Transgender individuals increasingly present themselves at gender services during childhood, but the  impact of gender-affirming therapy started in early puberty on the kidney is unknown. As sex hormones are important determinants of kidney physiology, we hypothesize that gender-affirming therapy will affect multiple processes in the kidney, resulting in altered susceptibility to kidney dysfunction. We will address these questions using mouse models that mimic the clinical strategy applied in transgender youth, thereby providing important and novel insights in the underlying mechanisms, which may ultimately be leveraged for optimizing medical care for young-adolescent transgender individuals.