Effect of the urotensin receptor antagonist palosuran in hypertensive patients with type 2 diabetic nephropathy.
The urotensin system has been hypothesized to play an important role in the pathophysiology of diabetic nephropathy. In this multicenter, randomized, double-blind, placebo-controlled, 2-period crossover study, the effects of the urotensin receptor antagonist palosuran on urinary albumin excretion and blood pressure in hypertensive patients with type 2 diabetic nephropathy treated with a single blocker of the renin-angiotensin-aldosterone system were assessed. Patients with 24-hour albuminuria >0.5 and <3.0 g, systolic blood pressure >135 and <170 mm Hg, and/or diastolic blood pressure >85 and <110 mm Hg received both palosuran 125 mg BID and placebo for 4 weeks each. Fifty-four patients (20% women; mean age: 61.6 years, blood pressure: 155/84 mm Hg, and albuminuria: 1016 mg per 24 hours) were included in the per-protocol analysis. Palosuran did not affect albuminuria, blood pressure, glomerular filtration rate, or renal plasma flow significantly. These results question whether urotensin receptor antagonism represents a new treatment strategy in this high-risk patient population.
University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Liffert
L
Vogt
Carlos
C
Chiurchiu
Harbajan
H
Chadha-Boreham
Parisa
P
Danaietash
Jasper
J
Dingemanse
Samy
S
Hadjadj
Henry
H
Krum
Gerjan
G
Navis
Eric
E
Neuhart
Aneliya I
AI
Parvanova
Piero
P
Ruggenenti
Arend Jan
AJ
Woittiez
Reuven
R
Zimlichman
Giuseppe
G
Remuzzi
Dick
D
de Zeeuw
D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000517:prevention & control; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003404:Creatinine / Q000652:urine; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000150:complications*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy* / Q000652:urine; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011804:Quinolines / Q000627:therapeutic use*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors; D012084:Renin-Angiotensin System / Q000187:drug effects; D014508:Urea / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014579:Urotensins / Q000187:drug effects / Q000378:metabolism
D000959:Antihypertensive Agents; D010919:Placebos; D011804:Quinolines; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human; D014579:Urotensins; D014508:Urea; C029677:urotensin II; D003404:Creatinine; C493249:1-(2-(4-benzyl-4-hydroxypiperidin-1-yl)ethyl)-3-(2-methylquinolin-4-yl)urea