Advances in technology have made both kidney transplants and gender affirmation treatments more common. Due to a scarcity of data regarding renal replacement therapies (RRT) such as dialysis and kidney transplantation in transgender patients, however, much is still unknown about RRT safety and performance in the presence of gender-affirming hormone therapy. 

A  literature review published in the Canadian Journal of Kidney Health and Disease, explained the relationship between sex hormones and kidney disease, the challenges posed by what we know and don’t know concerning hormone therapy and disease progression, and what nephrologists need to consider when providing care for transgender patients.

Gender-Affirming Hormone Therapy Basics

Based on self-report, the use of hormone therapy, and the receipt of gender-affirming surgery, there are approximately 25 million transgender people worldwide. A transgender person is one whose gender identity does not align with their biological sex at birth. A cisgender person is one whose gender identity does align with their biological sex at birth.

For transgender men, the general goal of hormone therapy is to reduce the effects of endogenous (naturally occurring) estrogen, and develop masculine secondary sexual characteristics that match their masculine gender identity. This is achieved through the use of either injectable or transdermal testosterone to raise the person’s testosterone levels.

For transgender women, the general goal of hormone therapy is to reduce the effects of endogenous testosterone, and develop feminine secondary sex characteristics that match their feminine gender identity. This is done by adding estrogen, usually by injection.

Potential Impact of Gender-Affirming Hormones on CKD Patients

Hormone therapies can carry health risks for CKD patients. The risk of blood clots from estrogen can increase with dialysis, so the benefit-to-risk ratio of estrogen therapy for transgender women should be monitored and reassessed as the disease progresses. 

Estrogen also appears to increase the risk of cardiovascular (CV) events. In a Kaiser Permanente study, incidences (new cases) of ischemic stroke and myocardial infarction were higher in transwomen than in both cisgender men and female controls.

Testosterone levels are commonly reduced in patients with CKD. Low testosterone can cause: 

• Reduced Muscle Mass 
• Frailty  
• Arterial Stiffness 
• CV Issues 

It is unknown whether low testosterone levels in transgender women result from the effects of estrogen hormone therapy or the surgical removal of the testes. Testosterone therapy in transgender men, however, increases the risk of polycythemia–an increase in red blood cell production that causes blood to thicken, increasing the risk of blood clots and other complications. 

Challenges of Estimating GFR in Transgender Patients

Gender-affirming hormone therapies involving testosterone, estrogen/estradiol, and anti-androgens (testosterone-blockers) change a person’s body composition and lean body mass. This influences the production of creatinine (cree-AT-uh-neen), a waste product of muscle and protein metabolism which is used to help diagnose CKD and monitor its progression. Creatinine levels in the blood, along with age, race, and sex, help doctors estimate a patient’s glomerular filtration rate (GFR), which is the percentage of remaining kidney function. 

The impacts of gender-affirming hormone therapy on GFR changes in CKD are not yet clear. One of the ways in which it muddies the waters lies in the fact that cisgender females produce less creatinine than do cisgender males. Without factoring in sex, GFR is often overestimated in cisgender females, meaning that their kidney function is estimated to be better than it may actually be.

The issue with using sex in eGFR equations for transgender patients is that their body composition and muscle mass–and therefore their creatinine production–may not be the same as their cisgender counterparts. 

For transgender patients not using hormone therapy, since their muscle mass is likely to reflect their birth sex, the authors of the study recommend that eGFR equations use patients’ birth sex rather than their affirmed gender, solely for the purpose of obtaining more accurate results. 

Consequences of Inaccurate eGFR

Inaccurate eGFR values, whether overestimated or underestimated, can be harmful.

Overestimation of eGFR can lead to delayed care, including:

• Referral to a Nephrologist 
• Vascular Access 
• Transplantation

Underestimation can lead to:

• Earlier-than-Necessary Start of Dialysis
• Inadequate use or Dosing of Drugs 
• Limited Access to Diagnostic Imaging
• Exclusion from Research

Currently, measured GFR is more accurate than estimated GFR, but the measuring process is invasive, costly, and time-consuming. A new, more accurate and inclusive measuring tool is called for that will benefit more patients and result in better outcomes.

Further Research Necessary

The dearth of research focusing on transgender kidney disease patients cannot continue if health equity is to be achieved. The nephrology community must include transgender people in both epidemiological studies and clinical trials. Providers can start small by collecting sex and gender information separately during the intake process, and differentiations can be made between transgender and cisgender participants in clinical trials. Critical topics for new research proposed by the study authors include:

• Performance and accuracy of eGFR equations for transgender patients, 
• Effects, including safety, of gender-affirming hormone therapy on the kidneys, and 
• Impact of gender identity on health outcomes for people living with kidney disease.

*Collister, D., Saad, N., Christie, E., Ahmed, S. (2021, Jan. 20). Providing Care for Transgender Persons With Kidney Disease: A Narrative Review. Canadian Journal of Kidney Health and Disease. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829603/