Prediction of acute renal allograft rejection by urinary monokine induced by IFN-gamma (MIG).
Early diagnosis of acute allograft rejection (AR) is still decisive for long-term renal allograft survival. The aim of this study was to define the role of the chemokine monokine induced by IFN-gamma (MIG) (CXCL9) and IFN-gamma-inducible protein 10 (IP-10) (CXCL10) as early markers of AR in renal transplantation (NTX). In a prospective study, 69 de novo renal transplant recipients were monitored and urine samples were collected after NTX for a median of 29 d. In pH-adjusted urine, MIG and IP-10 were determined by modified ELISA. AR was clinically diagnosed in 15 of 69 recipients and confirmed by biopsy in 14 of 15 AR patients (Banff classification). Corresponding to CXCR3-positive infiltrates in renal tissue, urinary MIG was elevated in 14 of 15 AR patients with a median of 2809 pg/ml (quartile 25% and 75% = 870 and 13,000; n = 15), being significantly (P < 0.0001) different from both nonrejecting allograft patients (NO-AR) (median, 25%, and 75%: 96, 1.0, and 161, n = 54) and healthy controls (median, 25%, and 75%: 144, 19, and 208, n = 13). Urinary MIG predicted AR with a sensitivity of 93% and a specificity of 89%. In AR and NO-AR groups, MIG values correlated well with IP-10 (P < 0.001). MIG values indicated both imminent rejection and response to successful antirejection therapy. MIG was not related to intercurrent infections or other causes for impairment of renal function. In a multivariate analysis, MIG correlated best (P < 0.001) with AR from all AR-associated parameters. In conclusion, urinary MIG serves as a very sensitive and specific predictor for AR, mirrors response to antirejection therapy, and thus may contribute to improved long-term renal allograft survival.
Hauser
Ingeborg A
IA
Medical Clinic IV, Department of Nephrology, Clinic of the J.W. Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany. i.hauser@em.uni-frankfurt.de
Spiegler
Sandra
S
Kiss
Eva
E
Gauer
Stefan
S
Sichler
Olaf
O
Scheuermann
Ernst H
EH
Ackermann
Hanns
H
Pfeilschifter
Josef M
JM
Geiger
Helmut
H
Gröne
Hermann-Josef
HJ
Radeke
Heinfried H
HH
D000208:Acute Disease; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000652:urine*; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy / Q000209:etiology / Q000652:urine*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D036341:Intercellular Signaling Peptides and Proteins / Q000652:urine*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies
D015415:Biomarkers; C114753:CXCL10 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D007166:Immunosuppressive Agents; D036341:Intercellular Signaling Peptides and Proteins