title: Influence of irbesartan on the urinary excretion of cytokines in patients with chronic kidney disease.
abstract: BACKGROUND
  The non-hemodynamic effects of angiotensin receptor blocker (ARB) in the delay of progression of chronic kidney disease (CKD) remain unclear. In this study, we investigated the influence of irbesartan on the urinary excretion of cytokines in patients with CKD.
  
  
  METHODS
  In this randomized perspective clinical trial, different doses of irbesartan (150 mg/d and 300 mg/d) were given to two groups of patients in a cross-over design. Blood pressure (BP), creatinine clearance (Ccr) and 24-hour proteinuria were examined. Urinary excretion of cytokines was determined by human inflammatory cytokine antibody array. A two-fold change in spot intensity was considered significant.
  
  
  RESULTS
  Urinary excretion of cytokines (granulocyte colony stimulating factor (GCSF), intercellular cell adhesion molecule-1 (ICAM-1), interferon γ (IFN-γ), interleukin 1β (IL-1b), IL-2, IL-6, IL-8, IL-11, IL-15 and macrophage inflammatory protein 1d (MIP-1d)) in group B (irbesartan 300 mg/d) was significantly decreased in comparison to group A (irbesartan 150 mg/d) after 8-week treatment. In group A, 8 weeks of treatment induced a two- to nine-fold reduction in urinary cytokine levels (GCSF, GM-CSF, IFN-γ, IL-1a, IL-11, IL-12p40, MCP-2, MIP-1a), while increasing the dosage to 300 mg/d further decreased the excretion of GCSF, GM-CSF, IL-12p40, MCP-2 and MIP-1a by week 18. There was no significant difference in BP or Ccr between the two groups. However, 24-hour proteinuria was significantly reduced in both groups, and in group A the reduction was dose dependent.
  
  
  CONCLUSIONS
  Irbesartan offers additional renoprotection in a dose-dependent manner by reducing pro-inflammatory cytokines excretion in the urine of CKD patients.
authors.affiliation: Institute of Nephrology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ni
authors.forename: Hai-Quan
authors.initials: HQ
authors.lastname: Huang
authors.forename: Lin-Li
authors.initials: LL
authors.lastname: Lü
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.forename: Bi-Cheng
authors.initials: BC
authors.lastname: Liu
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D002908:Chronic Disease; D003404:Creatinine / Q000378:metabolism; D018592:Cross-Over Studies; D016207:Cytokines / Q000652:urine*; D006801:Humans; D000077405:Irbesartan; D007674:Kidney Diseases / Q000188:drug therapy* / Q000276:immunology; D011446:Prospective Studies; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D016207:Cytokines; D013777:Tetrazoles; D003404:Creatinine; D000077405:Irbesartan