Molecular Profiles of Renal Allograft Biopsies at 12 Months Post Renal Transplant in Patients Exposed to Low Dose CNI and Everolimus vs. Patients Exposed to Full Dose CNI and MMF.
1Nephrology, Transplant Center, Northwestern University, Chicago
2University of Virginia, Charlottesville
Meeting: 2017 American Transplant Congress
Abstract number: 69
Keywords: Gene expression, Immunosuppression, Kidney transplantation
Session Information
Session Name: Concurrent Session: Novel Immunosuppression Regimens - Tacrolimus Combinations
Session Type: Concurrent Session
Date: Sunday, April 30, 2017
Session Time: 2:30pm-4:00pm
Presentation Time: 2:42pm-2:54pm
Location: E450b
CNIs serve as the cornerstone of immunosuppression (IS) after kidney transplant. However chronic CNI nephrotoxicity has been implicated in allograft dysfunction. We hypothesize that lower CNI exposure combined with Everolimus may result in better graft outcomes.
Methods: Prospective study in 40 adult kidney transplant recipients randomized to steroid free IS with low dose Tac and Everolimus (Ev) or standard (control) dose Tac and MMF after Alemtuzumab induction. End points: patient and graft survival, rejection free survival, renal allograft function and allograft immunohistopathology and gene expression profiles at 3 and 12 months post-tx. Results: Graft and patient survival were a 100% in both groups. Rejection free graft survival was not statistically different between the two groups, and eGFR remained similar between the two groups at 3,6,12 months post-Tx. Immunohistopathology at 3 and 12 months post-TX revealed no different between the two groups. When we evaluate gene expression profiles on a total of 56 graft biopsies (collected at 3 and 12 months post-Tx) we found that the analysis of biopsies at 3-months post-Tx showed minimal differences between groups. The analysis of samples at 12-months post-Tx showed no statistical differences in pathways related to immune response. However, pathways associated with growth factors and fibrosis developments were down-regulated in the Ev group (TGF-beta, THBS1, TNC, TGFB2, and SMAD5, among others). Additionally, up-stream regulators showed an inhibited predicted activation and included TGB1 (p-value of overlap-=3.7E-09), EDN1 (p-value of overlap-=4.12E-08), HGF (p-value of overlap= 6.4-08and Vegf (p-value of overlap= 6.7E-08). The expression of genes associated with renal necrosis/cell death was down-regulated in the Ev group (TMX1, EMP1, STK4, BAG2).
Conclusions. No differences on clinical outcomes between the two groups at one year post-Tx. However differences in gene expression were observed mainly at 12-month post-Tx with down regulation of genes associated with growth factors and fibrosis development in the Ev group. Longer follow up is underway to evaluate if these gene expressions findings at 12 months post-Tx will translate on better graft histology and renal allograft outcomes.
CITATION INFORMATION: Gallon L, Leventhal J, Maluf D, Sai Bontha V, Shetty A, Traitanon O, Ansari M, Mathew J, Wongpraphairot S, Mas V. Molecular Profiles of Renal Allograft Biopsies at 12 Months Post Renal Transplant in Patients Exposed to Low Dose CNI and Everolimus vs. Patients Exposed to Full Dose CNI and MMF. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Gallon L, Leventhal J, Maluf D, Bontha VSai, Shetty A, Traitanon O, Ansari M, Mathew J, Wongpraphairot S, Mas V. Molecular Profiles of Renal Allograft Biopsies at 12 Months Post Renal Transplant in Patients Exposed to Low Dose CNI and Everolimus vs. Patients Exposed to Full Dose CNI and MMF. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/molecular-profiles-of-renal-allograft-biopsies-at-12-months-post-renal-transplant-in-patients-exposed-to-low-dose-cni-and-everolimus-vs-patients-exposed-to-full-dose-cni-and-mmf/. Accessed May 13, 2025.« Back to 2017 American Transplant Congress