title: Renin angiotensin system blockade reduces urinary levels of soluble urokinase plasminogen activator receptor (suPAR) in patients with type 2 diabetes.
abstract: Soluble urokinase plasminogen activator receptor (suPAR) is associated with faster decline in kidney function and the pathogenesis of diabetic nephropathy. However, little is known about the impact of treatment on plasma and urinary levels of suPAR. We aimed to investigate the impact of renin angiotensin system (RAS) single and dual blockade on suPAR levels in patients with type 2 diabetes and albuminuria. We conducted a post-hoc analysis of a randomized controlled crossover trial. Urine and plasma samples were analyzed for suPAR levels. The placebo period was considered reference and all treatment periods were compared to placebo. Patients (n = 22) were treated for 2-month periods with either placebo, irbesartan 300 mg once daily, aliskiren 300 mg once daily or irbesartan/aliskiren combination in random order. Placebo geometric mean plasma (SEM) levels of suPAR were 3.3 ng/mL (1.1) and urine levels were 4.0 ng/mL (1.1). None of the treatments had significant effects on plasma levels of suPAR compared to placebo. Compared to placebo, irbesartan and combination treatment decreased urinary levels of suPAR significantly (-1.3 ng/mL), while aliskiren did not. In patients with type 2 diabetes urinary levels of suPAR were reduced during RAS blockade treatment, which may contribute to renoprotection.
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark. Electronic address: frip@steno.dk.
authors.forename: Frederik
authors.initials: F
authors.lastname: Persson
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.
authors.forename: Simone
authors.initials: S
authors.lastname: Theilade
authors.affiliation: Hvidovre Hospital, Hvidovre, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Eugen-Olsen
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark; NNF Center for Basic and Metabolic Research, Copenhagen University, Denmark; HEALTH, Aarhus University, Aarhus, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Rossing
authors.affiliation: HEALTH, Aarhus University, Aarhus, Denmark; Dept. of Medical Endocrinology, Rigshospitalet, Copenhagen University Hospital, Denmark.
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Parving
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000188:drug therapy; D000577:Amides / Q000008:administration & dosage / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000652:urine*; D004359:Drug Therapy, Combination; D005260:Female; D005650:Fumarates / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D055293:Receptors, Urokinase Plasminogen Activator / Q000032:analysis* / Q000097:blood*; D012084:Renin-Angiotensin System; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000577:Amides; D001713:Biphenyl Compounds; D005650:Fumarates; D055293:Receptors, Urokinase Plasminogen Activator; D013777:Tetrazoles; C446481:aliskiren; D000077405:Irbesartan
keywords: Albuminuria; Biomarkers; Diabetes; Renin angiotensin system; SuPAR