A Retrospective Analysis of Creatinine-Based Kidney Function With and Without Sex Assigned at Birth Among Transgender Adults

Abstract

Background Clinicians use sex-based kidney function estimating equations, but the appropriate sex modifier for transgender adults undergoing hormone therapy (HT) is undetermined. Objectives Compare median estimated creatinine clearance (eCrCL; Cockcroft-Gault) and estimated glomerular filtration rates (eGFRs; Modification of Diet in Renal Disease [MDRD] and Chronic Kidney Disease Epidemiology Study [CKD-EPI]) before and during HT when estimated with and without sex assigned at birth. Methods Single-system retrospective cohort study of transgender adults (2007-2017) prescribed ≥90 days HT (index date = first order) and measured serum creatinine ≤6 months pre-index date (baseline) and ≤12 months post-index date. We grouped patients based on testosterone or estrogen treatment and compared eCrCL and eGFRs at baseline up to 6-12 months post-index date using equations based on sex assigned at birth (female or male modifier in testosterone or estrogen groups, respectively) or gender identity (male or female modifier in testosterone or estrogen groups, respectively). We used Wilcoxon signed-rank tests (Bonferroni correction) for all comparisons. Results In total, 29 (median age 26 years, follow-up 259 days) and 41 patients (29 years, 250 days) were prescribed testosterone or estrogen, respectively. In the testosterone group, the maximum eCrCL and eGFR changes based on sex assigned at birth were −14%, P = 0.0181; −18%; P = 0.0009, respectively, and based on gender identity were +5%, P > 0.025 and +11%, P = 0.0094, respectively. In the estrogen group, eCrCL or eGFRs based on sex assigned at birth did not change from baseline but based on gender identity were −17%, P < 0.0001 and −26%, P < 0.0001, respectively. Conclusion and Relevance Female-based equations may underestimate kidney function in transgender adults undergoing testosterone or estrogen treatment. Prospective cohort studies are needed to confirm the clinical significance of these findings.

Underestimation of kidney function due to poorly controlled 21‐hydroxylase deficiency

“…In this case, we observed that the patient's serum testosterone level continued to increase for 3 years preceding the referral, and sCre was eventually elevated at the time of referral. Testosterone, the primary androgen in males, can stimulate muscle protein synthesis via testosterone receptors in skeletal muscle 2–5 . Although a trend in sCre during this period was not confirmed, the patient's sCre and weight increased with normal kidney function, suggesting that the serum testosterone levels increased muscle mass, thereby increasing sCre of the patient regardless of kidney function.…”

Comment: A Retrospective Analysis of Creatinine-Based Kidney Function With and Without Sex Assigned at Birth Among Transgender Adults

“…5 In contrast, eCrCl and eGFR did not significantly change in transgender women (estrogen group) when using the sex assigned at birth but significantly worsened when using the identified gender. 5 Interestingly, serum creatinine significantly increased over time among transgender men but did not significantly change in transgender women. 5 These results highlight the significant effect of the sex coefficient on the assessment of renal function among various estimating equations, despite relatively small absolute changes in serum creatinine.…”

“…5 Interestingly, serum creatinine significantly increased over time among transgender men but did not significantly change in transgender women. 5 These results highlight the significant effect of the sex coefficient on the assessment of renal function among various estimating equations, despite relatively small absolute changes in serum creatinine. Although serum creatinine may be more similar between estimating equations using identified gender compared to sex assigned at birth after 6 months of gender-affirming hormone therapy, clinicians should be aware that transgender men may have an overestimation of renal function and transgender women may have an underestimation of renal function when using creatinine-based equations.…”

“…3,4 The recent retrospective article in Annals of Pharmacotherapy sought to investigate the changes in estimated creatinine clearance (eCrCl) and estimated glomerular filtration rates (eGFR) between identified gender and sex assigned at birth after initiating gender-affirming hormone therapy. 5 The authors observed that eCrCl and eGFR significantly worsened in transgender men (testosterone group) when using the sex assigned at birth, but significantly improved when using the identified gender. 5 In contrast, eCrCl and eGFR did not significantly change in transgender women (estrogen group) when using the sex assigned at birth but significantly worsened when using the identified gender.…”

“…5 The authors observed that eCrCl and eGFR significantly worsened in transgender men (testosterone group) when using the sex assigned at birth, but significantly improved when using the identified gender. 5 In contrast, eCrCl and eGFR did not significantly change in transgender women (estrogen group) when using the sex assigned at birth but significantly worsened when using the identified gender. 5 Interestingly, serum creatinine significantly increased over time among transgender men but did not significantly change in transgender women.…”