Low Plasma Lecithin: Cholesterol Acyltransferase (LCAT) Concentration Predicts Chronic Kidney Disease
Low high-density lipoprotein-cholesterol (HDL-c) is the most remarkable lipid trait both in mild-to-moderate chronic kidney disease (CKD) patients as well as in advanced renal disease stages, and we have previously shown that reduced lecithin:cholesterol acyltransferase (LCAT) concentration is a maj...
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MDPI AG
2020-07-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/9/7/2289 |
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| author | Andrea Baragetti Alice Ossoli Arianna Strazzella Sara Simonelli Ivano Baragetti Liliana Grigore Fabio Pellegatta Alberico L. Catapano Giuseppe Danilo Norata Laura Calabresi |
| author_facet | Andrea Baragetti Alice Ossoli Arianna Strazzella Sara Simonelli Ivano Baragetti Liliana Grigore Fabio Pellegatta Alberico L. Catapano Giuseppe Danilo Norata Laura Calabresi |
| author_sort | Andrea Baragetti |
| collection | DOAJ |
| description | Low high-density lipoprotein-cholesterol (HDL-c) is the most remarkable lipid trait both in mild-to-moderate chronic kidney disease (CKD) patients as well as in advanced renal disease stages, and we have previously shown that reduced lecithin:cholesterol acyltransferase (LCAT) concentration is a major determinant of the low HDL phenotype. In the present study, we test the hypothesis that reduced LCAT concentration in CKD contributes to the progression of renal damage. The study includes two cohorts of subjects selected from the PLIC study: a cohort of 164 patients with CKD (NefroPLIC cohort) and a cohort of 164 subjects selected from the PLIC participants with a basal estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m<sup>2</sup> (PLIC cohort). When the NefroPLIC patients were categorized according to the LCAT concentration, patients in the 1st tertile showed the highest event rate at follow-up with an event hazard ratio significantly higher compared to the 3rd LCAT tertile. Moreover, in the PLIC cohort, subjects in the 1st LCAT tertile showed a significantly faster impairment of kidney function compared to subjects in the 3rd LCAT tertile. Serum from subjects in the 1st LCAT tertile promoted a higher reactive oxygen species (ROS) production in renal cells compared to serum from subjects in the third LCAT tertile, and this effect was contrasted by pre-incubation with recombinant human LCAT (rhLCAT). The present study shows that reduced plasma LCAT concentration predicts CKD progression over time in patients with renal dysfunction, and, even more striking, it predicts the impairment of kidney function in the general population. |
| first_indexed | 2024-03-10T18:23:17Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T18:23:17Z |
| publishDate | 2020-07-01 |
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| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-f2d9476a970649e4995b646915357d072023-11-20T07:14:00ZengMDPI AGJournal of Clinical Medicine2077-03832020-07-0197228910.3390/jcm9072289Low Plasma Lecithin: Cholesterol Acyltransferase (LCAT) Concentration Predicts Chronic Kidney DiseaseAndrea Baragetti0Alice Ossoli1Arianna Strazzella2Sara Simonelli3Ivano Baragetti4Liliana Grigore5Fabio Pellegatta6Alberico L. Catapano7Giuseppe Danilo Norata8Laura Calabresi9Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20133 Milano, ItalyCentro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università Degli Studi di Milano, 20133 Milano, ItalyCentro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università Degli Studi di Milano, 20133 Milano, ItalyCentro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università Degli Studi di Milano, 20133 Milano, ItalyDepartment of Nephrology and Dialysis, Ospedale Bassini, ASST Nord Milano-Cinisello Balsamo, 20092 Milano, ItalyS.I.S.A. Centro per lo Studio della Aterosclerosi, Ospedale Bassini, Cinisello Balsamo, 20092 Milano, ItalyS.I.S.A. Centro per lo Studio della Aterosclerosi, Ospedale Bassini, Cinisello Balsamo, 20092 Milano, ItalyDipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20133 Milano, ItalyDipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, 20133 Milano, ItalyCentro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università Degli Studi di Milano, 20133 Milano, ItalyLow high-density lipoprotein-cholesterol (HDL-c) is the most remarkable lipid trait both in mild-to-moderate chronic kidney disease (CKD) patients as well as in advanced renal disease stages, and we have previously shown that reduced lecithin:cholesterol acyltransferase (LCAT) concentration is a major determinant of the low HDL phenotype. In the present study, we test the hypothesis that reduced LCAT concentration in CKD contributes to the progression of renal damage. The study includes two cohorts of subjects selected from the PLIC study: a cohort of 164 patients with CKD (NefroPLIC cohort) and a cohort of 164 subjects selected from the PLIC participants with a basal estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m<sup>2</sup> (PLIC cohort). When the NefroPLIC patients were categorized according to the LCAT concentration, patients in the 1st tertile showed the highest event rate at follow-up with an event hazard ratio significantly higher compared to the 3rd LCAT tertile. Moreover, in the PLIC cohort, subjects in the 1st LCAT tertile showed a significantly faster impairment of kidney function compared to subjects in the 3rd LCAT tertile. Serum from subjects in the 1st LCAT tertile promoted a higher reactive oxygen species (ROS) production in renal cells compared to serum from subjects in the third LCAT tertile, and this effect was contrasted by pre-incubation with recombinant human LCAT (rhLCAT). The present study shows that reduced plasma LCAT concentration predicts CKD progression over time in patients with renal dysfunction, and, even more striking, it predicts the impairment of kidney function in the general population.https://www.mdpi.com/2077-0383/9/7/2289lecithin:cholesterol acyltransferasechronic kidney diseasehigh-density lipoproteins |
| spellingShingle | Andrea Baragetti Alice Ossoli Arianna Strazzella Sara Simonelli Ivano Baragetti Liliana Grigore Fabio Pellegatta Alberico L. Catapano Giuseppe Danilo Norata Laura Calabresi Low Plasma Lecithin: Cholesterol Acyltransferase (LCAT) Concentration Predicts Chronic Kidney Disease Journal of Clinical Medicine lecithin:cholesterol acyltransferase chronic kidney disease high-density lipoproteins |
| title | Low Plasma Lecithin: Cholesterol Acyltransferase (LCAT) Concentration Predicts Chronic Kidney Disease |
| title_full | Low Plasma Lecithin: Cholesterol Acyltransferase (LCAT) Concentration Predicts Chronic Kidney Disease |
| title_fullStr | Low Plasma Lecithin: Cholesterol Acyltransferase (LCAT) Concentration Predicts Chronic Kidney Disease |
| title_full_unstemmed | Low Plasma Lecithin: Cholesterol Acyltransferase (LCAT) Concentration Predicts Chronic Kidney Disease |
| title_short | Low Plasma Lecithin: Cholesterol Acyltransferase (LCAT) Concentration Predicts Chronic Kidney Disease |
| title_sort | low plasma lecithin cholesterol acyltransferase lcat concentration predicts chronic kidney disease |
| topic | lecithin:cholesterol acyltransferase chronic kidney disease high-density lipoproteins |
| url | https://www.mdpi.com/2077-0383/9/7/2289 |
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