Tremor induced by Calcineurin inhibitor immunosuppression: a single-centre observational study in kidney transplanted patients

Erro, Roberto; Bacchin, Ruggero; Magrinelli, Francesca; Tomei, Paola; Geroin, Christian; Squintani, Giovanna; Lupo, Antonio; Zaza, Gianluigi; Tinazzi, Michèle

doi:10.1007/s00415-018-8904-x

Cited by 20 publications

(24 citation statements)

References 19 publications

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“…However, we are unable to confirm the effects of phenoconversion on tacrolimus PK/PD because the approach to tacrolimus dose adjustments due to potential drug-drug interactions with strong and moderate CYP3A4/5 and P-gp inhibitors was inconsistent among our prescribers. Second, there was a lack of standardized documentation to fully evaluate tacrolimus-induced neurotoxicity, which often manifests as tremor [67][68][69]. Therefore, in our ongoing prospective CYP3A4/5-guided study, we have included tacrolimus-induced toxicities, including both neurotoxicity and nephrotoxicity, using the Common Terminology Criteria for Adverse Events v5.0 criteria [70] and comprehensive medication reconciliation to monitor for new prescriptions, over-the-counter medications, and herbal supplements, as well as relevant dose changes to those medications and products.…”

Section: Discussionmentioning

confidence: 99%

Influence of Germline Genetics on Tacrolimus Pharmacokinetics and Pharmacodynamics in Allogeneic Hematopoietic Stem Cell Transplant Patients

Zhu

Patel

Miller

et al. 2020

IJMS

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Tacrolimus exhibits high inter-patient pharmacokinetics (PK) variability, as well as a narrow therapeutic index, and therefore requires therapeutic drug monitoring. Germline mutations in cytochrome P450 isoforms 4 and 5 genes (CYP3A4/5) and the ATP-binding cassette B1 gene (ABCB1) may contribute to interindividual tacrolimus PK variability, which may impact clinical outcomes among allogeneic hematopoietic stem cell transplantation (HSCT) patients. In this study, 252 adult patients who received tacrolimus for acute graft versus host disease (aGVHD) prophylaxis after allogeneic HSCT were genotyped to evaluate if germline genetic variants associated with tacrolimus PK and pharmacodynamic (PD) variability. Significant associations were detected between germline variants in CYP3A4/5 and ABCB1 and PK endpoints (e.g., median steady-state tacrolimus concentrations and time to goal tacrolimus concentration). However, significant associations were not observed between CYP3A4/5 or ABCB1 germline variants and PD endpoints (e.g., aGVHD and treatment-emergent nephrotoxicity). Decreased age and CYP3A5*1/*1 genotype were independently associated with subtherapeutic tacrolimus trough concentrations while CYP3A5*1*3 or CYP3A5*3/*3 genotypes, myeloablative allogeneic HSCT conditioning regimen (MAC) and increased weight were independently associated with supratherapeutic tacrolimus trough concentrations. Future lines of prospective research inquiry are warranted to use both germline genetic and clinical data to develop precision dosing tools that will optimize both tacrolimus dosing and clinical outcomes among adult HSCT patients.

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Section: Discussionmentioning

confidence: 99%

Influence of Germline Genetics on Tacrolimus Pharmacokinetics and Pharmacodynamics in Allogeneic Hematopoietic Stem Cell Transplant Patients

Zhu

Patel

Miller

et al. 2020

IJMS

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“…Tremor (47), diarrhea and nausea, increased risk of infections and hypertension. Lower glucose tolerance and post-transplant diabetes mellitus.…”

Section: Corticosteroids: Prednisolon®mentioning

confidence: 99%

Identifying Core Variables Associated With Health Literacy in Kidney Transplant Recipients

et al. 2020

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Background: A kidney transplantation requires complex self-care skills and adequate follow-up from health-care providers. Identifying strengths and limitations in different aspects of health literacy (HL) and associated variables are central to being able to improve health care. The objective of this study was to identify core variables associated with independent domains of HL 8 weeks following a kidney transplantation. Methods: A single-center cross-sectional study was conducted, wherein 159 kidney transplant recipients answered the Health Literacy Questionnaire (HLQ). Multivariable linear regression with backward elimination was used to investigate variables possibly associated with the 9 domains of HL. Results: The transplant recipients had the lowest scores in “appraisal of health information” and “navigating the healthcare system.” The highest scores were found in “feeling understood and supported by health-care providers” and “ability to actively engage with health-care provider.” General perceived self-efficacy, transplant-specific knowledge, and general health were the driving variables in several of the HL domains. Conclusions: The HLQ provides a more complex picture of strengths and limitations related to HL, as well as important knowledge about vulnerable groups following a kidney transplantation. The study offers an important supplement to the field of HL in kidney transplant care.

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“…CsA. In a more recent trial, less than 20% of patients treated with CsA experienced tremors, while tacrolimus-related neurotoxic events occurred in up to 40% of patients [42]. In general, tremors involved both upper and lower limbs, with some patients even experiencing tremors in the head/facial muscles.…”

Section: Classification Of Immunosuppressantsmentioning

confidence: 99%

Recent Topics on the Mechanisms of Immunosuppressive Therapy-Related Neurotoxicities

Zhang¹,

Egashira²,

Masuda³

2019

Preprint

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Although transplantation procedures have been developed for patients with end-stagec hepatic insufficiency or other diseases, allograft rejection still threatens patient health and lifespan. Over the last few decades, the emergence of immunosuppressive agents, such as calcineurin inhibitors (CNIs) and mammalian target of rapamycin (mTOR) inhibitors, have strikingly increased graft survival. Unfortunately, immunosuppressive agent-related neurotoxicity is commonly occurred in clinical situations, with the majority of neurotoxicity cases caused by CNIs. The possible mechanisms whereby CNIs cause neurotoxicity include: increasing the permeability or injury of the blood-brain barrier, alterations of mitochondrial function, and alterations in electrophysiological state. Other immunosuppressants can also induce neuropsychiatric complications. For example, mTOR inhibitors induce seizures; mycophenolate mofetil induces depression and headache; methotrexate affects the central nervous system; mouse monoclonal immunoglobulin G2 antibody against cluster of differentiation 3 also induces headache; and patients using corticosteroids usually experience cognitive alteration. Therapeutic drug monitoring, individual therapy based on pharmacogenetics, and early recognition of symptoms have greatly reduced neurotoxic events. Once neurotoxicity occurs, a reduction in the drug dosage, switching to other immunosuppressants, using drugs to treat the neuropsychiatric manifestation, or blood purification therapy have proven to be effective against neurotoxicity. In this review, we summarize the recent topics on the mechanisms of neurotoxicity of immunosuppressive drugs. In addition, some information about neuroprotective effects of several immunosuppressants are also discussed.

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Tremor induced by Calcineurin inhibitor immunosuppression: a single-centre observational study in kidney transplanted patients

Cited by 20 publications

References 19 publications

Influence of Germline Genetics on Tacrolimus Pharmacokinetics and Pharmacodynamics in Allogeneic Hematopoietic Stem Cell Transplant Patients

Influence of Germline Genetics on Tacrolimus Pharmacokinetics and Pharmacodynamics in Allogeneic Hematopoietic Stem Cell Transplant Patients

Identifying Core Variables Associated With Health Literacy in Kidney Transplant Recipients

Recent Topics on the Mechanisms of Immunosuppressive Therapy-Related Neurotoxicities

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