Kidney Week

Abstract: TH-PO0628

Kidney Function Modifies the Association Between Circulating Osteopontin and Cardiovascular Outcomes: Evidence from the UK Biobank

Session Information

• CKD: Clinical - Guidelines, Biomarkers, Progression, Procedures, Outcomes, and More
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2202 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Sinha, Satyesh K., University of California Los Angeles, Los Angeles, California, United States

Satyesh K. Sinha, PhD

• Sarver, Dylan C., University of California Los Angeles, Los Angeles, California, United States

Dylan C. Sarver, PhD

• Lusis, Aldons J., University of California Los Angeles, Los Angeles, California, United States

Aldons J. Lusis, PhD

• Hilser, James R., University of California Los Angeles, Los Angeles, California, United States

James R. Hilser, PhD, MPH

• Allayee, Hooman, University of California Los Angeles, Los Angeles, California, United States

Hooman Allayee, MA, PhD

• Nicholas, Susanne B., University of California Los Angeles, Los Angeles, California, United States

Susanne B. Nicholas, MD, PhD, MPH

Background

Chronic kidney disease (CKD) affects ~10–15% of the global population and is associated with markedly increased cardiovascular (CV) mortality, accounting for ~50% of deaths. While shared mechanisms such as inflammation and vascular remodeling contribute, key molecular mediators linking CKD to CVD remain unclear. Osteopontin (OPN), a pro-inflammatory matricellular protein implicated in fibrosis and vascular pathology, is elevated in CKD and CVD, but its role across graded kidney function is not well defined. We used the UK Biobank to assess whether the association between circulating OPN and CV outcomes (myocardial infarction/stroke (MS) and heart failure HF) and all-cause mortality (ACM) is modified by kidney function.

Methods

We used circulating OPN and clinical data from the UK Biobank (2006-2010), a population-based cohort of >500,000 participants (40–69 years) with standardized phenotyping and longitudinal follow-up. Baseline kidney function was assessed with estimated glomerular filtration rate (eGFR), and participants were stratified by 2021 CKD-EPI eGFR (>90, 60–90, and <60 mL/min/1.73 m²). OPN levels were analyzed in quartiles. Incident CV outcomes and ACM were ascertained through linked hospital and ACM records. Associations between OPN and clinical outcomes were evaluated by Kaplan–Meier analyses and Cox proportional hazards models, and interaction testing assessed effect modification by kidney function.

Results

Higher OPN levels were associated with adverse CV outcomes in a kidney function–dependent manner. In individuals with preserved kidney function (eGFR >90 mL/min/1.73 m²), OPN was associated with ACM (P=6.05E-08) but not incident CV outcome. In contrast, the association between OPN and CV outcomes became progressively stronger with declining kidney function, including >2-fold increased risk of incident MS (HR 2.18, P= 1.65E-03), HF (HR 2.51, P= 1.88E-05) and ACM (HR- 2.46, p- 9.69E-09) in participants with eGFR <60 mL/min/1.73 m². Significant interaction testing confirmed that impaired kidney function amplified the relationship between OPN and adverse outcomes across all major endpoints (MS, P-int= 9.56E-03; HF, P-int= 3.61E-06; ACM, P-int= 6.46E-04).

Conclusion

These findings indicate that impaired kidney function modifies the association between OPN and CV outcomes, supporting a potential role for OPN in mediating the cardio–kidney axis.