Nature study: Estrogen protects kidneys – Research from Dresden and Heidelberg confirms the relevance of gender-specific medicine for disease understanding and therapy

Worldwide, the number of people suffering from kidney diseases is increasing. According to estimates by the World Health Organization (WHO), kidney diseases are expected to be among the five leading causes of death by 2050. Often, kidney diseases remain undetected for a long time, so that damage is already advanced and usually irreversible when it is finally noticed. Since the underlying disease mechanisms are not yet fully understood, intensified research is essential for better understanding, effective prevention, and early detection. A research team from Dresden and Heidelberg, together with international partners, has now identified new mechanisms that explain why kidney damage differs significantly between females and males. This is attributed to the effect of the hormone estrogen. The study, “Multiple oestradiol functions inhibit ferroptosis and acute kidney injury”, has now been published in the renowned journal Nature.

A major cause of acute kidney injury is so-called ferroptosis, the “biological rust.” Through this process, nephrons—the functional units of the kidney—are lost. In their study, the research team led by Prof. Andreas Linkermann, working at the Medical Clinic III at the University Hospital Dresden (UKD) and Director of the V. Medical Clinic at the University Medical Center Mannheim, and Prof. Stefan Bornstein, Director of MK III at UKD, demonstrated that the female sex hormone estrogen protects kidneys in multiple ways against damage caused by ferroptosis.

“Recently, it has become increasingly clear that mechanisms of kidney damage differ between female and male individuals,” explains Dr. Wulf Tonnus, one of the three first authors of this study and an early-career researcher at MK III. “It turned out that estradiol, a hormone from the estrogen group, increases resistance to ferroptosis. Endogenous metabolites of estradiol directly neutralize damaging radicals, while the parent hormone activates a complex genetic program to prevent ferroptosis.”

These findings further emphasize the importance of sex hormones for numerous processes in the body. A better fundamental understanding of their mechanisms can, in the long term, also help develop effective therapies for people with kidney diseases. Overall, a gender-specific understanding of diseases represents an important step toward individualized approaches and greater gender equity in medicine.

“This study is a major scientific achievement. That young clinician-scientists can achieve this together with recognized researchers highlights the excellent research environment offered by the Medical Faculty of TU Dresden and the Medical Clinic and Polyclinic III,” explains Prof. Esther Troost, Dean of the Medical Faculty.
“The new insights give us the opportunity to treat kidney diseases more precisely in the future. At the University Hospital Dresden, we can develop new, individualized therapies so that kidney diseases can be detected early and treated effectively—for better health and quality of life,” adds Prof. Uwe Platzbecker, Medical Director of the University Hospital Dresden.

Publication: “Multiple oestradiol functions inhibit ferroptosis and acute kidney injury” (DOI 10.1038/s41586-025-09389-x): https://www.nature.com/articles/s41586-025-09389-x.

Accompanying editorial “News and Views”: https://doi.org/10.1038/d41586-025-02422-z

Background

:The research project was financially supported primarily by the German Research Foundation (DFG): https://gepris.dfg.de/gepris/projekt/522190184, along with numerous other funding programs.

Contact: 
Prof. Dr. med. Andreas Linkermann, FASN
Direktor V. Medizinische Klinik - Nephrologie/Hypertensiologie/Transplantationsmedizin
Endokrinologie/Diabetologie/Lipidologie/Rheumatologie/Pneumologie
Facharzt für Innere Medizin, Nephrologe, Transplantationsmediziner
Visiting Professor at Albert Einstein College of Medicine – Department of Nephrology
Medizinische Fakultät der Ruprecht-Karls-Universität Heidelberg
Universitätsklinikum Mannheim GmbH

Tel.: +49 (0) 621 383 3660

Dr. med. Wulf Tonnus
Facharzt für Innere Medizin und Nephrologie
Junior Group Leader // Funktionsoberarzt
Sektion Nephrologie - Medizinische Klinik und Poliklinik III
Universitätsklinikum Carl Gustav Carus
an der Technischen Universität Dresden
Tel.: +49 (0) 351 458 19520