Kidney Week

Abstract: FR-PO0266

Comparison of Two Soluble Klotho Assays in Humans with CKD: Findings from the Systolic Blood Pressure Intervention Trial

Session Information

• Bone and Mineral Metabolism: Clinical Epidemiology and Outcomes
  November 07, 2025 | 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

• 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 Medical Center, 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., The University of Alabama at Birmingham, Birmingham, Alabama, United States

Javier A. Neyra, MD, MS, FASN

Background

αKlotho is produced within the kidney and in transmembrane form, acts a cofactor with FGF-23. Klotho is also released into circulation as soluble klotho. There is significant interest in soluble klotho as a potential biomarker in chronic kidney disease (CKD), but it is unclear which klotho assay to utilize in humans, and how soluble klotho, as measured by different assays, relates to kidney and mineral metabolism biomarkers.

Methods

Soluble klotho was measured by two distinct assays using baseline samples from the Systolic Blood Pressure Intervention Trial. All individuals had CKD and never-thawed serum available for klotho measurement. The first assay was an immuno-precipitation immunoblot assay (IP-IB) utilizing two separate anti-klotho antibodies (sb-106 for IP and KM2076 for IB), while the second assay was a commercial ELISA (IBL®). We determined the correlation between klotho concentrations obtained from each assay, and the linear relations between klotho assays and other kidney biomarkers, including eGFRcr-cys, serum bicarbonate, and measures of mineral metabolism.

Results

There were 2291 subjects with klotho IP-IB measures (mean eGFRcr-cys = 49.8 (12.1) and 1216 subjects with klotho ELISA measures (mean eGFRcr-cys = 49.8(12.3)). The intra-assay CVs of the klotho assays were 6.9% and 6.1% for IPIB & ELISA, respectively. The median [25^th, 75^th] 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. The Pearson correlation between the two assays was 0.36 (0.31, 0.40). The correlations of Klotho by IPIB and ELISA with kidney and mineral metabolism biomarkers, including after adjustment for eGFRcr-cys, are presented in Table 1.

Conclusion

There was only modest correlation between the klotho measuresments by IP-IB and ELISA in samples of CKD participants. Klotho concentrations assayed by IP-IB were more strongly correlated with eGFRcr-cys, serum bicarbonate, and the majority of mineral metabolism measures.

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.20251fy139hn