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

BACKGROUND: Men with chronic kidney disease (CKD) tend to experience a faster estimated glomerular filtration rate (eGFR) decline than women, potentially due to 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, as 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 one year of GAHT.

METHODS: As part of the European Network for the Investigation of Gender Incongruence (ENIGI) 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.

RESULTS: In transgender women, cystatin C decreased by 0.069 mg/L (95% CI, 0.049 to 0.089), corresponding with a 7 mL/min/1.73m2 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/1.73m2 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 employed in the equation.

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