Fasting and Postprandial Plasma Citrulline and the Correlation to Intestinal Function Evaluated by 72‐Hour Metabolic Balance Studies in Short Bowel Jejunostomy Patients With Intestinal Failure

Fjermestad, Hilde; Hvistendahl, Mark; Jeppesen, Palle Bekker

doi:10.1177/0148607116687497

Cited by 14 publications

(7 citation statements)

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“…In addition, citrulline was not sampled under fasting conditions. However, Fjermestad et al reported that the difference between fasting and postprandial citrulline levels in patients with SBSeIF was only 12% [15]. Similarly, studies of healthy subjects show that meal intake has minor effects on citrulline levels, which return to baseline in 3e4 h [15,38].…”

Section: Discussionmentioning

confidence: 99%

“…However, these analyses have included predominantly patients with colon-in-continuity and most enrolled a mixed population of PS-dependent and nonePS-dependent patients. A recent report evaluating a relatively homogenous population of PS-dependent patients with end jejunostomy demonstrated no association between plasma citrulline and small bowel length [15]. Similarly, data regarding the ability of citrulline to function specifically as a biomarker of intestinal absorptive capacity or enteral autonomy are conflicting.…”

Section: Introductionmentioning

confidence: 99%

“…Some studies have demonstrated a positive correlation between plasma citrulline levels and absorption of fat, protein, or D-xylose [10,17,18], whereas others have reported no association [15,16,19]. Likewise, results of some [10,18,20], but not all [12,15,19], analyses have suggested that citrulline levels can distinguish PSdependent and PS-independent populations. Together, these data suggest that aspects of disease characteristics contributing to the SBS patient population heterogeneity may influence the effectiveness of citrulline as a potential generalizable biomarker in SBSeIF.…”

Section: Introductionmentioning

confidence: 99%

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Citrulline correlations in short bowel syndrome–intestinal failure by patient stratification: Analysis of 24 weeks of teduglutide treatment from a randomized controlled study

et al. 2020

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Background & aims: Disease-associated factors influence parenteral support (PS) reduction in response to teduglutide in patients with intestinal failure associated-short bowel syndrome (SBSeIF). We sought to determine correlative relationships between plasma citrulline levels, small bowel length, and PS volume. Methods: A post hoc analysis of plasma citrulline levels from patients in the STEPS 24-week study of teduglutide in patients with SBSÀIF. Plasma citrulline was assessed in all patients; patients were stratified 3 times into subgroups based on bowel anatomy, cause of SBSeIF, and baseline PS volumes. Correlation analyses used simple linear regression models. Statistical comparisons between study groups were conducted using 2-sided t tests for 2 independent mean differences. Results: Baseline plasma citrulline correlated with remnant small bowel length (r ¼ 0.355, P ¼ 0.002), but not with baseline PS volume (r ¼ À0.167, P ¼ 0.14), in the overall population. There was a robust correlation between the baseline and Week 24 citrulline (r ¼ 0.705, P < 0.0001), and an inverse correlation between change from baseline in citrulline and PS volume from baseline to Week 24 (r ¼ À0.359, P ¼ 0.001). In all subgroups, patients treated with teduglutide showed numerically greater increases in plasma citrulline at Week 24 compared with placebo. Conclusion: Baseline plasma citrulline showed significant correlations with small bowel length in patients with !50% colon remaining/no stoma/colon-in-continuity, and patients with SBSeIF causes other than IBD/vascular disease. Citrulline levels may correlate with PS changes in response to teduglutide and more research may reveal a relationship between citrulline levels within the heterogeneous population of patients with SBSÀIF. ClinicalTrials.gov NCT00798967, ClinicalTrialsRegister.eu 2008-006193-15.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Citrulline correlations in short bowel syndrome–intestinal failure by patient stratification: Analysis of 24 weeks of teduglutide treatment from a randomized controlled study

et al. 2020

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“…In congruence with standard collection methods employed for other biochemical assays, studies in humans have demonstrated that the optimal timing for citrulline measurements is during the post-absorptive fasting state, likely related to citrulline's enterocyte origin [18]. However, the ideal timing of blood draws in relation to food intake and time of day is poorly defined in animal models.…”

