Calprotectin: a novel noninvasive marker for intestinal allograft monitoring

To identify a noninvasive screening test for intestinal allograft monitoring.

Intestinal allograft rejection is difficult to distinguish from other causes of diarrhea and can rapidly lead to severe exfoliation or death. Protocol biopsies are standard for allograft monitoring but may cause serious complications. No noninvasive test has shown clinical utility for monitoring of the intestinal allograft.

Calprotectin levels (n = 68) were measured in this pilot study from ileostomy effluent in patients with histologic evidence of acute rejection (n = 12), viral enteritis (n = 5), and nonspecific inflammation (n = 16) and compared with those with normal allograft histology (n = 35).

Median stool calprotectin levels from patients with rejection were significantly higher than those from patients with viral enteritis or normal biopsies [198 mg/kg compared with 7 and 19 mg/kg, respectively (P = 0.0002)]. Receiver operator characteristics suggest the optimal cut-off level to distinguish rejection from other diagnoses is 92 mg/kg with specificity of 77% and sensitivity of 83%. Although false-positive results occurred in 26% of patients with normal biopsies and 30% with nonspecific changes, no treated episode of acute rejection was below the cutoff. In addition, in 2 patients with serial levels, elevations in the calprotectin levels preceded histologic changes by 6 to 18 days.

Low stool calprotectin levels correlate well with a low risk for intestinal allograft rejection. If confirmed, biopsies may be reserved in the future for confirmation of rejection, eliminating protocol biopsies, and immunosuppressive changes could potentially be made before allograft injury.