Peritubular Capillary Rarefaction and Lymphangiogenesis in Chronic Allograft Failure

Abstract

The present results identify contrasting changes in the microanatomy of vascular and lymphatic beds in endstage renal allografts associated with subpopulations of infiltrating macrophages and B cells that potentially regulate some of these changes. These cells and processes could become a new therapeutic target in chronic allograft failure.

Depletion of Cells of Monocyte Lineage Prevents Loss of Renal Microvasculature in Murine Kidney Transplantation

“…The finding of peritubular capillary loss in association with rejection resonates with our previous work demonstrating loss of the microvasculature in renal biopsies from patients with chronic allograft dysfunction (13). Indeed, in these human studies we noted increased expression of iNOS in the renal interstitium (13) and it is therefore of interest that previous work in human renal allografts demonstrated significantly increased expression of iNOS in rejecting grafts compared with those with stable function (37).…”

“…M infiltration is common to many renal pathologies such as acute rejection (6), infection (26), urinary obstruction (27) and chronic allograft dysfunction (13), and the specific contributions of M and M-derived mediators in these different contexts may differ.…”

“…Loss of the renal microvasculature and the resultant tissue hypoxia and ischemia would promote progression of renal injury and scarring (12). Our recent work demonstrates significant loss of peritubular capillaries in end-stage chronic allograft failure in association with infiltrating graft M (13), suggesting M involvement in endothelial cell injury.…”

Late Kidney Allograft Loss

“…In end-stage grafts with TA/ IF, reduced microvascular density has been associated with increased endothelial proliferation of remaining cells (96). Interstitial lymphatics that contain macrophages were also prevalent in these failed grafts, associated with enhanced expression of inducible nitric oxide synthase and vascular endothelial growth factor-C.…”

Linfangiogênese no transplante renal: análise clínico-patológica e imunofenotípica de biópsias de aloenxertos renais de doadores falecidos

“…A linfangiogênese foi também associada à ocorrência de agregados linfocitários ativos contendo linfócitos T e B com atividade proliferativa (Kerjaschki et al, 2004). Por fim, a presença de linfáticos no córtex do enxerto renal foi observada em espécimes com alterações morfológicas crônicas (Adair et al, 2007).…”