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

Association between increased plasma ceramides and chronic kidney disease in patients with and without ischemic heart disease
Association between increased plasma ceramides and chronic kidney disease in patients with and without ischemic heart disease
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(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)] 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-GFR CKD-EPI < 60 ml/min/1.73 m 2 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(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), and Cer(d18:1/24:1) 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 < 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.
CKD, Cardiovascular risk, Ceramides, Kidney dysfunction
1262-3636
Mantovani, Alessandro
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Lunardi, Gianluigi
018121bb-19bd-44fd-bc5c-225fb8b43a84
Bonapace, Stefano
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Dugo, Clementina
ae0fcca7-760a-471e-91a5-b29477d0e127
Altomari, Anna
ebf7e9ec-56d4-4e98-95d8-57d148b6b38e
Molon, Giulio
f8998111-3b15-4eca-b6eb-caa9e384c523
Conti, Antonio
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Bovo, Chiara
9647f617-63c0-495f-b151-d0a3aa3e8d66
Laaksonen, Reijo
5ef4e783-678c-4552-8418-07427ff2d410
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
Bonnet, Fabrice
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Targher, Giovanni
043e0811-b389-4922-974e-22e650212c5f
Mantovani, Alessandro
19fc8a1f-60fe-403a-b70e-6b6884929e03
Lunardi, Gianluigi
018121bb-19bd-44fd-bc5c-225fb8b43a84
Bonapace, Stefano
3f859b0d-9099-486e-9a91-0ba007741683
Dugo, Clementina
ae0fcca7-760a-471e-91a5-b29477d0e127
Altomari, Anna
ebf7e9ec-56d4-4e98-95d8-57d148b6b38e
Molon, Giulio
f8998111-3b15-4eca-b6eb-caa9e384c523
Conti, Antonio
5c50dea6-372c-4553-9b94-99c1860efdec
Bovo, Chiara
9647f617-63c0-495f-b151-d0a3aa3e8d66
Laaksonen, Reijo
5ef4e783-678c-4552-8418-07427ff2d410
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
Bonnet, Fabrice
fffc5d1a-655a-442d-b083-6f9dde6f21e5
Targher, Giovanni
043e0811-b389-4922-974e-22e650212c5f

Mantovani, Alessandro, Lunardi, Gianluigi, Bonapace, Stefano, Dugo, Clementina, Altomari, Anna, Molon, Giulio, Conti, Antonio, Bovo, Chiara, Laaksonen, Reijo, Byrne, Christopher, Bonnet, Fabrice and Targher, Giovanni (2021) Association between increased plasma ceramides and chronic kidney disease in patients with and without ischemic heart disease. Diabetes & Metabolism, 47 (1), [101152]. (doi:10.1016/j.diabet.2020.03.003).

Record type: Article

Abstract

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(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)] 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-GFR CKD-EPI < 60 ml/min/1.73 m 2 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(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), and Cer(d18:1/24:1) 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 < 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.

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Accepted/In Press date: 1 April 2020
e-pub ahead of print date: 10 April 2020
Published date: 1 February 2021
Keywords: CKD, Cardiovascular risk, Ceramides, Kidney dysfunction

Identifiers

Local EPrints ID: 439193
URI: http://eprints.soton.ac.uk/id/eprint/439193
ISSN: 1262-3636
PURE UUID: ff71215c-77ba-4305-ab10-bffc96458c49
ORCID for Christopher Byrne: ORCID iD orcid.org/0000-0001-6322-7753

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Date deposited: 06 Apr 2020 16:36
Last modified: 17 Mar 2024 05:27

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Contributors

Author: Alessandro Mantovani
Author: Gianluigi Lunardi
Author: Stefano Bonapace
Author: Clementina Dugo
Author: Anna Altomari
Author: Giulio Molon
Author: Antonio Conti
Author: Chiara Bovo
Author: Reijo Laaksonen
Author: Fabrice Bonnet
Author: Giovanni Targher

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