Transgender Analysis of Nephrological Studies Focused on Renal Metrics (TRANSFORM)

April 17, 2026 updated by: Daniel van Raalte, Amsterdam UMC, location VUmc
This study investigates how sex hormones affect kidney function in people undergoing gender-affirming hormone therapy (GAHT). We know men have a faster progression of kidney disease. Earlier studies suggest that the female sex hormone estradiol may have a protective effect on kidney function while the male sex hormone testosterone may have the opposite effect. But the reasons why this happens remain unclear. By studying participants undergoing (GAHT) we gain insight into the mechanisms by which testosterone and estradiol influence the kidneys. People undergoing GAHT provide a unique chance to study how sex hormones interact with the kidneys. The results may help us to understand why men and women exhibit differences in kidney disease development. This study will include 30 men and 30 women, aged 18 to 40, who start GAHT. Participants will have three study visits, two of which will happen during their scheduled healthcare appointments. During the first visit, a screening will take place to check if patients can take part in the study. At study visits before and after one year of therapy, kidney function is measured, kidney MRI is performed, urine is collected and a small sample of fat tissue. Taking part in the study does not delay the start of GAHT.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Sex differences in kidney physiology are a vastly understudied area, despite known differences in sex-specific rates of chronic kidney disease. Kidney function decline is accelerated in men compared to women, suggesting a potential harmful role for testosterone. Transgender individuals undergoing hormone therapy provide a unique model to study the effects of gender affirming hormone therapy on kidney function and renal physiology. The central objectives of this study are to comprehensively assess the effects of gender affirming hormone therapy (GAHT; testosterone in transgender men or estradiol and an anti-androgen in transgender women) therapy on kidney function and physiology. This study is a prospective observational study. In total we will include 60 transgender individuals (30 transgender men and 30 transgender women) between 18-40 years old, scheduled to start GAHT. The primary endpoint is measured glomerular filtration rate (GFR) by iohexol clearance. Secondary endpoints include effects of GAHT on measures of intrarenal hemodynamic function including effective renal plasma flow (ERPF), proximal tubular function, insulin sensitivity and multiparametric kidney MRI (phase-contrast MRI [perfusion], arterial spin labeling [perfusion], BOLD imaging with a multi-echo spin-echo mapping R2* [oxygenation] and diffusion-weighted MRI [diffusion]). We will also isolate urinary tubuloids to further study the effect of sex hormones on kidney physiology and in these tubuloids we will assess whether the kidney protective effects are affected by sex hormones in vitro. Furthermore, endothelial cells will be harvested by J-wire, and single-cell RNA sequencing will be performed to investigate the transcriptional effects of GAHT in endothelial cells. And finally, we will look at adipose tissue gene expression.The burden for participants consists of three study visits, two of which will replace scheduled meetings that are a part of standard healthcare practice. In total, participants will receive one venipuncture and four intravenous cannulas, from which blood will be sampled (study total of 275 mL) and iohexol and p-aminohippurate will be administered to measure GFR and ERPF respectively. After measurement of kidney function, insulin sensitivity will be measured using a variable infusion of glucose and insulin (hyperinsulinemic euglycemic clamp). Patients will undergo kidney MRI which will take about 45 minutes; participants with claustrophobia are excluded. In addition, participants will be asked to collect a 24-hour urine sample on the days prior to the second and third study visit. Subcutaneous adipose tissue is collected by needle aspiration after local anesthesia. Finally, endothelial cells will be harvested. The total risk of negative effects for participants in the current study is considered low. The transgender population is a unique population in which the effects of exogenous cross-sex hormone administration can be studied. This study may provide additional data on the safety of hormone therapy in this population and may also lead to meaningful insights regarding the physiological effects of sex hormones on kidney function in humans that may help to understand observations from cohort studies which indicate differences in progression to kidney failure dependent on gender.

