Association between increased plasma ceramides and chronic kidney disease in patients with and without ischemic heart disease

A. Mantovani (1) , G. Lunardi (2) , S. Bonapace (2) , C. Dugo (2) , A. Altomari (1) , G. Molon (2) , A. Conti (2) , C. Bovo (1) , R. Laaksonen (3) , C.D. Byrne (4) , F. Bonnet (5) , G. Targher (1)

1 Azienda Ospedaliera Universitaria Integrata of Verona
2 IRCCS - Istituti di Ricovero e Cura a Carattere Scientifico
3 TUT - Tampere University of Technology [Tampere]
4 University of Southampton
5 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]

Aim Plasma levels of certain ceramides are increased in patients with ischemic heart disease (IHD). Many risk factors for IHD are also risk factors for chronic kidney disease (CKD), but it is currently uncertain whether plasma ceramide levels are increased in patients with CKD. Methods We measured six previously identified high-risk plasma ceramide concentrations [Cer(d181/160), Cer(d181/180), Cer(d181/200), Cer(d181/220), Cer(d181/240) and Cer(d181/241)] in 415 middle-aged individuals who attended our clinical Cardiology and Diabetes services over a period of 9 months. Results A total of 97 patients had CKD (defined as e-GFRCKD-EPI andlt; 60 ml/min/1.73 m2 and/or urinary albumin-to-creatinine ratio ≥ 30 mg/g), 117 had established IHD and 242 had type 2 diabetes. Patients with CKD had significantly (P = 0.005 or less) higher levels of plasma Cer(d181/160), Cer(d181/180), Cer(d181/200), Cer(d181/220), Cer(d181/240), and Cer(d181/241) compared to those without CKD. The presence of CKD remained significantly associated with higher levels of plasma ceramides (standardized beta coefficients ranging from 0.124 to 0.227, P andlt; 0.001) even after adjustment for body mass index, smoking, hypertension, diabetes, prior IHD, plasma LDL-cholesterol, hs-C-reactive protein levels and use of any lipid-lowering medications. Notably, more advanced stages of CKD and abnormal albuminuria were both associated (independently of each other) with increased levels of plasma ceramides. These results were consistent in all subgroups considered, including patients with and without established IHD or those with and without diabetes. Conclusion Increased levels of plasma ceramides are associated with CKD independently of pre-existing IHD, diabetes and other established cardiovascular risk factors.

Mots clés: Cardiovascular risk; Ceramides; CKD; Kidney dysfunction

Domaines: Sciences du Vivant [q-bio]; Endocrinologie et métabolisme

A. Mantovani, G. Lunardi, S. Bonapace, C. Dugo, A. Altomari, et al.. Association between increased plasma ceramides and chronic kidney disease in patients with and without ischemic heart disease. Diabetes & Metabolism, 2020, ⟨10.1016/j.diabet.2020.03.003⟩. ⟨hal-02865281⟩