U-shaped association between estimated glomerular filtration rate and mortality in HSV-positive adults: A retrospective cohort study.

Although estimated glomerular filtration rate (eGFR) is a key indicator of kidney function, its association with mortality in herpes simplex virus (HSV)-seropositive individuals remains unclear. We analyzed 17,848 HSV-1/HSV-2 seropositive participants from National Health and Nutrition Examination Survey (1999-2016). The eGFR was calculated using standard equations, and mortality data were linked to the National Death Index through December 31, 2019. Kaplan-Meier survival curves, Cox regression models, generalized additive models, and stratified analyses were used to assess the association between eGFR and all-cause and cardiovascular mortality. The mean age of participants was 33.85 years (standard deviation: 9.4), and the average eGFR was 110.4 mL/min/1.73 m2 (standard deviation: 18.7). During a median follow-up of 141 months, 598 participants (3.35%) died from all causes, and 139 (0.78%) died from cardiovascular causes. A U-shaped association was observed between eGFR and all-cause mortality. Below an inflection point of 85.22 mL/min/1.73 m2, each 10-unit increase in eGFR was associated with reduced risk of all-cause death (hazard ratio = 0.70; 95% confidence interval: 0.64-0.75; P < .0001). Above this threshold, higher eGFR was associated with increased mortality (hazard ratio = 1.12; 95% confidence interval: 1.05-1.20; P = .001). Similar trends were found for cardiovascular mortality, although the association with elevated eGFR was not statistically significant. These findings were consistent across stratified and sensitivity analyses. In HSV-infected individuals, eGFR showed a nonlinear relationship with mortality. Moderate eGFR levels were associated with the lowest mortality risk.