Biomarker Assessment of the Immunomodulator Effect of Atorvastatin in Stable Renal Transplant Recipients and Hypercholes
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Mol Diagn Ther 2010; 14 (6): 357-366 1177-1062/10/0006-0357/$49.95/0
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Biomarker Assessment of the Immunomodulator Effect of Atorvastatin in Stable Renal Transplant Recipients and Hypercholesterolemic Patients David Guille´n,1,2 Federico Cofa´n,3 Emilio Ros,4,5 Olga Milla´n,1,6 Montse Cofa´n4,5 and Merce` Brunet1,2,6 1 Pharmacology Laboratory (Biomedical Diagnosis Center), Hospital Clinic, Institut d’Investigacions Biome`diques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain 2 Departament de Salut Pu´blica, Facultat de Medicina, University of Barcelona, Barcelona, Spain 3 Renal Transplant Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain 4 Lipid Clinic, Endocrinology and Nutrition Service, Hospital Clinic, IDIBAPS, Barcelona, Spain 5 Centro de Investigacio´n Biome´dica en Red de Fisiopatologı´a de la Obesidad y Nutricio´n (CIBERobn), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain 6 Centro de Investigacio´n Biome´dica en Red de Enfermedades Hepa´ticas y Digestivas (CIBERehd), ISCIII, Barcelona, Spain
Abstract
Background: HMG-CoA reductase inhibitors (statins) have effects beyond lipid lowering, including immunomodulatory and anti-inflammatory properties. Statins are frequently combined with immunosuppressive agents in transplant recipients to modulate the hyperlipidemic side effects of the immunosuppressants. However, the role of statins in the immunosuppressive response that is achieved in individual patients remains to be assessed. Objective: The aim of this study was to evaluate the immunomodulatory effect of atorvastatin given alone and in combined treatment with tacrolimus and mycophenolate mofetil. Study Design: Two patient groups were studied: renal transplant recipients receiving tacrolimus and mycophenolate mofetil therapy, and hypercholesterolemic patients (the control group). Fasting blood samples were taken from participants before and 1 month after atorvastatin treatment was started to study a small battery of biomarkers that are able to reflect the range of the effects of immunosuppressive therapy and atorvastatin. Setting: All patients in the study were enrolled at the Hospital Clinic of Barcelona. Patients: All patients enrolled in the study were candidates for treatment with atorvastatin because of high cholesterol levels. One group consisted of 25 stable renal transplant recipients with low-density lipoprotein (LDL) cholesterol levels above 100 mg/dL after 3 months of therapeutic lifestyle changes, according to the guidelines of the National Kidney Foundation – Kidney Disease Outcomes Quality Initiative. The other group included 25 hypercholesterolemic patients with LDL cholesterol levels above target values for the patients’ overall risk, as derived from the National Cholesterol Education Program Adult Treatment Panel III criteria. Intervention: Atorvastatin (Lipitor) treatment was started at a fixed dose of 20 mg daily. Main Outcome Measure: The studied biomarkers were lymphocyte pro
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