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Sex and the kidneys: current understanding and research opportunities

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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.

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

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Acknowledgements

The authors thank all the invited speakers: K. Korach, S. Hammes, C. Smith, C. Disteche, F. Mauvais-Jarvis, A. Ricardo, J. Morton, J. Fuscoe, V. Garovic, J. Charlton and V. Miller, and all workshop participants for their thoughtful comments and ideas offered during the workshop. The authors thank the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) for providing funding for the workshop. The views expressed in this article are those of the authors and do not necessarily represent the views of the NIDDK, the US National Institutes of Health (NIH) or the United States Department of Health and Human Services.

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Glossary

Parental imprinting

A process that results in allele-specific differences in transcription, DNA methylation and DNA replication timing.

X chromosome mosaicism

The presence of two populations of cells in the body: some cells have two X chromosomes whereas others have only one X chromosome.

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Bairey Merz, C.N., Dember, L.M., Ingelfinger, J.R. et al. Sex and the kidneys: current understanding and research opportunities. Nat Rev Nephrol 15, 776–783 (2019). https://doi.org/10.1038/s41581-019-0208-6

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