Section: Introductionmentioning

confidence: 99%

Serum Citrulline Levels Exhibit Circadian Variation and Fluctuations in Relation to Food Intake in Mice

et al. 2019

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Background: Plasma citrulline is a nonessential amino acid synthesized almost exclusively by enterocytes of the small intestine. Correlation between post-operative plasma citrulline levels and remnant small bowel mass and function has led to its use as a simple biomarker of functional intestinal mass in adults and children, with a proposed prognostic value for achieving enteral autonomy in the setting of intestinal failure. While it is standard to measure fasting levels in humans, the optimal timing of blood draws in relation to food intake and time of day has not been standardized and is poorly studied in animal models. We hypothesize that serum citrulline levels vary both throughout the day and with relation to food intake in mice.Methods: Serum citrulline levels were measured from 12 C57BL/6 mice (6 -9 weeks old) in the mornings and evenings, either after ad libitum food intake or after 8 -12 h of access to water only. Blood draws for each experimental set-up were performed 1 week apart according to our Institutional Animal Care and Use Committee (IA-CUC) guidelines for acceptable blood collection volumes for survival procedures. At the end of the experiment, mice were euthanized and small intestine was harvested for morphometric measurements. Group means were compared using Student's t-test with significance assumed for P < 0.05. Results:After withholding chow for 8 -12 h, serum citrulline levels were significantly greater in the morning compared to levels drawn in the evening. When mice were allowed ad libitum chow, there was no significant difference in serum citrulline levels drawn in the morning compared to the evening. There was no difference detected in villus height across the different experimental conditions. Conclusions: Serum citrulline levels exhibit circadian variation and fluctuations in relation to food intake in mice, without apparent concurrent changes in enterocyte mass. There was no diurnal variation of serum citrulline levels in fed mice whereas fasted mice had significantly higher levels of serum citrulline in the morning compared to the evening. These findings underscore the paramount importance of consistent sample collection strategies in the setting of translational research.

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“…importantly, assessment of post-absorptive levels of citrulline is suggested in patients with gastrointestinal diseases [1, 46,47], showing also a correlation with absorption capacity measured with tracer ingestion methods [46]. in critical illness, specific assessment of a post-absorptive state is difficult, because patients are either not fed or receive enteral nutrition in a continuous manner.…”

Section: Discussion Of Existing Evidencementioning

confidence: 99%

Citrulline and intestinal fatty acid-binding protein as biomarkers for gastrointestinal dysfunction in the critically ill

Blaser¹,

Padar²,

Tang³

et al. 2019

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Review ARTicles citrulline and intestinal fatty acid-binding protein (i-FABP) have been increasingly studied since the turn of the millennium as potential biomarkers of intestinal dysfunction [1-5]. citrulline has been proposed as a marker of enterocyte (dys)function, whereas i-FABP is thought to be a promising biomarker of intestinal cellular damage reflecting ischaemia. The present narrative review summarizes pathophysiological aspects and existing evidence evaluating clinical usage of these two biomarkers in critical illness based on explorative literature searches. Additionally, important details and pitfalls in sampling, laboratory measurement and interpretation of values are discussed. Citrulline as a marker of enteroCyte funCtion Physiology and pathophysiology citrulline (ciT) is a non-essential amino acid which is not present in proteins, but which is intimately involved in the urea cycle as an intermediary of both glutamine and arginine. citrulline is

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Fasting and Postprandial Plasma Citrulline and the Correlation to Intestinal Function Evaluated by 72‐Hour Metabolic Balance Studies in Short Bowel Jejunostomy Patients With Intestinal Failure

Abstract: Based on findings in this small study, the optimal timing of p-citrulline measurement is on fasting samples. However, p-citrulline seems insufficiently discriminative to serve as a valid biomarker of bowel length, bowel absorptive function, or dependence on PS in patients with SBS-IF.

Cited by 14 publications

References 23 publications

Citrulline correlations in short bowel syndrome–intestinal failure by patient stratification: Analysis of 24 weeks of teduglutide treatment from a randomized controlled study

Citrulline correlations in short bowel syndrome–intestinal failure by patient stratification: Analysis of 24 weeks of teduglutide treatment from a randomized controlled study

Serum Citrulline Levels Exhibit Circadian Variation and Fluctuations in Relation to Food Intake in Mice

Citrulline and intestinal fatty acid-binding protein as biomarkers for gastrointestinal dysfunction in the critically ill

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