title: Low-dose combination therapy with temocapril and losartan reduces proteinuria in normotensive patients with immunoglobulin a nephropathy.
abstract: This study investigates the ability of low doses of angiotensin-converting-enzyme inhibitors, in combination with angiotensin II receptor blockers, to exert antiproteinuric effects in normotensive and proteinuric outpatients with immunoglobulin A (IgA) nephropathy confirmed by biopsy. We performed a prospective, randomized, 6-month study of the effects of temocapril 1 mg (n=10), losartan 12.5 mg (n=10), and both (n=11) on mild-to-moderate proteinuria 0.76+/-0.35 g/day (range, 0.4 to 1.6 g/day) and renal function. The study subjects comprised 31 normotensive and proteinuric outpatients with IgA nephropathy accompanied by normal, or mild-to-moderately reduced but stable renal function (glomerular filtration rate>50 ml/min) without steroid or immunosuppressive therapy. We prospectively evaluated blood pressure, proteinuria, renal function and biochemical parameters before and after 6 months of therapy. The combination therapy significantly reduced proteinuria (63.2%) compared with either temocapril or losartan alone (41.3% and 36.6%, respectively, p=0.04 and 0.01, respectively). Blood pressure was most decreased in the group that received combination therapy. The reduced proteinuria did not correlate with reduced systolic or diastolic blood pressure or mean arterial pressure in any of the groups. The glomerular filtration rate fell during the first 3 months of combined therapy, but became reversible after a further 3 months of therapy. The combination significantly decreased angiotensin II (p <0.01), and this decrease was greater than that by either drug alone. In conclusion, the effectiveness of the combined therapy may have been at least partly due to the greater inhibition of the action of angiotensin II in patients with IgA nephropathy. This strategy apparently reduced mild-to-moderate proteinuria in patients with normotensive IgA nephropathy.
authors.affiliation: Department of Internal Medicine, Nagasaki Municipal Medical Center, Fuchi-machi, Nagasaki, Japan. y-horita@h8.dion.ne.jp
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Horita
authors.forename: Masato
authors.initials: M
authors.lastname: Tadokoro
authors.forename: Koichi
authors.initials: K
authors.lastname: Taura
authors.forename: Naofumi
authors.initials: N
authors.lastname: Suyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Taguchi
authors.forename: Masanobu
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005922:Glomerulonephritis, IGA / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D019808:Losartan / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011507:Proteinuria / Q000188:drug therapy* / Q000503:physiopathology; D013841:Thiazepines / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D013841:Thiazepines; C055603:temocapril hydrochloride; D019808:Losartan