Abstract Body: Transgender females (TGFs) are born male but identify as female. Gender-affirming hormone therapy (GAHT) is used to treat gender dysphoria. In TGFs, GAHT includes 17β-estradiol (E2) combined with an anti-androgen or surgical intervention. Whether renal function is decreased in TGFs on GAHT compared to cis-gender controls is unknown. Thus, we tested the hypothesis that glomerular filtration rate (GFR) is reduced and that renal susceptibility to acute renal ischemia is enhanced in male rats that undergo cross-sex hormone therapy (CSHT) in young adulthood. Male Sprague Dawley rats were randomly assigned to Control (CON) or E2 [5 mg/day, silastic capsule s.c. replaced every 3 weeks] starting at 13 weeks of age (adulthood) followed by castration (CTX) two weeks later. At 25 weeks of age, rats in each group were randomly subdivided to undergo Sham or renal Ischemia/Reperfusion (I/R, 18 minute occlusion renal pedicles) (n=8-11/grp). Metabolic studies were conducted two days prior, then 1, 7, and 21 days after Sham or I/R with GFR measured (direct method of FITC-sinistrin) at end of study. Two-way ANOVA with Tukey’s post hoc analysis, P<0.05 considered significant. Results (Table): Body weight and lean mass (EchoMRI) were significantly decreased in E2+CTX vs. CONs (*P<0.0001). At 1-day post-surgery, proteinuria was decreased in E2+CTX vs. CONs (†P<0.05); yet, 3 weeks post-surgery, proteinuria was only reduced in E2+CTX I/R vs. CON Sham (†P<0.05). GFR did not differ but urinary creatinine, which may reflect lean mass, was decreased in both E2+CTX vs. CONs (*P<0.0001). These data suggest that the biological effect of CSHT in the male does not enhance renal risk in young adulthood.