The Effect of Gender-Affirming Hormone Treatment on Kidney Function Trajectories in Transgender and Gender Diverse Veterans

BACKGROUND: The impact of hormone therapy (HT) on kidney function in transgender and gender diverse (TGD) individuals remains poorly understood, and this lack of data poses challenges in caring for TGD individuals with kidney disease. We aimed to compare serum creatinine levels and estimated glomerular filtration rate (eGFR) slope, a critical marker of kidney function, in transgender women (TW) and transgender men (TM) relative to cisgender (non-TGD) controls. METHODS: We conducted a longitudinal cohort study of veterans using Veterans Health Administration (VHA) care from January 2006 to December 2019. Serum creatinine and eGFR were assessed using algorithms based on affirmed gender and sex assigned at birth. Within-group changes over time were assessed using generalized linear mixed effect models with random intercept and time modeled as a categorical variable. Two-way fixed effects models were used to assess changes in eGFR slopes relative to HT initiation compared with cisgender controls. RESULTS: The analytic dataset included 6,616 veterans of whom 262 were receiving HT (214 [3%] TW) and 48 [0.72%] TM) and 6,354 were cisgender not receiving HT (1,988 [30% cisgender women (CW) and 4,366 [66%] cisgender men (CM). Serum creatinine was higher as early as three months after HT initiation in TM veterans with stabilization by 12 months, whearas TW veterans did not demonstrate any significant change in their serum creatinine. eGFR was significantly lower in TM veterans after HT initiation, whereas it remained stable in TW veterans. CONCLUSIONS: Our findings suggest that HT is associated with divergent effects on kidney function. These findings suggest the need for individualized kidney monitoring and potentially refined eGFR calculations for TGD populations.