Sex-Related Aspects in Diabetic Kidney Disease-An Update

Abstract

Differences between the sexes exist in many diseases, and in most cases, being a specific sex is considered a risk factor in the development and/or progression. This is not quite so clear in diabetic kidney disease (DKD), the development and severity of which depends on many general factors, such as the duration of diabetes mellitus, glycemic control, and biological risk factors. Similarly, sex-specific factors, such as puberty or andro-/menopause, also determine the microvascular complications in both the male and female sex. In particular, the fact that diabetes mellitus itself influences sex hormone levels, which in turn seem to be involved in renal pathophysiology, highlights the complexity of the question of sex differences in DKD. The major objective of this review is to summarize and simplify the current knowledge on biological sex-related aspects in the development/progression but also treatment strategies of human DKD. It also highlights findings from basic preclinical research that may provide explanations for these differences.

Keywords: DKD; TGF-β1; diabetic kidney disease; gender; sex differences; sex hormones; transforming growth factor beta 1.

Figure 1

Determinants of sex differences in DKD. Various factors may be determinants of sex differences in the development and progression of DKD.

Figure 2

Sex bias in basic preclinical research and clinical trials. Male bias in animal studies as well as in human clinical trials may lead to reduced efficacy or harmful side effects in female patients that remain undetected until the post-marketing observation phase.