Skip to main content

Advertisement

Springer Nature Link
Log in

The effect of gender-affirming hormone treatment on serum creatinine in transgender and gender-diverse youth: implications for estimating GFR

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Background

Equations for estimated glomerular filtration rate (eGFR) based on serum creatinine include terms for sex/gender. For transgender and gender-diverse (TGD) youth, gender-affirming hormone (GAH) treatment may affect serum creatinine and in turn eGFR.

Methods

TGD youth were recruited for this prospective, longitudinal, observational study prior to starting GAH treatment. Data collected as part of routine clinical care were abstracted from the medical record.

Results

For participants designated male at birth (DMAB, N = 92), serum creatinine decreased within 6 months of estradiol treatment (mean ± SD 0.83 ± 0.12 mg/dL to 0.76 ± 0.12 mg/dL, p < 0.001); for participants designated female at birth (DFAB, n = 194), serum creatinine increased within 6 months of testosterone treatment (0.68 ± 0.10 mg/dL to 0.79 ± 0.11 mg/dL, p < 0.001). Participants DFAB treated with testosterone had serum creatinine similar to that of participants DMAB at baseline, whereas even after estradiol treatment, serum creatinine in participants DMAB remained higher than that of participants DFAB at baseline. Compared to reference groups drawn from the National Health and Nutritional Examination Survey, serum creatinine after 12 months of GAH was more similar when compared by gender identity than by designated sex.

Conclusion

GAH treatment leads to changes in serum creatinine within 6 months of treatment. Clinicians should consider a patient’s hormonal exposure when estimating kidney function via eGFR and use other methods to estimate GFR if eGFR based on serum creatinine is concerning.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

TGD:

Transgender/gender diverse

GAH:

Gender-affirming hormones

DMAB:

Designated Male at Birth

DFAB:

Designated Female at Birth

BMI:

Body Mass Index

GFR:

Glomerular Filtration Rate

eGFR:

Estimated Glomerular Filtration Rate

CKD:

Chronic Kidney Disease

NHANES:

National Health and Nutrition Examination Survey

CKD-EPI:

Chronic Kidney Disease Epidemiology Collaboration

References

  1. Hembree WC, Cohen-Kettenis PT, Gooren LJ, Hannema SE, Meyer WJ, Murad MH, Rosenthal SM, Safer JD, Tangpricha V, T’Sjoen GGR (2017) Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 102:3869–3903

    Article  Google Scholar 

  2. Turban JL, King D, Carswell JM, Keuroghlian AS (2020) Pubertal Suppression for Transgender Youth and Risk of Suicidal Ideation. Pediatrics 145:e20191725

    Article  Google Scholar 

  3. Fisher AD, Castellini G, Ristori J, Casale H et al (2016) Cross-sex hormone treatment and psychobiological changes in transsexual persons: Two-year follow-up data. J Clin Endocrinol Metab 101:4260–4269

    Article  CAS  Google Scholar 

  4. de Vries ALC, McGuire JK, Steensma TD, Wagenaar ECF, Doreleijers TAH, Cohen-Kettenis PT (2014) Young Adult Psychological Outcome After Puberty Suppression and Gender Reassignment. Pediatrics 134:696–704

    Article  Google Scholar 

  5. Chew D, Anderson J, Williams K, May T, Pang K (2018) Hormonal Treatment in Young People With Gender Dysphoria: A Systematic Review. Pediatrics 141:e20173742

    Article  Google Scholar 

  6. Olson-Kennedy J, Okonta V, Clark LF, Belzer M (2018) Physiologic Response to Gender-Affirming Hormones Among Transgender Youth. J Adolesc Heal 62:397–401

    Article  Google Scholar 

  7. Millington K, Finlayson C, Olson-Kennedy J, Garofalo R, Rosenthal SM, Chan Y-M (2021) Association of High-Density Lipoprotein Cholesterol with Sex Steroid Treatment in Transgender and Gender-Diverse Youth. JAMA Pediatr 175:520–521

    Article  Google Scholar 

  8. Nokoff NJ, Scarbro SL, Moreau KL, Zeitler P, Nadeau KJ, Juarez-Colunga E, Kelsey MM (2020) Body Composition and Markers of Cardiometabolic Health in Transgender Youth Compared With Cisgender Youth. J Clin Endocrinol Metab 105:704–714

    Article  Google Scholar 

  9. Jarin J, Pine-Twaddell E, Trotman G, Stevens J, Conard LA, Tefera E, Gomez-Lobo V (2017) Cross-Sex Hormones and Metabolic Parameters in Adolescents With Gender Dysphoria. Pediatrics 139:e20163173

