title: Targeting albumin excretion rate in the treatment of the hypertensive diabetic patient with renal disease.
abstract: Combination of an angiotensin-converting enzyme inhibitor (ACEI) with an angiotensin II receptor blocker is advocated as a treatment option in diabetic patients with nephropathy and residual albuminuria while on antihypertensive therapy. Abrogation of albuminuria is a key treatment goal to prevent disease progression. The assumption is that albuminuria reduction is the result of more complete blockade of the renin angiotensin system; thus, the ACEI-angiotensin II receptor blocker combination would have a greater albuminuria-lowering effect than the combination of an ACEI with a calcium channel blocker such as amlodipine, which causes similar reductions in BP but does not affect the renin angiotensin system. Twenty-eight patients who had type 1 diabetes and known diabetic renal disease and had a persistently elevated albumin creatinine ratio (ACR) > 10 mg/mmol despite office BP recordings < or = 140/80 mmHg on maximal recommended dose of the ACEI lisinopril were studied. Patients were allocated to receive either candesartan (16 mg/d) or amlodipine (10 mg/d) in addition to preexisting ACEI inhibition and followed for 24 wk in a randomized, double-blind, parallel-group trial. By week 24, ACR fell by 56% with candesartan and 54% with amlodipine (P < 0.01 versus baseline for both) with no significant difference between groups. Mean arterial BP fell between 3 and 6 mmHg similarly in both groups. In neither group was a significant correlation found between the change in ACR and the change in BP. Candesartan and amlodipine lowered ACR and BP by a similar degree. The fall in ACR was disproportionate to the fall of systemic BP and independent of it. The mechanism of the reduction in albuminuria seen with these agents in combination with an ACEI remains to be elucidated.
authors.affiliation: Unit for Metabolic Medicine, Department of Diabetes Endocrinology and Internal Medicine, GKT School of Medicine, Kings College London, Guys Hospital, London, United Kingdom.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Krimholtz
authors.forename: Janaka
authors.initials: J
authors.lastname: Karalliedde
authors.forename: Stephen
authors.initials: S
authors.lastname: Thomas
authors.forename: Rudy
authors.initials: R
authors.lastname: Bilous
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Viberti
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D017311:Amlodipine / Q000008:administration & dosage*; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy; D003928:Diabetic Nephropathies / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D007677:Kidney Function Tests; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D013777:Tetrazoles / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D017311:Amlodipine; C081643:candesartan