Dear Editor,

We have noticed, with great interest, the recently published original communication by Luo et al.1 The conclusion that fasting plasma citrulline concentrations do not reflect intestinal absorption capacity are in line with our own data.2 However, besides this, we could not corroborate previous studies suggesting citrulline to be a biomarker of remnant small intestinal bowel length.3 Failure to wean parenteral nutrition (PN) in patients with remnant bowel lengths < 50 cm and, to the contrary, successful intestinal adaptation in small bowel (SB) patients with a > 150-cm remnant bowel length merely reflect the common and predictable clinical course. The most challenging group in terms of prediction to wean PN in this perspective are those patients with intermediate remnant bowel lengths between 50 and 150 cm, in which PN dependence cannot be reliably estimated simply based on the patient's remnant small bowel length. In our patient cohort, with remnant small bowel lengths between 50 and 150 cm, no relation between fasting citrulline and residual small bowel length was observed.

Looking at the scatter plot relating fasting plasma citrulline concentrations and residual small bowel length (r = 0.47, P = .03; figure IA) by Luo et al, we would be very interested to know the correlation coefficient if the 3 patients with > 300 cm of remnant bowel would be excluded from analysis.

Second, we were attracted by the fasting plasma glutamine concentration of zero in one of the patients in figure 1B. Could you please elaborate whether this was due to readout problems using ion exchange chromatography?

Yours sincerely,

Job H. C. Peters, MD

Chris J. J. Mulder, MD, PhD

Ad A. van Bodegraven, MD, PhD

Department of Gastroenterology & Hepatology,

Small Bowel Unit

VU University Medical Center, Amsterdam,

the Netherlands

References

1. Luo M, Fernandez-Estivariz C, Manatunga AK, et al. Are plasma citrulline and glutamine biomarkers of intestinal absorptive function in patients with short bowel syndrome? JPEN J Parenter Enteral Nutr. 2007;31:1-7.

2. Peters JH, Wierdsma NJ, Teerlink T, van Leeuwen PA, Mulder CJ, van Bodegraven AA. Sensitivity and specificity of fasting plasma citrulline concentration to assess enterocyte dysfunction [abstract]. JPEN J Parenter Enteral Nutr. 2007;31:S55. Abstract S29.

3. Crenn P, Coudray-Lucas C, Thuillier F, Cynober L, Messing B. Postabsorptive plasma citrulline concentration is a marker of absorptive enterocyte mass and intestinal failure in humans. Gastroenterology. 2000;119:1496-1505.

Response

Dear Editor,

We appreciate the letter and comments of Dr Peters et al, and their comment on the consistency of their preliminary data relative to our major conclusion that fasting plasma citrulline concentrations do not reflect functional intestinal absorption capacity in adult patients with short bowel syndrome.1,2 In response to the query of Dr Peters et al, we reanalyzed our data on the observed positive correlation of plasma citrulline with residual small bowel length by omitting the 3 subjects with residual small bowel lengths of >300 cm. Upon removal of these subjects, thus leaving subjects with a residual small bowel length of <200 cm, there is no longer a statistically significant relationship between fasting plasma citrulline and residual small bowel length, consistent with their pilot findings.2 This suggests that perhaps plasma citrulline levels do not correlate with residual small bowel length in individuals with very short small bowel in situ (< 150-200 cm), an interesting point. We would like to suggest, however, that such a post hoc data analysis (excluding 3 subjects with the longest residual small bowel) has the potential to induce type II error regarding the biomarker role of citrulline in terms of small bowel length. For such a relationship to occur in the small data set we studied, a range of small bowel lengths is required to answer this research question. As we point out in our article,1 additional and larger studies are needed to define the role of plasma citrulline as a biomarker of gut length and function in patients with short bowel syndrome. With regard to the one unphysiologic glutamine concentration in Figure 1B, we agree that this was an obvious readout problem. Elimination of this value does not statistically change the lack of any relationship between plasma glutamine and residual small bowel length in our short bowel patients.

Sincerely,

Thomas R. Ziegler, MD

Menghua Luo, MD

Department of Medicine and Center for Clinical and

Molecular Nutrition

Emory University School of Medicine, Atlanta, GA

References

1. Luo M, Fernandez-Estivariz C, Manatunga AK, et al. Are plasma citrulline and glutamine biomarkers ot intestinal absorptive function in patients with short bowel syndrome? JPEN J Parenter Enteral Nutr. 2007;31:1-7.

2. Peters JH, Wierdsma NJ, Teerlink T, van Leeuwen PA, Mulder CJ, van Bodegraven AA. Sensitivity and specificity of fasting plasma citrulline concentration to assess enterocyte dysfunction [abstract]. JPEN J Parenter Enteral Nutr. 2007;31:S55. Abstract S29.