    Article  Google Scholar 

  10. Cheung AS, Lim HY, Cook T, Zwickl S, Ginger A, Chiang C, Zajac JD (2020) Approach to Interpreting Common Laboratory Pathology Tests in Transgender Individuals. J Clin Endocrinol Metab 106:893–901

    Article  Google Scholar 

  11. Mian AN, Schwartz GJ (2017) Measurement and Estimation of Glomerular Filtration Rate in Children. Adv Chronic Kidney Dis 24:348–356

    Article  Google Scholar 

  12. Stevens LA, Coresh J, Greene T, Levey AS (2006) Assessing Kidney Function — Measured and Estimated Glomerular Filtration Rate. N Engl J Med 354:2473–2483

    Article  CAS  Google Scholar 

  13. Baxmann AC, Ahmed MS, Marques NC, Menon VB, Pereira AB, Kirsztajn GM, Heilberg IP (2008) Influence of muscle mass and physical activity on serum and urinary creatinine and serum cystatin C. Clin J Am Soc Nephrol 3:348–354

    Article  CAS  Google Scholar 

  14. Levey AS, Stevens LA, Schmid CH, Zhang YL et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612

    Article  Google Scholar 

  15. Diao JA, Inker LA, Levey AS, Tighiouart H, Powe NR, Manrai AK (2021) In Search of a Better Equation — Performance and Equity in Estimates of Kidney Function. N Engl J Med 384:396–399

    Article  Google Scholar 

  16. Bonham VL, Green ED, Pérez-Stable EJ (2018) Examining How Race, Ethnicity, and Ancestry Data Are Used in Biomedical Research. JAMA 320:1533–1534

    Article  Google Scholar 

  17. Inker LA, Eneanya ND, Coresh J, Tighiouart H et al (2021) New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. N Engl J Med 385:1737–1749

    Article  CAS  Google Scholar 

  18. Delgado C, Baweja M, Burrows NR, Crews DC et al (2021) Reassessing the Inclusion of Race in Diagnosing Kidney Diseases: An Interim Report from the NKF-ASN Task Force. J Am Soc Nephrol 32:1305–1317

    Article  CAS  Google Scholar 

  19. Collister D, Saad N, Christie E, Ahmed S (2021) Providing Care for Transgender Persons With Kidney Disease: A Narrative Review. Can J Kidney Heal Dis. https://doi.org/10.1177/2054358120985379

    Article  Google Scholar 

  20. Whitley CT, Greene DN (2017) Transgender man being evaluated for a kidney transplant. Clin Chem 63:1680–1683

    Article  CAS  Google Scholar 

  21. Pierce CB, Muñoz A, Ng DK, Warady BA, Furth SL, Schwartz GJ (2021) Age- and sex-dependent clinical equations to estimate glomerular filtration rates in children and young adults with chronic kidney disease. Kidney Int 99:948–956

    Article  CAS  Google Scholar 

  22. Olson-Kennedy J, Chan Y-M, Garofalo R, Spack N, Chen D, Clark L, Ehrensaft D, Hidalgo M, Tishelman A, Rosenthal S (2019) The Impact of Early Medical Treatment in Transgender Youth: The Trans Youth Care Study (Preprint). JMIR Res Protoc. https://doi.org/10.2196/14434

    Article  PubMed  PubMed Central  Google Scholar 

  23. Pottel H, Björk J, Courbebaisse M, Couzi L et al (2021) Development and validation of a modified full age spectrum creatinine-based equation to estimate glomerular filtration rate. Ann Intern Med 174:183–191

    Article  Google Scholar 

  24. (2017) National Health and Nutrition Examination Survey Laboratory Protocol. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Hyattsville, MD

  25. Pottel H, Hoste L, Dubourg L, Ebert N, Schaeffner E, Eriksen BO, Melsom T, Lamb EJ, Rule AD, Turner ST, Glassock RJ, De Souza V, Selistre L, Mariat C, Martens F, Delanaye P (2016) An estimated glomerular filtration rate equation for the full age spectrum. Nephrol Dial Transplant 31(5):798–806. https://doi.org/10.1093/ndt/gfv454

    Article  Google Scholar 

  26. Staples A, Leblond R, Watkins S, Wong C, Brandt J (2010) Validation of the revised Schwartz estimating equation in a predominantly non-CKD population. Pediatr Nephrol 25:2321–2326

    Article  Google Scholar 

  27. National Kidney Foundation (2002) K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification.

  28. Pottel H, Hoste L, Delanaye P (2015) Abnormal glomerular filtration rate in children, adolescents and young adults starts below 75 mL/min/1.73 m2. Pediatr Nephrol 30:821–828

