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An Increase in Myeloid-Related Protein Serum Levels Precedes Acute Renal Allograft Rejection

KLAUS BURKHARDT^*, MARTIN RADESPIEL-TRÖGER, HARALD D. RUPPRECHT^*, MARGARETE GOPPELT-STRUEBE^*, REGINE RIESS, LUTZ RENDERS^*, INGEBORG A. HAUSER and ULRICH KUNZENDORF^*

^* Medical Clinic IV, Friedrich Alexander-University, Erlangen-Nuremberg, Germany
Institute for Medical Information, Biometrics, and Epidemiology, Friedrich Alexander-University, Erlangen-Nuremberg, Germany
Pathology Institute, Nuremberg Clinic South, Nuremberg, Germany
Medical Clinic IV, Nephrology, Johann Wolfgang Goethe University, Frankfurt, Germany.

Correspondence to Dr. Klaus Burkhardt, Medizinische Klinik IV, Transplantzentrale, Klinikum Nürnberg Süd, Breslauerstrasse 201, 90471 Nürnberg, Germany. Phone: 0049-911-3985151; Fax: 0049-911-890647; E-mail: klaus.burkhardt{at}rzmail.uni-erlangen.de

Abstract. Upon interaction with activated endothelium, monocytes and neutrophils form complexes of myeloid-related protein 8 (MRP8) (S100A8) and MRP14 (S100A9), two members of the calcium-binding S100 family that are secreted during transendothelial migration. In a pilot study of 20 renal transplant recipients and a validation study of 36 renal transplant recipients, MRP8/14 serum levels were measured with an enzyme-linked immunosorbent assay for 28 d, associated with C-reactive protein and creatinine serum levels, and grouped according to biopsy-proven acute rejection. Serum levels of MRP8/14 but not C-reactive protein were significantly increased for several days during the first 2 wk for the acute rejection groups in both studies (P < 0.005, on day 6 after transplantation). As determined by using receiver operating characteristic curves, the optimal cutoff for 100% specificity and high sensitivity (67%) for acute rejection on day 6 after transplantation was calculated to be 4.2 µg/ml for MRP8/14 in the pilot study; this value was confirmed in the validation study. Positive MRP8/14 serum levels preceded acute rejection episodes by a median of 5 d. A 3-d course of intravenous methylprednisolone therapy reduced prerejection MRP8/14 serum levels from 5.7 µg/ml to 3.3 µg/ml (P < 0.05). All MRP8/14 serum levels were below the cutoff during urinary tract infections, delayed graft function, or cytomegalovirus infections, and these values did not differ significantly from control values. It is concluded that the MRP8/14 complex is a very early serum marker suitable for monitoring of acute rejection with high sensitivity and specificity.

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				S Miyamoto, M Ueda, M Ikemoto, T Naruko, A Itoh, S Tamaki, R Nohara, F Terasaki, S Sasayama, and M Fujita Increased serum levels and expression of S100A8/A9 complex in infiltrated neutrophils in atherosclerotic plaque of unstable angina Heart, August 1, 2008; 94(8): 1002 - 1007. [Abstract] [Full Text] [PDF]

				M. Ikemoto, T. Tanaka, Y. Takai, H. Murayama, K. Tanaka, and M. Fujita New ELISA System for Myeloid-related Protein Complex (MRP8/14) and Its Clinical Significance as a Sensitive Marker for Inflammatory Responses Associated with Transplant Rejection Clin. Chem., April 1, 2003; 49(4): 594 - 600. [Abstract] [Full Text] [PDF]

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673