938. PubMed PMID: 32979400.\u003c/li\u003e\n \u003cli\u003evan Besouw NM, Verjans GM, Zuijderwijk JM, Litjens NH, Osterhaus AD, Weimar W. Systemic varicella zoster virus reactive effector memory T-cells impaired in the elderly and in kidney transplant recipients. J Med Virol. 2012;84(12):2018-25. doi: 10.1002/jmv.23427. PubMed PMID: 23080511.\u003c/li\u003e\n \u003cli\u003eChaves Tdo S, Lopes MH, de Souza VA, Dos Santos Sde S, Pereira LM, Reis AD, et al. Seroprevalence of antibodies against varicella-zoster virus and response to the varicella vaccine in pediatric renal transplant patients. Pediatr Transplant. 2005;9(2):192-6. doi: 10.1111/j.1399-3046.2005.00279.x. PubMed PMID: 15787792.\u003c/li\u003e\n \u003cli\u003eYoeli JK, Yoeli D, Miloh TA, Rana A, Goss JA, Munoz-Rivas F. Measles, mumps, rubella (vaccine) and varicella vaccines in pediatric liver transplant: An initial analysis of post-transplant immunity. Pediatr Transplant. 2019;23(5):e13490. Epub 20190620. doi: 10.1111/petr.13490. PubMed PMID: 31219224.\u003c/li\u003e\n \u003cli\u003eBarton M, Wasfy S, Melbourne T, Hebert D, Moore D, Robinson J, et al. Sustainability of humoral responses to varicella vaccine in pediatric transplant recipients following a pretransplantation immunization strategy. Pediatr Transplant. 2009;13(8):1007-13. Epub 20081215. doi: 10.1111/j.1399-3046.2008.01113.x. PubMed PMID: 19207222.\u003c/li\u003e\n \u003cli\u003eLiman AYJ, Wozniak LJ, de St Maurice A, Dunkel GL, Wanlass EM, Venick RS, et al. Low post-transplant measles and varicella titers among pediatric liver transplant recipients: A 10-year single-center study. Pediatr Transplant. 2022;26(6):e14322. Epub 20220517. doi: 10.1111/petr.14322. PubMed PMID: 35582739.\u003c/li\u003e\n \u003cli\u003eWebb NJ, Fitzpatrick MM, Hughes DA, Brocklebank TJ, Judd BA, Lewis MA, et al. Immunisation against varicella in end stage and pre-end stage renal failure. Trans-Pennine Paediatric Nephrology Study Group. Arch Dis Child. 2000;82(2):141-3. doi: 10.1136/adc.82.2.141. PubMed PMID: 10648369; PubMed Central PMCID: PMCPMC1718197.\u003c/li\u003e\n \u003cli\u003ePrevention CfDCa. Varicella Vaccine Recommendations. 2025.\u003c/li\u003e\n \u003cli\u003eBianchi FP, Tafuri S, Larocca AMV, Germinario CA, Stefanizzi P. Long -term persistence of antibodies against varicella in fully immunized healthcare workers: an Italian retrospective cohort study. BMC Infect Dis. 2021;21(1):475. Epub 20210525. doi: 10.1186/s12879-021-06180-x. PubMed PMID: 34034659; PubMed Central PMCID: PMCPMC8152326.\u003c/li\u003e\n \u003cli\u003eHinman AR, Orenstein WA, Mortimer EA, Jr. When, where, and how do immunizations fail? Ann Epidemiol. 1992;2(6):805-12. doi: 10.1016/1047-2797(92)90074-z. PubMed PMID: 1342333.\u003c/li\u003e\n \u003cli\u003eEberhardt CS, Wieland A, Nasti TH, Grifoni A, Wilson E, Schmid DS, et al. Persistence of Varicella-Zoster Virus-Specific Plasma Cells in Adult Human Bone Marrow following Childhood Vaccination. J Virol. 2020;94(13). Epub 20200616. doi: 10.1128/JVI.02127-19. PubMed PMID: 32321817; PubMed Central PMCID: PMCPMC7307153.\u003c/li\u003e\n \u003cli\u003eLevin MJ, Weinberg A. Immune Responses to Varicella-Zoster Virus Vaccines. Curr Top Microbiol Immunol. 2023;438:223-46. doi: 10.1007/82_2021_245. PubMed PMID: 35102438.\u003c/li\u003e\n \u003cli\u003eMurata K, Hoshina T, Onoyama S, Tanaka T, Kanno S, Ishimura M, et al. Reduction in the Number of Varicella-Zoster Virus-Specific T-Cells in Immunocompromised Children with Varicella. Tohoku J Exp Med. 2020;250(3):181-90. doi: 10.1620/tjem.250.181. PubMed PMID: 32213753.\u003c/li\u003e\n \u003cli\u003eJiang W, Withers B, Sutrave G, Clancy LE, Yong MI, Blyth E. Pathogen-Specific T Cells Beyond CMV, EBV and Adenovirus. Curr Hematol Malig Rep. 2019;14(4):247-60. doi: 10.1007/s11899-019-00521-z. PubMed PMID: 31228095.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Patient demographics.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"756\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33.3778%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003eTotal (n=45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003eMaintained Immunity \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(n=34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003eLost Immunity (n=11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.3511%;\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33.3778%;\"\u003e\n \u003cp\u003eAge at transplant, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e16.7 (12.7-18.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e17.3 (13.4-19.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e12.4 (3.9-17.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.3511%;\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33.3778%;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.3511%;\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33.3778%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e29 (64.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e20 (58.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e9 (81.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.3511%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33.3778%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e16 (35.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e14 (41.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e2 (18.