Related Experiment Videos

Acute rejection in low-toxicity regimens: clinical impact and risk factors in the Symphony study

Ulrich Frei1, Pierre Daloze, Stefan Vítko

  • 1Department of Nephrology and Medical Intensive Care, Charité, Virchow-Klinikum, Berlin, Germany.

Clinical Transplantation
|September 18, 2009
PubMed

Insights

Reduced immunosuppressant doses in kidney transplants, particularly low-dose tacrolimus with mycophenolate mofetil (MMF), lowered acute rejection rates and improved graft function. This combination offers superior efficacy and reduced toxicity.

Area of Science:

  • Nephrology
  • Immunology
  • Transplantation Medicine

Background:

  • Optimizing immunosuppression post-kidney transplant is crucial for balancing efficacy and toxicity.
  • Mycophenolate mofetil (MMF)-based regimens with reduced adjunct immunosuppressants were explored in the Symphony study.
  • Acute rejection remains a significant factor influencing long-term graft survival and function.

Purpose of the Study:

  • To evaluate the impact of acute rejection and its risk factors within the Symphony study.
  • To compare the incidence and severity of acute rejection across different immunosuppressive regimens.
  • To determine the association between acute rejection and graft function (GFR) and graft loss.

Main Methods:

  • Analysis of biopsy-proven acute rejection rates in patients receiving MMF with varying doses of tacrolimus, cyclosporine, or sirolimus.
  • Assessment of rejection severity (grade ≥II) and its correlation with graft loss and estimated glomerular filtration rate (eGFR).
  • Cox regression modeling to identify risk factors for acute rejection, including HLA mismatches, donor type, recipient age, and MMF dose.

Main Results:

  • Low-dose tacrolimus demonstrated significantly lower acute rejection incidence compared to cyclosporine and sirolimus groups.
  • Acute rejection was linked to a 10 mL/min GFR reduction and a 5.3% increase in 12-month graft loss.
  • The combination of 2g MMF and low-dose tacrolimus yielded the highest GFR, irrespective of rejection status.
  • HLA mismatches and expanded criteria donors increased rejection risk; recipient age, living related donor, and MMF dose reduced risk.

Conclusions:

  • The 2g MMF plus low-dose tacrolimus regimen is the most effective strategy, showing reduced acute rejection and superior GFR.
  • While acute rejection negatively impacts outcomes, it does not fully account for the observed differences between treatment groups.
  • Minimizing adjunct immunosuppressant doses, particularly with tacrolimus, can enhance kidney transplant outcomes.

Related Concept Videos

Drug Toxicity: Risk factors01:24

Drug Toxicity: Risk factors

Adverse Drug Reactions (ADRs) are potential complications that arise during pharmacotherapy, influenced by multiple risk factors. Age plays a significant role; both neonates and the elderly are at heightened risk due to their respective immature and diminished metabolic and elimination processes. Gender also impacts ADRs, with females experiencing a 1.5 to 1.7-fold greater risk than males, which may be linked to pharmacokinetic, pharmacodynamic, and hormonal differences. Notably, neonates, the...
Drug toxicity: Idiosyncratic Reactions01:16

Drug toxicity: Idiosyncratic Reactions

Idiosyncratic drug reactions represent abnormal chemical responses that vary significantly among individuals, ranging from extreme sensitivity to low doses to insensitivity to high doses. These reactions often occur due to the drug's covalent binding with serum proteins, forming a foreign hapten that triggers an immunotoxicological response. The variability in drug reactions has a strong pharmacogenetic foundation, with genetic differences crucial in how individuals metabolize drugs. For...
Therapeutic Drug Monitoring: Affecting Factors01:29

Therapeutic Drug Monitoring: Affecting Factors

Therapeutic Drug Monitoring (TDM) is the clinical practice of measuring specific drug levels in a patient's blood or body tissues to manage and optimize therapy. TDM is crucial for drugs with narrow therapeutic windows, like warfarin and phenytoin, where incorrect doses can lead to treatment failure or severe side effects. This monitoring ensures the dosage administered is within a safe and effective range. The factors affecting therapeutic drug monitoring include:Patient-Specific Factors:a.
Drug Toxicity: Allergic Reactions01:30

Drug Toxicity: Allergic Reactions

Drug-related allergies are immune-mediated responses triggered by the administration of pharmacological agents. These hypersensitivity reactions are classified based on the immune mechanisms involved. The four primary types—Type I, II, III, and IV—are mediated by different immunological pathways and exhibit distinct clinical manifestations.Type I Hypersensitivity/ IgE-Mediated Reactions: Immunoglobulin E (IgE) immediately mediates Type I hypersensitivity reactions. Upon initial exposure to a...
Drug Toxicity: Dose-Dependent Reactions01:24

Drug Toxicity: Dose-Dependent Reactions

Drug toxicities can be stratified into pharmacological, pathological, or genotoxic based on their mechanisms. The incidence and severity of these toxicities generally increase with the drug's concentration in the body and exposure time.Pharmacological toxicity is evident when the therapeutic effects of drugs overshoot into adverse reactions in a predictable, dose-dependent manner. Central nervous system (CNS) depression from barbiturates is a classic example, with effects escalating from...
Drug Toxicity: Overview01:00

Drug Toxicity: Overview

Drug toxicity quantifies the harm a compound causes to an organism, varying by dose and potentially impacting whole systems or specific organs like the liver. Toxic reactions may arise from venomous insect or spider bites, with effects ranging from mild symptoms to severe outcomes such as brain damage or death. Common forms of acute poisoning include ethanol intoxication and overdose of pain or fever medications, with substances like GHB and heroin being particularly lethal at doses close to...