Candesartan improves blood pressure control and reduces proteinuria in renal transplant recipients: results from SECRET.
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.
Philipp
Thomas
T
Medizinische Klinik, Universitätsklinikum, Essen, Germany. thomas.philipp@uk-essen.de
Martinez
Franck
F
Geiger
Helmut
H
Moulin
Bruno
B
Mourad
Georges
G
Schmieder
Roland
R
Lièvre
Michel
M
Heemann
Uwe
U
Legendre
Christophe
C
D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003404:Creatinine / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D016030:Kidney Transplantation / Q000009:adverse effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood; D011446:Prospective Studies; D011507:Proteinuria / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013777:Tetrazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D003404:Creatinine; C077793:candesartan cilexetil; D011188:Potassium