OR31-06 Gender-Affirming Hormone Therapy Affects Serum Cystatin C-based eGFR In Transgender Individuals

Disclosure: S.A. van Eeghen: None. C. Wiepjes: None. N. Nokoff: None. P. Bjornstad: None. M. Den Heijer: None. D. van Raalte: None. Background: Previous studies in transgender individuals have shown that masculinizing (testosterone) hormone therapy increases and feminizing (estradiol combined with anti-androgen) hormone therapy decreases serum creatinine. Translating this into estimated glomerular filtration rate (eGFR) according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, eGFR increases in transwomen and decreases in transmen during gender-affirming hormone therapy (GAHT). However, serum creatinine is significantly correlated with lean body mass (LBM), which also changes during GAHT, with transmen gaining and transwomen loosing muscle mass. Thus changes in creatinine-derived eGFR during hormone therapy may not reflect true changes in GFR. Another manner to estimate GFR, which is not affected by body composition, is by measuring plasma cystatin C concentrations. Therefore, we studied the effects of GAHT on serum cystatin C, a sex-independent marker for GFR. Methods: In this prospective, observational sub study of the European Network for the Investigation of Gender Incongruence (ENIGI), serum cystatin C was measured in 266 transwomen and 285 transmen before and at 12 months of GAHT. Transwomen received feminizing hormone therapy, consisting of oral (n= 122) or transdermal administration (n= 144) of estrogen in combination with the oral anti-androgen cyproteroneacetate. Transmen received masculinizing hormone therapy, which consisted of intramuscular (n= 144) or transdermal (n= 141) administration of testosterone. Serum cystatin C-based eGFR was calculated according to the full-age-spectrum equation (FAScysC; mL/min/1.73m(2)). Linear regression was used to assess the means. Results: In transwomen (baseline characteristics; median age 29 (IQR 23-43) years; median BMI 22.9 (IQR 20.8-26.4) kg/m(2); creatinine 78.6 ± 9.9 μmol/L; creatinine-based CKD-EPI eGFR 110 ± 14 mL/min/1.73m(2)), cystatin C decreased by 0.07 (95% CI, 0.05 to 0.09) mg/L; from 0.94 ± 0.17 mg/L before GAHT to 0.87 ± 0.15 mg/L during GAHT. This corresponds with an increase in FAScysC of 7 (95% CI, 5 to 9) mL/min/1.73m(2); from 93 ± 17 to 100 ± 18 mL/min/1.73m(2). On the contrary, in transmen (baseline characteristics; median age 22 (IQR 20-28) years; median BMI 24.7 (IQR 21.4-30.1) kg/m(2); creatinine 66.8 ± 9.3 μmol/L; creatinine-based CKD-EPI eGFR 110 ± 15 mL/min/1.73m(2)) cystatin C increased by 0.05 (95% CI, 0.03 to 0.07) mg/L; from 0.89 ± 0.17 mg/L before GAHT to 0.95 ± 0.16 mg/L during 12 months of GAHT. This is consistent with a decrease in FASCysC of 6 (95% CI, 4 to 8) mL/min/1.73m(2); from 101 ± 19 to 94 ± 15 mL/min/1.73m(2). Conclusions: In this large-sized cohort of transgender individuals, cystatin C-based eGFR increased with feminizing hormone therapy and decreased with masculinizing hormone therapy, indicating true biological effects of sex hormones on kidney physiology, which warrants further investigation. Presentation: Sunday, June 18, 2023