Incidence, risk factors, morbidity and cost of herpes zoster in patients on dialysis: the ZONA-REIN national study

Abstract Background and Hypothesis Herpes zoster has an incidence of 3-5 cases per 1,000 person-years in the general population and increases with age. However, its incidence, risk factors, complications, and costs in dialysis patients remain poorly characterized. This study evaluates these outcomes in dialysis patients. Methods This retrospective national registry-based study included incident patients initiating hemodialysis and peritoneal dialysis between 2009 and 2023, identified from the French REIN registry and linked to the French National Health Data System (SNDS), covering a period that preceded the commercial availability of the recombinant herpes zoster vaccine in France. Patients aged <18 years or with preemptive kidney transplantation were excluded. Herpes zoster was defined by antiviral therapy receipt (acyclovir, valacyclovir, or famciclovir) for 7 days to <3 months; repeated or chemotherapy-associated prescriptions were excluded. Postherpetic neuralgia was defined by neuropathic pain medication dispensing. Incidence rates per 1,000 person-years and risk factors were estimated using Poisson regression, with Fine-Gray models accounting for death as a competing risk. Results Among 144,893 dialysis patients followed until death, transplantation, loss to follow-up, or 31 December 2023, 4,007 received antiviral therapy for herpes zoster. The mean age of the the entire cohort was 68.4±15 years, 64.5% were male, 89.6% on hemodialysis, 45.1% had diabetes, and 25.6% had heart failure. Patients with herpes zoster had longer follow-up (4.8±3.1 vs. 2.9±2.6 years, P<0.001). Herpes zoster occurred 2.3±2.1 years after dialysis initiation. Incidence was 9.65 per 1,000 person-years (95%CI 9.40-9.95). Poisson regression identified older age and female sex as risk factors for herpes zoster while diabetes was not significant in competing-risk analysis. After antiviral therapy, 792 patients (19.8%) received neuropathic painkillers, costing €43,293/month. Concomitantly, 927 patients (23.1%) were hospitalized. Total hospitalization costs reached €3.4 million, including €1.0 million for zoster-related admissions and treatment-related intoxications. Conclusions Herpes zoster incidence is high among dialysis patients and is independently associated with age and female sex. It imposes a substantial clinical and economic burden reflected by frequent neuropathic pain treatment and hospitalizations.