title: Cilostazol effectively attenuates deterioration of albuminuria in patients with type 2 diabetes: a randomized, placebo-controlled trial.
abstract: Cilostazol is an antiplatelet, antithrombotic agent with anti-inflammatory properties. To date, no clinical study has specifically evaluated the efficacy of cilostazol in patients with diabetic nephropathy (DN). We hypothesized that cilostazol might delay renal deterioration in DN patients at high risk of progression. Between April 2008 and April 2010, we screened 156 consecutive patients aged 35-80 years who were first diagnosed with type 2 diabetes after the age of 30 years. Of these, 90 patients with DN, as defined by morning spot urine microalbuminuria (MAU) >20 mg/L or an albumin-to-creatinine ratio (ACR) >30 μg/mg on at least two consecutive occasions within the prior 3 months, were enrolled into a 52-week randomized, single-blinded, placebo-controlled trial of oral cilostazol 100 mg twice daily or placebo (45 subjects in each group). Morning spot urine samples were collected to determine MAU and ACR. Fasting plasma levels of metabolic, endothelial variables, and inflammatory markers were examined. Following 52 weeks of treatment, urinary MAU and ACR were significantly reduced in the cilostazol group compared with the placebo group (P = 0.024 and P = 0.02, respectively). In regression analyses, changes in monocyte chemotactic protein-1, E-selectin, and soluble vascular cell adhesion molecule-1 (sVCAM-1) were significantly associated with changes in MAU and ACR. Net changes of E-selectin (P < 0.001) and sVCAM-1 (P < 0.05) were independent predictors of change in MAU and ACR, respectively. Our results suggest that cilostazol may effectively attenuate deterioration of albuminuria in patients with type 2 diabetes. This effect is likely mediated by an improvement of adhesion molecules.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Chen-Kung Rd., Nei-Hu, Taipei, Taiwan.
authors.forename: Wen-Hao
authors.initials: WH
authors.lastname: Tang
authors.forename: Fu-Huang
authors.initials: FH
authors.lastname: Lin
authors.forename: Chien-Hsing
authors.initials: CH
authors.lastname: Lee
authors.forename: Feng-Chih
authors.initials: FC
authors.lastname: Kuo
authors.forename: Chang-Hsun
authors.initials: CH
authors.lastname: Hsieh
authors.forename: Fone-Ching
authors.initials: FC
authors.lastname: Hsiao
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Hung
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000378:metabolism; D000419:Albuminuria / Q000209:etiology* / Q000517:prevention & control*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018932:Chemokine CCL2 / Q000378:metabolism; D000077407:Cilostazol; D003404:Creatinine / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy*; D018450:Disease Progression; D019040:E-Selectin / Q000378:metabolism; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D000418:Albumins; D000893:Anti-Inflammatory Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D019040:E-Selectin; D013777:Tetrazoles; D019010:Vascular Cell Adhesion Molecule-1; D003404:Creatinine; D000077407:Cilostazol