Study Type

Observational

Enrollment (Estimated)

60

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • North Holland
      • Amsterdam, North Holland, Netherlands
        • Amsterdam UMC, location VU medical centre, internal medicine
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

The source population consists of adult patients with gender dysphoria, who are scheduled to start with GAHT in the Amsterdam University Medical Centre (AUMC) in Amsterdam. A total of 60 transgender individuals (30 transgender women, 30 transgender men) will be selected from this outpatient clinic.

Description

Inclusion Criteria:

  • Diagnosed with gender dysphoria according to DSM-V
  • Expected to start gender-affirming hormone treatment in the upcoming month

Exclusion Criteria:

  • Current or prior use of gender-affirming hormone therapy
  • Participation in other studies
  • Concomitant use of medication (specifically: antihypertensive agents, products, antidepressants, antipsychotic agents)
  • Known kidney disease (eGFR < 60 ml/min; UACR > 2.5 mg/mmol)
  • Diabetes mellitus
  • A history of cardiovascular disease (myocardial infarction; cardiac surgery or revascularization, unstable angina, heart failure, transient ischemic attack, cerebrovascular disease, or a previously undiagnosed arrhythmia)
  • Known iodine-related allergies
  • Metal in the body (such as pacemaker, ICD, neurostimulator, cochlear implant, or other metal)
  • Pregnancy
  • Claustrophobia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Transgender males
Individuals clinically scheduled to start GAHT with testosterone therapy
Diagnostic test: P-aminohippurate clearance study
To measure effective renal plasma flow (ERPF), small doses of a substance called p-aminohippurate will be used
Diagnostic test: Iohexol infusion
To measure glomerular filtration rate (GFR) iohexol clearance will be performed
Diagnostic test: Hyperinsulinemic clamp
Glucose/insulin infusion to measure insulin sensitivity
Transgender women
Individuals clinically scheduled to start GAHT with estradiol and anti-androgen therapy
Diagnostic test: P-aminohippurate clearance study
To measure effective renal plasma flow (ERPF), small doses of a substance called p-aminohippurate will be used
Diagnostic test: Iohexol infusion
To measure glomerular filtration rate (GFR) iohexol clearance will be performed
Diagnostic test: Hyperinsulinemic clamp
Glucose/insulin infusion to measure insulin sensitivity

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in measured glomerular filtration rate (GFR)
Time Frame: Baseline, 12 months after start GAHT
Baseline, 12 months after start GAHT

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in effective renal plasma flow (ERPF)
Time Frame: Baseline, 12 months after start GAHT
Baseline, 12 months after start GAHT
Change in systemic hemodynamic function
Time Frame: Baseline, 12 months after start GAHT
Baseline, 12 months after start GAHT
Change in insulin sensitivity
Time Frame: Baseline, 12 months after start GAHT
Baseline, 12 months after start GAHT
Change in markers of tubular physiology
Time Frame: Baseline, 12 months after start GAHT
Baseline, 12 months after start GAHT
Changes in multiparametric kidney MRI
Time Frame: Baseline, 12 months after start GAHT
Including (phase-contrast MRI (perfusion), arterial spin labeling (perfusion), BOLD imaging with multi-echo spin-echo mapping R2* (oxygenation) and diffusion-weighted (DW) MRI (diffusion)
Baseline, 12 months after start GAHT
Changes in endothelial function
Time Frame: Baseline, 12 months after start GAHT
Baseline, 12 months after start GAHT
Change in adipose tissue gene expression and adipose tissue biology
Time Frame: Baseline, 12 months after start GAHT
Baseline, 12 months after start GAHT
Change in tubular effects of kidney protective therapies in vitro
Time Frame: Baseline, 12 months after start GAHT
Baseline, 12 months after start GAHT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Amsterdam UMC, location VUmc

Collaborators

Dutch Kidney Foundation

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2026

Primary Completion (Estimated)

September 1, 2028

Study Completion (Estimated)

September 1, 2028

Study Registration Dates

First Submitted

April 10, 2026

First Submitted That Met QC Criteria

April 17, 2026

First Posted (Actual)

April 21, 2026

Study Record Updates

Last Update Posted (Actual)

April 21, 2026

Last Update Submitted That Met QC Criteria

April 17, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL-011071

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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