UACR as a clinical predictor of incident osteoarthritis: prospective evidence from the UK Biobank.

BACKGROUND

Osteoarthritis (OA) is a common joint disorder causing disability, marked by pain and stiffness, with current therapies only relieving symptoms. This highlights the need for early biomarkers. The urinary albumin-to-creatinine ratio (UACR) is an indicator of renal dysfunction and systemic inflammation, while OA is also closely associated with inflammatory processes. However, the direct relationship between UACR and OA risk remains unclear. We investigated the prospective association between UACR and incident OA.

METHODS

We analyzed data from 445,860 UK Biobank participants without OA, measuring UACR from urine samples and classifying it into normo- (< 30 mg/g), micro- (30 to 300 mg/g), and macroalbuminuria (> 300 mg/g). Incident OA was identified from medical records, and Cox models adjusted for various factors estimated hazard ratios and confidence intervals, with dose-response relationships assessed using cubic splines and further characterized by Kaplan-Meier curves and subgroup analyses.

RESULTS

A median follow-up of nearly 18 years revealed a significant, dose-dependent link between UACR and OA, with HRs of 1.11 for microalbuminuria and 1.20 for macroalbuminuria compared to normo-albuminuria. A nonlinear, J-shaped relationship was observed, with OA risk increasing sharply after UACR exceeded approximately 25 mg/g-a threshold that aligns with the upper limit of mild microalbuminuria and may represent an early stage of subclinical vascular dysfunction. These findings were supported by Kaplan-Meier curves showing progressively higher OA incidence with rising UACR (log-rank P < 0.0001). This association was consistent across subgroups and highest in non-obese individuals (HR = 1.52 for UACR > 300 mg/g).

CONCLUSION

Elevated UACR is linked to increased OA in a nonlinear manner, remaining significant after adjustments, suggests that UACR, as a marker of systemic microvascular and endothelial health, could help identify individuals at higher risk for OA, potentially enabling earlier and more targeted preventive interventions. Key Points • Elevated urinary albumin-to-creatinine ratio (UACR) is independently associated with higher risk of incident osteoarthritis (OA) in a large population-based cohort. • The association follows a nonlinear dose-response pattern, with OA risk rising sharply after UACR exceeds 25 mg/g. • The predictive link between UACR and OA remains consistent across subgroups and is strongest in non-obese individuals. • UACR may serve as a novel, readily available biomarker for identifying individuals at increased OA risk(especially in lean non-obese individuals),and parallel increases in 18-year allcause mortality provide epidemiological evidence linking systemic endothelial damage to joint degeneration.