Low-Dose Calcineurin Inhibitor Regimen Combined With Mammalian Target of Rapamycin Inhibitors Preserves Kidney Functions in Renal Transplant Recipients Without Allograft Nephropathy

Kaçar, Serdar; Gürkan, Alp; Karaca, Cezmi; Varılsüha, Can; Tilif, S.

doi:10.1016/j.transproceed.2010.08.043

Cited by 7 publications

(4 citation statements)

References 31 publications

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“…Although the chemical structures of sirolimus and everolimus are similar to that of tacrolimus, the mechanism of action of mTOR inhibitors is distinct from calcineurin inhibitors, which allows the application of combination regimens. Additionally, the main advantages of mTOR inhibitors are their nonnephrotoxic properties; therefore, mTOR inhibitors in combination with reduced dose calcineurin inhibitors can augment the calcineurin inhibitor-induced nephrotoxicity [43][44][45].…”

Section: Mtor (Mammalian Target Of Rapamycin) Inhibitorsmentioning

confidence: 99%

“…The major drawback of calcineurin inhibitor therapy is the risk of nephrotoxicity which appears to be dose dependent. The combination of low calcineurin inhibitor doses with mTOR inhibitors was found to be beneficial regarding retaining low rejection rates and lowering the risk of nephrotoxicity [44,63]. To avoided renal dysfunction, the complete substitution of calcineurin inhibitors for mTOR inhibitors was attempted; however, the substitution showed an increase in graft failure in patients treated with merely mTOR inhibitors [64].…”

Section: Combined Immunosuppressive Therapymentioning

confidence: 99%

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Metabolic Drug Interactions with Immunosuppressants

Monostory¹

2018

Organ Donation and Transplantation - Current Status and Future Challenges

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Organ transplantation has become a routine clinical practice for patients with endstage disease of liver, kidney, heart, or lung. Although improved immunosuppressant therapy substantially contributes to the success of transplantation, clinicians continue to face challenges because of wide interindividual variations in blood concentrations resulting in subtherapeutic or supratherapeutic levels. Many undesired side-effects or therapeutic failure of immunosuppressants as a consequence are the results of differences or changes in drug metabolism. Considering genetic and nongenetic factors, such as co-medication, can refine the immunosuppressant therapy, facilitating personalized treatments to individual recipients. This review provides an up-to-date summary of functional polymorphisms of enzymes involved in the metabolism of immunosuppressants with low molecular weight and of the clinical significance of metabolic drug interactions between immunosuppressive agents and other drugs in therapeutic regimens of transplant recipients.

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Section: Mtor (Mammalian Target Of Rapamycin) Inhibitorsmentioning

confidence: 99%

Section: Combined Immunosuppressive Therapymentioning

confidence: 99%

Metabolic Drug Interactions with Immunosuppressants

Monostory¹

2018

Organ Donation and Transplantation - Current Status and Future Challenges

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“…Everolimus is used as an immunosuppressive drug to prevent allograft rejection. mTOR‐inhibitors are increasingly used in immunosuppressive regimens after organ transplantation due to the unfavourable nephrotoxicity profile of another class of immunosuppressive drugs, the calcineurin inhibitors . For prophylaxis of allograft rejection with everolimus in a calcineurin‐free regimen, the consensus therapeutic drug monitoring (TDM) target is a trough level of 6–10 μg l –1 .…”

Section: Introductionmentioning

confidence: 99%

A pharmacological rationale for improved everolimus dosing in oncology and transplant patients

Heine

Erp

Guchelaar

et al. 2018

Brit J Clinical Pharma

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“…Furthermore, EVR per se has recently been shown to decrease the risk of BKV viremia in de novo renal ABO‐compatible transplant recipients compared with MPA . In addition, recent studies indicate that immunosuppressive regimens that include an mTor inhibitor as well as minimizing Tac could preserve renal function better than standard‐dose Tac given to ABO‐compatible kidney‐transplant recipients.…”

Section: Introductionmentioning

confidence: 99%

Pilot conversion trial from mycophenolic acid to everolimus in ABO-incompatible kidney-transplant recipients with BK viruria and/or viremia

et al. 2015

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SummaryImmunosuppression using everolimus (EVR) plus low-dose tacrolimus (Tac) is commonly used in organ transplantation. EVR has potential antiviral effects. Herein, the long-term outcomes and impacts of Tac-EVR on the BK virus are reported in ABO-incompatible kidney-transplant recipients. The initial immunosuppressive regimen combined steroids, Tac, and mycophenolic acid (MPA). At a median of 141 (34-529) days post-transplantation, seven stable ABO-incompatible kidney-transplant recipients were converted from MPA to EVR because of active BK replication, and compared with a reference group of fourteen ABOincompatible patients receiving classical Tac plus MPA. At 1 month before conversion, at 1, 3 months after, and at last follow-up, clinical and biological parameters were monitored. The median time from conversion to the last follow-up was 784 (398-866) days. Conversion to EVR caused no change to rejection episodes or immunological status (isoagglutinin titers, anti-HLA antibodies). At last follow-up, median eGFR was similar in the Tac-MPA versus vs. 54.5 ml/min/1.73 m 2 [range: 0-128], P = 0.07). The major adverse event was dyslipidemia. Interestingly, conversion from MPA to EVR decreased BK viral load in five patients. ABO-incompatible kidney-transplant recipients with an active BK virus infection may benefit from conversion to EVR.

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Low-Dose Calcineurin Inhibitor Regimen Combined With Mammalian Target of Rapamycin Inhibitors Preserves Kidney Functions in Renal Transplant Recipients Without Allograft Nephropathy

Cited by 7 publications

References 31 publications

Metabolic Drug Interactions with Immunosuppressants

Metabolic Drug Interactions with Immunosuppressants

A pharmacological rationale for improved everolimus dosing in oncology and transplant patients

Pilot conversion trial from mycophenolic acid to everolimus in ABO-incompatible kidney-transplant recipients with BK viruria and/or viremia

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