Activated cells in urine and monocyte chemotactic peptide-1 (MCP-1) - Sensitive rejection markers in renal graft recipients

Chemokines induced during an acute immune alloresponse cause cellular infiltration of the allograft. These chemokines and cells are excreted with urine. The aim of the study was to assess the diagnostic utility of urinary excretion of monocyte chemotactic peptide-1 and certain cells involved in infiltration i.e. CD3+, CD64+ and HLA-DR+ cells. The study entailed 35 patients with acute renal rejection and 65 with a stable graft function. Urinary sediments were prepared by means of cytospin and stained with anti-CD3, anti-CD64, anti-HLA-DR labeled monoclonal antibodies. Urinary expression of MCP-1 was assayed by ELISA. In the patients with acute rejection MCP-1 level was ten-fold higher than in the patients with a stable graft function (6.1 +/- 3.4 vs 0.6 +/- 0.4 ng/mg creatinine). The number of CD3+ cells was over 5 times higher than in the non-rejection patients (13.4 +/- 4.6 vs 2.5 +/- 2.2). The number of HLA-DR+ cells was 6 times higher in the acute rejection patients (15.7 +/- 5.9 vs 2.5 +/- 2.7). The number of CD64+ cells was significantly increased in the patients during an acute rejection episode (p<0.0001). CD3+, HLA-DR+ and CD64+ cell counts strongly correlated with urine excretion of MCP-1. The counts of CD3+ and HLA-DR+ cells correlated with Banff score. The assessment of MCP-1 as well as CD3+, CD64+ and HLA-DR+ cells can provide a useful non-invasive device for the diagnosis of acute rejection. A sole assay of HLA-DR+ cell excretion provides enough specificity and sensitivity for the routine monitoring of patients after kidney transplantation, saving costs and time. (c) 2007 Elsevier B.V All rights reserved.