Introduction: Sex differences in renal physiology is a vastly understudied area, despite known differences in sex-specific rates of chronic kidney disease. Progression of kidney diseases is slower in females compared to males. This observation has led to believe that estrogen may have protective effects on renal function and androgens may predispose to kidney injury. The transgender population is a unique population in which the effects of exogenous cross-sex hormone administration can be studied. A hiatus in our current knowledge regarding sex differences in nephrology lies in the fact that previous studies on sex hormones and renal function have mostly been performed in animal or in vitro models. It is difficult to translate sex differences in animal models to human physiology due to differences in gender between species. In addition, the studies in humans are often of a cross-sectional design, secondary analyses of other studies or based on registry data. Prospective studies regarding the effects of sex hormones on state-of-the art renal function tests in humans are scarce, indicating the need for more prospective research in this field.

Method: The KNIGHT (Kidney fuNction In people receiving Gender affirming Hormone Therapy) study is a prospective observational pilot study. We will enroll 40 transgender individuals (20 transmen and 20 transwomen) between 18 and 30 years old, scheduled to start hormone therapy. The main study endpoint is the measurement of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) as measured by iohexol and p-amminuohippurate (PAH) clearance, before and after 3 months of hormone therapy.

Discussion: The current study aims to investigate the effects of gender affirming hormone therapy on kidney function and renal physiology. This study may 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.