Urinary monocyte chemoattractant protein-1 levels and interstitial changes in the renal cortex and their relationship with loss of renal function in renal transplant patients with delayed graft function

BACKGROUND: Inflammatory cell infiltration and residual areas of fibrosis in kidneys after renal transplantation can lead to functional abnormalities with long-term implications. OBJECTIVES: The aim of this study was to determine urinary monocyte chemoattractant protein-1 (uMCP-1) levels, relative cortical interstitial area (RCIA), and cortical tubulointerstitial macrophage infiltration in renal transplant patients with delayed graft function (DGF) and their possible correlation with graft outcome. DESIGN: Patients were followed after biopsies for one year, and their renal function and structure were evaluated, as well as parameters of inflammatory process. SETTING: Clinical Hospital of the School of Medicine of Ribeirão Preto. PATIENTS: Twenty-two cadaveric kidney transplant recipients with DGF were followed for one year. MEASUREMENTS: Renal function, RCIA, macrophages infiltration and uMCP-1 levels were evaluated. METHODS: Renal function was evaluated by plasma creatinine levels. RCIA was determined by morphometry. Immunohistochemical staining of macrophages was performed using an anti-CD68 monoclonal antibody. uMCP-1 levels were determined using a human MCP-1/CCL2 immunoassay kit. RESULTS: There was a significant increase in uMCP-1 levels in transplant patients compared with controls (p < 0.001). RCIA was 7.1% (6.4 to 9.2; median and 25th to 75th percentiles) in controls and 37.1% (28.1 to 43.7) in patients with kidney transplants (p < 0.001). The patients who presented with a higher RCIA in the first biopsy showed higher levels of plasma creatinine one year after transplantation (r = 0.44; p < 0.05). The number of tubulointerstitial macrophages per 0.10 mm(2) grid field was higher in the renal cortex of transplant patients compared with the controls (19.4 (9.0 to 47.1) vs. 2.5 (1.8 to 3.4), p < 0.001). There was also a positive correlation between the RCIA and the number of tubulointerstitial macrophages in the renal cortex of these patients (r = 0.49; p < 0.001). LIMITATIONS: The number of patients studied was relatively small and may not be reflecting outcomes over a larger spectrum of kidney cadaveric transplants. CONCLUSIONS: Our results demonstrate increased levels of uMCP-1 in transplant patients with DGF, in addition to increased tubulointerstitial macrophage infiltration and RCIA, which could predict the outcome of renal function in these patients.