INCREASED URINARY-EXCRETION OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 DURING ACUTE RENAL-ALLOGRAFT REJECTION

Background. Acute rejection is characterized histologically by infiltr ation of the interstitium by mononuclear cells. Monocyte chemoattracta nt protein 1 (MCP-1) has recently been identified as a monocyte chemot actic factor. This study examined the possible role of MCP-1 in renal transplantation. Methods. The concentration of MCP-1 in urine and seru m of 19 renal transplant patients was investigated using an inhibition radioimmunoassay. The patients were divided into a non-rejection (NRj ) and a rejection (Rj) group. Normal healthy volunteers were included as controls. Immunoperoxidase staining for MCP-1 and CD14, as a marker for macrophages, was performed in renal biopsies of transplant patien ts with rejection and six biopsies from histologically normal kidneys, as controls. The size of urinary MCP-1 was determined by gel filtrati on chromatography and in a number of fractions assessed for monocyte c hemotactic activity using a modified Boyden chamber assay. Results. Ur inary excretion of MCP-1 in the Rj group ranged between 250 ng/mmol Cr and 3148 ng/mmol Cr with a median of 612 ng/mmol Cr. This is signific antly higher than the results in the NRj group, ranging between 47 ng/ mmol Cr and 388 ng/mmol Cr with a median of 229 ng/mmol Cr. In the nor mal control group, urinary MCP-1 levels ranged between 38 ng/mmol Cr a nd 74 ng/mmol Cr with a median of 50 ng/mmol Cr. The fractional excret ion of MCP-1, calculated on the basis of MCP-1 and creatinine clearanc es, was found also to be significantly higher in the Rj group as compa red to the NRj group. However, there was no significant difference in the serum levels of MCP-1 between the Rj, NRj, and normal control grou p. The intensity of MCP-1 staining in tubular epithelial cells and the degree of CD14(+) cells in the interstitium was significantly higher in renal allograft biopsies than in the normal kidneys. In addition, M CP-1 isolated from urine of renal transplant patients with rejection w as filtered with apparent molecular weight of 13 kDa and 11 kDa. Both sizes are chemotactically active for monocytes. Conclusions. These dat a suggest that urinary excretion of MCP-1 can be used as a marker for the episodes of acute rejection. The increase of urinary excretion of MCP-1 most likely is the result of local production by tubular epithel ial cells. MCP-1 produced locally may, at least in part, be responsibl e for the influx of macrophages into the interstitium during rejection .