Kidney Week

Abstract: TH-PO152

Soluble Klotho and Baseline Clinical Characteristics in the Systolic Blood Pressure Intervention Trial

Session Information

• CKD-MBD: Clinical
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 502 Bone and Mineral Metabolism: Clinical

Authors

• Drew, David A., Tufts Medical Center, Boston, Massachusetts, United States

David A. Drew, MD, MS

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

Johanne Virginia Pastor, ScD

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

Xilong Li

• Ix, Joachim H., UC San Diego Health, San Diego, California, United States

Joachim H. Ix, MD, FASN

• Sarnak, Mark J., Tufts Medical Center, Boston, Massachusetts, United States

Mark J. Sarnak, MD, MS

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

Orson W. Moe, MD

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

Javier A. Neyra, MD, MS, FASN

Background

αKlotho is produced within the kidney and is released into circulation as soluble klotho. Animal data demonstrate that klotho is directly correlated with GFR. Due to promising preclinical data, there is significant interest in klotho as a potential biomarker in chronic kidney disease.

Methods

Soluble klotho was measured by two distinct assays using baseline samples from the Systolic Blood Pressure Intervention Trial. All individuals had chronic kidney disease (eGFRcr-cys < 60 ml/min/1.73m²) and never-thawed serum samples available for klotho measurement. The first assay was an immuno-precipitation immunoblot assay (IP-IB) utilizing two separate anti-klotho antibodies, while the second assay was a commercially available ELISA (IBL). Demographics, clinical characteristics, and laboratory data were examined for linear trends across quartiles of klotho concentrations.

Results

There were 2291 subjects with klotho IPIB measures and 1216 subjects with klotho ELISA measures. The intra-assay CVs of the klotho assays were 6.9% and 6.1% (IPIB & ELISA respectively). The median [25th,75th] klotho concentration was 11.0 pM [7.7,16.0] for the IP-IB and 4.6 pM [3.4,6.6] for the ELISA. For both assays, higher quartiles of klotho were significantly associated with higher eGFR. For the IPIB, higher klotho was associated with a lower proportion of current smokers and loop diuretic use, and fewer number of anti-hypertensives. Higher IP-IB klotho was associated with higher serum magnesium, calcium, and bicarbonate, higher urine calcium, and lower serum FGF-23. For the ELISA assay, there was a similar but weaker association with mineral metabolism markers.

Conclusion

Both klotho assays had acceptable performance and results were consistent with known klotho pathobiology. The IP-IB klotho concentrations were more consistently associated with other measures of mineral metabolism.

Quartiles of Klotho IPIB in SPRINT

Funding

• NIDDK Support