title: The metabolic and toxicological considerations for immunosuppressive drugs used during pancreas transplantation.
abstract: BACKGROUND
  Pancreas-kidney transplant is an effective treatment for patients with insulin-dependent dabetes and chronic renal failure. Reduction in technical failure loss and early acute rejection rates contributed to prolong pancreas graft survival. However, drug toxicity affects negatively both short- and long-term follow-ups.
  
  
  METHODS
  This article reviews the existing literature and knowledge of the immunosuppressive drugs that are frequently used in pancreas transplant, including calcineurin inhibitors, sirolimus, corticosteroids, and mycophenolate. The article also discusses the short- and long-term adverse effects of these drugs. The article also reports and discusses the most relevant in vitro studies, providing additional information to in vivo findings. Some clinically relevant drug interactions with immunosuppressive drugs are also highlighted. Over- and underimmunosuppression effects will not be addressed.
  
  
  CONCLUSIONS
  Immunosuppressive regimen after pancreas transplant is very effective and contributed to pancreas allograft survival. However, they present several side effects that are potentiated when drugs are combined. Modifiable and non-modifiable risk factors can aggravate metabolic and toxicological effects of immunosuppressive drugs. It is important to critically analyze the results of clinical studies and investigate new immunosuppressive drugs and/or novel drug combinations. It is equally important to comprehend and interpret experimental data. Therefore, minimization of side effects, based on safe approaches, can prolong pancreas allograft survival.
authors.affiliation: Federal University of São Paulo, SP, Brazil. erikabr@uol.com.br
authors.forename: Erika B
authors.initials: EB
authors.lastname: Rangel
mesh_terms: D000305:Adrenal Cortex Hormones / Q000009:adverse effects* / Q000493:pharmacokinetics; D001847:Bone Diseases / Q000209:etiology / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000503:physiopathology; D005767:Gastrointestinal Diseases / Q000209:etiology / Q000503:physiopathology; D006084:Graft Rejection / Q000188:drug therapy; D006085:Graft Survival / Q000187:drug effects; D006402:Hematologic Diseases / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D006947:Hyperkalemia / Q000209:etiology / Q000503:physiopathology; D033461:Hyperuricemia / Q000209:etiology / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D009173:Mycophenolic Acid / Q000009:adverse effects* / Q000493:pharmacokinetics; D009422:Nervous System Diseases / Q000209:etiology / Q000503:physiopathology; D016035:Pancreas Transplantation; D011014:Pneumonia / Q000209:etiology / Q000503:physiopathology; D051436:Renal Insufficiency, Chronic / Q000209:etiology / Q000503:physiopathology; D020123:Sirolimus / Q000009:adverse effects* / Q000493:pharmacokinetics
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D020123:Sirolimus