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.3511%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33.3778%;\"\u003e\n \u003cp\u003eRace/Ethnicity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.3511%;\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33.3778%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Hispanic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e29 (64.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e23 (67.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e6 (54.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.3511%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33.3778%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Non-Hispanic White\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e9 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e6 (17.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e3 (27.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.3511%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33.3778%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Non-Hispanic Black\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e5 (11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e4 (11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e1 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.3511%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33.3778%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Asian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e2 (4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e1 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.3511%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33.3778%;\"\u003e\n \u003cp\u003eOriginal disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.3511%;\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33.3778%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;CAKUT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e21 (46.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e14 (41.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e7 (63.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.3511%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33.3778%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;FSGS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e5 (11.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e3 (8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e2 (18.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.3511%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33.3778%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Glomerulonephritis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e10 (22.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e9 (26.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e1 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.3511%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33.3778%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Other\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e9 (20.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e8 (23.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e1 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.3511%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33.3778%;\"\u003e\n \u003cp\u003eDeceased-donor renal transplant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e40 (88.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e31 (91.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e9 (81.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.3511%;\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33.3778%;\"\u003e\n \u003cp\u003eRepeat transplant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e2 (4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e1 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.3511%;\"\u003e\n \u003cp\u003e0.43\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33.3778%;\"\u003e\n \u003cp\u003eHighly sensitized (PRA \u0026gt; 30%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e6 (13.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e3 (8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e3 (27.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.3511%;\"\u003e\n \u003cp\u003e0.15\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33.3778%;\"\u003e\n \u003cp\u003eInduction agent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.3511%;\"\u003e\n \u003cp\u003e\u0026gt;0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33.3778%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Lymphocyte depleting agent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e38 (84.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e29 (85.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e9 (81.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.3511%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33.3778%;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;Non-lymphocyte depleting agent\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e7 (15.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e5 (14.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e2 (18.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.3511%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33.3778%;\"\u003e\n \u003cp\u003eSteroid-based immunosuppression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e20 (44.