Conversion From Calcineurin Inhibitors to Sirolimus in Kidney Transplant Patients Reduces the Urinary Transforming Growth Factor-β1 Concentration

IntroductionChronic 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-β) are increased. Sirolimus is an immunosuppressive agent with a distinct mechanism of action compared with CNI.AimThis study assessed variations in levels of fibrogenic mediators among CAD patients treated with CNIs, before and after conversion to sirolimus.Patients and methodsWe studied twelve renal transplant patients with CAD on CNI treatment. TGF-β in plasma and urine, endothelin-1, and vascular endothelial growth factor (VEGF) were studied before and 8 months after conversion to sirolimus treatment.ResultsTGF-β 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).ConclusionsPatients undergoing conversion from CNI to sirolimus treatment for CAD presented a significant decrease in TGF-β urine levels, representing a decreased mediator of the CAD fibrogenic process.