Noninvasive detection of acute and chronic injuries in human renal transplant by elevation of multiple cytokines/chemokines in urine.
BACKGROUND
Injuries in kidney transplant is currently diagnosed by needle biopsy. A noninvasive test that sensitively detects these injuries would benefit the patients.


METHODS
Urine samples were collected from healthy controls and kidney transplant recipients. Urine samples were screened first with an antibody array consisting of 120 chemokines and cytokines and then with a multiplex beads assay. Representative parameters, including macrophage inflammatory protein-1Delta, osteoprotegerin, monokine induced by interferon-gamma (IFN), and IFN-gamma-induced protein of 10 kDa, were simultaneously determined by a quadruplex assay in urine samples from 84 patients with renal allograft injury, 29 patients with stable graft function, and 19 healthy individuals.


RESULTS
Twenty-three cytokines/chemokines were found to be elevated in urine samples of patients with acute rejection by the antibody array. The second round of screening confirmed that 11 of the 23 parameters were elevated in the patients but not in the healthy controls. Induced protein of 10 kDa and monokine induced by IFN-gamma were significantly elevated in urine samples of patients with acute renal injury, and macrophage inflammatory protein-1Delta and osteoprotegerin were significantly elevated in patients with both acute and chronic renal injuries. The combination of the four parameters had a high positive detection rate (97.6%) for renal transplant injury and could differentiate between acute and chronic injury.


CONCLUSIONS
These results might indicate that the present multiplex assay provides a basis to establish a noninvasive method for the diagnosis and monitoring of renal transplant injury.
Hu
Huaizhong
H
Renovar Inc., 505 South Rosa Road, Madison, WI, USA.
Kwun
Jean
J
Aizenstein
Brian D
BD
Knechtle
Stuart J
SJ
D015415:Biomarkers / Q000097:blood / Q000652:urine; D001707:Biopsy, Needle; D054357:Chemokine CXCL10 / Q000235:genetics / Q000652:urine; D018925:Chemokines / Q000235:genetics / Q000652:urine*; D003404:Creatinine / Q000097:blood*; D016207:Cytokines / Q000235:genetics / Q000652:urine*; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000652:urine*; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D053244:Osteoprotegerin / Q000235:genetics / Q000652:urine; D012016:Reference Values; D015203:Reproducibility of Results; D014184:Transplantation, Homologous / Q000473:pathology
D015415:Biomarkers; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D018925:Chemokines; D016207:Cytokines; D053244:Osteoprotegerin; D003404:Creatinine