Use of De Novo mTOR Inhibitors in Hypersensitized Kidney Transplant Recipients: Experience From Clinical Practice.
Adult
Aged
Calcineurin Inhibitors
/ administration & dosage
Desensitization, Immunologic
/ adverse effects
Drug Therapy, Combination
/ adverse effects
Everolimus
/ administration & dosage
Female
Glucocorticoids
/ administration & dosage
Graft Rejection
/ immunology
HLA Antigens
/ immunology
Humans
Immunosuppressive Agents
/ administration & dosage
Isoantibodies
/ immunology
Kidney Transplantation
/ adverse effects
Male
Middle Aged
Mycophenolic Acid
/ administration & dosage
Retrospective Studies
Sirolimus
/ administration & dosage
TOR Serine-Threonine Kinases
/ antagonists & inhibitors
Tacrolimus
/ administration & dosage
Treatment Outcome
Journal
Transplantation
ISSN: 1534-6080
Titre abrégé: Transplantation
Pays: United States
ID NLM: 0132144
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
entrez:
1
8
2020
pubmed:
1
8
2020
medline:
21
10
2020
Statut:
ppublish
Résumé
It is commonly believed that mTOR inhibitors (mTORi) should not be used in high-immunological risk kidney transplant recipients due to a perceived increased risk of rejection. However, almost all trials that examined the association of optimal-dose mTORi with calcineurin inhibitor (CNI) have excluded hypersensitized recipients from enrollment. To shed light on this issue, we examined 71 consecutive patients with a baseline calculated panel reactive antibody (cPRA) ≥50% that underwent kidney transplantation from June 2013 to December 2016 in our unit. Immunosuppression was based on CNI (tacrolimus), steroids and alternatively mycophenolic acid (MPA; n = 38), or mTORi (either everolimus or sirolimus, n = 33, target trough levels 3-8 ng/mL). Demographic and immunological risk profiles were similar, and almost 90% of patients in both groups received induction with lymphocyte-depleting agents. Cox-regression analysis of rejection-free survival revealed better results for mTORi versus MPA in terms of biopsy-proven acute rejection (hazard ratio [confidence interval], 0.32 [0.11-0.90], P = 0.031 at univariable analysis and 0.34 [0.11-0.95], P = 0.040 at multivariable analysis). There were no differences in 1-year renal function, Banff chronicity score at 3- and 12-month protocol biopsy and development of de novo donor-specific antibodies. Tacrolimus trough levels along the first year were not different between groups (12-mo levels were 8.72 ± 2.93 and 7.85 ± 3.07 ng/mL for MPA and mTORi group respectively, P = 0.277). This single-center retrospective cohort analysis suggests that in hypersensitized kidney transplant recipients receiving tacrolimus-based immunosuppressive therapy similar clinical outcomes may be obtained using mTOR inhibitors compared to mycophenolate.
Sections du résumé
BACKGROUND
It is commonly believed that mTOR inhibitors (mTORi) should not be used in high-immunological risk kidney transplant recipients due to a perceived increased risk of rejection. However, almost all trials that examined the association of optimal-dose mTORi with calcineurin inhibitor (CNI) have excluded hypersensitized recipients from enrollment.
METHODS
To shed light on this issue, we examined 71 consecutive patients with a baseline calculated panel reactive antibody (cPRA) ≥50% that underwent kidney transplantation from June 2013 to December 2016 in our unit. Immunosuppression was based on CNI (tacrolimus), steroids and alternatively mycophenolic acid (MPA; n = 38), or mTORi (either everolimus or sirolimus, n = 33, target trough levels 3-8 ng/mL).
RESULTS
Demographic and immunological risk profiles were similar, and almost 90% of patients in both groups received induction with lymphocyte-depleting agents. Cox-regression analysis of rejection-free survival revealed better results for mTORi versus MPA in terms of biopsy-proven acute rejection (hazard ratio [confidence interval], 0.32 [0.11-0.90], P = 0.031 at univariable analysis and 0.34 [0.11-0.95], P = 0.040 at multivariable analysis). There were no differences in 1-year renal function, Banff chronicity score at 3- and 12-month protocol biopsy and development of de novo donor-specific antibodies. Tacrolimus trough levels along the first year were not different between groups (12-mo levels were 8.72 ± 2.93 and 7.85 ± 3.07 ng/mL for MPA and mTORi group respectively, P = 0.277).
CONCLUSIONS
This single-center retrospective cohort analysis suggests that in hypersensitized kidney transplant recipients receiving tacrolimus-based immunosuppressive therapy similar clinical outcomes may be obtained using mTOR inhibitors compared to mycophenolate.
Identifiants
pubmed: 32732848
doi: 10.1097/TP.0000000000003021
pii: 00007890-202008000-00030
doi:
Substances chimiques
Calcineurin Inhibitors
0
Glucocorticoids
0
HLA Antigens
0
Immunosuppressive Agents
0
Isoantibodies
0
Everolimus
9HW64Q8G6G
MTOR protein, human
EC 2.7.1.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Mycophenolic Acid
HU9DX48N0T
Sirolimus
W36ZG6FT64
Tacrolimus
WM0HAQ4WNM
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1686-1694Références
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