Prevention of calcineurin inhibitor nephrotoxicity in renal transplantation

Jacquet, Antoine; François, H.; Frangié, C.; Ahmad, Lama; Charpentier, B; Dürrbach, Antoine

doi:10.1016/j.trim.2008.09.002

Cited by 17 publications

(11 citation statements)

References 37 publications

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“…General aspiration to under-immunosuppression because of potential side effects may pose a danger and it should be brought to the physician's attention. Prevention of CNI nephrotoxicity in renal transplantation (CNI withdrawal, CNI minimization regimens, or CNI-free protocols [19]) should be used very carefully with monitoring of DSA to avoid AMR lesions.…”

Section: Discussionmentioning

confidence: 99%

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A Significant Role for Anti–Human Leukocyte Antigen Antibodies and Antibody-Mediated Rejection in the Biopsy-for-Cause Population

Banasik

Kościelska‐Kasprzak

Márta

et al. 2014

Transplantation Proceedings

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Section: Discussionmentioning

confidence: 99%

“…The second is underimmunosuppression used to avoid CNI-induced toxicity, which appears as the nonspecific hyalinosis and fibrosis in late biopsy specimens [15]. It may stimulate clinicians to minimize immunosuppression, which is a mistaken action in case of anti-HLA activity [19].…”

mentioning

confidence: 99%

A Significant Role for Anti–Human Leukocyte Antigen Antibodies and Antibody-Mediated Rejection in the Biopsy-for-Cause Population

Banasik

Kościelska‐Kasprzak

Márta

et al. 2014

Transplantation Proceedings

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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%

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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“…Several strategies have been proposed to address this problem. Dose reduction is one of the strategies that has been evaluated by clinicians along with using other agents such as sirolomus or everolimus, which are found to be effective in improving long-term effects in renal transplant cases 17,18 .Several formulations have been investigated to improve the aqueous solubility of TAC, enhance its efficacy, and reduce its toxicity [19][20][21][22][23] . Polymeric nanoparticles (NPs) are a promising effective alternative to traditional drug formulations.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Mitigation of Tacrolimus-Associated Nephrotoxicity by PLGA Nanoparticulate Delivery Following Multiple Dosing to Mice while Maintaining its Immunosuppressive Activity

Alshamsan

Binkhathlan

Kalam

et al. 2020

Sci Rep

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the aim of this study was to assess the ability of pLGA nanoparticles (nps) to reduce the tacrolimus (tAc)-associated nephrotoxicity following multiple dose administration. the mean diameter of prepared NPs was in the range of 227 to 263 nm with an 8.32% drug loading (w/w). Moreover, in vitro release profile of TAC-loaded NPs showed a sustained release of the drug with only less than 30% release within 12 days. Flow cytometry as well as fluorescence microscopy results confirmed the uptake of FITClabelled pLGA nps by dendritic cells. the ex vivo study showed that TAC-loaded NPs caused a significant suppression of the proliferation of CD4 + and CD8 + cells, which was comparable to the control formulation (prograf). In vivo immunosuppressive activity as well as the kidney function were assessed following drug administration to mice. The animals received TAC subcutaneously at a daily dose of 1 mg/kg for 30 days delivered as the control formulation (Prograf) or TAC-loaded NPs. The results revealed significantly lower drug-associated toxicity with an activity comparable to prograf for tAc-loaded pLGA nps. these findings show a potential for PLGA NPs in reducing the nephrotoxicity of TAC while preserving the immunosuppressive activity.Tacrolimus is a potent immunosuppressive agent used clinically to reduce the risk of graft rejection in post-operative transplants patients 1-3 . It acts by suppressing interleukin-2 (IL-2) production in T-cells 4 , and also by inhibiting phosphatase activity of calcineurin through binding to the intracellular immunophilin FKBP-12 5 . The currently available intravenous formulation of TAC (Prograf) contains HCO-60 (PEGylated castor oil) as a surfactant, which is reported to cause several side effects including hypersensitivity reactions 6-8 . TAC is available in oral dosage forms including immediate release capsules (Prograf), extended release capsules (Astagraf XL and Advagraf), and extended release tablets (Envarsus XR). Several adverse effects have been reported with the use of TAC including hypertension, pruritus, leucocytosis, neurotoxicity, nephrotoxicity, cardiotoxicity and hepatotoxicity [9][10][11][12][13] . open Scientific RepoRtS | (2020) 10:6675 | https://doi.org/10.1038/s41598-020-63767-1 www.nature.com/scientificreports www.nature.com/scientificreports/ Drug-induced nephrotoxicity is the major dose-limiting side effect of TAC with a reported overall incidence as high as 44% 14 . Unfortunately, nephrotoxicity can lead to severe complications such as negative impact on graft survival and life expectancy of the patients. Indeed, nephrotoxic effects present challenges during therapeutic regimen with these drugs 15,16 . Several strategies have been proposed to address this problem. Dose reduction is one of the strategies that has been evaluated by clinicians along with using other agents such as sirolomus or everolimus, which are found to be effective in improving long-term effects in renal transplant cases 17,18 .Several formulations have been investigated to improve the aqueous ...

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Prevention of calcineurin inhibitor nephrotoxicity in renal transplantation

Cited by 17 publications

References 37 publications

A Significant Role for Anti–Human Leukocyte Antigen Antibodies and Antibody-Mediated Rejection in the Biopsy-for-Cause Population

A Significant Role for Anti–Human Leukocyte Antigen Antibodies and Antibody-Mediated Rejection in the Biopsy-for-Cause Population

Metabolic Drug Interactions with Immunosuppressants

Mitigation of Tacrolimus-Associated Nephrotoxicity by PLGA Nanoparticulate Delivery Following Multiple Dosing to Mice while Maintaining its Immunosuppressive Activity

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