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The Influence of Sex and Hormones on Organelle Stress in Kidney Injury: Insights from Preclinical Models
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Departamento de Procesos Tecnológicos e Industriales, Instituto Tecnologico y de Estudios Superiores de Occidente (ITESO), Tlaquepaque 45604, Jalisco, Mexico
2
Departamento de Clinicas, Centro Universitario de los Altos, Universidad de Guadalajara, Tepatitlan de Morelos 47620, Jalisco, Mexico
3
Investigadora por Mexico, Secretaria de Ciencia, Humanidades, Tecnologia e Innovacion (SECIHTI), Mexico City 03940, Mexico
4
Departamento de Ciencias de la Salud, Centro Universitario de los Altos, Universidad de Guadalajara, Tepatitlan de Morelos 47620, Jalisco, Mexico
*
Author to whom correspondence should be addressed.
Biology 2026, 15(2), 173; https://doi.org/10.3390/biology15020173 (registering DOI)
Submission received: 13 December 2025
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Revised: 8 January 2026
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Accepted: 14 January 2026
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Published: 17 January 2026
(This article belongs to the Special Issue Advances in Cell and Experimental Biology: Cellular Organelle Stress and Homeostasis in Physiology and Diseases)
Simple Summary
Kidney disorders are influenced by many factors, but biological sex and hormones play important roles in many diseases that affect the kidney, showing clear differences between men and women. Chronic Kidney Disease, for example, is more common in women, yet men often lose kidney function faster, partly because male hormones can worsen disease progression. After menopause, women lose some of the protective effects of female hormones, which further highlights how sex influences vulnerability to kidney problems. Kidney cells face many kinds of everyday and disease-related stress. At first, the cells can adjust to these challenges, but if the stress continues, it can overwhelm important parts of the cell. Organelles are cell structures such as mitochondria, the cell’s energy center; the endoplasmic reticulum, which helps make and fold proteins; and primary cilia, small cellular sensors. Organelles work together to maintain cell metabolism and kidney function, but when they are stressed, the cell’s normal activities and communication break down, leading to problems such as reduced energy, inflammation, and scarring. This is a review of animal studies that describe how sex and hormones affect stress in cellular organelles and how these differences may help explain why men and women may experience kidney disease differently.
Abstract
Kidney cells are exposed to a wide range of physiological and pathological stresses, including hormonal changes, mechanical forces, hypoxia, hyperglycemia, and inflammation. These insults can trigger adaptive responses, but when they persist, they can lead to organelle stress. Organelles such as mitochondria, the endoplasmic reticulum, and primary cilia sustain cellular metabolism and tissue homeostasis. When organelle stress occurs, it disrupts cellular processes and organelle communication, leading to metabolic dysfunction, inflammation, fibrosis, and progression of kidney disease. Sex and hormonal factors play a significant role in the development of renal disorders. Many glomerular diseases show distinct differences between the sexes. Chronic Kidney Disease is more common in women, while men often experience a faster decline in kidney function, partly due to the influence of androgens. Additionally, the loss of female hormonal protection after menopause highlights the importance of sex as a factor in renal susceptibility. This narrative review synthesizes preclinical evidence on how sexual dimorphism and sex hormones affect organelle stress in mitochondria, the endoplasmic reticulum, and primary cilia, from 33 studies identified through a non-systematic literature search of the PubMed database, to provide an overview of how these mechanisms contribute to sex-specific differences in kidney disease pathophysiology.
Keywords:
organelles; stress; kidney; CKD; sex; hormones; mitochondria; endoplasmic reticulum; cilia
