Immunosuppression-related neurological disorders in kidney transplantation

Faravelli, Irene; Velardo, Daniele; Podestà, Manuel Alfredo; Ponticelli, Claudio

doi:10.1007/s40620-020-00956-1

Cited by 19 publications

(16 citation statements)

References 108 publications

(113 reference statements)

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“…Tremor, burning paresthesia, headache, flushing, depression, confusion, and insomnia are dose-dependent and are more frequent and more severe with TAC compared to CsA. Convulsions, aphasia, paralysis, and disabling pain syndrome can also occur [ 45 ]. Other rare complications are hearing loss, tinnitus, or otalgia.…”

Section: Calcineurin Inhibitorsmentioning

confidence: 99%

Old and New Calcineurin Inhibitors in Lupus Nephritis

Ponticelli

Reggiani

Moroni

2021

JCM

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Calcineurin inhibitors (CNIs) are drugs that inhibit calcineurin, a key phosphatase that dephosphorylates a transcription factor called the nuclear factor of activated T cells (NFAT), allowing its translocation into the nucleus of quiescent T cells. In the nucleus, NFAT activates interleukin 2, which stimulates the proliferation and differentiation of T-cells. CNIs can also stabilize the actin cytoskeleton of podocytes reducing proteinuria. Thanks to these characteristics, CNIs have been often used in the treatment of autoimmune diseases. However, the therapeutic index of CNIs is narrow, and their interactions with other drugs can increase toxicity or reduce efficacy. In lupus nephritis, cyclosporine and tacrolimus have been used both in induction and maintenance therapies. Observational studies and randomized controlled trials showed that both cyclosporine and tacrolimus can increase efficacy. Tolerance is satisfactory if low doses are used and the patient is carefully monitored. More recently, a new CNI, called voclosporin (VCS), has been approved by the Food and Drug Administration for use in lupus nephritis. VCS offers potential advantages over other CNIs. In two large multiethnic trials, VCS was not associated with adverse renal and metabolic events and obtained positive results despite a novel and rapid corticosteroid tapering regime.

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Section: Calcineurin Inhibitorsmentioning

confidence: 99%

Old and New Calcineurin Inhibitors in Lupus Nephritis

Ponticelli

Reggiani

Moroni

2021

JCM

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“…Glucocorticoids easily pass the blood-brain barrier and reach all brain cells, which results in HPA axis suppression and neuropsychiatric and neurodegenerative side effects. Prolonged exposure to glucocorticoids in SOT patients and high GC doses and concentrations ( e.g ., during treatment of acute rejection) increase the risk of neuropsychiatric side effects because of structural remodeling in neurons, synoptic loss, and maladaptive alterations in glial function[ 118 ]. GCs cause different neurologic side effects, such as headache, tremor, seizure, stroke, and pseudotumor cerebri.…”

Section: Side Effectsmentioning

confidence: 99%

“…GCs cause different neurologic side effects, such as headache, tremor, seizure, stroke, and pseudotumor cerebri. GC-induced psychiatric adverse effects vary from minor mood changes and confusion, sleep disorders, anxiety to severe psychotic features[ 6 , 118 ].…”

Section: Side Effectsmentioning

confidence: 99%

Current status of glucocorticoid usage in solid organ transplantation

Dashti‐Khavidaki¹,

Saidi²,

Lü³

2021

WJT

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Glucocorticoids (GCs) have been the mainstay of immunosuppressive therapy in solid organ transplantation (SOT) for decades, due to their potent effects on innate immunity and tissue protective effects. However, some SOT centers are reluctant to administer GCs long-term because of the various related side effects. This review summarizes the advantages and disadvantages of GCs in SOT. PubMed and Scopus databases were searched from 2011 to April 2021 using search syntaxes covering “transplantation” and “glucocorticoids”. GCs are used in transplant recipients, transplant donors, and organ perfusate solution to improve transplant outcomes. In SOT recipients, GCs are administered as induction and maintenance immunosuppressive therapy. GCs are also the cornerstone to treat acute antibody- and T-cell-mediated rejections. Addition of GCs to organ perfusate solution and pretreatment of transplant donors with GCs are recommended by some guidelines and protocols, to reduce ischemia-reperfusion injury peri-transplant. GCs with low bioavailability and high potency for GC receptors, such as budesonide, nanoparticle-mediated targeted delivery of GCs to specific organs, and combination use of dexamethasone with inducers of immune-regulatory cells, are new methods of GC application in SOT patients to reduce side effects or induce immune-tolerance instead of immunosuppression. Various side effects involving different non-targeted organs/tissues, such as bone, cardiovascular, neuromuscular, skin and gastrointestinal tract, have been noted for GCs. There are also potential drug-drug interactions for GCs in SOT patients.

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“…Advanced age, diabetes, ototoxic drug use, and uremia can partially explain this situation; it is possible that the immunosuppressive drugs used, especially tacrolimus, may also have ototoxic effects. It is accepted that mTOR inhibitors do not have neurotoxicity ( 7 - 9 ). There are only a few studies in the literature investigating hearing problems in kidney transplant patients.…”

Section: Introductionmentioning

confidence: 99%