The CKD plasma lipidome varies with disease severity and outcome

Duranton, Flore; Laget, Jonas; Gayrard, Nathalie; Saulnier-Blache, Jean Sébastien; Lundin, Ulrika; Schanstra, Joost P.; Mischak, Harald; Weinberger, Klaus M.; Servel, Marie-Françoise; Argilés, Àngel

doi:10.1016/j.jacl.2018.07.010

Cited by 17 publications

(7 citation statements)

References 40 publications

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“…Additionally, higher blood concentrations of LPC are positively correlated with the muscle insulin sensitivity index in diabetic patients [ 138 ] and inversely correlate with impaired fasting glucose and diabetes incidence [ 139 , 140 , 141 , 142 ]. Importantly, a reduction in LPCs was associated with a risk of adverse outcome in chronic kidney disease patients [ 143 ].…”

Section: Future Directions Of Lpc As a Biomarkermentioning

confidence: 99%

An Updated Review of Pro- and Anti-Inflammatory Properties of Plasma Lysophosphatidylcholines in the Vascular System

Knuplez

Marsche

2020

IJMS

128

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Lysophosphatidylcholines are a group of bioactive lipids heavily investigated in the context of inflammation and atherosclerosis development. While present in plasma during physiological conditions, their concentration can drastically increase in certain inflammatory states. Lysophosphatidylcholines are widely regarded as potent pro-inflammatory and deleterious mediators, but an increasing number of more recent studies show multiple beneficial properties under various pathological conditions. Many of the discrepancies in the published studies are due to the investigation of different species or mixtures of lysophatidylcholines and the use of supra-physiological concentrations in the absence of serum or other carrier proteins. Furthermore, interpretation of the results is complicated by the rapid metabolism of lysophosphatidylcholine (LPC) in cells and tissues to pro-inflammatory lysophosphatidic acid. Interestingly, most of the recent studies, in contrast to older studies, found lower LPC plasma levels associated with unfavorable disease outcomes. Being the most abundant lysophospholipid in plasma, it is of utmost importance to understand its physiological functions and shed light on the discordant literature connected to its research. LPCs should be recognized as important homeostatic mediators involved in all stages of vascular inflammation. In this review, we want to point out potential pro- and anti-inflammatory activities of lysophospholipids in the vascular system and highlight recent discoveries about the effect of lysophosphatidylcholines on immune cells at the endothelial vascular interface. We will also look at their potential clinical application as biomarkers.

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Section: Future Directions Of Lpc As a Biomarkermentioning

confidence: 99%

An Updated Review of Pro- and Anti-Inflammatory Properties of Plasma Lysophosphatidylcholines in the Vascular System

Knuplez

Marsche

2020

IJMS

128

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“…CKD is frequently associated with dyslipidemia, low-grade inflammation, and vascular calcification [6,7]. The entire plasma lipidome changes with the severity of CKD [8]. Patients with CKD exhibit proatherogenic dyslipidemia similar to that of patients with type 2 diabetes, with low high-density lipoprotein (HDL) levels and high lipoprotein (a) (Lp(a)) levels [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Cholesterol-Lowering Action of a Novel Nutraceutical Combination in Uremic Rats: Insights into the Molecular Mechanism in a Hepatoma Cell Line

Lupo

Biancorosso

Brilli³

et al. 2020

Nutrients

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Appropriate nutraceutical combinations may represent a valid approach to prevent vascular calcification associated with chronic kidney disease (CKD). In the present study, we tested the effect of a new nutraceutical combination named RenaTris®, containing MK-7, magnesium carbonate, and Sucrosomial® Iron, on vascular calcification in uremic rats. Rats were randomly divided into three groups, i.e., control (high-phosphate diet), uremic (high-phosphate diet containing 0.5% adenine), and supplemented uremic diet (0.5% adenine, MK-7, magnesium carbonate, and Sucrosomial® Iron). After six weeks, sera and vascular calcification were examined. The uremic diet increased creatinine and phosphate levels and induced extensive vascular calcification. The uremic condition also induced a mild hypercholesterolemic condition (+52% of total cholesterol; p < 0.05). The supplemented uremic diet did not reduce creatinine, phosphate levels, or vascular calcification, however, we observed a significant hypocholesterolemic effect (−18.9% in supplemental uremic vs. uremic diet; p < 0.05). Similar to simvastatin, incubation of cultured human hepatoma cells (Huh7) with MK-7 significantly reduced cholesterol biosynthesis (−38%) and induced 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase and low-density lipoprotein receptor (LDLR) at both mRNA and protein levels. The effect of MK-7 on LDLR was counteracted by the co-incubation with squalene. Unlike simvastatin, MK-7 reduced PCSK9 in Huh7. These results indicated that the new nutraceutical combination significantly impacts cholesterol metabolism and its supplementation may help to control mild hypercholesterolemic conditions in CKD patients.

