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Conversion from calcineurin inhibitors to sirolimus in kidney transplant patients reduces the urinary transforming
A Saurina1, J M Campistol, S Lario
1Department of Nephrology, Hospital de Terrassa, Barcelona, Spain. 31584ass@comb.es
Introduction:
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.
Aim:
This study assessed variations in levels of fibrogenic mediators among CAD patients treated with CNIs, before and after conversion to sirolimus.
Patients And 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.
Insights
Converting renal transplant patients from calcineurin inhibitors (CNIs) to sirolimus significantly reduced urine transforming growth factor beta (TGF-beta) levels. This suggests sirolimus may mitigate the fibrogenic process in chronic allograft dysfunction (CAD).
Area of Science:
- Nephrology
- Transplant Immunology
- Pharmacology
Background:
- Chronic allograft dysfunction (CAD) is a primary cause of late kidney transplant failure.
- Calcineurin inhibitor (CNI) toxicity contributes to CAD, characterized by vascular and tubulointerstitial damage.
- Fibrogenic mediators like transforming growth factor beta (TGF-beta) are elevated in CAD patients.
Purpose of the Study:
- To assess changes in fibrogenic mediator levels in CAD patients after switching from CNIs to sirolimus.
- To evaluate the impact of sirolimus conversion on TGF-beta, endothelin-1, and VEGF in renal transplant recipients with CAD.
Main Methods:
- A study involving twelve renal transplant patients with CAD on CNI treatment.
- Measurement of plasma and urine TGF-beta, plasma endothelin-1, and plasma VEGF before and 8 months after conversion to sirolimus.
- Statistical analysis to determine significant variations in mediator levels post-conversion.
Main Results:
- A significant decrease in urine TGF-beta levels was observed (P = .049).
- Plasma TGF-beta showed a decreasing trend (P = .079).
- Endothelin-1 levels decreased (P = .1), and VEGF levels showed a trend of increase (P = .051).
Conclusions:
- Conversion from CNIs to sirolimus therapy in CAD patients leads to a significant reduction in urinary TGF-beta.
- This reduction in TGF-beta suggests a potential decrease in the fibrogenic process associated with CAD.
- Sirolimus may offer a therapeutic advantage in managing CNI-induced nephrotoxicity in renal transplantation.
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