Sex and the kidneys: current understanding and research opportunities

Abstract

Concerns regarding sex differences are increasingly pertinent in scientific and societal arenas. Although biological sex and socio-cultural gender are increasingly recognized as important modulators of renal function under physiological and pathophysiological conditions, gaps remain in our understanding of the mechanisms underlying sex differences in renal pathophysiology, disease development, progression and management. In this Perspectives article, we discuss specific opportunities for future research aimed at addressing these knowledge gaps. Such opportunities include the development of standardized core data elements and outcomes related to sex for use in clinical studies to establish a connection between sex hormones and renal disease development or progression, development of a knowledge portal to promote fundamental understanding of physiological differences between male and female kidneys in animal models and in humans, and the creation of new or the development of existing resources and datasets to make them more readily available for interrogation of sex differences. These ideas are intended to stimulate thought and interest among the renal research community as they consider sex as a biological variable in future research projects.

Fig. 1 |. Strategies to aid understanding of sex differences in kidney health and disease.

In recognition of the need to address controversies and knowledge gaps related to understanding the role of sex in kidney physiology and pathophysiology, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) asked leading experts in the field to discuss key considerations and identify opportunities for future research. They identified several challenges to basic and clinical science research related to sex differences, some of which could be overcome by developing new research tools and experimental models, and by expanding the availability of existing datasets for interrogation to answer relevant scientific questions around sex and gender differences that affect kidney health and disease. Improving our understanding of the complex interplay of factors that contribute to sex differences in kidney health and disease could contribute to improving the health of both women and men.