Use of mTOR Inhibitors in Hypersensitized Kidney Transplant Recipients: Breaking False Myths
1Renal Transplant Unit, Hospital Clínic, Barcelona, Spain, 2Complejo Hospitalario Universitario, Albacete, Spain
Meeting: 2019 American Transplant Congress
Abstract number: A230
Keywords: Antibodies, Hypersensitivity, Rapamycin, Rejection
Session Information
Session Name: Poster Session A: Kidney Immunosuppression: Novel Regimens and Drug Minimization
Session Type: Poster Session
Date: Saturday, June 1, 2019
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall C & D
*Purpose: Many centers avoid the use of mTOR inhibitors (mTORi) in hypersensitized kidney transplant recipients and usually employ an immunosuppression based on Mycophenolic Acid (MPA), along with tacrolimus and prednisone. This attitude is due to a general feeling that mTORi are associated with an increased risk of rejection. In order to clarify this issue, we revised our experience, comparing hypersensitized patients who received MPA with those who received mTORi (either sirolimus or everolimus).
*Methods: Analysis of all kidney transplant recipients with a cPRA I+II > 50% transplanted from June 2013 to December 2016 in our Hospital (n=77). Baseline analysis as well as 1-year outcomes and trough levels were collected. Basal immunosuppression included tacrolimus and prednisone, along with either MPA (n=44), or an mTORi (n=33).
*Results: patients taking MPA more likely received a graft from a living donor (59.1% versus 24.2%, respectively, P<0.01). Close to 90% of patients in both groups received induction with a lymphocyte-depleting antibody. Patients with a known DSA at time of transplantation were 29.5% and 36.4% of MPA and mTORi patients, respectively (P=0.69). Biopsy-proven acute rejection (either cellular or antibody-mediated) during the first year was more frequent in the MPA group (43.2% versus 15.2%, P=0.01). Renal function was equal at one year (creatinine 1.59 ± 0.67 versus 1.46 ± 0.69 for MPA and mTORi, respectively, P=0.42) as well as graft failure (Table 1). The beneficial effects of mTORi on acute rejection were confirmed in logistic regression analysis and when data was analyzed per-protocol (not shown). Mean tacrolimus trough levels during the first year were 8.85 ± 1.52 ng/ml in the MPA group versus 8.22 ± 1.06 ng/ml in the mTORi group (P=0.04), while mTORi trough levels where 3.87 ± 0.92 ng/ml.
*Conclusions: In contrast to what is commonly believed, an immunosuppressive schedule based on optimal-dose mTORi along with tacrolimus and prednisone was associated even with better outcomes compared to a classical regimen based on mycophenolate in hypersensitized kidney transplant recipients.
| Variable | MPA-based (n=44) | mTORi-based (n=33) | P-value |
| cPRA I+II (%) | 86.57 ± 15.41 | 84.55 ± 15.61 | 0.57 |
| HLA A-B-DR mismatches | 3.18 ± 1.76 | 3.64 ± 1.36 | 0.22 |
| Induction with anti-lymphocyte antibodies (%yes) | 86.4% | 87.9% | 0.93 |
| 1-year biopsy-proven rejection (%yes) | 43.2% | 15.2% | 0.01 |
| 1-year acute cellular rejection (%yes) | 11.4% | 0.0% | 0.12 |
| 1-year acute humoral rejection (%yes) | 34.1% | 15.2% | 0.10 |
| 1-year Graft failure (%yes) | 6.8% | 0.0% | 0.12 |
To cite this abstract in AMA style:
Cucchiari D, Molina-Andujar A, Montagud-Marrahi E, Centellas-Pérez FJ, Revuelta I, Oppenheimer F, Diekmann F. Use of mTOR Inhibitors in Hypersensitized Kidney Transplant Recipients: Breaking False Myths [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/use-of-mtor-inhibitors-in-hypersensitized-kidney-transplant-recipients-breaking-false-myths/. Accessed November 21, 2024.« Back to 2019 American Transplant Congress