    Article  Google Scholar 

  29. Schwartz GJ, Haycock GB, Edelmann CMJ, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263

    Article  CAS  Google Scholar 

  30. Lichtenecker DCK, Argeri R, de Moura Castro CH, Dias-da-Silva MR, Gomes GN (2021) Cross-Sex Testosterone Therapy Modifies the Renal Morphology and Function in Female Rats and Might Underlie Increased Systolic Pressure. Clin Exp Pharmacol Physiol 48:978–986

    Article  CAS  Google Scholar 

  31. Levey AS, Inker LA, Coresh J (2014) GFR estimation: From physiology to public health. Am J Kidney Dis 63:820–834

    Article  Google Scholar 

  32. Inker LA, Schmid CH, Tighiouart H, Eckfeldt JH et al (2012) Estimating Glomerular Filtration Rate from Serum Creatinine and Cystatin C. N Engl J Med 367:20–29

    Article  CAS  Google Scholar 

  33. Vinge E, Lindergård B, Nilsson-Ehle P, Grubb A (1999) Relationships among serum cystatin C, serum creatinine, lean tissue mass and glomerular filtration rate in healthy adults. Scand J Clin Lab Invest 59:587–592

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by National Institutes of Health (R01 HD082554) and the Doris Duke Charitable Foundation (Grant 2019119 to KM).

Author information

Authors and Affiliations

  1. Division of Endocrinology, Boston Children’s Hospital, 300 Longwood Ave, Boston, MA, 02115, USA

    Kate Millington, Ellis Barrera & Yee-Ming Chan

  2. Department of Pediatrics, Harvard Medical School, Boston, MA, USA

    Kate Millington, Ankana Daga, Nina Mann & Yee-Ming Chan

  3. Division of Nephrology, Boston Children’s Hospital, Boston, MA, USA

    Ankana Daga & Nina Mann

  4. Department of Pediatrics, Children’s Hospital Los Angeles, Los Angeles, CA, USA

    Johanna Olson-Kennedy

  5. Division of Adolescent Medicine, Lurie Children’s Hospital, Chicago, IL, USA

    Robert Garofalo

  6. Division of Pediatric Endocrinology, Benioff Children’s Hospital, University of California at San Francisco, San Francisco, CA, USA

    Stephen M. Rosenthal

Authors
  1. Kate Millington
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ellis Barrera
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ankana Daga
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nina Mann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Johanna Olson-Kennedy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Robert Garofalo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Stephen M. Rosenthal
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yee-Ming Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kate Millington.

Ethics declarations

Conflict of Interest

The authors have no relevant financial conflicts of interest to disclose.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 23 KB)

Supplementary file2 (DOCX 22 KB)

Supplementary file3 (DOCX 18 KB)

Supplementary file4 (DOCX 19 KB)

467_2022_5445_MOESM5_ESM.pdf

Supplementary file5 Flowsheet of participant selection for analysis. GAH = Gender-affirming hormones, DMAB = Designated male at birth, DFAB = Designated female at birth. (PDF 45 KB)

467_2022_5445_MOESM6_ESM.pdf

Supplementary file6 Correlation between change in serum creatinine and change in serum testosterone in participants designated male at birth (DMAB) treated with estradiol (A) and participants designated female at birth (DFAB) treated with testosterone (B). Solid line is the regression line and dotted lines are the 95% CI for the regression line. Although there was a trend toward a direct relationship between decrease in serum testosterone and decrease in serum creatinine in participants DMAB, this was not statistically significant (slope (95% CI) 954.3 (–6.4,1915.0) ng testosterone/mg creatinine, R2 = 0.14, p = 0.051). For participants DFAB, there was a significant direct relationship between the increase in serum testosterone during testosterone treatment and the increase in serum creatinine (slope (95% CI) 663.4 (237.0,1089.7) ng testosterone/mg creatinine, R2 = 0.11, p = 0.003). (PDF 46 KB)

467_2022_5445_MOESM7_ESM.pdf

Supplementary file7 Change in creatinine Z-scores (based on NHANES reference data) during gender-affirming hormone treatment in participants designated male at birth (DMAB) treated with estradiol (A) and in participants designated female at birth (DFAB) treated with testosterone. Z-scores were calculated using reference data from NHANES correlating to the participants’ sex designated at birth (closed triangles and solid line) and using reference data corresponding to the participants’ gender identity (open triangles and dashed lines). Symbols indicate means and vertical lines indicate standard deviations. An asterisk indicates a significant change from the prior timepoint (p < 0.05). There was a significant change in the Z-score from 0 to 12 months in all groups. (PDF 27 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Millington, K., Barrera, E., Daga, A. et al. The effect of gender-affirming hormone treatment on serum creatinine in transgender and gender-diverse youth: implications for estimating GFR. Pediatr Nephrol 37, 2141–2150 (2022). https://doi.org/10.1007/s00467-022-05445-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-022-05445-0

Keywords

Search

Navigation