The macrophage is the predominant inflammatory cell in renal allograft intimal arteritis.

BACKGROUND: Intimal arteritis defines acute vascular rejection in the Banff 97 schema. The arteritis is generally considered to be lymphocytic, although the cellular infiltrate in tubulitis is composed of both lymphocytes and macrophages. This study aimed to determine the extent of macrophage involvement in renal allograft intimal arteritis. METHODS: We obtained archival biopsy material from 57 biopsies of 34 renal allografts transplanted between March 1999 and February 2002. All biopsies were diagnostic. We examined clinical and histological parameters. Biopsies were graded using the Banff 97 criteria. We identified macrophages and memory T cells using immunohistochemistry for CD68 and CD45RO, respectively. RESULTS: In all, 24 biopsies showed borderline rejection, and 12 biopsies showed grade IA, 13 showed grade IB, and 8 showed grade II or III acute rejection. Both lymphocytes and macrophages were present in the tubulointerstitium in all grades of acute rejection. We identified intimal arteritis in 10 vessels in eight biopsies. The infiltrating cells invariably included CD68-positive cells; however, we saw intimal CD45RO-positive cells in only seven vessels. There were significantly more CD68-positive cells than CD45RO-positive cells (mean, 9.5 vs. 4.4 positive cells per vessel, P< 0.01). CD45RO cells were never the predominant component of the intimal inflammatory infiltrate. CONCLUSIONS: In the intimal arteritis of biopsies graded as Banff II or III acute rejection, the infiltrating cells were predominantly macrophages. T cells were in the minority. This finding challenges the assumption that the mononuclear cells in intimal arteritis are predominantly lymphocytic.

Calcineurin inhibitor nephrotoxicity: reduction in dose results in marked improvement in renal function in patients with coexisting chronic allograft nephropathy.

BACKGROUND: Calcineurin inhibitors (CNI) have significantly reduced the incidence of acute rejection. Nephrotoxicity however, may contribute to long-term allograft dysfunction. METHODS: Forty-six biopsies from patients who had been transplanted for more than 6 months were examined. Sixteen biopsies had evidence of chronic allograft nephropathy (CAN) alone, 21 biopsies had evidence of coexisting CAN in addition to histological evidence of calcineurin inhibitor nephrotoxicity (CNIN) while nine had neither evidence of nephrotoxicity nor CAN. Patients with evidence of nephrotoxicity underwent a reduction in dose of CNI while those with CAN alone had no change in therapy. Renal function was followed for a mean of 17.4 months after biopsy. RESULTS: The serum creatinine at the time of diagnostic renal biopsy was comparable between those with CAN alone (mean 0.25 +/- 0.18 mmol/L) and those with coexisting CNIN (mean 0.23 +/- 0.05 mmol/L, p=0.33). The patients with CNIN however, had a rapid improvement in renal function within 1 month after dose reduction. This was sustained for the duration of follow-up (mean serum creatinine 0.162 +/- 0.038 mmol/L at 1 yr after dose reduction; p=0.001). In comparison, those with CAN alone had a gradual decline in renal function with a serum creatinine at 1 yr after biopsy of 0.31 +/- 0.187, p=0.01. CONCLUSION: Reduction in the dose of CNI in those with histological evidence of nephrotoxicity resulted in a sustained improvement in renal function.