Peritubular capillary rarefaction and lymphangiogenesis in chronic allograft failure.
BACKGROUND
Chronic renal allograft failure is a common and multifactorial but incompletely understood process with no effective treatment strategy.


METHODS
We used immunohistochemistry to evaluate changes in density and turnover (proliferation) of the microvasculature and lymphatic vessels in endstage human transplant nephrectomies and control tissue derived from macroscopically normal areas of native nephrectomy specimens removed for renal carcinoma. We also examined the expression of angiogenic and lymphangiogenic growth factors in the associated inflammatory infiltrate.


RESULTS
Endstage allografts showed reduced microvascular density in cortex and medulla compared with controls (P<0.0001), despite the presence of endothelial cell proliferation. However, the grafts also showed new lymphatic vessels in the tubulointerstitium, not evident in controls, and which appeared to be functional with luminal macrophages. Double labeling studies showed a subpopulation of the graft-infiltrating macrophages to be immunopositive for inducible nitric oxide synthase or vascular endothelial growth factor-C (a lymphatic-specific growth factor). B cells also strongly expressed the inflammatory and angiogenic cytokine vascular endothelial growth factor A.


CONCLUSIONS
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.
Adair
Anya
A
Phagocyte Laboratory, MRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
Mitchell
David R
DR
Kipari
Tiina
T
Qi
Feng
F
Bellamy
Christopher O C
CO
Robertson
Faye
F
Hughes
Jeremy
J
Marson
Lorna P
LP
D000293:Adolescent; D000328:Adult; D000368:Aged; D002196:Capillaries / Q000473:pathology*; D005260:Female; D006801:Humans; D042583:Lymphangiogenesis / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D011183:Postoperative Complications / Q000453:epidemiology; D014184:Transplantation, Homologous; D017211:Treatment Failure; D014652:Vascular Diseases / Q000453:epidemiology / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D042461:Vascular Endothelial Growth Factor A; D052247:Nitric Oxide Synthase Type II