Glucocorticoids use in kidney transplant setting

Lucena, Débora D. de; Rangel, Érika B.

doi:10.1080/17425255.2018.1530214

Cited by 43 publications

(25 citation statements)

References 132 publications

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“…Compared with tacrolimus-MMF, the 12-month AR rate was only 0.5% higher for belatacept-sirolimus, but Like CNIs, corticosteroids are associated with systemic AEs, including dyslipidemia, diabetes, and cardiovascular events. 43 Therefore, CNI-and corticosteroid-free regimens are being sought for the long-term treatment of renal transplant recipients. In the above phase 2 trial (NCT00455013), 40 patients received only a 4-day corticosteroid course.…”

Section: Alternative Reg Imen: B El Atacep T Plus An Mtorimentioning

confidence: 99%

Optimization of de novo belatacept-based immunosuppression administered to renal transplant recipients

Kirk

Adams

Dürrbach

et al. 2021

American Journal of Transplantation

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In the United States (US), more than 90% of renal transplant recipients are maintained on calcineurin inhibitor (CNI)-based immunosuppressive regimens. 1 CNIs (cyclosporine or tacrolimus) have been associated with systemic adverse effects (AEs), including dyslipidemia, diabetes, nephrotoxicity, and neurotoxicity, 2-14 and have the potential to negatively impact both patient and graft survival. 9,15 Belatacept is a soluble fusion protein composed of the human IgG1 Fc domain linked to the modified extracellular domain of

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Section: Alternative Reg Imen: B El Atacep T Plus An Mtorimentioning

confidence: 99%

Optimization of de novo belatacept-based immunosuppression administered to renal transplant recipients

Kirk

Adams

Dürrbach

et al. 2021

American Journal of Transplantation

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“…All recipients used corticosteroids in our study. Their diabetogenic effects are attributable to either direct events (increase in insulin resistance associated to higher rates of gluconeogenesis in the liver) or indirect events (weight gain, hyperphagia, the increase in lipolysis-induced dyslipidemia, and the reduction in muscle mass, in glucose uptake, and in glycogen synthesis in skeletal muscle cells) [7]. However, withdrawal of 5 mg prednisolone may not modify significantly insulin sensitivity [30].…”

Section: Journal Of Diabetes Researchmentioning

confidence: 99%

“…Major risk factors for development of PTDM are metabolic adverse effects of immunosuppressive regimen, including calcineurin inhibitors, mammalian target of rapamycin inhibitors (mTORi), and corticosteroids, posttransplant viral infections, and hypomagnesaemia, in addition to the traditional risk factors seen in patients with type 2 DM [5][6][7][8]. Therefore, modifiable and nonmodifiable variables are risk factors for PTDM.…”

Section: Introductionmentioning

confidence: 99%

Modifiable Variables Are Major Risk Factors for Posttransplant Diabetes Mellitus in a Time-Dependent Manner in Kidney Transplant: An Observational Cohort Study

Lucena

Sá

Medina‐Pestana

et al. 2020

Journal of Diabetes Research

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Modifiable and nonmodifiable risk factors for developing posttransplant diabetes mellitus (PTDM) have already been established in kidney transplant setting and impact adversely both patient and allograft survival. We analysed 450 recipients of living and deceased donor kidney transplants using current immunosuppressive regimen in the modern era and verified PTDM prevalence and risk factors over three-year posttransplant. Tacrolimus (85%), prednisone (100%), and mycophenolate (53%) were the main immunosuppressive regimen. Sixty-one recipients (13.5%) developed PTDM and remained in this condition throughout the study, whereas 74 (16.5%) recipients developed altered fasting glucose over time. Univariate analyses demonstrated that recipient age (46.2±1.3vs. 40.7±0.6 years old, OR 1.04; P=0.001) and pretransplant hyperglycaemia and BMI≥25 kg/m2 (32.8% vs. 21.6%, OR 0.54; P=0.032 and 57.4% vs. 27.7%, OR 3.5; P<0.0001, respectively) were the pretransplant variables associated with PTDM. Posttransplant transient hyperglycaemia (86.8%. 18.5%, OR 0.03; P=0.0001), acute rejection (P=0.021), calcium channel blockers (P=0.014), TG/HDL (triglyceride/high-density lipoprotein cholesterol) ratio≥3.5 at 1 year (P=0.01) and at 3 years (P=0.0001), and tacrolimus trough levels at months 1, 3, and 6 were equally predictors of PTDM. In multivariate analyses, pretransplant hyperglycaemia (P=0.035), pretransplant BMI≥25 kg/m2 (P=0.0001), posttransplant transient hyperglycaemia (P=0.0001), and TG/HDL ratio≥3.5 at 3-year posttransplant (P=0.003) were associated with PTDM diagnosis and maintenance over time. Early identification of risk factors associated with increased insulin resistance and decreased insulin secretion, such as pretransplant hyperglycaemia and overweight, posttransplant transient hyperglycaemia, tacrolimus trough levels, and TG/HDL ratio may be useful for risk stratification of patients to determine appropriate strategies to reduce PTDM.

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“…Pharmacologically, GCs are widely used to treat acute and chronic inflammatory diseases, such as asthma, allergies, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis etc., due to their potent anti-inflammatory actions. In addition, GCs are commonly prescribed to prevent graft-vs.-host immune responses after organ transplantation and for certain cancer types, such as lymphoma (6, 7). Currently, it is estimated that 1–3% of the adult Western population are receiving GCs, demonstrating their broad applications (8).…”

Section: Introductionmentioning

confidence: 99%

Fighting the Fire: Mechanisms of Inflammatory Gene Regulation by the Glucocorticoid Receptor

et al. 2019

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For many decades, glucocorticoids have been widely used as the gold standard treatment for inflammatory conditions. Unfortunately, their clinical use is limited by severe adverse effects such as insulin resistance, cardiometabolic diseases, muscle and skin atrophies, osteoporosis, and depression. Glucocorticoids exert their effects by binding to the Glucocorticoid Receptor (GR), a ligand-activated transcription factor which both positively, and negatively regulates gene expression. Extensive research during the past several years has uncovered novel mechanisms by which the GR activates and represses its target genes. Genome-wide studies and mouse models have provided valuable insight into the molecular mechanisms of inflammatory gene regulation by GR. This review focusses on newly identified target genes and GR co-regulators that are important for its anti-inflammatory effects in innate immune cells, as well as mutations within the GR itself that shed light on its transcriptional activity. This research progress will hopefully serve as the basis for the development of safer immune suppressants with reduced side effect profiles.

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Glucocorticoids use in kidney transplant setting

Cited by 43 publications

References 132 publications

Optimization of de novo belatacept-based immunosuppression administered to renal transplant recipients

Optimization of de novo belatacept-based immunosuppression administered to renal transplant recipients

Modifiable Variables Are Major Risk Factors for Posttransplant Diabetes Mellitus in a Time-Dependent Manner in Kidney Transplant: An Observational Cohort Study

Fighting the Fire: Mechanisms of Inflammatory Gene Regulation by the Glucocorticoid Receptor

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