Progression of chronic kidney disease (CKD) is generally faster in cisgender men than cisgender women, suggesting a protective effect of female sex. An observational study in 44 transgender individuals who initiated either feminizing (estradiol and antiandrogens) or masculinizing (testosterone) hormone therapy provides new insights into the effects of sex hormones on the kidney. “This population provides a unique opportunity to study the effects of well-defined changes in sex hormone concentrations,” says researcher Sarah van Eeghen.

Sex hormone therapy also resulted in changes in the concentrations of tubular injury biomarkers, with decreases in urinary NGAL, MCP1 and YKL-40 with feminizing therapy and increases in urinary YKL-40 and plasma TNFR1 with masculinizing therapy. “These results suggest that estradiol may protect against early tubular injury and inflammation, whereas testosterone may promote kidney inflammation,” comments van Eeghen. In addition, a plasma proteomics analysis identified several circulating proteins with kidney-protective properties that increased during feminizing therapy and/or decreased during masculinizing therapy. Many of these proteins were positively associated with estradiol and negatively associated with testosterone, including proteins with roles in endothelial function, modulation of inflammation and preservation of kidney structural integrity.