Valacyclovir-associated neurotoxicity among patients on hemodialysis and peritoneal dialysis: A nationwide population-based study

Yi-Chun Wang; Shu-Hui Juan; Ching-Hao Li; Chu-Lin Chou; Li-Ying Chen; Li-Nien Chien; Te-Chao Fang

doi:10.3389/fmed.2022.997379

Valacyclovir-associated neurotoxicity among patients on hemodialysis and peritoneal dialysis: A nationwide population-based study

Front Med (Lausanne). 2022 Sep 20:9:997379. doi: 10.3389/fmed.2022.997379. eCollection 2022.

Authors

Yi-Chun Wang^{1

2}, Shu-Hui Juan³, Ching-Hao Li³, Chu-Lin Chou^{4

5

6

7}, Li-Ying Chen⁸, Li-Nien Chien^{9

10}, Te-Chao Fang^{4

5

11}

Affiliations

¹ Division of Nephrology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.
² School of Medicine, Tzu Chi University, Hualien, Taiwan.
³ Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁴ TMU Research Center of Urology and Kidney, Taipei Medical University, Taipei, Taiwan.
⁵ Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁶ Division of Nephrology, Department of Internal Medicine, Hsin Kuo Min Hospital, Taipei Medical University, Taoyuan City, Taiwan.
⁷ Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
⁸ Health Data Analytics and Statistics Center, Office of Data Science, Taipei Medical University, Taipei, Taiwan.
⁹ Institute of Health and Welfare Policy, College of Medicince, National Yang Ming Chiao Tung University, Taipei, Taiwan.
¹⁰ Graduate Institute of Data Science, College of Management, Taipei Medical University, Taipei, Taiwan.
¹¹ Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.

Abstract

Whether valacyclovir-associated neurotoxicity (VAN) occurs more frequently in patients with end-stage renal disease (ESRD) on dialysis is unknown. This is the first population-based study to examine the risk of VAN associated with ESRD patients on dialysis. Among 2,284,800 patients diagnosed as having herpes zoster from 2002 to 2016, patients with ESRD on dialysis and individuals with normal renal function were enrolled in this study. Following propensity score matching, we compared the risk of altered mental status between valacyclovir users and non-users in the ESRD and normal renal function cohorts over a 30-day follow-up period. In the ESRD cohort, the incidence of altered mental status was 1.68 and 0.52 per 1,000 person-day in valacyclovir users and non-users, respectively, with an adjusted hazard ratio (HR) of 3.22 (95% confidence interval [CI]: 2.04-4.99, P < 0.001). The incidence of altered mental status of valacyclovir users on hemodialysis (HD) and peritoneal dialysis (PD) was higher than that of non-users. The adjusted HR was 3.20 (95% CI: 1.98-5.15, P < 0.001) for those on HD and 3.44 (95% CI: 1.13-10.49, P = 0.030) for those with PD. However, altered mental status was not observed in patients on HD receiving ≤500 mg of valacyclovir three times per week or in those on PD receiving ≤500 mg of valacyclovir per day. The findings demonstrate that adjusting the valacyclovir dosage and monitoring VAN in patients with HD and PD who have herpes zoster is crucial.

Keywords: hemodialysis (HD); neurotoxicity; peritoneal dialysis; population-based study; valacyclovir.