Conversion from calcineurin inhibitors to sirolimus in kidney transplant patients reduces the urinary transforming growth factor-beta1 concentration.
BACKGROUND
Chronic allograft dysfunction (CAD) is the main cause of late transplant failure. Although several etiologies have been postulated, toxicity for calcineurin inhibitors (CNIs) is one of the most important causes of CAD, characterized by arteriolar hyalinosis, luminal narrowing, increased glomerulosclerosis, and tubulointerstitial damage. It's known that in transplant patients with CAD, fibrogenic mediators such as transforming growth factor beta (TGF-beta) are increased. Sirolimus is an immunosuppressive agent with a distinct mechanism of action compared with CNI.


OBJECTIVE
This study assessed variations in levels of fibrogenic mediators among CAD patients treated with CNIs, before and after conversion to sirolimus.


METHODS
We studied twelve renal transplant patients with CAD on CNI treatment. TGF-beta in plasma and urine, endothelin-1, and vascular endothelial growth factor (VEGF) were studied before and 8 months after conversion to sirolimus treatment.


RESULTS
TGF-beta urine levels decreased from 24.7 +/- 11.2 to 12.8 +/- 5.1 ng/24 h (P = .049). In plasma, a similar decrease trend was observed (22.2 +/- 32 to 10.3 +/- 3 ng/mL), although it was not significant (P = .079). Endothelin-1 showed a decrease (8.1 +/- 3 to 5.2 +/- 1.1 pmol/L; P = .1) and VEGF in plasma increased from 34.3 +/- 37 to 92.2 +/- 86 pg/mL (P = .051).


CONCLUSIONS
Patients undergoing conversion from CNI to sirolimus treatment for CAD presented a significant decrease in TGF-beta urine levels, representing a decreased mediator of the CAD fibrogenic process.
Saurina
A
A
Department of Nephrology, Hospital de Terrassa, Barcelona, Spain. 31584ass@comb.es
Campistol
J M
JM
Lario
S
S
Oppenheimer
F
F
Diekmann
F
F
D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors; D019332:Endothelin-1 / Q000097:blood / Q000652:urine; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000187:drug effects / Q000652:urine*; D014184:Transplantation, Homologous / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000652:urine
D065095:Calcineurin Inhibitors; D019332:Endothelin-1; D007166:Immunosuppressive Agents; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D020123:Sirolimus