A Randomized Trial Comparing Renal Function in Older Kidney Transplant Patients Following Delayed Versus Immediate Tacrolimus Administration

Andrés, Amado; Budde, Klemens; Clavien, Pierre‐Alain; Becker, Thomas; Kessler, Michèle; Pisarski, Przemyslaw; Fornara, Paolo; Burmeister, Dirk; Hené, Ronald J.; Cassuto‐Viguier, E.

doi:10.1097/tp.0b013e3181ba06ee

Cited by 47 publications

(28 citation statements)

References 28 publications

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“…Total CNI avoidance, 3,5,9 -38 CNI minimization, 17,39 -55 and delayed introduction of CNI 49,50,[55][56][57][58][59][60][61][62] were investigated in 32 (n ϭ 5791), 17 (n ϭ 4131), and 10 studies (n ϭ 1519) respectively. Two studies 50,55 investigated CNI delay followed by minimization: to avoid "double counting" these were analyzed as "delay" studies initially, but if subgroup analyses were necessary (due to heterogeneity), then the same study was considered separately in both the "minimization" and "delay" subanalyses.…”

Section: Resultsmentioning

confidence: 99%

Meta-Analysis of Calcineurin-Inhibitor-Sparing Regimens in Kidney Transplantation

Sharif

Shabir

Chand

et al. 2011

Journal of the American Society of Nephrology

127

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Calcineurin-inhibitor-sparing strategies in kidney transplantation may spare patients the adverse effects of these drugs, but the efficacy of these strategies is unknown. Here, we conduct a meta-analysis to assess outcomes associated with reducing calcineurin inhibitor exposure from the time of transplantation. We search Medline, Embase, and Cochrane Register of Controlled Trials for randomized controlled trials published between 1966 and 2010 that compared de novo calcineurin-inhibitor-sparing regimens to calcineurin-inhibitor-based regimens. In this analysis, we include 56 studies comprising data from 11337 renal transplant recipients. Use of the contemporary agents belatacept or tofacitinib, in combination with mycophenolate, decreased the odds of overall graft failure (OR 0.61; 95% CI 0.39 -0.96; P ϭ 0.03). Similarly, minimization of calcineurin inhibitors in combination with various induction and adjunctive agents reduces the odds of graft failure (OR 0.73; 95% CI 0.58 -0.92; P ϭ 0.009). Conversely, the use of inhibitors of mammalian target of rapamycin (mTOR), in combination with mycophenolate, increases the odds of graft failure (OR 1.43; 95% CI 1.08 -1.90; P ϭ 0.01). Calcineurin-inhibitor-sparing strategies are associated with less delayed graft function (OR 0.89; 95% CI 0.80 -0.98; P ϭ 0.02), improved graft function, and less new-onset diabetes. The more contemporary protocols did not seem to increase rates of acute rejection. In conclusion, this meta-analysis suggests that reducing exposure to calcineurin inhibitors immediately after kidney transplantation may improve clinical outcomes.

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Section: Resultsmentioning

confidence: 99%

Meta-Analysis of Calcineurin-Inhibitor-Sparing Regimens in Kidney Transplantation

Sharif

Shabir

Chand

et al. 2011

Journal of the American Society of Nephrology

127

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“…They found that tacrolimus troughs were significantly lower day 5 and 7 post transplant in patients with ACR within the first 3 months than those that had no episodes of rejection ( P = 0.009, 0.006) . Delaying tacrolimus in the setting of basiliximab induction had no effect on ACR or DGF in a randomized controlled trial conducted by Andres and colleagues, however ( n = 132, each group) . Barraclough and colleagues demonstrated a significant increase in ACR within the first month post transplant in patients in the lowest tertile of drug exposure POD#4 (as measured by AUC) to combined cellcept, prednisone and tacrolimus vs. the remainder of patients in the middle and highest tertiles of exposure ( P = 0.001).…”

Section: Induction To Facilitate Calcineurin Inhibitor Minimizationmentioning

confidence: 98%

Induction immunosuppression in liver transplantation: a review

Turner

Knechtle

2013

Transpl Int

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Summary Antibody therapy for induction is seldom used in liver transplantation in the United States, but continues to be used in approximately 10% of patients. The most commonly used antibody at the current time is basiliximab (Simulect, Novartis) and is used in adults with renal dysfunction at the time of liver transplantation with the intention of delaying introduction of calcineurin‐inhibitors. In children, the same antibody is commonly used in order to reduce rates of acute rejection. Most patients, adult and pediatric, are treated with initially higher levels of tacrolimus rather than antibody induction.

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“…When addressing chronic immunosuppression, there is receding evidence to support delayed introduction, avoidance or withdrawal of calcineurin inhibitors (CNI). CNIs have recognized vasoconstrictive properties and their discontinuation in presence of DGF appears intuitive but may be nonbeneficial or even harmful (184,185). Recently, 254 patients, on average age 66 years old, were enrolled in a randomized open label trial to study early posttransplant tacrolimus dosing strategies (169).…”

Section: Treating Dgfmentioning

confidence: 99%

Delayed Graft Function in the Kidney Transplant

Siedlecki

Irish

Brennan

2011

American Journal of Transplantation

654

563

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Acute kidney injury occurs with kidney transplantation and too frequently progresses to the clinical diagnosis of delayed graft function (DGF). Poor kidney function in the first week of graft life is detrimental to the longevity of the allograft. Challenges to understand the root cause of DGF include several pathologic contributors derived from the donor (ischemic injury, inflammatory signaling) and recipient (reperfusion injury, the innate immune response, and the adaptive immune response). Progressive demand for renal allografts has generated new organ categories which continue to carry high risk for DGF for deceased donor organ transplantation. New therapies seek to subdue the inflammatory response in organs with high likelihood to benefit from intervention. Future success in suppressing the development of DGF will require a concerted effort to anticipate and treat tissue injury throughout the arc of the transplantation process.

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A Randomized Trial Comparing Renal Function in Older Kidney Transplant Patients Following Delayed Versus Immediate Tacrolimus Administration

Abstract: Delayed tacrolimus with basiliximab induction did not provide an advantage in preserving renal function or reducing delayed graft function in older kidney transplant patients.

Cited by 47 publications

References 28 publications

Meta-Analysis of Calcineurin-Inhibitor-Sparing Regimens in Kidney Transplantation

Meta-Analysis of Calcineurin-Inhibitor-Sparing Regimens in Kidney Transplantation

Induction immunosuppression in liver transplantation: a review

Delayed Graft Function in the Kidney Transplant

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