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“…Untargeted lipidomics has been applied to the lipid disorders of the patients with chronic kidney disease (Afshinnia et al, 2016;Duranton et al, 2019;Afshinnia et al, 2020). Afshinnia et al found that a distinct panel of lipids may improve prediction of progression of chronic kidney disease beyond estimated glomerular filtration rate and urine protein-to-creatinine ratio (Afshinnia et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Polyporus Umbellatus Protects Against Renal Fibrosis by Regulating Intrarenal Fatty Acyl Metabolites

Wang

Zhang

et al. 2021

Front. Pharmacol.

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Background: Chronic renal failure (CRF) results in significant dyslipidemia and profound changes in lipid metabolism. Polyporus umbellatus (PPU) has been shown to prevent kidney injury and subsequent kidney fibrosis.Methods: Lipidomic analysis was performed to explore the intrarenal profile of lipid metabolites and further investigate the effect of PPU and its main bioactive component, ergone, on disorders of lipid metabolism in rats induced by adenine. Univariate and multivariate statistical analyses were performed for choosing intrarenal differential lipid species in CRF rats and the intervening effect of n-hexane extract of PPU and ergone on CRF rats.Results: Compared with control group, decreased creatinine clearance rate indicated declining kidney function in CRF group. Based on the lipidomics, we identified 65 lipid species that showed significant differences between CRF and control groups. The levels of 12 lipid species, especially fatty acyl lipids including docosahexaenoic acid, docosapentaenoic acid (22n-3), 10,11-Dihydro-12R-hydroxy-leukotriene C4, 3-hydroxydodecanoyl carnitine, eicosapentaenoic acid, hypogeic acid and 3-hydroxypentadecanoic acid had a strong linear correlation with creatinine clearance rate, which indicated these lipid species were associated with impaired renal function. In addition, receiver operating characteristics analysis showed that 12 lipid species had high area under the curve values with high sensitivity and specificity for differentiating CRF group from control group. These changes are related to the perturbation of fatty acyl metabolism. Treatment with PPU and ergone improved the impaired kidney function and mitigated renal fibrosis. Both chemometrics and cluster analyses showed that rats treated by PPU and ergone could be separated from CRF rats by using 12 lipid species. Intriguingly, PPU treatment could restore the levels of 12 lipid species, while treatment with ergone could only reverse the changes of six fatty acids in CRF rats.Conclusion: Altered intrarenal fatty acyl metabolites were implicated in pathogenesis of renal fibrosis. PPU and ergone administration alleviated renal fibrosis and partially improved fatty acyl metabolism. These findings suggest that PPU exerted its renoprotective effect by regulating fatty acyl metabolism as a potential biochemical mechanism. Therefore, these findings indicated that fatty acyl metabolism played an important role in renal fibrosis and could be considered as an effective therapeutic avenue against renal fibrosis.

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The CKD plasma lipidome varies with disease severity and outcome

Cited by 17 publications

References 40 publications

An Updated Review of Pro- and Anti-Inflammatory Properties of Plasma Lysophosphatidylcholines in the Vascular System

An Updated Review of Pro- and Anti-Inflammatory Properties of Plasma Lysophosphatidylcholines in the Vascular System

Cholesterol-Lowering Action of a Novel Nutraceutical Combination in Uremic Rats: Insights into the Molecular Mechanism in a Hepatoma Cell Line

Polyporus Umbellatus Protects Against Renal Fibrosis by Regulating Intrarenal Fatty Acyl Metabolites

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