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e11 (32.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e9 (81.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.3511%;\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 33.3778%;\"\u003e\n \u003cp\u003eFollow-up time, months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e14.9 (11.9-32.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e22.8 (12.0-33.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.757%;\"\u003e\n \u003cp\u003e12.6 (8.8-14.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 13.3511%;\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;Values are expressed as n (%) or median (interquartile range). CAKUT, congenital anomalies of the kidney and urinary tract; FSGS, focal segmental glomerulosclerosis; PRA, panel of reactive antibodies.\u003cbr\u003e\u003cbr\u003eTable 2. Varicella zoster vaccination and IgG titer pre- and post-transplant.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"808\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 256px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003eTotal (n=45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 157px;\"\u003e\n \u003cp\u003eMaintained Immunity \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;(n=34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 145px;\"\u003e\n \u003cp\u003eLost Immunity (n=11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 100px;\"\u003e\n \u003cp\u003eP\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 256px;\"\u003e\n \u003cp\u003eNumber of pre-transplant VZV doses\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 157px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 145px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 100px;\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 256px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003e2 (4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 157px;\"\u003e\n \u003cp\u003e2 (5.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 145px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 256px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003e34 (75.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 157px;\"\u003e\n \u003cp\u003e27 (79.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 145px;\"\u003e\n \u003cp\u003e7 (63.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 256px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003e7 (15.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 157px;\"\u003e\n \u003cp\u003e4 (11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 145px;\"\u003e\n \u003cp\u003e3 (27.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 256px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003e2 (4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 157px;\"\u003e\n \u003cp\u003e1 (2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 145px;\"\u003e\n \u003cp\u003e1 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 256px;\"\u003e\n \u003cp\u003eTime between last VZV vaccine and transplant, months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003e98.1 (15.2-146.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 157px;\"\u003e\n \u003cp\u003e103.9 (42.6-151.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 145px;\"\u003e\n \u003cp\u003e10.7 (4.4-98.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 100px;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 256px;\"\u003e\n \u003cp\u003eTime between last VZV vaccine and transplant\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 157px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 145px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 100px;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 256px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026le; 12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003e10 (22.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 157px;\"\u003e\n \u003cp\u003e4 (11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 145px;\"\u003e\n \u003cp\u003e6 (54.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 256px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; 12-24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003e4 (8.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 157px;\"\u003e\n \u003cp\u003e3 (8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 145px;\"\u003e\n \u003cp\u003e1 (9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 256px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026gt; 24 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003e31 (68.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 157px;\"\u003e\n \u003cp\u003e27 (79.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 145px;\"\u003e\n \u003cp\u003e4 (36.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 100px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 256px;\"\u003e\n \u003cp\u003eTime between pre-transplant VZV IgG and transplant, months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003e8.8 (4.8-13.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 157px;\"\u003e\n \u003cp\u003e10.5 (5.1-13.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 145px;\"\u003e\n \u003cp\u003e5.1 (3.3-15.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 100px;\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 256px;\"\u003e\n \u003cp\u003ePre-transplant VZV IgG, index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003e1.9 (1.3-2.