Lymphatic Neoangiogenesis in Human Renal Allografts: Results from Sequential Protocol Biopsies

Abstract

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.

Lymphangiogenesis Is Upregulated in Kidneys of Patients With Multiple Myeloma

“…In each population studied, LV length density showed a certain variation, a finding also observed in the study by Stuht et al (2007) and which is due to a widespread distribution of lymph vessels in humans. Nevertheless, the overlap of the LV length densities in the different groups was minor.…”

“…Their function as so-called exit routes could explain an even better kidney graft function if lymphatics are present within nodular infiltrates. This hypothesis is supported by the work from Stuht et al (2007), who showed that kidney graft function 1 year after transplantation was better in cases with increased lymphangiogenesis. More recently, Adair et al (2007) also demonstrated new interstitial lymph vessels in nephrectomized end-stage allografts.…”

“…In both cases, the number of lymph vessels was much higher when compared with native nephrectomy tissue; however, there was no significant difference in LV density between different Banff rejection grades and chronic allograft nephropathy (Stuht et al, 2007).…”

“…Most data about renal lymphangiogenesis have so far been obtained in kidney transplant recipients with either acute graft rejection or chronic allograft nephropathy (Kerjaschki et al, 2004;Adair et al, 2007;Stuht et al, 2007). In both cases, the number of lymph vessels was much higher when compared with native nephrectomy tissue; however, there was no significant difference in LV density between different Banff rejection grades and chronic allograft nephropathy (Stuht et al, 2007).…”

“…The medulla of a healthy person rarely possesses any lymphatics (Cuttino et al, 1989). Just a few years ago, the Kerjaschki group showed that neolymphangiogenesis occurs in allograft kidney transplants, a finding confirmed by another report 3 years later (Adair et al, 2007;Stuht et al, 2007). In another study, Kerjaschki et al (2006) demonstrated that lymphatic endothelial cells in renal transplants originated from recipient-derived lymphatic progenitor cells.…”