Plasma Nitrite and Nitrate Levels as a Noninvasive Marker of Pathology After Human Small Bowel Transplantation

Abstract

Small bowel transplantation provides a potentially life-saving treatment of severe intestinal failure. Lack of a noninvasive marker of disease makes diagnosis of rejection dependent on frequent endoscopy and biopsy. We hypothesized that increased plasma nitrite and nitrate (NOx) levels measured after small bowel transplant would be associated with abnormal final pathology. We measured total plasma NOx levels (the stable end products of the L-arginine/nitric oxide biosynthetic pathway) in 120 prospectively collected samples taken from 27 patients after small bowel transplantation. We used immunohistochemistry to detect inducible nitric oxide synthetase expression in 19 tissue biopsies from 9 patients. We found NOx concentrations to be statistically different between pathologic categories (e.g., normal, mild, moderate, and severe rejections, nonspecific enteritis), although there was sufficient overlap to prompt caution clinically. After establishing from the dataset a "normal" plasma NOx level of 50 microM, we found that combined assessment of plasma NOx levels and clinical suspicion of pathology could accurately predict which patients were histologically normal and those requiring further evaluation with endoscopy and biopsy. We conclude that serum NOx levels are significantly associated with small bowel pathology after transplant, although not specifically enough with rejection to be relied on for clinical discrimination.