Cystatin C-Based eGFR Changes during Gender-Affirming Hormone Therapy in Transgender Individuals

Men with CKD tend to experience a faster eGFR decline than women, potentially because of sex hormones. Limited research exists regarding the effect of gender-affirming hormone therapy (GAHT) on kidney function. Furthermore, monitoring kidney function during GAHT is challenging because serum creatinine is confounded by body composition. To investigate the relationship between sex hormones and kidney function, we studied the changes of serum creatinine and serum cystatin C, a filtration marker less affected by sex, during 1 year of GAHT.

As part of the European Network for the Investigation of Gender Incongruence study, we measured serum creatinine and serum cystatin C in 260 transgender women and 285 transgender men before and 12 months after initiating GAHT. Transgender women received estradiol plus cyproterone acetate, while transgender men received testosterone. Cystatin C-based eGFR was calculated using the full-age-spectrum equation.

In transgender women, cystatin C decreased by 0.069 mg/L (95% confidence interval [CI], 0.049 to 0.089), corresponding with a 7 ml/min per 1.73 m 2 increase in eGFR. In transgender men, cystatin C increased by 0.052 mg/L (95% CI, 0.031 to 0.072), corresponding with a 6 ml/min per 1.73 m 2 decrease in eGFR. Creatinine concentrations decreased (-0.065 mg/dl; 95% CI, -0.076 to -0.054) in transgender women and increased (+0.131 mg/dl; 95% CI, 0.119 to 0.142) in transgender men. Changes in creatinine-based eGFR varied substantially depending on the sex used in the equation.

In this cohort of transgender individuals, cystatin C-based eGFR increased with estradiol and antiandrogen therapy and decreased with testosterone therapy.