Figure 1.

Potential sources of sex differences in AKI. Sex differences may be conferred in the baseline physiologic framework and can be seen in responses to injury and repair. (A) Baseline physiology. Chromosomal complement, X inactivation, and epigenetic changes leading to X-inactivation escape may establish different gene expression profiles. The presence of gonadal tissues and thus the ratios of sex hormones released lead to hormone-receptor interaction and subsequent gene and protein expression changes. The sex-based differences in density and localization of hormone receptors along the nephron may give rise to different capability to respond to physiologic and pathophysiologic signals. Changes occurring in hormonal abundance and additional molecular changes may lead to different outcomes in development, puberty, adulthood, and aging. (B) Susceptibility and resistance. Differences in responses between men and women may occur with different etiologies of AKI, and decreased susceptibility in women may lead to lower prevalence and different clinical severity or temporal courses, including transition to CKD. Differences in mitochondrial number, size, and dynamics, including mitochondrial fission and fusion, as well as differences in mitochondrial bioenergetics and induction of oxidative phosphorylation may be based on the basis of sex. Mitochondrial functional aspects may be altered by ambient temperatures. Temporal differences and extent of damage to epithelia and endothelia, and in the inflammatory response, may underlie sex hormonal or chromosomal influence. Degree and timing of cellular repair may differ between men and women or males and females. AR-A, androgen receptor A; AR-B, androgen receptor B; ERα, estrogen receptor α; ERβ, estrogen receptor β; GPER, G-protein–coupled estrogen receptor; Sry, sex-determining region Y. The Figure was partly generated using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license.