Dataset Information

The association between TMAO, CMPF, and clinical outcomes in advanced chronic kidney disease: results from the European QUALity (EQUAL) Study.

ABSTRACT:

Background

Trimethylamine N-oxide (TMAO), a metabolite from red meat and fish consumption, plays a role in promoting cardiovascular events. However, data regarding TMAO and its impact on clinical outcomes are inconclusive, possibly due to its undetermined dietary source.

Objectives

We hypothesized that circulating TMAO derived from fish intake might cause less harm compared with red meat sources by examining the concomitant level of 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), a known biomarker of fish intake, and investigated the association between TMAO, CMPF, and outcomes.

Methods

Patients were recruited from the European QUALity (EQUAL) Study on treatment in advanced chronic kidney disease among individuals aged ≥65 y whose estimated glomerular filtration rate (eGFR) had dropped for the first time to ≤20 mL/min per 1.73 m2 during the last 6 mo. The association between TMAO, CMPF, and outcomes including all-cause mortality and kidney replacement therapy (KRT) was assessed among 737 patients. Patients were further stratified by median cutoffs of TMAO and CMPF, suggesting high/low red meat and fish intake.

Results

During a median of 39 mo of follow-up, 232 patients died. Higher TMAO was independently associated with an increased risk of all-cause mortality (multivariable HR: 1.46; 95% CI: 1.17, 1.83). Higher CMPF was associated with a reduced risk of both all-cause mortality (HR: 0.79; 95% CI: 0.71, 0.89) and KRT (HR: 0.80; 95% CI: 0.71, 0.90), independently of TMAO and other clinically relevant confounders. In comparison to patients with low TMAO and CMPF, patients with low TMAO and high CMPF had reduced risk of all-cause mortality (adjusted HR: 0.49; 95% CI: 0.31, 0.73), whereas those with high TMAO and high CMPF showed no association across adjusted models.

Conclusions

High CMPF conferred an independent role in health benefits and might even counteract the unfavorable association between TMAO and outcomes. Whether higher circulating CMPF concentrations are due to fish consumption, and/or if CMPF is a protective factor, remains to be verified.

SUBMITTER: Dai L

PROVIDER: S-EPMC9761748 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

The association between TMAO, CMPF, and clinical outcomes in advanced chronic kidney disease: results from the European QUALity (EQUAL) Study.

Dai Lu L Massy Ziad A ZA Stenvinkel Peter P Chesnaye Nicholas C NC Larabi Islam Amine IA Alvarez Jean Claude JC Caskey Fergus J FJ Torino Claudia C Porto Gaetana G Szymczak Maciej M Krajewska Magdalena M Drechsler Christiane C Wanner Christoph C Jager Kitty J KJ Dekker Friedo W FW Evenepoel Pieter P Evans Marie M

The American journal of clinical nutrition 20221201 6

<h4>Background</h4>Trimethylamine N-oxide (TMAO), a metabolite from red meat and fish consumption, plays a role in promoting cardiovascular events. However, data regarding TMAO and its impact on clinical outcomes are inconclusive, possibly due to its undetermined dietary source.<h4>Objectives</h4>We hypothesized that circulating TMAO derived from fish intake might cause less harm compared with red meat sources by examining the concomitant level of 3-carboxy-4-methyl-5-propyl-2-furanpropionate (C ...[more]

PMID: 36166845

Similar Datasets

Project description:Rationale & objectiveCardiovascular disease is the leading cause of morbidity and mortality in chronic kidney disease (CKD). We investigated 184 inflammatory and cardiovascular proteins to determine their potential as biomarkers for major cardiovascular events (MACEs).Study designThe European Quality (EQUAL) is an observational cohort study that enrolled people aged ≥65 years with an estimated glomerular filtration rate ≤20 mL/min/1.73 m2.Setting & participantsRecruited participants were split into the discovery (n = 611) and replication cohorts (n = 292).ExposureLevels of 184 blood proteins were measured at the baseline visit, and each protein was analyzed individually.OutcomeMACE.Analytical approachCox proportional hazard models adjusted for age, sex, estimated glomerular filtration rate, previous MACE, and country were used to determine the risk of MACE. Proteins with false discovery rate adjusted P values of <0.05 in the discovery cohort were tested in the replication cohort. Sensitivity analyses were performed by adjusting for traditional risk factors, CKD-specific risk factors, and level of proteinuria and segregating atherosclerotic and nonatherosclerotic MACE.ResultsDuring a median follow-up of 2.9 years, 349 people (39%) experienced a MACE. Forty-eight proteins were associated with MACE in the discovery cohort; 9 of these were reproduced in the replication cohort. Three of these proteins maintained a strong association with MACE after adjustment for traditional and CKD-specific risk factors and proteinuria. Tenascin (TNC), fibroblast growth factor-23 (FGF-23), and V-set and immunoglobulin domain-containing protein 2 (VSIG2) were associated with both atherosclerotic and nonatherosclerotic MACE. All replicated proteins except carbonic anhydrase 1 and carbonic anhydrase 3 were associated with nonatherosclerotic MACE.LimitationsSingle protein concentration measurements and limited follow-up time.ConclusionsOur findings corroborate previously reported relationships between FGF-23, vascular cell adhesion protein-1, TNC, and placental growth factor with cardiovascular outcomes in CKD. We identify 5 proteins not previously linked with MACE in CKD that may be targets for future therapies.Plain-language summaryKidney disease increases the risk of heart disease, stroke, and other vascular conditions. Blood tests that predict the likelihood of these problems may help to guide treatment, but studies are needed in people with kidney disease. We analyzed blood tests from older people with kidney disease, looking for proteins associated with higher risk of these conditions. Nine proteins were identified, of which 3 showed a strong effect after all other information was considered. This work supports previous research regarding 4 of these proteins and identifies 5 additional proteins that may be associated with higher risk. Further work is needed to confirm our findings and to determine whether these proteins can be used to guide treatment.

Dataset Information

The association between TMAO, CMPF, and clinical outcomes in advanced chronic kidney disease: results from the European QUALity (EQUAL) Study.

Background

Objectives

Methods

Results

Conclusions

Publications

The association between TMAO, CMPF, and clinical outcomes in advanced chronic kidney disease: results from the European QUALity (EQUAL) Study.

Similar Datasets

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