PMID- 24515306
OWN - NLM
STAT- MEDLINE
DCOM- 20150904
LR  - 20211203
IS  - 1437-7799 (Electronic)
IS  - 1342-1751 (Linking)
VI  - 18
IP  - 6
DP  - 2014 Dec
TI  - Influence of conversion from calcineurin inhibitors to everolimus on fibrosis, 
      inflammation, tubular damage and vascular function in renal transplant patients.
PG  - 961-7
LID - 10.1007/s10157-014-0939-4 [doi]
AB  - 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-beta (TGF-beta), 
      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-beta 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-beta 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). 
      CONCLUSION: Conversion from CNI to everolimus resulted in significant decreases 
      of serum TGF-beta and urinary NGAL which may represent less fibrosis and tubular 
      damage. Association of urinary TGF-beta with NGAL and MCP-1 suggests that tubular 
      damage, fibrosis and inflammation may act together for progression of CAD.
FAU - Alpay, Nadir
AU  - Alpay N
AD  - Division of Nephrology, Department of Internal Medicine, Istanbul Faculty of 
      Medicine, Istanbul School of Medicine, Istanbul University, Fatih, 34093, 
      Istanbul, Turkey.
FAU - Ozkok, Abdullah
AU  - Ozkok A
FAU - Caliskan, Yasar
AU  - Caliskan Y
FAU - Akagun, Tulin
AU  - Akagun T
FAU - Cinar, Suzan Adin
AU  - Cinar SA
FAU - Deniz, Gunnur
AU  - Deniz G
FAU - Sariyar, Muzaffer
AU  - Sariyar M
FAU - Yildiz, Alaattin
AU  - Yildiz A
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140211
PL  - Japan
TA  - Clin Exp Nephrol
JT  - Clinical and experimental nephrology
JID - 9709923
RN  - 0 (Acute-Phase Proteins)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Calcineurin Inhibitors)
RN  - 0 (Chemokine CCL2)
RN  - 0 (FGF23 protein, human)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (LCN2 protein, human)
RN  - 0 (Lipocalin-2)
RN  - 0 (Lipocalins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - 62031-54-3 (Fibroblast Growth Factors)
RN  - 7Q7P4S7RRE (Fibroblast Growth Factor-23)
RN  - 9HW64Q8G6G (Everolimus)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Acute-Phase Proteins/metabolism
MH  - Adult
MH  - Calcineurin Inhibitors/pharmacology/*therapeutic use
MH  - Chemokine CCL2/metabolism
MH  - Everolimus
MH  - Female
MH  - Fibroblast Growth Factor-23
MH  - Fibroblast Growth Factors/metabolism
MH  - Fibrosis/pathology/prevention & control
MH  - Graft Rejection/epidemiology
MH  - Humans
MH  - Immunosuppressive Agents/pharmacology/*therapeutic use
MH  - *Kidney Transplantation
MH  - Kidney Tubules/drug effects/*pathology
MH  - Lipocalin-2
MH  - Lipocalins/metabolism
MH  - Male
MH  - Middle Aged
MH  - Nephritis/metabolism/pathology/*prevention & control
MH  - Proto-Oncogene Proteins/metabolism
MH  - Pulse Wave Analysis
MH  - Renal Artery/*physiopathology
MH  - Risk Factors
MH  - Sirolimus/*analogs & derivatives/pharmacology/therapeutic use
MH  - Transforming Growth Factor beta/metabolism
MH  - Transplant Recipients
EDAT- 2014/02/12 06:00
MHDA- 2015/09/05 06:00
CRDT- 2014/02/12 06:00
PHST- 2013/10/04 00:00 [received]
PHST- 2014/01/17 00:00 [accepted]
PHST- 2014/02/12 06:00 [entrez]
PHST- 2014/02/12 06:00 [pubmed]
PHST- 2015/09/05 06:00 [medline]
AID - 10.1007/s10157-014-0939-4 [doi]
PST - ppublish
SO  - Clin Exp Nephrol. 2014 Dec;18(6):961-7. doi: 10.1007/s10157-014-0939-4. Epub 2014 
      Feb 11.