Kidney function decline in the elderly: Impact of lipoprotein-associated phospholipase A₂

Background: Whether lipoprotein-associated phospholipase A₂ (Lp-PLA₂) levels are associated with kidney function decline has not been well studied. Methods: We investigated associations of Lp-PLA₂ antigen and activity with kidney function decline and rapid decline over 5.7 years in the Cardiovascular Health Study (n = 4,359). We estimated kidney function by cystatin C (eGFRcys) in repeated measures, and defined rapid decline as ≥3 ml/min/1.73 m² per year. We stratified by baseline preserved GFR (≥60 ml/min/1.73 m²). Results: Mean age was 72 ± 5 years. Average eGFRcys decline was -1.79 ml/min/1.73 m² (SD = 2.60) per year. Among persons with preserved GFR, compared to the lowest quartile of Lp-PLA₂ antigen, eGFRcys decline was faster among persons in the second, β -0.31 (95% CI -0.52, -0.10), third -0.19 (-0.41, 0.02) and fourth quartiles -0.26 (-0.48, -0.04) after full adjustment. Persons in the highest quartile of Lp-PLA₂ antigen had increased odds of rapid decline 1.34 (1.03, 1.75), compared to the lowest. There was no significant association between levels of Lp-PLA₂ activity and eGFRcys decline or rapid decline. Associations were not statistically significant among persons with low eGFR (<60 ml/min/1.73 m²) at baseline. Conclusion: Higher levels of Lp-PLA₂ antigen but not activity were significantly associated with faster rates of kidney function decline. These findings may suggest a novel vascular pathway for kidney disease progression.