Tacrolimus in pancreas transplant: a focus on toxicity, diabetogenic effect and drug–drug interactions

Rangel, Érika B.

doi:10.1517/17425255.2014.964205

Cited by 56 publications

(28 citation statements)

References 165 publications

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“…Interestingly, chronic mTOR inhibition disrupts the autophagic pathway in podocytes in vitro [43], and it has yet to be discovered at which dose and how long treatment with RP is detrimental or beneficial to promote podocyte autophagy flux in vivo . Nonetheless, RP is obviously unsuitable for CKD treatment due to its multiple side effects [44, 45] and its contradictory effect on autophagy flux in podocytes.…”

Section: Discussionmentioning

confidence: 99%

Role of FOXO1 in aldosterone-induced autophagy: A compensatory protective mechanism related to podocyte injury

Wang

Ding

et al. 2016

Oncotarget

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This study was undertaken to elucidate whether and how autophagy was regulated in aldosterone (Aldo)-induced podocyte injury and to examine its role in this model both in vitro and in vivo. In cultured podocytes, Aldo increased autophagy flux as indicated by the enhanced expression of LC3-II/LC3-I and the reduction of p62. Autophagy induction with rapamycin (RP) provided a cytoprotective effect, and inhibition of autophagy with Atg7-specific siRNA, chloroquine (CQ) or 3-methyladenine (3-MA) worsened Aldo-induced podocyte injury by attenuating endoplasmic reticulum (ER) stress. Aldo inhibited Akt phosphorylation but increased the mammalian target of rapamycin (mTOR) signaling pathway; however, Aldo up-regulated the expression of FOXO1 and its downstream effector Rab7. Either knockdown of FOXO1 or Rab7 inhibited Aldo-induced autophagy. Additionally, an elevated level of P300-regulated acetylation of FOXO1 and the interaction of acetylated FOXO1 and Atg7 were also confirmed to be involved in regulating autophagy in Aldo-induced podocytes. Similar results were further confirmed in vivo. We propose that autophagy enhancement through enhancing of the FOXO1/Rab7 axis and post-translational modification of FOXO1 may represent a potential therapeutic strategy against podocyte injury by promoting autophagy.

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Section: Discussionmentioning

confidence: 99%

Role of FOXO1 in aldosterone-induced autophagy: A compensatory protective mechanism related to podocyte injury

Wang

Ding

et al. 2016

Oncotarget

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“…Both calcineurin inhibitors are known to cause toxicity to pancreatic islet beta cells and may also directly affect transcriptional regulation of insulin expression (5). Evidence suggests that tacrolimus causes greater incidence of severe swelling-vacuolization, endoplasmic reticulum stress and apoptosis of pancreatic islet beta cells when compared to cyclosporine (8). Tacrolimus associated diabetogenic effects threaten the health and longevity of the allograft by predisposing the recipients to microvascular and macrovascular diabetic complications which subsequently reduce allograft survival.…”

Section: Discussionmentioning

confidence: 99%

Tacrolimus-associated diabetic ketoacidosis: a case report and literature review

Pak¹,

Hirschbeck²,

Valencia³

et al. 2018

Southwest J Pulm Crit Care

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Post-transplant diabetes mellitus is a well-established adverse effect of calcineurin inhibitors, such as tacrolimus and cyclosporine. Failure to identify and manage this side effect in a timely manner could lead to life-threatening complications like diabetic ketoacidosis (DKA). To the best of our knowledge, this is the seventh published case of an uncommon but severe, and potentially fatal, adverse effect from tacrolimus after renal transplantation. The purpose of this case report is to add to the scant body of literature on tacrolimus-induced diabetes following renal transplantation.

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“…Yet, numerous adverse drug effects are recognized, ranging from nephrologic and neurologic manifestations to hyperglycemia [10], myelodepression, hypertension or hyperkalemia. Since co-medication of CYP3A4 inhibitors or inducers effect tacrolimus levels, regular monitoring of blood levels is required [6].…”

Section: Introductionmentioning

confidence: 99%

Tacrolimus Suppositories in Therapy-Resistant Ulcerative Proctitis

et al. 2018

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Background: Ulcerative proctitis may often be managed with topical salicylates or steroids alone, but in some patients, symptoms are persistent and severe. We analyzed the efficacy of tacrolimus suppositories in patients who had proven refractory to combined topical and systemic treatment. Methods: In this retrospective analysis, ulcerative colitis activity index (CAI), side effects, co-medication and drug levels were assessed in 43 patients with distal ulcerative colitis who received suppositories containing 2 mg of tacrolimus b.i.d. as add-on medication. Results: A total of 23 patients with ulcerative proctitis presented to follow-up within ≤50 days (mean 27.0 days) after suppositories were started. A decrease in CAI (from 8.0 to 5.5 points) was observed and 52.3% reached clinical remission (CAI ≤4). In total, 43 patients were available for analysis, of whom 9 had inflammation of the sigmoid colon as well. For the entire cohort, the median treatment duration was 76 days; 60% were in remission on the last documented visit. Serum measurements revealed a substantial tacrolimus level with a mean of 5.5 ng/mL. We observed one case of mild reversible acute kidney injury. Conclusions: In ulcerative proctitis, adding tacrolimus suppositories can be an effective and safe option when topical mesalazine, corticoid formulations and concomitant oral or parenteral medications have failed.

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Tacrolimus in pancreas transplant: a focus on toxicity, diabetogenic effect and drug–drug interactions

Cited by 56 publications

References 165 publications

Role of FOXO1 in aldosterone-induced autophagy: A compensatory protective mechanism related to podocyte injury

Role of FOXO1 in aldosterone-induced autophagy: A compensatory protective mechanism related to podocyte injury

Tacrolimus-associated diabetic ketoacidosis: a case report and literature review

Tacrolimus Suppositories in Therapy-Resistant Ulcerative Proctitis

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