Sex-related differences in diabetic kidney disease: A review on the mechanisms and potential therapeutic implications

Federica Piani; Isabella Melena; Kalie L Tommerdahl; Natalie Nokoff; Robert G Nelson; Meda E Pavkov; Daniël H van Raalte; David Z Cherney; Richard J Johnson; Kristen J Nadeau; Petter Bjornstad

doi:10.1016/j.jdiacomp.2020.107841

Sex-related differences in diabetic kidney disease: A review on the mechanisms and potential therapeutic implications

J Diabetes Complications. 2021 Apr;35(4):107841. doi: 10.1016/j.jdiacomp.2020.107841. Epub 2020 Dec 31.

Authors

Affiliations

¹ Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA; Department of Medicine and Surgery Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy; Department of Medicine, Division of Nephrology, University of Colorado School of Medicine, Aurora, CO, USA.
² Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA.
³ Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA; Department of Medicine, Division of Nephrology, University of Colorado School of Medicine, Aurora, CO, USA.
⁴ Chronic Kidney Disease Section, Phoenix Epidemiology and Clinical Research Branch, NIDDK, Phoenix, AZ, USA.
⁵ Division of Diabetes Translation, Center for Disease Control and Prevention, Atlanta, GA, USA.
⁶ Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Center, location VUmc, Amsterdam, the Netherlands.
⁷ Department of Medicine, Division of Nephrology, University of Toronto School of Medicine, Toronto, Ontario, Canada.
⁸ Department of Medicine, Division of Nephrology, University of Colorado School of Medicine, Aurora, CO, USA.
⁹ Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA; Department of Medicine, Division of Nephrology, University of Colorado School of Medicine, Aurora, CO, USA. Electronic address: petter.bjornstad@childrenscolorado.org.

Abstract

Sexual dimorphism may play a key role in the pathogenesis of diabetic kidney disease (DKD) and explain differences observed in disease phenotypes, responses to interventions, and disease progression between men and women with diabetes. Therefore, omitting the consideration of sex as a biological factor may result in delayed diagnoses and suboptimal therapies. This review will summarize the effects of sexual dimorphism on putative metabolic and molecular mechanisms underlying DKD, and the potential implications of these differences on therapeutic interventions. To successfully implement precision medicine, we require a better understanding of sexual dimorphism in the pathophysiologic progression of DKD. Such insights can unveil sex-specific therapeutic targets that have the potential to maximize efficacy while minimizing adverse events.

Keywords: Diabetic kidney disease; Diabetic nephropathy; Sex-related differences; Sexual dimorphism.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Diabetic Nephropathies* / diagnosis
Diabetic Nephropathies* / epidemiology
Diabetic Nephropathies* / therapy
Female
Humans
Male
Precision Medicine
Sex Characteristics

Abstract

Publication types

MeSH terms

Grants and funding