Effect of different immunosuppressive regimens on the evolution of distinct metabolic parameters: evidence from the Symphony study

Nephrol Dial Transplant. 2012 Feb;27(2):850-7. doi: 10.1093/ndt/gfr238. Epub 2011 May 26.

Abstract

Background: The metabolic syndrome (MS) is an important risk factor for graft dysfunction and patient death after renal transplantation. The aim of this sub-analysis of the Symphony study was to assess the progression of the laboratory parameters associated with MS in the first year after transplantation.

Methods: Data collected from the Symphony study were used; 1645 patients were randomized to receive standard-dose cyclosporine (Stand-CsA), low-dose cyclosporine (Low-CsA), tacrolimus (Low-Tac) or sirolimus (Low-SRL), in addition to mycophenolate mofetil (MMF) and corticosteroids. Data were collected for levels and progression over the first year post-transplantation of systolic and diastolic blood pressure, uric acid, triglycerides, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and fasting glucose levels by treatment arm.

Results: The low-SRL group had significantly higher levels of triglycerides and LDL. The two CsA arms were associated with the highest uric acid levels at each time point. There were no significant differences in overall levels or changes in glucose or HDL. Patients in the standard-CsA arm had significantly higher diastolic blood pressure than those in the Low-SRL and Low-Tac arms. Systolic blood pressure was higher in the Low-CsA arm than in the Low-Tac arm. The use of antihypertensive and antidiabetic agents was similar between the treatment arms. In the Low-SRL arm, more patients were treated with lipid-lowering therapy. Mean daily steroid doses were the highest in the Low-SRL arm.

Conclusions: This sub-analysis demonstrates that there is a difference in metabolic parameters between immunosuppressive groups. CsA therapy was associated with the highest values of uric acid and systolic and diastolic blood pressure. Patients on SRL therapy had the worst lipaemic control. A possible effect of Tac on new-onset diabetes could not be excluded.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / administration & dosage
  • Adrenal Cortex Hormones / adverse effects
  • Adult
  • Blood Chemical Analysis
  • Blood Pressure Determination
  • Body Mass Index
  • Cyclosporine / administration & dosage
  • Cyclosporine / adverse effects
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Graft Rejection
  • Graft Survival
  • Humans
  • Hyperlipidemias / diagnosis
  • Hyperlipidemias / epidemiology
  • Immunosuppressive Agents / administration & dosage*
  • Kidney Failure, Chronic / diagnosis
  • Kidney Failure, Chronic / surgery*
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / immunology
  • Kidney Transplantation / methods
  • Male
  • Metabolic Syndrome / etiology*
  • Metabolic Syndrome / physiopathology
  • Middle Aged
  • Monitoring, Physiologic / methods
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / adverse effects
  • Mycophenolic Acid / analogs & derivatives
  • Prognosis
  • Reference Values
  • Risk Assessment
  • Sirolimus / administration & dosage
  • Sirolimus / adverse effects
  • Tacrolimus / administration & dosage
  • Tacrolimus / adverse effects
  • Transplantation Immunology*

Substances

  • Adrenal Cortex Hormones
  • Immunosuppressive Agents
  • Cyclosporine
  • Mycophenolic Acid
  • Sirolimus
  • Tacrolimus