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Impact of Low Dose Tacrolimus with Everolimus Regimen on Renal Pathology and T-Regulatory Cells in Kidney Transplant.

A. Shetty,1 T. Opas,1 J. Mathew,1 V. Mas,2 J. Leventhal,1 N. Sustento-Reodica,1 L. Gallon.1

1Northwestern University, Feinberg School of Medicine, Chicago, IL
2University of Virginia, Charlottesville, VA.

Meeting: 2016 American Transplant Congress

Abstract number: 38

Keywords: Calcineurin, Immunosuppression, T cells

Session Information

Session Name: Concurrent Session: Kidney Transplant: CNI Minimization

Session Type: Concurrent Session

Date: Sunday, June 12, 2016

Session Time: 2:30pm-4:00pm

 Presentation Time: 3:18pm-3:30pm

Location: Room 311

Calcineurin inhibitors (CNI) serve as the cornerstone of immunosuppression (IS) after kidney transplant. However chronic CNI nephrotoxicity has been implicated in allograft dysfunction. We hypothesize low dose CNI with low dose Everolimus (Ev) may be associated with lower IFTA on allograft biopsy and less rejection.

Methods: We studied allograft pathology on protocol biopsies at 12 months post-transplant in 35 kidney transplant recipients randomized to steroid free IS with either low dose Tacrolimus (Tac) and Everolimus or standard dose Tac and Mycophenolate Mofetil (MMF) after Alemtuzumab induction. Everolimus levels were maintained between 3-8 ng/ml. We also analyzed circulating T cell populations in each group. Clinical outcomes included rejection free graft survival and estimated GFR (eGFR).

Results: Baseline characteristics were statistically similar between the two groups. Mean follow up was 14±4 and 17±5 months (p=0.02)and mean Tac levels were 4.5±1.9 and 6.4±1.5 ng/ml (p=0.03) in the Tac+Ev and Tac+MMF group respectively. Rejection free graft survival was greater in the Tac+Ev group (p=0.04), possibly related to increased circulating Tregs . The 2 groups had similar eGFR and similar degress of IFTA, glomerulosclerosis, isometric vacuolization and arteriosclerosis on biopsy

Allograft Pathology FK + Ev FK + MMF p value
  n=19 n=16  
Patients with moderate to severe IFTA (n) 1  1 1
Patients with isometric vacuoliization (n) 1  0 1
Patients with >25% Glomerusclerosis (n) 0    0  1
Patients with arteriosclerosis (n)  6   4 0.7

. Incidence of denovo DSA without overt rejection was also similar between groups.

Conclusion: Patients immunosuppressed with low dose Tac+ Ev compared to standard dose Tac+ MMF showed longer rejection free graft survival associated with greater circulating Tregs and similar degress of chronic changes on allograft biopsy. Further studies with longer clinical follow up are warranted.

CITATION INFORMATION: Shetty A, Opas T, Mathew J, Mas V, Leventhal J, Sustento-Reodica N, Gallon L. Impact of Low Dose Tacrolimus with Everolimus Regimen on Renal Pathology and T-Regulatory Cells in Kidney Transplant. Am J Transplant. 2016;16 (suppl 3).

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To cite this abstract in AMA style:

Shetty A, Opas T, Mathew J, Mas V, Leventhal J, Sustento-Reodica N, Gallon L. Impact of Low Dose Tacrolimus with Everolimus Regimen on Renal Pathology and T-Regulatory Cells in Kidney Transplant. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/impact-of-low-dose-tacrolimus-with-everolimus-regimen-on-renal-pathology-and-t-regulatory-cells-in-kidney-transplant/. Accessed June 4, 2025.

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