Abstract
Currently, the primary question facing renal transplantation is how to prolong renal allograft survival. Given the need to balance immunosuppressive requirements and potential drug toxicities, the optimal long-term therapeutic strategy remains uncertain. It is also unclear whether mTOR inhibitors offer unique advantages in maintaining normal allograft structure and function. Methods: In this prospective study, we examined the clinical and histological consequences of converting 63 low-risk adult renal transplant recipients (RTR). Those without subclinical rejection at 3 mos were converted to either low-dose tacrolimus (LoTAC) (4-6 ng/ml) or sirolimus (SLR) (5-10 ng/ml). Demographics for both groups were similar except that the LoTAC group had more ECD transplants (23% vs. 4%, p=0.05) and diabetic RTR (58% vs. 28%, p=0.02). Protocol biopsies were performed at implantation, 3 and 12 mos. All RTR received rabbit anti-thymocyte globulin induction therapy (3-5 mg/kg/total dose) along with standard dose TAC (levels 10-15 ng/ml), EC-MPS (Myfortic) and low-dose prednisone. Results: Seven patients were not randomized due to subclinical rejection present in the 3 mo. biopsy (Gr.1A n=1, Borderline, n= 6) leaving 26 randomized to SLR and 31 to LoTAC. Eight RTR in the SLR group were withdrawn due to adverse events including 1 AHR, 1 ACR, 3 infections, 1 hyperlipidemia and 2 proteinuria, but none had graft loss. Only 2 RTR in the LoTAC arm were withdrawn due to graft loss from BK and non-compliance (p=0.03). EC-MPS dose reductions occurred only in the SRL arm due to infections. Renal function (eGFR ml/min) was equal in the remaining LoTAC and SRL treated RTR (75±14 vs. 65±16 at 1 yr. and 68±17 vs. 67±18 at 2 yrs. respectively). Both groups exhibited equivalent increases in average IF/TA indices (LoTAC 0.09 - 0.58; SRL 0.01 - 0.86) and overall CADI scores (LoTAC 1.1 - 2.16; SRL 1.0 - 2.0) between the 3 and 12 mo. biopsies respectively. Three LoTAC and 4 SRL RTR had subclinical rejection in the 12 mo. biopsy. Conclusion: When combined with EC-MPS and steroids, early conversion to Lo-TAC is better tolerated with equivalent graft function and histology compared to SLR. Protocol biopsies are invaluable for risk assessment when altering or decreasing immunosuppressive therapy.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.