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Circulating Endocannabinoids and Mortality in Hemodialysis Patients.

ABSTRACT: BACKGROUND:Mortality in patients with end-stage renal disease (ESRD) on maintenance hemodialysis (MHD) remains exceptionally high. While traditional risk factors such as obesity are paradoxically associated with better survival, nontraditional risk factors including cachexia increase the likelihood of poor outcomes. There is accumulating evidence that the endocannabinoid (ECB) system plays a major role in energy preservation and storage, factors which can prevent the deleterious effects of cachexia. Hence, in this study, we evaluated the association of circulating ECB levels with mortality in MHD patients. METHODS:Serum concentrations of anandamide (AEA) and 2-arachidonoyl-sn-glycerol (2-AG), major ECB ligands, were measured in MHD patients. Their correlation with various clinical/laboratory indices and association with 12-month all-cause mortality were examined. RESULTS:Serum 2-AG levels positively correlated with body mass index, serum triglycerides and body anthropometric measures. Meanwhile, serum AEA levels correlated positively with serum interleukin-6, and negatively with serum very low-density lipoprotein levels. While increased serum 2-AG levels were associated with reduced risk of all-cause mortality (hazard ratio [HR] 0.52, 95% CI 0.28-0.98), there was no clear association between serum AEA levels and mortality (HR 0.91, 95% CI 0.48-1.72). CONCLUSIONS:In MHD patients, the circulating levels of ECB ligand, 2-AG, may play an important role in determining body mass and risk of mortality. These observations were unique to 2-AG as similar findings were not obtained with serum AEA. Future studies need to investigate the mechanisms responsible for these associations and examine the modulation of the ECB system as a potential target for therapy in ESRD.

SUBMITTER: Moradi H

PROVIDER: S-EPMC7158229 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Circulating Endocannabinoids and Mortality in Hemodialysis Patients.

Moradi Hamid H Park Christina C Streja Elani E Argueta Donovan A DA DiPatrizio Nicholas V NV You Amy S AS Rhee Connie M CM Vaziri Nosratola D ND Kalantar-Zadeh Kamyar K Piomelli Daniele D

American journal of nephrology 20200114 2

<h4>Background</h4>Mortality in patients with end-stage renal disease (ESRD) on maintenance hemodialysis (MHD) remains exceptionally high. While traditional risk factors such as obesity are paradoxically associated with better survival, nontraditional risk factors including cachexia increase the likelihood of poor outcomes. There is accumulating evidence that the endocannabinoid (ECB) system plays a major role in energy preservation and storage, factors which can prevent the deleterious effects ...[more]

PMID: 31935741

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Project description:In the general population, low serum magnesium levels are associated with poor outcomes and death. While limited data suggest that low baseline magnesium levels may be associated with higher mortality in hemodialysis (HD) patients, the impact of changes in magnesium levels over time is unknown.We examined the association of time-varying serum magnesium levels with all-cause mortality using multivariable time-varying survival models adjusted for clinical characteristics and other time-varying laboratory measures.9,359 maintenance HD patients treated in a large dialysis organization between 2007 and 2011.Time-varying serum magnesium levels across 5 magnesium increments (<1.8, 1.8-<2.0, 2.0-<2.2, 2.2-<2.4, and ?2.4mg/dL).All-cause mortality.2,636 individuals died over 5 years. Time-varying serum magnesium levels < 2.0mg/dL were associated with higher mortality after adjustment for demographics and comorbid conditions, including hypertension, diabetes, and malignancies (reference: magnesium, 2.2-<2.4mg/dL): adjusted HRs for serum magnesium level < 1.8 and 1.8 to <2.0mg/dL were 1.39 (95% CI, 1.23-1.58; P<0.001) and 1.20 (95% CI, 1.06-1.36; P=0.004), respectively. Some associations were attenuated to the null after incremental adjustment for laboratory test results, particularly serum albumin. However, among patients with serum albumin measurements, low albumin level (<3.5g/dL) and magnesium level < 2.0mg/dL were associated with an additional death risk (adjusted HR, 1.17; 95% CI, 1.05-1.31; P=0.004), whereas patients with high serum albumin levels (?3.5g/dL) exhibited low death risk (adjusted HRs of 0.53 and 0.53 [P?0.001] for magnesium < 2.0 and ?2.0mg/dL, respectively; reference: albumin < 3.5g/dL and magnesium ? 2.0mg/dL).Causality cannot be determined, and residual confounding cannot be excluded given the observational study design.Lower serum magnesium levels are associated with higher mortality in HD patients, including those with hypoalbuminemia. Interventional studies are warranted to examine whether correction of hypomagnesemia ameliorates adverse outcomes in this population.

Dataset Information

Circulating Endocannabinoids and Mortality in Hemodialysis Patients.

Publications

Circulating Endocannabinoids and Mortality in Hemodialysis Patients.

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