Chronic kidney disease and sex dimorphism

This review highlights studies published in the last 18 months focusing on sex dimorphism in clinical and preclinical areas related to chronic kidney disease (CKD).

Hypertension, cardiorenal disease, hormone exposure, heat stress and dietary intake are all risk factors with sexually dimorphic effects thus contributing differentially to the development of chronic kidney disease. In CKD, GFR decline and cardiovascular mortality are more pronounced in males. Females have higher STEMI related in hospital mortality. When on dialysis, females have higher cardiovascular events rate. Males develop anemia and hyperparathyroidism earlier. Hyperphosphatemia is more prevalent in males. Vitamin D deficiency is associated with CKD in males only. Males are more likely to develop severe sarcopenia. The renoprotective effects of estrogen or estrogen agonists are mediated in part through GPER. ET-1 dual antagonism offset the action of GPER. ET-1 dual antagonism abolished the sex differences in acclimation to high salt. Sodium transport and oxygen consumption across the different renal segments is sexually dimorphic. Sexually dimorphic gene expression is mostly seen in the proximal tubules and is under androgen control.

The above findings emphasize the need to systematically include female models in preclinical and clinical research which will improve clinical management and allow for development and implementation of precision medicine tailored to sex.