title: Sirolimus-based regimen is associated with decreased expression of glomerular vascular endothelial growth factor.
abstract: BACKGROUND
  Sirolimus (SRL) is a potent immunosuppressant used in organ transplantation. It is known to decrease vascular endothelial growth factor (VEGF) synthesis, making it an interesting treatment option for transplant patients who develop Kaposi sarcoma or other malignant diseases. Because VEGF plays a key role in glomerular function and vascular remodelling, we determined the effect of SRL on renal VEGF expression.
  
  
  METHODS
  Using immunohistochemistry and quantitative image analysis, we examined renal VEGF expression in routine kidney biopsies performed at 1 year post-transplant in the CONCEPT study, a prospective randomized study comparing a cyclosporine (CsA)-based regimen to a SRL-based regimen in association with mycophenolate mofetil (MMF).
  
  
  RESULTS
  A total of 74 patients were included in this substudy; 35 were randomized to the CsA group and 39 to the SRL group. Using continuous variables, the mean percentage of glomerular VEGF expression at Week 52 was significantly lower in the SRL group (14.7 ± 13%) compared to CsA group (21.2 ± 14%: P = 0.02). The percentage of glomerular VEGF expression at Week 52 was not influenced by recipient or donor age, gender, renal function, CsA dose, CsA blood level, SRL dose or SRL blood level. It was significantly lower in patients with a proteinuria over versus below 0.5 g/day (11.58 ± 7.9 versus 19.45 ± 15.53; P = 0.036).
  
  
  CONCLUSIONS
  There is emerging evidence that the VEGF system can play either a beneficial or a detrimental role depending on the specific pathologic situations. Therefore, modulating the renal VEGF axis by using an SRL-based regimen may influence the evolution of kidney injury associated with renal transplantation.
authors: Department of Nephrology and Transplantation, University Hospital, Reims, France.
authors: Vincent
authors: V
authors: Vuiblet
authors: Philippe
authors: P
authors: Birembaut
authors: Arnaud
authors: A
authors: François
authors: Carole
authors: C
authors: Cordonnier
authors: Laure-Helene
authors: LH
authors: Noel
authors: Jean-Michel
authors: JM
authors: Goujon
authors: Francois
authors: F
authors: Paraf
authors: Marie-Christine
authors: MC
authors: Machet
authors: Sandrine
authors: S
authors: Girardot-Seguin
authors: Yvon
authors: Y
authors: Lebranchu
authors: Philippe
authors: P
authors: Rieu