title: Influence of conversion from calcineurin inhibitors to everolimus on fibrosis, inflammation, tubular damage and vascular function in renal transplant patients.
abstract: BACKGROUND
  Conversion from calcineurin inhibitor (CNI) to mTOR inhibitors may reduce and even halt the progression of chronic allograft dysfunction (CAD) which is the most important cause of renal allograft loss. We aimed to investigate the effects of conversion from CNI to everolimus on parameters of fibrosis, inflammation, glomerulotubular damage and vascular functions in renal transplant recipients.
  
  
  METHODS
  Fifteen stable renal transplant recipients who were under CNI treatment (male/female 13/2, mean age 41 ± 10 years) were enrolled and switched to everolimus. Serum and urinary transforming growth factor-β (TGF-β), urinary neutrophil gelatinase-associated lipocalin (NGAL) and monocyte chemoattractant protein-1 (MCP-1) were measured as markers of fibrosis, tubular damage and inflammation. As parameters of vascular functions, pulse wave velocity (PWV), augmentation index (AIx), serum asymmetric dimethyl-arginine and fibroblast growth factor-23 (FGF-23) were measured. All these measurements were repeated at the 3rd month of conversion.
  
  
  RESULTS
  Estimated GFR (52 ± 7-57 ± 11 ml/min/l.73 m(2), p = 0.02) (was increased after conversion to everolimus. However, serum uric acid levels were significantly decreased (6.21 ± 1.21-5.50 ± 1.39 mg/dL, p = 0.01). Serum TGF-β levels (8727 ± 2897-1943 ± 365 pg/mL, p = 0.03) and urinary NGAL levels (26 ± 10-12 ± 2 ng/mg creatinine, p = 0.05) were significantly decreased. However, urinary MCP-1, FGF-23, PWV and AIx did not change. Urinary TGF-β was associated with urinary NGAL (r = 0.62, p = 0.01), urinary MCP-1 (r = 0.68, p = 0.005) and proteinuria (r = 0.50, p = 0.05).
  
  
  CONCLUSIONS
  Conversion from CNI to everolimus resulted in significant decreases of serum TGF-β and urinary NGAL which may represent less fibrosis and tubular damage. Association of urinary TGF-β with NGAL and MCP-1 suggests that tubular damage, fibrosis and inflammation may act together for progression of CAD.
authors: Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul School of Medicine, Istanbul University, Fatih, 34093, Istanbul, Turkey.
authors: Nadir
authors: N
authors: Alpay
authors: Abdullah
authors: A
authors: Ozkok
authors: Yasar
authors: Y
authors: Caliskan
authors: Tulin
authors: T
authors: Akagun
authors: Suzan Adın
authors: SA
authors: Cinar
authors: Gunnur
authors: G
authors: Deniz
authors: Muzaffer
authors: M
authors: Sariyar
authors: Alaattin
authors: A
authors: Yildiz
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D000328:Adult; D065095:Calcineurin Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D018932:Chemokine CCL2 / Q000378:metabolism; D000068338:Everolimus; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005355:Fibrosis / Q000473:pathology / Q000517:prevention & control; D006084:Graft Rejection / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009393:Nephritis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D063177:Pulse Wave Analysis; D012077:Renal Artery / Q000503:physiopathology*; D012307:Risk Factors; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000378:metabolism; D066027:Transplant Recipients
chemical_list: D000209:Acute-Phase Proteins; C111835:CCL2 protein, human; D065095:Calcineurin Inhibitors; D018932:Chemokine CCL2; C000717427:FGF23 protein, human; D007166:Immunosuppressive Agents; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D016212:Transforming Growth Factor beta; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D000068338:Everolimus; D020123:Sirolimus