NDT Advance Access published online on November 3, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp581
Candesartan improves blood pressure control and reduces proteinuria in renal transplant recipients: results from SECRET
1 Medizinische Klinik, Universitätsklinikum, Essen, Germany 2 Hôpital Necker & Université Paris Descartes, Paris, France 3 Medizinische Klinik III-Nephrologie, Klinikum der Johann-Wolfgang-Goethe-Universität, Frankfurt, Germany 4 Service de Néphrologie-Transplantation Rénale, Hôpital Civil, Strasbourg, France 5 Department of Nephrology and Transplantation, Hôpital Lapeyronie, Montpellier, France 6 Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany 7 Service de Pharmacologie Clinique-UMR5558, Université Lyon 1, Lyon, France 8 Abteilung für Nephrologie der II.Medizinischen Klinik und Poliklinik, Klinikum rechts der Isar der TU München, München, Germany
Correspondence and offprint requests to: Thomas Philipp; E-mail: thomas.philipp{at}uk-essen.de
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Abstract |
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Background. Hypertension is a risk factor for the two leading causes of death in renal transplant recipients: cardiovascular disease (CVD) and graft failure. Despite this, the optimum medication for post-transplant hypertension is unclear.
Methods. The Study on Evaluation of Candesartan Cilexetil after Renal Transplantation (SECRET) was an international multicentre, double-blind, randomized investigation of the angiotensin II type 1 receptor blocker (ARB) candesartan cilexetil versus placebo in renal allograft recipients originally designed to study 700 patients for 3 years. The candesartan dose was escalated from 4 to 16 mg daily, followed by addition of co-medication, if needed, with the aim of achieving a diastolic blood pressure (BP) <85 mmHg. The primary efficacy variable was a composite of all-cause mortality, cardiovascular morbidity and graft failure.
Results. SECRET was stopped prematurely as the primary event rate was much lower than expected. At that point, 502 patients were enrolled; 255 received candesartan and 247 placebo. Thirteen primary events had occurred in each group. Control of both systolic and diastolic BP was better in the candesartan group. Urinary protein excretion and protein/creatinine ratio decreased on candesartan but increased on placebo. Serum creatinine and potassium were increased in candesartan patients, but these changes were generally small.
Conclusions. SECRET provides insights into the design and conduct of studies in this area and evidence for the utility of candesartan, which showed good safety and tolerability, improved BP control and decreased proteinuria in renal transplant recipients.
Keywords: angiotensin II type 1 receptor blocker; blood pressure; candesartan; kidney transplantation; proteinuria
Received for publication: 5. 2.09
Revision received 1.10.09.
Accepted in revised form: 9.10.09