Highlights• Researchers detected transient increases in enzymes indicative of kidney health that correlated with specific phases of the female reproductive hormone cycle.• The findings indicate that nonreproductive organs may undergo periodical adaptations phased by menstrual cycle–driven hormone changes.

More than 2 million people worldwide receive treatment for kidney failure.

Newswise — Washington, DC (April 28, 2016) — Female hormones may play a role in women’s decreased risk of developing kidney failure relative to men, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). The findings may be helpful for future attempts at safeguarding women’s and men’s kidney health in sex-specific ways.

Sex differences between men and women affect most, if not all, organ systems in the body, but there is a significant gap in knowledge of female physiology aside from organ functions involved in reproduction. Regarding the kidneys, while international registries show that fewer women than men develop kidney failure, the underlying causes are unknown.

To investigate, a team led by Judith Lechner, PhD and Thomas Seppi, PhD (Medical University of Innsbruck, in Austria) examined whether hormone changes due to the female menstrual cycle might affect the health of kidney cells. For this purpose, urinary samples from healthy women of reproductive age were collected daily and analyzed for menstrual cycle–associated changes of different proteins. Specifically, the researchers measured 2 enzymes—fructose-1,6-bisphosphatase and glutathione-S-transferase-alpha—that are found in proximal tubular cells, the most populous cell type in the kidney. When proximal tubular cells are damaged, these enzymes are released into the urine, making them important clinical markers for kidney injury.

The investigators detected transient increases of fructose-1,6-bisphosphatase and glutathione-S-transferase-alpha correlating with specific phases of the female reproductive hormone cycle, namely ovulation and menses. “This result suggests that cyclical changes of female hormones might affect kidney cell health, potentially providing women with an increased resistance against kidney damage,” said Dr. Lechner. “It is conceivable that recurring changes of sex hormone levels, as brought about by the natural menstrual cycle, might be involved in periodic tissue re-modeling not only in reproductive organs, but to a certain extent in the kidneys as well.”

Understanding the mechanisms that might be responsible for women’s lower susceptibility to kidney failure may help researchers design better kidney-related therapies for women and men.

Study co-authors include Sinikka Prajczer, MD, PhD, Maria-Magdalena Dörler, Msc, Oliver Eiter, Daniel Hekl, Msc, Meinhard Nevinny-Stickel, MD, Iraida Skvortsova, MD, Gerhard Gstraunthaler, PhD, and Peter Lukas, MD.

Disclosures: The authors gratefully acknowledge financial support by the Austrian Central Bank, Anniversary Fund, project number: 13671 (Jubiläumsfonds der Österreichischen Nationalbank).

The article, entitled “Sex Differences in Renal Proximal Tubular Cell Homeostasis,” will appear online at http://jasn.asnjournals.org/ on April 28 2016, doi: 10.1681/ASN.2015080886. The content of this article does not reflect the views or opinions of The American Society of Nephrology (ASN). Responsibility for the information and views expressed therein lies entirely with the author(s). ASN does not offer medical advice. All content in ASN publications is for informational purposes only, and is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. This content should not be used during a medical emergency or for the diagnosis or treatment of any medical condition. Please consult your doctor or other qualified health care provider if you have any questions about a medical condition, or before taking any drug, changing your diet or commencing or discontinuing any course of treatment. Do not ignore or delay obtaining professional medical advice because of information accessed through ASN. Call 911 or your doctor for all medical emergencies.Founded in 1966, and with nearly 16,000 members, the American Society of Nephrology (ASN) leads the fight against kidney disease by educating health professionals, sharing new knowledge, advancing research, and advocating the highest quality care for patients.