title: Twenty-Four-Hour Urine α1-Microglobulin as a Marker of Hypertension-Induced Renal Impairment and Its Response on Different Blood Pressure-Lowering Drugs.
abstract: The purpose of this study was to assess the role of urine α1-microglobulin as a marker of hypertension-induced renal damage compared with estimated glomerular filtration rate, (eGFR), urine albumin, and urine albumin-to-creatinine ratio (ACR). Its response on different blood pressure (BP)-lowering drugs was also studied. Sixty never-treated hypertensive patients (65.0% men, 46.9 years, BP 141.4/94.0 mm Hg) were randomized to an irbesartan (an angiotensin receptor blocker [ARB]) or a diltiazem (a nondihydropyridine calcium channel blocker [CCB])-based regimen. Patients with diabetes or established cardiovascular, renal, or liver disease were excluded. Blood samples and 24-hour urine were analyzed at baseline and 6 months after pharmaceutical BP normalization. Serum creatinine was measured and eGFR was calculated. Urine albumin, creatinine, and α1-microglobulin were measured and ACR was calculated. Minor changes (P=not significant [NS]) in eGFR were noted during follow-up in both groups (from 111.0 mL/min/1.73 m2to 108.4 mL/min/1.73 m2in the ARB group and from 111.3 mL/min/1.73 m2to 114.0 mL/min/1.73 m2in the CCB group). Twenty-four-hour urine indices were all significantly improved (P<.01) in the ARB group (albumin from 19.4 mg/L to 8.2 mg/L, ACR from 21.5 mg/g to 10.0 mg/g, α1-microglobulin from 5.06 mg/L to 3.64 mg/L) but not (P=NS) in the CCB group (albumin from 15.6 mg/L to 13.9 mg/L, ACR from 17.6 mg/g to 17.1 mg/g, α1-microglobulin from 4.94 mg/L to 4.79 mg/L). These differences between groups remained significant (P<.05) after adjusting for office heart rate and BP. α1-Microglobulin was significantly correlated (P<.05) with albumin and ACR both at baseline (r=0.283 and 0.299, respectively) and at the end of follow-up (r=0.432 and 0.465, respectively) but not (P=NS) with eGFR. It was also significantly related (P<.05) to cardiovascular risk scores (Framingham and HeartScore) both at baseline (r=0.264 and 0.436, respectively) and at the end of follow-up (r=0.308 and 0.472, respectively). Urine α1-microglobulin emerges as a potentially usable marker of hypertension-induced renal impairment. Its excretion rate and its response to treatment appears similar to that of albumin. Irbesartan but not diltiazem seems to be associated with reduced excretion of α1-microglobulin in urine.
authors.affiliation: 1st Cardiology Department, Hippokration Hospital, University of Athens Medical School, Athens, Greece. bliakos@med.uoa.gr.
authors.forename: Charalampos I
authors.initials: CI
authors.lastname: Liakos
authors.affiliation: 1st Cardiology Department, Hippokration Hospital, University of Athens Medical School, Athens, Greece.
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Vyssoulis
authors.affiliation: 1st Cardiology Department, Hippokration Hospital, University of Athens Medical School, Athens, Greece.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Markou
authors.affiliation: Cardiology Department, "KAT" General Hospital of Attica, Athens, Greece.
authors.forename: Nikolaos V
authors.initials: NV
authors.lastname: Kafkas
authors.affiliation: 1st Cardiology Department, Hippokration Hospital, University of Athens Medical School, Athens, Greece.
authors.forename: Konstantinos P
authors.initials: KP
authors.lastname: Toutouzas
authors.affiliation: 1st Cardiology Department, Hippokration Hospital, University of Athens Medical School, Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tousoulis
mesh_terms: D000328:Adult; D000510:Alpha-Globulins / Q000652:urine*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000652:urine; D001713:Biphenyl Compounds / Q000008:administration & dosage; D004110:Diltiazem / Q000008:administration & dosage; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine*; D000077405:Irbesartan; D007674:Kidney Diseases / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000510:Alpha-Globulins; D000959:Antihypertensive Agents; D015415:Biomarkers; D001713:Biphenyl Compounds; D013777:Tetrazoles; C016001:alpha-1-microglobulin; D004110:Diltiazem; D000077405:Irbesartan