Kidney FuNction in people receiving Gender affirming Hormone Therapy

Rationale: Sex differences in renal physiology is a vastly understudied area, despite known differences in sex-specific rates of chronic kidney disease. Renal function decline is accelerated in men compared to women, suggesting a potential harmful role for testosterone. Transgender individuals undergoing hormone therapy provide a unique model to study the effects of gender affirming hormone therapy on kidney function and renal physiology.
Objective: The central objectives of this study are to comprehensively detail (intra)renal hemodynamic function and tubular function in transgender individuals before and after gender affirming hormone therapy.
Study design: Prospective observational study
Study population: Transgender individuals (20 transmen and 20 transwomen) between 18-30 years old, scheduled to start hormone therapy.
Intervention (if applicable): n/a
Main study parameters/endpoints: The main study parameters/endpoints are the measurement of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) as measured by iohexol and p-amminohippurate (PAH) clearance. Secondary endpoints are the estimation of intrarenal hemodynamic parameters derived from Gomez equations, markers of tubular injury and changes in systemic hemodynamic properties. Additionally, the M-value as a marker of insulin sensitivity will be determined using a hyperinsulinemic euglycemic clamp technique.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness:
The burden for participants consists of three study visits, two of which will replace scheduled meetings that are a part of standard healthcare practice. In total, participants will receive one venapuncture and four intravenous cannulas, from which blood will be sampled (study total of 275L) and iohexol + p-amminohippurate will be administered to measure GFR and effective renal plasma flow respectively. After measurement of renal function, insulin sensitivity will be measured using a variable infusion of glucose and insulin (hyperinsulinemic euglycemic clamp). In addition, participants will be asked to collect two 24-hr urine samples on the days prior to the second and third study visit. During the test visits, four additional urine samples will be collected. Finally, participants will be subjected to two different non-invasive measurement techniques: finger-plethysmography (Nexfin®) and pulse-wave-analysis (SphygmoCor®). The total risk of negative effects for participants in the current study is considered low.
The transgender population is a unique population in which the effects of exogenous cross-sex hormone administration can be studied. This study may provide additional data on the safety of hormone therapy in this population and may also lead to meaningful insights regarding the physiologic effects of sex hormones on renal function in humans that may help to understand observations from cohort studies which indicate differences in progression to end stage kidney disease (ESKD) dependent on gender.

Sex differences in renal physiology is a vastly understudied area, despite known differences in sex-specific rates of chronic kidney disease. Renal function decline is accelerated in men compared to women, suggesting a potential harmful role for testosterone. Transgender individuals undergoing hormone therapy provide a unique model to study the effects of gender affirming hormone therapy on kidney function and renal physiology.

13 weeks