Q&A: AKI, CKD prevalence in transgender patients
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AKI and chronic kidney disease prevalence is high among transgender patients, but this is rarely researched, according to a cross-sectional study published in the Clinical Journal of the American Society of Nephrology.
Currently, there are limited data regarding kidney disease in transgender populations. The first study of its kind examined a cohort of 274 transgender patients receiving gender-affirming hormone therapy (TFH) (transfeminine [TF]=74, TFH=82, transmasculine [TM]=96, and TMH=22). Analyses revealed a 32% prevalence for AKI and 36% for CKD among the patients.
Healio interviewed Han Eckenrode, MA, they/them, the lead author of the study and a graduate student at the University of Alabama at Birmingham (UAB), and Lisa M. Curtis, PhD, she/her, an associate professor at UAB and Han’s mentor, to discuss their research regarding kidney disease in transgender patients.
Healio Nephrology: This is the first study to investigate AKI and CKD prevalence in transgender patients. Why do you think this is?
Eckenrode: As a queer and non-binary individual, I'd say that I am closer to this community than a cisgender straight person. When I learned that there were sex differences in kidney disease, my proximity to the community made me ask the question: “What about trans people?” People aren't aware how many trans individuals there are; people think that it's rarer than it is because of their limited exposure to this population. This isn't always due to their lack of a connection with a trans patient though, it may be that they aren't aware that a patient is trans. Sometimes trans patients feel that their care is going to be affected by how they're perceived by their provider, so they may not feel comfortable disclosing that information. This can lead to a lack of exposure and awareness for physicians.
Healio Nephrology: Are there any adverse events that you and your team are concerned about?
Eckenrode: I would like to see more scientific journals publish studies that explore trans medicine, but that also requires more scientists and physicians to launch studies. For trans individuals, I believe that kidney disease and cardiovascular diseases, early life stress and just stress in general may be predisposing factors, but we didn't look into it. These transgender individuals may have a higher prevalence rate of such conditions for some reason that hasn't been elicited yet, so future studies should investigate that. It is also important to note that these biomarkers change with sex hormones. For example, Mayo recently did a study where they looked at trans folks and their serum creatinine levels over their transition period. That's a great example of researchers being aware of how those clinical indicators might change.
Curtis: Right now, clinicians are trying to put pieces together to address their transgender patients’ issues without any literature to support one option vs. another. There's been a push in the last 10 to 15 years to begin to look at sex differences beyond blood pressure effects due to sex and pregnancy, which have been relatively well described. Transgender patients represent a part of the umbrella of sex differences, but this area of study just has not been on people's radar to begin to ask those questions in the first place.
Healio Nephrology: What is clinically important about your findings?
Eckenrode: While we didn't look at cisgender comparisons, we found that the AKI and CKD prevalence is high in the transgender community that we examined.
Curtis: When we speak of a higher prevalence in transgender individuals, that's based upon an understanding of the currently available literature which, of course, is largely cisgender.
Healio Nephrology: Did anything surprise you about your findings?
Curtis: The population that we examined was almost 50% African American. Because we know that African Americans have a higher incidence of kidney diseases broadly, that might have contributed to this higher prevalence in our population. The unique features of transgender patients who have undergone stresses, such as early life stress, may also play into this picture. I think that was the most surprising finding, that it represented such a large percentage relative to what the understanding was in the specialty. We were only looking at UAB patients, so we were limited by the demographics in our state of Alabama. I believe our data suggest that there may be something unique about transgender patients that is not well described in the literature and not well understood in terms of how their necessary therapy fundamentally affects kidney disease.
Eckenrode: Because we know that cisgender women have a lower prevalence of AKI and lower severity of CKD compared with cisgender men, my original hypothesis was that estrogen would be protective and testosterone would be detrimental. But we did not find that the prevalence of trans men taking testosterone that was increased relative to trans men not taking testosterone, in either AKI or CKD. I was surprised, especially when it came to CKD prevalence. The general understanding is that cisgender women have a higher prevalence of CKD. But cisgender men typically have more severe CKD. It didn't reach statistical significance, but in both groups comparing the non-hormone to hormone, there was a stark difference where the group receiving hormones had a lower prevalence.
Curtis: Yes, it is surprising, but it also makes us ask the question, "For patients who are not on hormones, is there another medical reason why they're not on hormones? Is there a confounder here that we haven't evaluated?" This is the first study of its kind, so it provides some insights. But I do think that understanding the nuances within the cohorts that we examined and amplifying that by other locations doing a similar type of study, is going to improve our perspective about what the gender-affirming hormone therapy does in the context of kidney disease. We hope that this work, coupled with others’ investigations, will help physicians determine whether to use the standard of care that they use for cisgender individuals, or develop a new standard of care. More research is needed to provide that nuanced understanding.
Healio Nephrology: Do you plan to continue researching kidney disease in transgender populations?
Eckenrode: I’m going to continue this work as a PhD student. Currently, I’m working on developing and validating preclinical models, as well as clinical studies in this area, but some of the things I'm doing are going further into the patients who identify with AKI and CKD and looking to see if the phenotypes differ. For example, is the progression of CKD different for a trans individual on hormones different than if they were not taking hormones? That is something that I'm continuing to study and would love to see more folks interested in as well.
Curtis: With my focus on basic science, Han is working on some preclinical modeling in my laboratory as part of their thesis, and we use preclinical modeling to look specifically at AKI, but we're also delving into CKD models. As a laboratory-based scientist, I want to pursue this research going forward as well.
Healio Nephrology: What are the take-home messages for the physicians reading this study?
Eckenrode: I want to emphasize that in the trans community, there is a common fear that is colloquially known as "trans broken arm syndrome." This is when a trans patient comes in for something that’s unrelated to their arm. A physician’s immediate question after finding out that the patient is transgender is, “Is this because you’re on hormones? Maybe we should take you off hormones as the first attempt of treatment?” Occasionally, there are indications when hormones may be an inappropriate therapy for someone, and it's worth checking in with an endocrinologist who is familiar with trans care. The most important thing to understand is that gender-affirming hormone therapy is life altering and, for a lot of people, lifesaving. Stopping the therapy isn't always the best choice, but if a physician does decide to alter it in some way, it's best to explain to the patient the pros and cons and why it might help. Physicians need to make sure that they're having an open dialogue with their patients about what the current recommendations are and what data suggest.
Curtis: Generally speaking, one of the things that drives you is the idea that perhaps your basic research might affect the health care of a patient. Given how the perspective among many transgender patients have been overlooked at best, and perhaps even disregarded or disrespected, the idea that our research is laying some groundwork is a take-home message, but it's not the final analysis. More research is needed in this area. There may be much that we have not discovered about kidney disease in transgender individuals, and that should be something other scientists or physicians walk away thinking about.
Healio Nephrology: Is there anything you would like to add?
Curtis: I'm hopeful that this research drives toward an endpoint where transgender individuals are seen as themselves and that their care is directed to them. Cisgender standard of care may not be applicable to transgender patients, and assuming that it always leads to less trust in physicians by transgender patients because they can't rely on their physicians. Physicians don't have the knowledge because we haven't studied these questions. Our research is a starting point, but hopefully, we will see physicians equipped with the knowledgebase to confidently address any issue that a transgender patient has and not just simply assume it is their hormone therapy. More research is needed to better understand those dynamics so that we can ensure a positive physician and patient relationship.
For more information:
Han Eckenrode, MA, can be reached at heckenro@uab.edu. Lisa M. Curtis, PhD, can be reached at lisacurtis@uabmc.edu.
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