PMID- 30265586
OWN - NLM
STAT- MEDLINE
DCOM- 20181026
LR  - 20181026
IS  - 1744-7607 (Electronic)
IS  - 1742-5255 (Linking)
VI  - 14
IP  - 10
DP  - 2018 Oct
TI  - Glucocorticoids use in kidney transplant setting.
PG  - 1023-1041
LID - 10.1080/17425255.2018.1530214 [doi]
AB  - INTRODUCTION: Despite major advances in kidney transplant, glucocorticoids (GCs) 
      or steroids remain one of the mainstay treatments. They possess adverse events 
      (AEs) that are related to cumulative dosage, as documented in experimental and 
      clinical studies. Therefore, it is important to comprehend and interpret 
      experimental data and equally important to critically review clinical studies. 
      Areas covered: This article provides a broad overview of the structure, 
      pharmacokinetics, and pharmacodynamics of systemically administered GCs in 
      transplant setting. It further discusses at length the results of in vitro and 
      pre-clinical studies, as well as steroid avoidance (SA) or withdrawal (SW)-based 
      clinical studies. We summarized the main AEs and discussed the alternatives to 
      minimize these events. Some clinically relevant drug-drug interactions are also 
      highlighted. Expert opinion: Although SA/SW in kidney transplant is a desirable 
      strategy due to its AEs, there is no evidence to support that strategy based on 
      the available data, despite some encouraging reports. Furthermore, early 
      diagnosis and treatment of GC-induced AEs seem to be the most efficacious 
      strategies. Likewise, some risks factors predate transplant and could be used to 
      risk-stratify patients to determine appropriate risk-reduction strategies. 
      Additional randomized-controlled studies are required to assess the impact of 
      SA/SW during short and long follow-ups. ABBREVIATIONS: ACTH: Adrenocorticotropic 
      hormone (also adrenocorticotropin and corticotropin); ADA: American Diabetes 
      Association; AEs: Adverse events; ADX: Adrenalectomized; AR: Acute rejection; 
      AUC: Area under the curve; BMI: Body mass index; BMD: Bone mineral density; BPAR: 
      Biopsy-proven acute rejection; cAMP: cyclic adenosine monophospahte; CBG: 
      Corticosteroid-binding globulin; CBP: CREB binding protein; C(max): Mean maximal 
      serum concentration; CNIs: Calcineurin inhibitors; COX-2: cyclo-oxygenase-2; 
      cPLA(2): cytosolic phospholipase A(2;) CSA: Cyclosporine; CYP: Cytochrome; DEX: 
      Dexamethasone; DM: Diabetes mellitus; ESW: Early steroid withdrawal; GCs: 
      Glucocorticoids; GRs: Glucocorticoid receptors; GREs: Glucocorticoid receptor 
      elements; CSA: Cyclosporine; DEX: Dexamethasone; Glycated hemoglobin: HbA(1c); 
      HDL: High-density lipoproteins; HLA: Human leukocyte anrigen; HPA axis: 
      Hypothalamic-pituitary-adrenal axis; HR: Hazard ratio; HSP: Heat shock proteins; 
      11beta-HSD: 11beta-Hydroxysteroid dehydrogenase; IC(50): Half of maximal inhibitory 
      concentration; IFG: Impaired fasting glucose; IGT: Impaired glucose tolerance; 
      imTOR: Inhibitors of mammalian target of rapamycin; iNOS: Inducible oxide nitric 
      synthase; K(d): Dissociation constant; KDIGO: Kidney Disease: Improving Global 
      Outcomes; LSW: Late steroid withdrawal; LDL: Low-density lipoproteins; MCP-1: 
      Monocyte chemoattractant protein-1; MMF: Mycophenolate mofetil; MPS: 
      Mycophenolate sodium; NSAIDS: non-steroidal anti- inflammatory drugs; NF-kappaB: 
      Nnuclear factor-kappaB TNF; OPTN/UNOS: Organ Procurement and Transplant 
      Network/United Network of Organ Sharing database; PK/PD: 
      Pharmacokinetic/pharmacodynamics; PRA: Panel reactive antibodies; PTDM: 
      Post-transplantation diabetes mellitus; PTH: Parathyroid hormone; RCT: Randomized 
      controlled trial; RR: Risk ratio; SA: Steroid avoidanceSGLT-2: Sodium-glucose 
      co-transporter 2; SW: Steroid withdrawal; TAC: Tacrolimus or FK506; TG/HDL: 
      Triglyceride to high-density lipoprotein ratio; TNF-alpha: Tumor necrosis factor-alpha; 
      TGF-beta: Transforming growth factor-beta.
FAU - De Lucena, Debora Dias
AU  - De Lucena DD
AD  - a Department of Medicine, Division of Nephrology , Federal University of Sao 
      Paulo/Hospital do Rim e Hipertensao , Sao Paulo , Brazil.
FAU - Rangel, Erika Bevilaqua
AU  - Rangel EB
AUID- ORCID: 0000-0003-0982-2484
AD  - a Department of Medicine, Division of Nephrology , Federal University of Sao 
      Paulo/Hospital do Rim e Hipertensao , Sao Paulo , Brazil.
AD  - b Instituto Israelita de Ensino e Pesquisa , Hospital Israelita Albert Einstein , 
      Sao Paulo , Brazil.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20181005
PL  - England
TA  - Expert Opin Drug Metab Toxicol
JT  - Expert opinion on drug metabolism & toxicology
JID - 101228422
RN  - 0 (Glucocorticoids)
RN  - 0 (Immunosuppressive Agents)
SB  - IM
MH  - Animals
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Early Diagnosis
MH  - Glucocorticoids/*administration & dosage/adverse effects
MH  - Humans
MH  - Immunosuppressive Agents/*administration & dosage/adverse effects
MH  - Kidney Transplantation/*methods
MH  - Randomized Controlled Trials as Topic
MH  - Risk Assessment/methods
MH  - Risk Factors
OTO - NOTNLM
OT  - Glucocorticoids
OT  - adverse events
OT  - kidney transplant
OT  - pharmacokinetics
EDAT- 2018/09/29 06:00
MHDA- 2018/10/27 06:00
CRDT- 2018/09/29 06:00
PHST- 2018/09/29 06:00 [pubmed]
PHST- 2018/10/27 06:00 [medline]
PHST- 2018/09/29 06:00 [entrez]
AID - 10.1080/17425255.2018.1530214 [doi]
PST - ppublish
SO  - Expert Opin Drug Metab Toxicol. 2018 Oct;14(10):1023-1041. doi: 
      10.1080/17425255.2018.1530214. Epub 2018 Oct 5.