Author Interviews, Gender Differences, Kidney Disease, Transplantation, University of Pennsylvania / 22.04.2016
Females Tolerate Ischemia After Kidney Transplantion Better Than Males
MedicalResearch.com Interview with:
Matthew Levine, MD, PhD
Assistant Professor of Transplant Surgery
Perelman School of Medicine
University of Pennsylvania
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Levine: This work stemmed from a known finding that female mice tolerate kidney injury better than males and this is true of mice that share exactly the same genes. Therefore, the gender difference was the driving factor. My basic science laboratory works at the intersection between scientific discovery and clinical application and this led us to question whether the same phenomenon was true in humans and whether we could identify a way in which this could be used to improve injury tolerance above what is seen in untreated subjects. What we found was that the hormonal environment seems to impact ischemia tolerance, with female environment being protective and the male environment worsening injury tolerance in ischemia models where blood flow is interrupted and then restored. The kidneys seemed to adapt to take on the injury response of the host after transplantation, indicating that the differences were not forged into the kidney itself and therefore could be altered. We then found that estrogen therapy improved kidney injury tolerance when given to female mice in advance of injury, but no effect was seen in male mice. And most importantly, we found that in a large cohort of transplant recipients that female recipients had better injury tolerance after transplant than male recipients, as shown by ability to avoid dialysis in the first week after transplant, otherwise known as delayed graft function (DGF). This is a fairly major finding since it has not been observed in the literature despite several decades of transplant data being carefully studied.
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