W. Prodjosudjadi et al., INCREASED URINARY-EXCRETION OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 DURING ACUTE RENAL-ALLOGRAFT REJECTION, Nephrology, dialysis, transplantation, 11(6), 1996, pp. 1096-1103
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
.