Sympathetic Reinnervation is Associated With Antihypertensive Treatment Burden and Interstitial Fibrosis After Kidney Transplantation.

Background: Sympathetic reinnervation after kidney transplantation has been demonstrated histologically and functionally, but its clinical and molecular consequences remain unclear. Methods: In this single-center retrospective study, 50 adult living-donor kidney transplant recipients were evaluated. Based on tyrosine hydroxylase (TH) immunostaining at 3 months and subsequent biopsies, recipients were categorized into the following: regeneration group (TH-negative at 3 months and TH-positive thereafter), nonregeneration group (persistently TH-negative), and a histologically nonevaluable group (TH-positive from 3 months onward). Cortical interstitial fibrosis was quantified by Sirius Red morphometry, and fibrosis-related gene expression was assessed using NanoString Human Fibrosis V2 Panel. Results: Although all grafts showed TH-positive fibers immediately after transplantation, 58% became TH-negative at 3 months (29/50). Among these, 79% later demonstrated sympathetic reinnervation (23/29), whereas 6/29 remained persistently TH-negative. Antihypertensive agent use transiently decreased at 3 months but subsequently increased, predominantly in regeneration group. At 1 and 3 years, regeneration group required more antihypertensive medications than nonregeneration group (1 year: Conclusion: Sympathetic reinnervation was observed together with higher antihypertensive medication burden and greater interstitial fibrosis over time, along with transcriptomic signatures consistent with SASP-related fibrogenic pathways. However, given limited size of the nonregeneration subgroup and lack of functional validation, these findings should be interpreted cautiously and regarded as hypothesis-generating.