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 157px;\"\u003e\n \u003cp\u003e1.9 (1.6-2.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 145px;\"\u003e\n \u003cp\u003e1.7 (1.3-3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 100px;\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 256px;\"\u003e\n \u003cp\u003eTime from transplant to post-transplant VZV IgG, months *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003e14.9 (11.9-32.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 157px;\"\u003e\n \u003cp\u003e22.8 (12.0-33.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 145px;\"\u003e\n \u003cp\u003e12.6 (8.8-14.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 100px;\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 256px;\"\u003e\n \u003cp\u003ePost-transplant VZV IgG, index *\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003e1.49 (1.1-2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 157px;\"\u003e\n \u003cp\u003e1.8 (1.3-2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 145px;\"\u003e\n \u003cp\u003e0.8 (0.6-1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 100px;\"\u003e\n \u003cp\u003e0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 256px;\"\u003e\n \u003cp\u003eWBC count, 1000/uL **\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 149px;\"\u003e\n \u003cp\u003e5.9 (4.6-7.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 157px;\"\u003e\n \u003cp\u003e5.8 (4.6-7.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 145px;\"\u003e\n \u003cp\u003e5.9 (3.0-7.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 100px;\"\u003e\n \u003cp\u003e0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eValues are expressed as n (%) or median (interquartile range). VZV, varicella zoster virus; IgG, immunoglobulin G; WBC, white blood cell. * The most recent VZV IgG or the first negative VZV IgG post-transplant. ** WBC count at the time of post-transplant VZV IgG titer.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Infection, Pediatric, Seroconversion, Transplant, Varicella Zoster, Immunosuppression","lastPublishedDoi":"10.21203/rs.3.rs-6866072/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6866072/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: Varicella zoster (VZV) vaccination pre-kidney transplant (Tx) can help prevent severe disseminated VZV in immunosuppressed recipients, however, studies have shown loss of humoral immunity post-Tx.\u003c/p\u003e\n\u003cp\u003eMethods: A retrospective analysis of 45 pediatric kidney Tx recipients with positive pre-Tx VZV IgG (\u0026gt;1.09 index). VZV IgG was assessed annually and compared with the induction agent used, number of VZV vaccines received, and the interval between the last dose of VZV vaccine and Tx.\u003c/p\u003e\n\u003cp\u003eResults: Median age at Tx was 16.7 years (IQR 12.7-18.5). 11 of 45 (24.4%) patients lost immunity to VZV at a median of 12.6 months post-Tx. Those who lost VZV immunity were younger at the time of Tx, 12.4 years vs. 17.3 years (P=0.05) and more likely to be on steroid-based immunosuppression 81.8% vs. 32.4% (P=0.006). There were no differences between the induction agents used and the ability to maintain VZV IgG antibodies. Subjects who required ³3 doses of VZV vaccine to develop VZV IgG seropositivity were at a higher risk for losing their anti-varicella antibody post-Tx (HR 3.81, 95%CI 1.09-13.30, P=0.04). Receiving VZV vaccination \u0026lt;1 year prior to kidney Tx was associated with a higher risk for losing anti-varicella antibody after Tx (HR 6.97, 95%CI 2.08-23.34).\u003c/p\u003e\n\u003cp\u003eConclusion: In this small cohort, pediatric kidney Tx recipients are more likely to lose VZV IgG in those who were younger at the time of Tx, on steroid-based immunosuppression, required 3 or more doses of VZV vaccination to seroconvert, or received VZV vaccine \u0026lt;1 year before Tx.\u003c/p\u003e","manuscriptTitle":"Risk Factors for Loss of Varicella Immunity After Pediatric Kidney Transplantation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-17 08:57:34","doi":"10.21203/rs.3.rs-6866072/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major Revisions Needed","date":"2025-07-29T15:11:44+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-07-07T20:52:15+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-06-11T16:55:43+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-10T21:54:02+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Nephrology","date":"2025-06-10T16:23:49+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"680a74e4-16b0-4147-9f72-73da6122e5c5","owner":[],"postedDate":"June 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-11-17T16:02:24+00:00","versionOfRecord":{"articleIdentity":"rs-6866072","link":"https://doi.org/10.1007/s00467-025-07022-7","journal":{"identity":"pediatric-nephrology","isVorOnly":false,"title":"Pediatric Nephrology"},"publishedOn":"2025-11-13 15:58:12","publishedOnDateReadable":"November 13th, 2025"},"versionCreatedAt":"2025-06-17 08:57:34","video":"","vorDoi":"10.1007/s00467-025-07022-7","vorDoiUrl":"https://doi.org/10.1007/s00467-025-07022-7","workflowStages":[]},"version":"v1","identity":"rs-6866072","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6866072","identity":"rs-6866072","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}