Kidney Week

Abstract: TH-PO0359

Sex Hormones and Risk of CKD Progression Among Adults with Type 2 Diabetes and Obesity in the Look AHEAD Sex Hormone Ancillary Study

Session Information

• Diabetic Kidney Disease: From Early Biomarkers to Novel Therapeutic Targets
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 702 Diabetic Kidney Disease: Clinical

Authors

• Srialluri, Nityasree, Johns Hopkins Medicine, Baltimore, Maryland, United States

Nityasree Srialluri, MD, MS

• He, Jiahuan Helen, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States

Jiahuan Helen He

• Oyeka, Chigolum P, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States

Chigolum P Oyeka, MBBS, MPH

• Ma, Jianqiao, Johns Hopkins Medicine, Baltimore, Maryland, United States

Jianqiao Ma, MS

• Gisinger, Teresa, Medizinische Universitat Wien, Vienna, Austria

Teresa Gisinger, MD, PhD

• Michos, Erin D., Johns Hopkins Medicine, Baltimore, Maryland, United States

Erin D. Michos, MD

• Kalyani, Rita, Johns Hopkins Medicine, Baltimore, Maryland, United States

Rita Kalyani, MD

• Woodward, Mark, The George Institute for Global Health, Sydney, New South Wales, Australia

Mark Woodward, PhD

• Vaidya, Dhananjay, Johns Hopkins Medicine, Baltimore, Maryland, United States

Dhananjay Vaidya, MBBS, PhD, MPH

• Bennett, Wendy L, Johns Hopkins Medicine, Baltimore, Maryland, United States

Wendy L Bennett, MD, MPH

Background

Sex differences in CKD progression are well established, with males experiencing faster kidney disease progression. However, the biological basis for this difference remains unclear. We examined associations between baseline sex hormones and kidney outcomes.

Methods

Look AHEAD was a randomized trial comparing intensive lifestyle intervention to control in adults with T2D and overweight/obesity. The Sex Hormone ancillary study included 2,334 participants with measured estradiol (E2), total testosterone (T), and sex hormone–binding globulin (SHBG); bioavailable T (bioT) was calculated using the Vermeulen equation. This analysis included 1,120 females and 1,126 males with baseline eGFR ≥60 mL/min/1.73 m² and UACR ≤300 mg/g. Hormones were log-transformed and standardized. The primary outcome was incident high-risk CKD, defined as eGFR <60 mL/min/1.73 m² or UACR >300 mg/g. Associations between baseline hormone levels and CKD risk were assessed using Cox proportional hazards models. Longitudinal changes in eGFR and UACR were evaluated using linear mixed-effects models. Analyses were stratified by sex and adjusted for demographic, clinical covariates, and treatment assignment.

Results

At baseline, the mean age was 60 years; females had higher BMI, and males had greater waist circumference. A higher proportion of Black and Hispanic participants were female. Baseline kidney function was similar between sexes. In males, each 1 SD increase in SHBG was associated with reduced incident CKD risk (HR 0.79; 95% CI 0.70–0.89), while each 1 SD increase in bioT was associated with increased risk (HR 1.42; 95% CI 1.21–1.66). Each 1 SD Total and bioT were associated with greater annual increases in albuminuria (1.1% and 0.9%, respectively; p < 0.01), and slower annual eGFR decline (β for total T = 0.21; 95% CI 0.14–0.28; β for bioT = 0.17; 95% CI 0.10–0.24; both p < 0.001). No significant associations were seen in females.

Conclusion

Among overweight/obese males with T2D, higher baseline bioT and lower SHBG levels were associated with greater CKD risk. Higher Total and Bio T levels were also linked to greater albuminuria progression. These findings highlight a potential role for androgenic signaling in CKD progression and risk stratification.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025xrnpcwrm