Calprotectin: a novel noninvasive marker for intestinal allograft monitoring.
OBJECTIVE
To identify a noninvasive screening test for intestinal allograft monitoring.


BACKGROUND
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Department of Transplant, University of Nebraska Medical Center, Omaha, NE 68198, USA. dsudan@unmc.edu
Debra
D
Sudan
Luciano
L
Vargas
Yimin
Y
Sun
Lisette
L
Bok
Gerard
G
Dijkstra
Alan
A
Langnas
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000737:chemistry; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007223:Infant; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism*; D008875:Middle Aged; D010865:Pilot Projects; D011237:Predictive Value of Tests; D012372:ROC Curve; D012189:Retrospective Studies; D014184:Transplantation, Homologous
D015415:Biomarkers; D039841:Leukocyte L1 Antigen Complex