Calcineurin inhibitors in HLA-identical living related donor kidney transplantation

Verghese, Priya S.; Dunn, Ty B.; Chinnakotla, Srinath; Gillingham, K.; Matas, Arthur J.; Mauer, Michael

doi:10.1093/ndt/gft447

Cited by 20 publications

(20 citation statements)

References 24 publications

(31 reference statements)

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“…There was no difference in patient and graft survival between those who did receive CNIs, with a trend toward higher rates of chronic allograft nephropathy in CNI-exposed patients, leading to the conclusion that CNI maintenance was not warranted in this patient population. 25 Our study confirms these earlier findings by showing that CNIs can be withdrawn in white recipients of 2-haplotype matched living related kidneys, but extends these findings by further showing that this privileged group of patients do not require induction therapy. This is an important observation with implications for the immunosuppressive management and overall costs of care for these patients.…”

Section: Discussionsupporting

confidence: 90%

The Privilege of Induction Avoidance and Calcineurin Inhibitors Withdrawal in 2 Haplotype HLA Matched White Kidney Transplantation

Brifkani

Brennan

Lentine

et al. 2017

Transplantation Direct

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BackgroundWhite recipients of 2-haplotype HLA-matched living kidney transplants are perceived to be of low immunologic risk. Little is known about the safety of induction avoidance and calcineurin inhibitor withdrawal in these patients.MethodsWe reviewed our experience at a single center and compared it to Organ Procurement and Transplantation Network (OPTN) registry data and only included 2-haplotype HLA-matched white living kidney transplants recipients between 2000 and 2013.ResultsThere were 56 recipients in a single center (where no induction was given) and 2976 recipients in the OPTN. Among the OPTN recipients, 1285 received no induction, 903 basiliximab, 608 thymoglobulin, and 180 alemtuzumab. First-year acute rejection rates were similar after induction-free transplantation among the center and induced groups nationally. Compared with induction-free transplantation in the national data, there was no decrease in graft failure risk over 13 years with use of basiliximab (adjusted hazard ratio [aHR], 0.86; confidence interval [CI], 0.68-1.08), Thymoglobulin (aHR, 0.92; CI, 0.7-1.21) or alemtuzumab (aHR, 1.18; CI, 0.72-1.93). Among induction-free recipients at the center, calcineurin inhibitor withdrawal at 1 year (n = 27) did not significantly impact graft failure risk (HR,1.62; CI, 0.38-6.89).ConclusionsThis study may serve as a foundation for further studies to provide personalized, tailored, immunosuppression for this very low-risk population of kidney transplant patients.

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Section: Discussionsupporting

confidence: 90%

The Privilege of Induction Avoidance and Calcineurin Inhibitors Withdrawal in 2 Haplotype HLA Matched White Kidney Transplantation

Brifkani

Brennan

Lentine

et al. 2017

Transplantation Direct

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“…But, were permanent IS to continue significant morbidity and mortality would occur even in the modern era (16). That regulatory T cells might play a predominant role in HLA identity is not surprising, given the receptive environment in which they can act (17, 18).…”

Section: Discussionmentioning

confidence: 99%

Nonchimeric HLA-Identical Renal Transplant Tolerance: Regulatory Immunophenotypic/Genomic Biomarkers

Leventhal

Mathew

Salomon³

et al. 2016

American Journal of Transplantation

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We previously described early results of a non-chimeric operational tolerance protocol in HLA identical living donor renal transplants and now update these results. Recipients given alemtuzumab, tacrolimus/MPA with early sirolimus conversion were multiply infused with donor hematopoietic CD34+ stem cells. Immunosuppression was withdrawn by 24 months. Twelve months later operational tolerance was confirmed by rejection-free transplant biopsies. Five of the first 8 enrollees were initially tolerant one year off immunosuppression. Biopsies of 3 others after total withdrawal showed Banff 1A acute cellular rejection without renal dysfunction. With longer follow-up including 5 year post-transplant biopsies 4 of the 5 tolerant recipients remain without rejection while one developed Banff 1A without renal dysfunction. We now add 7 new subjects (2 operationally tolerant), and demonstrate time-dependent increases of circulating CD4+CD25+++CD127−FOXP3+ Tregs vs. losses of Tregs in non-tolerant subjects (p< 0.001). Gene expression signatures, developed using global RNA expression profiling of sequential whole blood and protocol biopsy samples, were highly associative with operational tolerance as early as 1 year post-transplant. The blood signature was validated by an external ITN data set. Our approach to non-chimeric operational HLA identical tolerance reveals association with Treg immunophenotypes and serial gene expression profiles.

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“…Some studies reported superior outcomes when calcineurin inhibitors were added, 7,8 while others indicated it might not be needed. [9][10][11] The subjects in this group had lower rates of acute rejection (10%), although few were on induction therapy and none took calcineurin inhibitors due to service protocol restrictions.…”

Section: Discussionmentioning

confidence: 99%

Different induction therapies for kidney transplantation with living donor

Nga¹,

Garcia²,

Contti³

et al. 2015

Jornal Brasileiro De Nefrologia

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Calcineurin inhibitors in HLA-identical living related donor kidney transplantation

Abstract: This study confirmed that there are no benefits of CNIs for HLA-identical LRD recipients. Moreover, we did find evidence of potential harm. Thus, monotherapy or early discontinuation of CNI should be given consideration in these patients.

Cited by 20 publications

References 24 publications

The Privilege of Induction Avoidance and Calcineurin Inhibitors Withdrawal in 2 Haplotype HLA Matched White Kidney Transplantation

The Privilege of Induction Avoidance and Calcineurin Inhibitors Withdrawal in 2 Haplotype HLA Matched White Kidney Transplantation

Nonchimeric HLA-Identical Renal Transplant Tolerance: Regulatory Immunophenotypic/Genomic Biomarkers

Different induction therapies for kidney transplantation with living donor

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