Lymphatic neoangiogenesis in human renal allografts: results from sequential protocol biopsies

Neoangiogenesis of lymphatic vessels may be important for the cellular immune response in renal transplants. To determine the prevalence and chronology of lymph vessel proliferation and its relation to cellular infiltrates and allograft function, we analyzed sequential protocol biopsies (n = 162), taken at 6, 12 and 26 weeks after transplantation. Biopsies were stained with an antibody against podoplanin and lymphatic vessel density was quantified per square millimeter. The prevalence of lymph vessel-positive biopsies and the lymph vessel density were similar at 6, 12 and 26 weeks after transplantation. Biopsies with acute cellular rejection showed no significantly different lymph vessel density compared to those below the threshold for acute rejection or chronic allograft nephropathy. While lymphatic neoangiogenesis was equally prevalent in biopsies with and without infiltrates, the lymph vessel density was significantly higher in areas with cellular infiltrates than in areas without. Graft function at 1 year after transplantation was better in cases with lymph vessels in their infiltrates compared to cases with lymph vessel-free infiltrates. In conclusion, lymphangiogenesis not only shows a clear association with cellular infiltrates but might also have an impact on the pathogenicity of these cellular infiltrates.