Randomized Trial of Immunosuppressive Regimens in Renal Transplantation

Guerra, Giselle; Ciancio, Gaetano; Gaynor, Jeffrey J.; Zarak, Alberto; Brown, R. W.; Hanson, Lois; Sageshima, Junichiro; Roth, David; Chen, Linda; Kupin, Warren; Tueros, Lissett; Ruiz, Phillip; Livingstone, Alan S.; Burke, George W.

doi:10.1681/asn.2011010006

Cited by 72 publications

(71 citation statements)

References 28 publications

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“…This is similar to findings in some other studies, a few of which had similar methodology to ours. [6,13] Several further studies, however, report a significantly greater role for tacrolimus in the causation of NODAT. [9,12] Our finding may reflect the relatively small number of patients who received tacrolimus compared with cyclosporine in our cohort.…”

Section: Researchmentioning

confidence: 99%

New-onset diabetes after transplant: Incidence, risk factors and outcome

et al. 2017

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Background. The outcome of renal transplantation depends on achieving effective immunosuppression while minimising the consequences of such treatment. The occurrence of new-onset diabetes in the post-transplant period has been associated with several risk factors including some immunosuppressive medication. Better understanding of the clinical and genetic risk factors associated with new-onset diabetes after transplant (NODAT) could enable risk stratification of patients in the pre-transplant period, with the goal of applying measures that will reduce the incidence. Objectives. To ascertain the incidence of and clinical and genetic risk factors that predispose to NODAT, and to examine its effect on the outcome of renal transplantation. Methods. We performed a retrospective cohort review of all renal transplants at Groote Schuur Hospital, Cape Town, South Africa, between 2004 and 2008. Patients who were lost to follow-up or had pre-transplant diabetes or primary non-function were excluded. A subset of the cohort who gave informed consent was enlisted for genetic tests. Results. We identified 111 patients who met the inclusion criteria. The incidence of NODAT was 18.0% (n=20 patients). Risk factors for NODAT included age at transplant (p=0.03), body weight (p=0.04), treatment for acute cellular rejection (p=0.02) and polycystic kidney disease as the cause of renal failure (p=0.005). None of the genes investigated (TCF7L2 rs11196205, rs12255372 and rs7903146 and HNF1β rs1800575, rs121918671 and rs121918672) was found to be significantly associated with the risk of NODAT. The genotype frequencies for the single-nucleotide polymorphisms studied were closer (although not identical) to those reported for Caucasians than to those reported for the Yoruba (black) population in West Africa. Overall patient survival was 78% at five years, while graft survival was 72%. There was no significant difference in patient or graft survival between the group with NODAT and the group without. Conclusions. NODAT was common in renal transplant recipients. Some risk factors predate transplant and could be used to risk-stratify patients to determine appropriate risk-reduction strategies. The genetic determinants for NODAT in this population may differ from those reported elsewhere. NODAT had no impact on patient or graft survival in this cohort.

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Section: Researchmentioning

confidence: 99%

New-onset diabetes after transplant: Incidence, risk factors and outcome

et al. 2017

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“…57 A randomized control trial by Guerra and associates suggested maintenance therapy with tacrolimus-MMF was more favorable than either tacrolimus-sirolimus or cyclosporinesirolimus. 58 To address the question regarding whether nephrotoxicity is an issue with tacrolimus, Ekberg and associates pooled data from 3 large randomized de novo RT studies (Symphony, Fixed-Dose concentration controlled, and OptiCept) and explored the relations of renal function at 1 year after RT (estimated GFR) with tacrolimus levels and MMF dose measured over the previous 6 months. Lower tacrolimus levels and higher MMF doses were associated with significantly better renal function.…”

Section: Rescue Therapymentioning

confidence: 99%

Untitled

Shrestha

2017

Exp Clin Transplant

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Tacrolimus, a calcineurin inhibitor, has been the cornerstone of immunosuppressive regimens in renal transplant over 2 decades. This has significantly improved the outcomes of renal transplant, including reduction of acute rejection episodes, improvement of renal function and graft survival, and reduction of some of the adverse effects associated with cy closporine. However, use of tacrolimus is associated with a number of undesirable effects, such as nephrotoxicity, posttransplant diabetes mellitus, neurotoxicity, and cosmetic and electrolyte disturbances. To alleviate these effects, several strategies have been adopted to minimize or eliminate tacrolimus from maintenance regimens of immuno suppression, with some success. This review focuses on advancements in the under standing of the basic science related to tacrolimus and the clinical evidences that have examined the efficacy and safety of tacrolimus in renal transplant over the past 2 decades and highlights the future directions.

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“…Therefore, concentration monitoring has been needed to prevent rejection and toxicity risk. Limited studies have been done so far to assess the transplant outcomes with an mTOR inhibitor-based initial regimen with CNI minimization, with the notable ones being the ASSET study (2012) [22][23][24][25][26][27][28][29] In 2012, Langer and associates in their ASSET study compared de novo introduction of very-lowdose tacrolimus (1.5-3 ng/mL) and everolimus (3-8 ng/mL) with low-dose tacrolimus (1.5-3 ng/mL) and everolimus (3-8 ng/mL). These have been used in a combination with oral steroids following basiliximab induction in renal transplant patients.…”

Section: Mammalian Target Of Rapamycin-based Initial Regimen With Lowmentioning

confidence: 99%

Untitled

Jayant

Bridson

Sharma³

et al. 2017

Exp Clin Transplant

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Objectives: This review focuses on the current limited evidence of graft function and graft survival in various immunosuppressive regimens involving mammalian target of rapamycin inhibitors with or without calcineurin inhibitors. Materials and Methods: We evaluated the current literature for describing the role of mammalian target of rapamycin inhibitors as an alternative to calcineurin inhibitors by searching the PubMed, EMBASE, Cochrane, Crossref, and Scopus databases using medical subject heading terms. Results: Our detailed analyses of all relevant literature showed use of mammalian target of rapamycin inhibitor-based de novo regimens, early calcineurin inhibitor withdrawal with subsequent introduction of mammalian target of rapamycin inhibitor-based regimens, and late conversion from a calcineurin inhibitor-based regimen to mammalian target of rapamycin inhibitor-based regimens. Notably, early calcineurin inhibitor withdrawal with subsequent introduction of mammalian target of rapamycin inhibitor-based regimen seemed to be a more practical and realistic approach toward immunosuppressive treatment of renal transplant recipients. However, in view of the high rejection rate observed in these studies, it is advisable not to offer these regimens to patients with moderate to high immunologic risk. Conclusions: The present evidences suggest that treatment with mammalian target of rapamycin inhibitors allows early and substantial calcineurin inhibitor minimization. The mammalian target of rapamycin inhibitors everolimus and sirolimus are preferred due to their complementary mechanisms of action and favorable nephrotoxicity profile, which have opened the way for calcineurin inhibitor reduction/withdrawal in the early posttransplant period.

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Randomized Trial of Immunosuppressive Regimens in Renal Transplantation

Cited by 72 publications

References 28 publications

New-onset diabetes after transplant: Incidence, risk factors and outcome

New-onset diabetes after transplant: Incidence, risk factors and outcome

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