Inflammatory lymphangiogenesis in a rat transplant model of interstitial fibrosis and tubular atrophy

Abstract

We have previously reported de novo lymphangiogenesis in human renal allograft nephrectomy specimens that exhibited interstitial fibrosis and tubular atrophy (IFTA). This study examined whether a similar pathology developed in an experimental model of renal transplantation in the rat. Renal transplants were carried out in rats comprising both isografts (Lewis kidneys → Lewis rats) and allografts (Fisher kidneys → Lewis rats). Animals were immunosuppressed in the immediate postoperative period and sacrificed at 12 months. Experimental readouts included lymphatic vessel number and location, inflammatory cell infiltration, interstitial fibrosis, renal function, blood pressure and proteinuria. Rat allografts demonstrated the characteristic features of IFTA with increased macrophage and T cell infiltration and scattered B cells aggregates. Rat allografts exhibited impaired renal function and proteinuria. Although there was no difference in the number of perivascular lymphatic vessels, there was a striking 18-fold increase in the number of interstitial lymphatic vessels in renal allografts. Furthermore, the lymphatic vessel number correlated with the extent of interstitial fibrosis. This rat allograft model of IFTA demonstrates a marked increase in the number of interstitial lymphatic vessels and mirrors previous work in failing human renal allografts.