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. 2023 Dec 1;18(12):1545-1554.
doi: 10.2215/CJN.0000000000000289. Epub 2023 Sep 6.

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

Sarah A van Eeghen  1   2 , Chantal M Wiepjes  1   2 , Guy T'Sjoen  3 , Natalie J Nokoff  4 , Martin den Heijer  1   2 , Petter Bjornstad  4   5 , Daniël H van Raalte  2   6   7
Affiliations

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

Sarah A van Eeghen et al. Clin J Am Soc Nephrol. .

Abstract

Background: 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.

Methods: 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.

Results: 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.

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

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Conflict of interest statement

P. Bjornstad reports consultancy for AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Horizon Pharma, LG Chemistry, Lilly, Novo Nordisk, Sanofi, and XORTX; research funding from AstraZeneca, Merck, and Horizon Pharma; advisory or leadership roles for AstraZeneca, Bayer, Boehringer-Ingelheim, Horizon Pharma, LG Chem, Lilly, and XORTX; roles on the advisory boards of AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Novo Nordisk, and XORTX; and role as a data monitoring committee chair for Bayer. M. den Heijer reports research funding from Kyowa Kirin and honoraria from Novartis. N.J. Nokoff reports consultancy for Ionis Pharmaceuticals and Neurocrine Biosciences, Inc.; research funding from Neurocrine Biosciences, Inc.; and other interests or relationships with Expert panel for World Athletics. N.J. Nokoff's spouse reports honoraria from Illumina. D.H. van Raalte reports consultancy from AstraZeneca, Bayer, Boehringer Ingelheim—Ely Lilly Alliance, Merck, MSD, and Sanofi and research funding from AstraZeneca, Boehringer Ingelheim—Ely Lilly Alliance, Merck, MSD, and Sanofi. All remaining authors have nothing to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Serum estradiol and testosterone changed during 1 year of gender-affirming hormone therapy. Median with IQR of serum estradiol (A) and serum testosterone (B) before and at 12 months of GAHT in transgender women and transgender men. *Significant changes between baseline and 12 months of GAHT (P < 0.001). GAHT, gender-affirming hormone therapy; IQR, interquartile range.
Figure 2
Figure 2
Serum cystatin C and cystatin C–based eGFR changed significantly during 1 year of gender-affirming hormone therapy. Mean±SD of serum cystatin C (A) and eGFR FASCys (B) before and at 12 months of GAHT in transgender women and transgender men. *Significant changes between baseline and 12 months of GAHT (P < 0.001).
Figure 3
Figure 3
Serum cystatin C was associated with serum sex hormones during 1 year of gender-affirming hormone therapy. Correlation of change in serum estradiol (A) and serum testosterone (B) and change in serum cystatin C before and at 12 months of GAHT in transgender women and transgender men together. r=Pearson correlation coefficient; R2=coefficient of determination; β=regression coefficient. CI, confidence interval.
Figure 4
Figure 4
Serum creatinine and creatinine-based eGFR changed significantly during 1 year of gender-affirming hormone therapy. Mean±SD of serum creatinine (A) and eGFR CKD-EPICr (B1 and C1) and eGFR FASCrea (B2 and C2) before and at 12 months of GAHT in transgender women and transgender men. At (B), eGFR at 12 months is calculated for sex assigned at birth. At (C), eGFR at 12 months is calculated for gender identity. *Significant changes (P < 0.001).
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Comment in

  • Does Gender-Affirming Hormone Therapy Affect the Kidney?
    Collister D, Ahmed SB. Collister D, et al. Clin J Am Soc Nephrol. 2023 Dec 1;18(12):1524-1526. doi: 10.2215/CJN.0000000000000339. Epub 2023 Oct 23. Clin J Am Soc Nephrol. 2023. PMID: 37871954 Free PMC article. No abstract available.

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