Gender-affirming Hormone Therapy and Changes in Kidney Function in Adults: A Retrospective Population-based Study

Rationale & Objective: Gender-affirming hormone therapy (GAHT) modifies lean body mass and body fat but its impact on kidney function is uncertain. We sought to evaluate the association of GAHT with kidney function and clinical outcomes. Study Design: A retrospective observational cohort study using linked health administrative databases. Setting & Participants: Transgender and gender diverse (TGD) adults in Manitoba, Canada from January 1, 2007, to March 31, 2018. Exposure: GAHT or no GAHT prescriptions. Outcomes: The primary outcome was the change in serum creatinine levels. Secondary outcomes included the change in urine albumin-to-creatinine ratio, incident acute kidney injury, chronic kidney disease, and hypertension. Analytical Approach: Outcomes were assessed for up to 2 years. Participants were censored at 3 months post-GAHT prescription if it was not refilled. Outcomes between TGD adults treated with and without GAHT (stratified by sex assigned at birth) were compared using multivariable linear regression and Cox proportional hazards models. Results: We identified 396 TGD adults assigned female at birth (AFAB) (277 receiving GAHT) and 322 TGD adults assigned male at birth (AMAB) (240 receiving GAHT) with longitudinal kidney function measurements. In AFAB persons treated with GAHT compared with no GAHT, serum creatinine levels increased from baseline at 18 months (+7.0 μmol/L, 95% CI, 0.5-14) and 21 months (+10.7 μmol/L, 95% CI, 3-18) but not at any other time point including 24 months. There were no differences in changes in creatinine in AMAB persons treated with GAHT compared with no GAHT. AFAB and AMAB persons initiating GAHT had no significant increased risks of incident chronic kidney disease or hypertension. Limitations: Limited sample size, missing data, and residual confounding. Conclusions: GAHT is associated with an increase in serum creatinine levels in AFAB persons. Additional research is needed to further evaluate the effect of GAHT on kidney function.