Calculating Creatinine-Based Kidney Function With and Without Sex Assigned at Birth Among Transgender Adults

Calculating Creatinine-Based Kidney Function With and Without Sex Assigned at Birth Among Transgender Adults
Laurie Grund, PharmD, Geritom Medical, Inc.

Background: Hormone therapy typically causes marked physiologic and body composition changes within months of initiation among transgender adults. The alterations in lean muscle mass due to hormone therapy is expected to have a corresponding impact on serum creatinine, as this is a known breakdown product of muscle. What is less understood is whether hormone therapy influences kidney function directly and how clinicians should utilize gender as it relates to estimated creatinine clearance (eCrCl) and glomerular filtration rate (eGFR) equations to provide the most accurate results. As a way to account for the average body composition differences between sexes, clinicians have recommended using equations based on gender identity, rather than one’s sex assigned at birth in transgender adults utilizing hormone therapy.

Objectives: The primary endpoint was the percent difference in median eCrCl three to six months and six to twelve months post initiation of hormone therapy compared with baseline using the Cockcroft-Gault (C-G) renal function estimation equation. The secondary objective was to re-analyze Cockcroft-Gault, modification of diet in renal disease (MDRD), and chronic kidney disease epidemiology study (CKD-EPI) estimates three to six months and six to twelve months post-index date using equations associated with gender identity (male-based equations in the testosterone group; female-based equations in the estrogen group) and compared these with baseline estimates using sex assigned at birth.

Study Design: This study was a single-system, multicenter, retrospective cohort study of healthy transgender adults. Patients were identified over a ten year period as having completed at least one transgender health-related clinical visit based on validated diagnosis codes. Eligible patients were prescribed hormone therapy, either testosterone or estrogen, for at least 90 days, with the index date set as the first hormone order date, and at least one creatinine measurement within six months pre-index date at baseline.

Results: In total, 989 patients completed at least one clinical visit for transgender related care. Of those 989 patients, 70 were analyzed, 29 of whom were prescribed testosterone and 41 were prescribed estrogen. At baseline and follow-up visits, laboratory values, body composition, eCrCL and eGFR using estimating equations based on sex assigned at birth, and gender identiy were assessed and recorded. In the testosterone group, using female-based equations, Cockcroft-Gault estimates significantly decreased from baseline only at the six to twelve month follow-up assessment. Also in the testosterone group, median MDRD and CKD-EPI estimates had a significant decrease at both the three to six month and six to twelve month follow-up when compared to baseline (see Table 1 below). In the estrogen group, using male-based equations, there were no statistically significant changes at either the three to six month or six to twelve month follow-up assessments. When applying gender identity, using male based equations in the testosterone group at follow-up, median MDRD and CKD-EPI estimates were significantly higher at both the three to six month and six to twelve month visits, compared to baseline (see Table 2 below). The authors note that these findings suggest on average, neither testosterone or estrogen treatment are likely associated with significant changes in estimated kidney function, and feel that these findings align with previous studies recommending clinicians use male-based equations after at least six months of testosterone therapy.

Table 1. Abbreviated Testosterone Group Results at Baseline and Follow-up (n = 29).

Percent Change

Baseline (range)

3-6 Months (range)

6-12 Month (range)

eCrCL C-G 

(ml/min)

120 (97-143)

94 (93 - 114)

-3%: female-based

P = 0.3125


+21%: male-based

P > 0.025

93 (83 - 119)

-14%: female-based

P = 0.0181


+5%: male-based

P > 0.025

eGFR MDRD (ml/min/1.73m2)

99 (83 - 120)

89 (81 - 96)

-7%: female-based

P = 0.0013


+26%: male-based

P = 0.0005

80 (71 - 100)

-18%: female-based

P = 0.0006


+11%: male-based

P = 0.0003

eGFR CKD-EPI

(ml/min/1.73m2)

116 (97 - 124)

105 (94 - 112)

-7%: female-based

P = 0.0046


+13%: male-based

P = 0.0007

94 (83 - 113)

-9%: female-based

P = 0.0009


+4%: male-based

P = 0.0094

Table 2. Abbreviated Estrogen Group Results at Baseline and Follow-up (n = 41).

Percent Change

Baseline (range)

3-6 Months (range)

6-12 Months (range)

eCrCL C-G 

(ml/min)

129 (112 - 153)

125 (116 - 144)

+5%: male-based

P = 0.2842


-12%: female-based

P < 0.0001

145 (105 - 163)

0%: male-based

P = 0.6567


-17%: female-based

P < 0.0001

eGFR MDRD (ml/min/1.73m2)

111 (94 - 125)

105 (101 - 120)

+4%: male-based

P = 0.2451


-23%: female-based

P < 0.0001

117 (90 - 133)

0%: male-based

P = 0.6476


-26%: female-based

P < 0.0001

eGFR CKD-EPI

(ml/min/1.73m2)

117 (104 - 126)

116 (109 - 126)

+1%: male-based

P = 0.2348


-19%: female-based

P < 0.0001

122 (101 - 130)

0%: male-based

P = 0.9705


-15%: female-based

P < 0.0001

Conclusions: It still remains unclear whether sex-based or gender-identity-based kidney function estimation equations are accurate for transgender adults using hormone therapy. Female-based equations may underestimate eCrCl or eGFR amoung transgender adults undergoing either testosterone or estrogen therapy within the first year of therapy. Clinicians should recognize the potential for underestimation of kidney function when utilizing female based estimation equations and dosing medications in transgender individuals when using kidney-based dose adjustments. Authors also note that larger prospective studies with measured GFRs are needed to determine the impact of hormone therapy on kidney function in transgender adults during both short and long-term therapy.

Reference:

  1. Fadich SK, Kalayjian A, Greene DN, Cirrincione LR. A Retrospective Analysis of Creatinine-Based Kidney Function With and Without Sex Assigned at Birth Among Transgender Adults. Annals of Pharmacotherapy. October 2021. doi:10.1177/106002802110501