title: Effect of addition of silymarin to renin-angiotensin system inhibitors on proteinuria in type 2 diabetic patients with overt nephropathy: a randomized, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  A large proportion of patients with type 2 diabetes mellitus have diabetic nephropathy. Despite current therapies including renin-angiotensin system inhibitors, diabetic nephropathy progresses to end-stage renal disease in most of these patients. Therefore, there is an urgent need to find new treatments for such patients. The aim of this study was to evaluate the efficacy of silymarin, an herbal drug with antioxidant and anti-inflammatory properties, in preventing the progression of diabetic nephropathy.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled, 2-arm parallel trial.
  
  
  METHODS
  60 patients with type 2 diabetes with macroalbuminuria (urinary albumin excretion >300 mg/24 h) despite treatment with the maximum dose of a renin-angiotensin system inhibitor for more than 6 months and estimated glomerular filtration rate >30 mL/min/1.73 m(2).
  
  
  METHODS
  Patients were randomly assigned to 2 equal groups to receive three 140-mg tablets of silymarin or 3 tablets of placebo daily for 3 months.
  
  
  RESULTS
  The primary outcome was absolute change in urinary albumin-creatinine ratio (UACR) from baseline to the end of the treatment phase.
  
  
  METHODS
  UACR and urinary and serum levels of TNF-α (tumor necrosis factor α; an inflammatory marker), malondialdehyde (MDA; an oxidative stress marker), and TGFβ (transforming growth factor β; a marker of fibrosis) at baseline and the end of the treatment phase.
  
  
  RESULTS
  Although UACR decreased in both groups, this decrement was significantly higher in the silymarin compared with the placebo group; mean difference in change in UACR between the 2 groups was -347 (95% CI, -690 to -4) mg/g. Urinary levels of TNF-α and urinary and serum levels of MDA also decreased significantly in the silymarin compared with the placebo group.
  
  
  CONCLUSIONS
  Small sample size and short duration of the treatment phase.
  
  
  CONCLUSIONS
  Silymarin reduces urinary excretion of albumin, TNF-α, and MDA in patients with diabetic nephropathy and may be considered as a novel addition to the anti-diabetic nephropathy armamentarium.
authors: AJA University of Medical Sciences, Tehran, Iran. kazem.fa@gmail.com
authors: Mohammad Kazem
authors: MK
authors: Fallahzadeh
authors: Banafshe
authors: B
authors: Dormanesh
authors: Mohammad Mahdi
authors: MM
authors: Sagheb
authors: Jamshid
authors: J
authors: Roozbeh
authors: Ghazal
authors: G
authors: Vessal
authors: Maryam
authors: M
authors: Pakfetrat
authors: Yahya
authors: Y
authors: Daneshbod
authors: Eskandar
authors: E
authors: Kamali-Sarvestani
authors: Kamran B
authors: KB
authors: Lankarani
mesh_terms: D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D000975:Antioxidants / Q000008:administration & dosage; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D012838:Silymarin / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D012838:Silymarin