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Gut Microbial Product Predicts Cardiovascular Risk in Chronic Kidney Disease Patients.
Am J Nephrol. 2018; 48(4):269-277.AJ

Abstract

BACKGROUND

The gut microbiota is altered in patients with chronic kidney disease (CKD), and cardiovascular risk increases with progressive CKD. This study examined the potential link between short chain fatty acids (SCFAs), which are produced by the gut microbiota, and cardiovascular outcomes in patients with CKD.

METHODS

SCFAs were measured using a targeted liquid chromatography-mass spectrometry platform in baseline plasma samples from 214 patients with CKD enrolled in the Clinical Phenotyping Resource and Biobank Core; 81 patients with coronary artery disease (CAD) and 133 without CAD were randomly assigned to training and validation subsets. The primary outcome was a history of CAD and the secondary outcome was a composite history of cardiovascular disease (CVD) at enrollment.

RESULTS

We found significantly higher levels of the SCFA valerate among patients with CAD as compared with patients without CAD in the training set (p < 0.001). The valerate concentrations were also significantly higher among subjects with composite outcomes of CVD compared to those without CVD (p = 0.006). These results were subsequently replicated in the validation set. Logistic regression analysis revealed a strong independent association between plasma valerate levels and CVD in both training and validation sets. When valerate was added to the base clinical model comprising of diabetes, hypertension, urinary protein-creatinine ratio, and estimated glomerular filtration rate, it increased the c-statistics for predicting CVD from 0.68 to 0.79 (p = 0.02) in the training set, an observation which was confirmed in the validation set. -Conclusion: This study provides evidence for alterations in gut-microbiota-derived SCFAs with advancing CKD, demonstrates the association of higher plasma valerate levels with pre-existing CVD, and reveals areas for future exploration of cardiovascular risk in patients with CKD.

Authors+Show Affiliations

Department of Internal Medicine-Nephrology, University of Michigan, Ann Arbor, Michigan, USA.Department of Internal Medicine-Nephrology, University of Michigan, Ann Arbor, Michigan, USA.Department of Internal Medicine-Nephrology, University of Michigan, Ann Arbor, Michigan, USA.Department of Internal Medicine-Nephrology, Temple University, Philadelphia, Pennsylvania, USA.Department of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA.Department of Internal Medicine-Nephrology, University of Michigan, Ann Arbor, Michigan, USA.Department of Internal Medicine-Nephrology, University of Michigan, Ann Arbor, Michigan, USA. Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Validation Study

Language

eng

PubMed ID

30326477

Citation

Jadoon, Adil, et al. "Gut Microbial Product Predicts Cardiovascular Risk in Chronic Kidney Disease Patients." American Journal of Nephrology, vol. 48, no. 4, 2018, pp. 269-277.
Jadoon A, Mathew AV, Byun J, et al. Gut Microbial Product Predicts Cardiovascular Risk in Chronic Kidney Disease Patients. Am J Nephrol. 2018;48(4):269-277.
Jadoon, A., Mathew, A. V., Byun, J., Gadegbeku, C. A., Gipson, D. S., Afshinnia, F., & Pennathur, S. (2018). Gut Microbial Product Predicts Cardiovascular Risk in Chronic Kidney Disease Patients. American Journal of Nephrology, 48(4), 269-277. https://doi.org/10.1159/000493862
Jadoon A, et al. Gut Microbial Product Predicts Cardiovascular Risk in Chronic Kidney Disease Patients. Am J Nephrol. 2018;48(4):269-277. PubMed PMID: 30326477.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gut Microbial Product Predicts Cardiovascular Risk in Chronic Kidney Disease Patients. AU - Jadoon,Adil, AU - Mathew,Anna V, AU - Byun,Jaeman, AU - Gadegbeku,Crystal A, AU - Gipson,Debbie S, AU - Afshinnia,Farsad, AU - Pennathur,Subramaniam, AU - ,, Y1 - 2018/10/16/ PY - 2018/07/31/received PY - 2018/09/15/accepted PY - 2018/10/17/pubmed PY - 2020/1/15/medline PY - 2018/10/17/entrez KW - Cardiovascular outcomes KW - Chronic kidney disease KW - Coronary artery disease KW - Short chain fatty acids KW - Valerate SP - 269 EP - 277 JF - American journal of nephrology JO - Am J Nephrol VL - 48 IS - 4 N2 - BACKGROUND: The gut microbiota is altered in patients with chronic kidney disease (CKD), and cardiovascular risk increases with progressive CKD. This study examined the potential link between short chain fatty acids (SCFAs), which are produced by the gut microbiota, and cardiovascular outcomes in patients with CKD. METHODS: SCFAs were measured using a targeted liquid chromatography-mass spectrometry platform in baseline plasma samples from 214 patients with CKD enrolled in the Clinical Phenotyping Resource and Biobank Core; 81 patients with coronary artery disease (CAD) and 133 without CAD were randomly assigned to training and validation subsets. The primary outcome was a history of CAD and the secondary outcome was a composite history of cardiovascular disease (CVD) at enrollment. RESULTS: We found significantly higher levels of the SCFA valerate among patients with CAD as compared with patients without CAD in the training set (p < 0.001). The valerate concentrations were also significantly higher among subjects with composite outcomes of CVD compared to those without CVD (p = 0.006). These results were subsequently replicated in the validation set. Logistic regression analysis revealed a strong independent association between plasma valerate levels and CVD in both training and validation sets. When valerate was added to the base clinical model comprising of diabetes, hypertension, urinary protein-creatinine ratio, and estimated glomerular filtration rate, it increased the c-statistics for predicting CVD from 0.68 to 0.79 (p = 0.02) in the training set, an observation which was confirmed in the validation set. -Conclusion: This study provides evidence for alterations in gut-microbiota-derived SCFAs with advancing CKD, demonstrates the association of higher plasma valerate levels with pre-existing CVD, and reveals areas for future exploration of cardiovascular risk in patients with CKD. SN - 1421-9670 UR - https://www.unboundmedicine.com/medline/citation/30326477/Gut_Microbial_Product_Predicts_Cardiovascular_Risk_in_Chronic_Kidney_Disease_Patients_ L2 - https://www.karger.com?DOI=10.1159/000493862 DB - PRIME DP - Unbound Medicine ER -