Urinary 3-hydroxyisovaleryl carnitine excretion, protein energy malnutrition and risk of all-cause mortality in kidney transplant recipients: Results from the TransplantLines cohort studies. Issue 4 (April 2021)

• Record Type: Journal Article
• Authors: Post, Adrian; Said, M. Yusof; Gomes-Neto, Antonio W.; Minović, Isidor; Groothof, Dion; Swarte, J. Casper; Boer, Theo; Kema, Ido P.; Heiner-Fokkema, M. Rebecca; Franssen, Casper F.M.; Bakker, Stephan J.L.
• Is Part Of: Clinical nutrition. Volume 40:Issue 4(2021)
• Page Start: 2109
• Page End: 2120
• Publication Date: 2021-04
• Subjects: Kidney transplant recipients -- 3-Hydroxyisovaleryl carnitine -- Biotin -- Leucine -- Mortality; Critically ill -- Nutrition -- Periodicals; Diet therapy -- Periodicals; Parenteral feeding -- Periodicals; Enteral feeding -- Periodicals; Enteral Nutrition -- Periodicals; Parenteral Nutrition -- Periodicals; Metabolism -- Periodicals; Diétothérapie -- Périodiques; Alimentation parentérale -- Périodiques; Alimentation entérale -- Périodiques; Nutrition -- Périodiques; Diet therapy; Enteral feeding; Nutrition; Parenteral feeding; Electronic journals; Periodicals; Electronic journals; 615.854
• DOI: 10.1016/j.clnu.2020.09.035
• Languages: English
• ISSNs: 0261-5614

Abstract

Summary: Background: Leucine is an essential amino acid and a potent stimulator of muscle protein synthesis. Since muscle wasting is a major risk factor for mortality in kidney transplant recipients (KTR), dietary leucine intake might be linked to long-term mortality. Urinary 3-hydroxyisovaleryl carnitine (3-HIC) excretion, a functional marker of marginal biotin deficiency, may also serve as a marker for dietary leucine intake. Objective: In this study we aimed to investigate the cross-sectional determinants of urinary 3-HIC excretion and to prospectively investigate the association of urinary 3-HIC excretion with all-cause mortality in KTR. Design: Urinary 3-HIC excretion and plasma biotin were measured in a longitudinal cohort of 694 stable KTR. Cross-sectional and prospective analyses were performed using ordinary least squares linear regression analyses and Cox regression analyses, respectively. Results: In KTR (57% male, 53 ± 13 years, estimated glomerular filtration rate 45 ± 19 mL/min/1.73 m 2 ), urinary 3-HIC excretion (0.80 [0.57–1.16] μmol/24 h) was significantly associated with plasma biotin (std. β = −0.17; P < 0.001). Subsequent adjustment for potential covariates revealed urinary creatinine excretion (std. β = 0.24; P < 0.001) and urinary urea excretion (std. β = 0.53; P < 0.001) as the primary determinant of urinary 3-HIC excretion. Whereas plasma biotin explained only 1% of the variance in urinary 3-HIC excretion, urinary urea excretion explained >45%. During median follow-up for 5.4 [4.8–6.1] years, 150 (22%) patients died. Log2 -transformed urinary 3-HIC excretion was inversely associated with all-cause mortality (HR: 0.52 [0.43–0.63]; P < 0.001). This association was independent of potential confounders. Conclusions: Urinary 3-HIC excretion more strongly serves as a marker of leucine intake than of biotin status. A higher urinary 3-HIC excretion is associated with a lower risk of all-cause mortality. Future studies are warranted to explore the underlying mechanism. Trial registration id: NCT02811835. Trial registration url: https://clinicaltrials.gov/ct2/show/NCT02811835 .