Apo AIV and Citrulline Plasma Concentrations in Short Bowel Syndrome Patients: The Influence of Short Bowel Anatomy

<div><p>Introduction</p><p>Parenteral nutrition (PN) dependence in short bowel syndrome (SBS) patients is linked to the functionality of the remnant small bowel (RSB). Patients may wean off PN following a period of intestinal adaptation that restores this functionality. Currently, plasma citrulline is the standard biomarker for monitoring intestinal functionality and adaptation. However, available studies reveal that the relationship the biomarker with the length and function of the RSB is arguable. Thus, having additional biomarkers would improve pointing out PN weaning.</p><p>Aim</p><p>By measuring concomitant changes in citrulline and the novel biomarker apolipoprotein AIV (Apo AIV), as well as taking into account the anatomy of the RSB, this exploratory study aims to a better understanding of the intestinal adaptation process and characterization of the SBS patients under PN.</p><p>Methods</p><p>Thirty four adult SBS patients were selected and assigned to adapted (aSBS) and non-adapted (nSBS) groups after reconstructive surgeries. Remaining jejunum and ileum lengths were recorded. The aSBS patients were either on an oral diet (ORAL group), those with intestinal insufficiency, or on oral and home parenteral nutrition (HPN group), those with chronic intestinal failure. Apo AIV and citrulline were analyzed in plasma samples after overnight fasting. An exploratory ROC analysis using citrulline as gold standard was performed.</p><p>Results</p><p>Biomarkers, Apo AIV and citrulline showed a significant correlation with RSBL in aSBS patients. In jejuno-ileocolic patients, only Apo AIV correlated with RSBL (r_b = 0.54) and with ileum length (r_b = 0.84). In patients without ileum neither biomarker showed any correlation with RSBL. ROC analysis indicated the Apo AIV cut-off value to be 4.6 mg /100 mL for differentiating between the aSBS HPN and ORAL groups.</p><p>Conclusions</p><p>Therefore, in addition to citrulline, Apo AIV can be set as a biomarker to monitor intestinal adaptation in SBS patients. As short bowel anatomy is shown to influence citrulline and Apo AIV plasma values, both biomarkers complement each other furnishing a new insight to manage PN dependence.</p></div

Plasma markers and short bowel anatomy of all adapted SBS patients (aSBS).

<p>Plasma markers and short bowel anatomy of all adapted SBS patients (aSBS).</p

Scatter plots for Apo AIV and citrulline plasma values with the RSBL in all adapted SBS patients.

<p>(●) HPN group (n = 7) and (o) ORAL group (n = 19).</p

Scatter plot for Apo AIV with citrulline plasma values in all adapted SBS patients.

<p>(●) HPN group (n = 7) and (o) ORAL group (n = 19). ROC analysis: tentative cut-off point of 32 AU (4.6 mg/100 mL) for Apo AIV (20 μM citrulline as gold standard). Grey circles show patients (‘G’, ‘H’, ‘Q’, ‘R’ and ‘S’) with similar RSBL (100 cm).</p

Scatter plots for Apo AIV and citrulline plasma values with the RSBL in adapted SBS patients without ileum.

<p>(●) HPN group (n = 4) and (o) ORAL group (n = 12).</p

Process of intestinal adaptation in nSBS patients.

<p>Bar diagrams for the evolution of Apo AIV and citrulline plasma values in three non-adapted SBS patients ‘1’, ‘2’ and ‘3’. RSBL: 60 cm without ileum ‘1’, 70 cm ‘2’ and 150 cm ‘3’. Measurements were performed on the same individual: before (baseline) and after surgery at 12–15 and at ≥ 60 months (full adaptation). Lines show the threshold values as described on <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0163762#pone.0163762.g006" target="_blank">Fig 6</a>.</p

Box plots for plasma concentrations of Apo AIV and citrulline in selected SBS patients and healthy subjects.

<p>SBS groups: non-adapted nSBS (n = 8), adapted SBS HPN group (n = 7), and adapted SBS ORAL group (n = 19). Healthy subjects -Control group (n = 39). Outliers shown as black squares. <i>P<</i> .05 between aSBS ORAL and Control groups.</p

Scatter plots for Apo AIV and citrulline plasma values with the RSBL and a remnant ileum length in adapted SBS patients with ileum and proximal part.

<p>(●) HPN group (n = 2) and (o) ORAL group (n = 6). Bootstrap resampling correlation was performed.</p