Vascular endothelial growth factor expression in human chronic renal allograft rejection

BACKGROUND: Chronic renal allograft rejection is characterized by interstitial fibrosis and vasculopathy. Vascular endothelial growth factor (VEGF) is an endothelial mitogen with increased expression in inflammation and vasculopathy. METHODS: Renal tissue from 17 patients with chronic rejection was examined for VEGF protein and the presence of CD 68-positive macrophages, and compared to biopsies from patients with temporary allograft dysfunction, acute rejection, and native kidneys with thin membrane disease. RESULTS: In the chronic rejection group, there was markedly increased expression of VEGF protein in the interstitium (P<0.0001). In serial sections, VEGF colocalized with the expression of CD 68-positive macrophages. Significantly more macrophages were in the tubulointerstitium in tissue with chronic rejection than in those with temporary allograft dysfunction (P<0.005). Additionally, VEGF protein expression in the glomeruli and the vascular compartment of patients with chronic rejection was increased. CONCLUSION: The up-regulation of VEGF in chronic renal allograft rejection may be important in inflammation and development of fibrosis.     

The macrophage is the predominant inflammatory cell in renal allograft intimal arteritis

BACKGROUND: Intimal arteritis defines acute vascular rejection in the Banff 97 schema. The arteritis is generally considered to be lymphocytic, although the cellular infiltrate in tubulitis is composed of both lymphocytes and macrophages. This study aimed to determine the extent of macrophage involvement in renal allograft intimal arteritis. METHODS: We obtained archival biopsy material from 57 biopsies of 34 renal allografts transplanted between March 1999 and February 2002. All biopsies were diagnostic. We examined clinical and histological parameters. Biopsies were graded using the Banff 97 criteria. We identified macrophages and memory T cells using immunohistochemistry for CD68 and CD45RO, respectively. RESULTS: In all, 24 biopsies showed borderline rejection, and 12 biopsies showed grade IA, 13 showed grade IB, and 8 showed grade II or III acute rejection. Both lymphocytes and macrophages were present in the tubulointerstitium in all grades of acute rejection. We identified intimal arteritis in 10 vessels in eight biopsies. The infiltrating cells invariably included CD68-positive cells; however, we saw intimal CD45RO-positive cells in only seven vessels. There were significantly more CD68-positive cells than CD45RO-positive cells (mean, 9.5 vs. 4.4 positive cells per vessel, P< 0.01). CD45RO cells were never the predominant component of the intimal inflammatory infiltrate. CONCLUSIONS: In the intimal arteritis of biopsies graded as Banff II or III acute rejection, the infiltrating cells were predominantly macrophages. T cells were in the minority. This finding challenges the assumption that the mononuclear cells in intimal arteritis are predominantly lymphocytic.     

The Initiating Dialysis Early and Late (IDEAL) study: study rationale and design.

OBJECTIVES: The primary objective of the IDEAL study is to determine whether the timing of dialysis initiation has an effect on survival in subjects with end-stage renal disease (ESRD). The secondary objectives are to determine the impact of "early start" versus "late start" dialysis on nutritional and cardiac morbidity, quality of life, and economic cost. DESIGN: Prospective multicenter randomized controlled trial. Patients are randomized to commence dialysis at a glomerular filtration rate (by Cockcroft-Gault) of either 10-14 mL/minute/1.73 m2 ("early start") or 5-7 mL/min/1.73 m2 ("late start"), with stratification for dialysis modality (hemodialysis vs peritoneal dialysis), study center, and the presence or not of diabetes mellitus. SETTING: Dialysis units throughout Australia and New Zealand. PATIENTS: Patients with ESRD commencing chronic dialysis therapy. OUTCOME MEASURES: Three years from randomization, all-cause mortality, morbidity, and economic impact; structural and functional cardiac status, nutritional state, and quality of life will be assessed. RESULTS: To date, 388 patients of a minimum 800 patients have been entered and randomized into the study. Current recruitment rates suggest sufficient patients will be enrolled by December 2004 and follow-up completed by December 2007. CONCLUSIONS: The IDEAL study will provide evidence for the optimal time to commence dialysis.     

Association of prevalent vascular disease with allograft failure and mortality in live‐donor kidney transplant recipients – a retrospective cohort study

Limited data exist regarding the impact of prevalent vascular disease after live‐donor kidney transplantation. We aimed to determine the associations between the number of prevalent vascular diseases, allograft, and patient outcomes following live‐donor transplantation. This cohort study used data from the Australia and New Zealand Dialysis and Transplant Registry. Rates between recipients of live‐donor kidney transplants ± prevalent vascular disease prior to transplantation were calculated. The associations between vascular disease, allograft failure, and all‐cause mortality were assessed using Cox regression modeling. Kaplan–Meier proportions were used to calculate all‐cause mortality and death with a function graft stratified by vascular disease burden. Of 4742 live‐donor recipients, 428 (9%) and 84 (2%) had prevalent vascular disease at 1 and ≥2 sites, respectively. Compared to recipients without vascular disease, the respective adjusted hazard ratios (95% confidence intervals) for patients with vascular disease at 1 and ≥2 sites were 1.78 (1.41–2.25) and 3.02 (2.03–4.50) for all‐cause mortality; and 1.54 (1.26–1.88) and 2.28 (1.54–3.38) for allograft failure. All‐cause mortality in recipients with vascular disease at 0, 1 and ≥2 sites was 0.028 (0.025, 0.031), 0.090 (0.073, 0.106) and 0.247 (0.196, 0.282) over the first 5‐year post‐transplant. There was an incremental association between the number of prevalent vascular disease sites and risk of allograft failure and all‐cause mortality in live‐donor kidney transplant recipients.