Journal of clinical lipidology · 2026
Lipoprotein(a) lipidome and chronic kidney disease: Enrichment in triacylglycerols and diacylglycerols.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Khan Muhammad A, Myagmarsuren Munkhtuya, Zhang Wei, Law Hayley G, Sanchez Mackenzie, Roshanravan Baback, Bang Heejung, Bishop Lauren M, Shen Tong, Fiehn Oliver, De Boer Ian H, Berglund Lars, Enkhmaa Byambaa
Аннотация
BACKGROUND: An elevated level of lipoprotein(a) (Lp[a]) is a genetically-determined cardiovascular risk factor. A size polymorphism in its apolipoprotein(a) (apo[a]) component, expressed as kringle (K) 4 repeat numbers, is a major contributor to variability in levels. While chronic kidney disease (CKD) increases Lp(a) levels, less is known about its effect on Lp(a) molecular properties.
OBJECTIVE: To assess and compare Lp(a) lipidomic properties in patients with CKD and controls.
METHODS: We assessed and compared Lp(a)-lipidomic properties in 54 nondiabetic, nondialysis patients with CKD and 39 controls. CKD was defined by an estimated glomerular filtration rate of <60 mL/min/1.73 m2.
RESULTS: The mean age of the cohort was 63 years, 48% were women, and 77% were of European descent. Lp(a)-bound oxidized phospholipids (Lp[a]-OxPL) concentrations were higher in patients with CKD vs controls (median [IQR] 2.7 [0.5; 7.4] vs 1.2 [0.5; 3.4] U/L, P = 0.031), in particular for the medium (23-27 K repeats) apo(a) size range (P = 0.002). Among Lp(a)-OxPL subspecies, 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine relative abundance was significantly higher in patients with CKD compared to controls (21% vs 16%, P = 0.0004). Of the 437 individual lipid species in Lp(a), 146 species primarily representing diacylglycerols (P = 0.009), acylcarnitines (P = 0.003), and triacylglycerols (P = 0.005) showed significantly higher abundance in patients with CKD vs controls. This pattern remained unchanged after adjusting for differences in Lp(a) levels, indicating an impact of the CKD condition on Lp(a) lipidomic properties.
CONCLUSION: Among individuals without diabetes, kidney impairment was characterized by higher Lp(a)-OxPL concentrations and proinflammatory Lp(a)-lipidomic properties. Mechanisms underlying these changes and relevance to cardiovascular risk warrant further investigations.
OBJECTIVE: To assess and compare Lp(a) lipidomic properties in patients with CKD and controls.
METHODS: We assessed and compared Lp(a)-lipidomic properties in 54 nondiabetic, nondialysis patients with CKD and 39 controls. CKD was defined by an estimated glomerular filtration rate of <60 mL/min/1.73 m2.
RESULTS: The mean age of the cohort was 63 years, 48% were women, and 77% were of European descent. Lp(a)-bound oxidized phospholipids (Lp[a]-OxPL) concentrations were higher in patients with CKD vs controls (median [IQR] 2.7 [0.5; 7.4] vs 1.2 [0.5; 3.4] U/L, P = 0.031), in particular for the medium (23-27 K repeats) apo(a) size range (P = 0.002). Among Lp(a)-OxPL subspecies, 1-palmitoyl-2-(5'-oxo-valeroyl)-sn-glycero-3-phosphocholine relative abundance was significantly higher in patients with CKD compared to controls (21% vs 16%, P = 0.0004). Of the 437 individual lipid species in Lp(a), 146 species primarily representing diacylglycerols (P = 0.009), acylcarnitines (P = 0.003), and triacylglycerols (P = 0.005) showed significantly higher abundance in patients with CKD vs controls. This pattern remained unchanged after adjusting for differences in Lp(a) levels, indicating an impact of the CKD condition on Lp(a) lipidomic properties.
CONCLUSION: Among individuals without diabetes, kidney impairment was characterized by higher Lp(a)-OxPL concentrations and proinflammatory Lp(a)-lipidomic properties. Mechanisms underlying these changes and relevance to cardiovascular risk warrant further investigations.