Kidney Week

Abstract: TH-OR047

Longitudinal Changes in α-Klotho Among Patients with CKD in the Systolic Blood Pressure Intervention Trial (SPRINT)

Session Information

• CKD Outcomes: Novel Biomarkers, Interventions, and Multiorgan Crosstalk
  October 22, 2026 | Location: Mile High Ballroom 1D, Convention Center
  Abstract Time: 04:40 PM - 04:50 PM

Category: CKD (Non-Dialysis)

• 2201 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

• Gurumurthy, Rohin, Tufts University School of Medicine, Boston, Massachusetts, United States

Rohin Gurumurthy

• Pastor, Johanne, The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Johanne Pastor

• Li, Xilong, The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Xilong Li

• Waddle, Carlos J., The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Carlos J. Waddle

• Gianella, Fabiola, The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Fabiola Gianella, MD

• Sarnak, Mark J., Tufts University School of Medicine, Boston, Massachusetts, United States

Mark J. Sarnak, MD, MS

• Ix, Joachim H., University of California San Diego, La Jolla, California, United States

Joachim H. Ix, MD, FASN

• Moe, Orson W., The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Orson W. Moe, MD

• Neyra, Javier A., University of Alabama at Birmingham Health System, Birmingham, Alabama, United States

Javier A. Neyra, MD, MS, FASN

• Drew, David A., Tufts University School of Medicine, Boston, Massachusetts, United States

David A. Drew, MD, MS

Background

α-klotho, a protein expressed in kidney tubular epithelial cells and present in serum as soluble klotho, has emerged as a promising biomarker of human kidney health. Chronic kidney disease (CKD) has been characterized as a state of systemic klotho deficiency, yet longitudinal serum klotho changes in CKD remain poorly characterized.

Methods

Soluble klotho was measured via immunoprecipitation-immunoblot (IP-IB) assay in 896 patients with CKD from the SPRINT cohort at baseline and 12 months. Patients were stratified by percentage change in klotho: 1. decrease ≤ -30%, 2. stable (± 30%), and 3. increase ≥ 30%. Clinical and laboratory correlates at baseline and at 12 months were compared across the tertiles, which included demographics, eGFR, UACR, mineral metabolism markers, blood pressure, and additional kidney biomarkers.

Results

At 12 months, klotho declined ≤ -30% in 195 patients (21.8%), remained stable in 475 (53%), and increased ≥ 30% in 226 (25.2%). Patients with declining klotho vs. increasing klotho at 12 months were older (74 vs 71 years, p=0.001), were more likely to be in the intensive treatment arm (61% vs 48%, p=0.03), and had higher baseline serum phosphate (3.6 vs 3.5, p=0.04) and PTH (50 vs 44, p=0.03). eGFR change at 12 months was significant across groups (p<0.001); patients in the increasing klotho tertile had the greatest eGFR improvement (+5.2), while those in the declining klotho tertile showed the largest decrease (-2.7). Declining (vs. increasing) klotho was also associated with greater reductions in systolic (-8.0 vs -4.3 mmHg, p=0.025) and diastolic BP (-7.5 vs -2.5 mmHg, p=0.003) at 12 months.

Conclusion

Longitudinal klotho levels were described for the first time in this large CKD cohort. Serum klotho levels varied substantially over time. Longitudinal klotho decline, compared with klotho increase, was associated with eGFR decline and larger reductions in systolic and diastolic blood pressure. These findings suggest changes in klotho concentrations mirror key measures of kidney health.

Funding

• NIDDK Support