Addition of silymarin to renin-angiotensin system blockers in normotensive patients with type 2 diabetes mellitus and proteinuria: a prospective randomized trial

Int Urol Nephrol. 2017 Dec;49(12):2195-2204. doi: 10.1007/s11255-017-1697-5. Epub 2017 Sep 25.

Abstract

Background: In the last decade, despite constant investigation, no current single treatment has been able to decrease the incidence of diabetic nephropathy and to significantly reduce progression of diabetic CKD.

Methods: Patients with type 2 diabetes mellitus and proteinuria (>0.5 g/day) after a screening and treatment optimization phase were randomly assigned to receive silymarin or placebo. The primary outcome was a composite outcome: mortality, decline of eGFR > 50% and renal replacement therapy. Secondary outcomes were a composite renal outcome (defined as a decline of eGFR ≥ 50% or ESRD) and also to test the effect of silymarin on the change in eGFR and proteinuria. We also assessed the adverse effects (hospitalizations, headache or gastrointestinal symptoms) during the study.

Results: One hundred and two patients were included in the study. There were no significant differences between the two study groups regarding the primary and renal outcomes (HR 0.62, 95% CI 0.3-1.2, p = 0.15; HR 0.56, 95% CI 0.26-1.24, p = 0.16, respectively). At study end, eGFR declined significantly in both arms (p < 0.001), irrespective of the treatment group allocation, and there were no significant changes in proteinuria. There was a significant difference in hospitalizations rates between the two study groups (0.61, 95% CI 0.44-0.85).

Conclusions: Silymarin did not show a significant reduction in the primary and secondary outcomes. Importantly, silymarin treatment was associated with a significant reduction in the hospitalization rate.

Keywords: Chronic kidney disease; Diabetes mellitus; Proteinuria; Silymarin; Survival.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Antihypertensive Agents / therapeutic use*
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetic Nephropathies / complications
  • Diabetic Nephropathies / physiopathology
  • Diabetic Nephropathies / therapy*
  • Disease Progression
  • Female
  • Glomerular Filtration Rate / drug effects*
  • Hospitalization / statistics & numerical data
  • Humans
  • Kidney Failure, Chronic / etiology
  • Male
  • Middle Aged
  • Prospective Studies
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*
  • Proteinuria / etiology
  • Renal Replacement Therapy
  • Silymarin / pharmacology
  • Silymarin / therapeutic use*
  • Survival Rate

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Protective Agents
  • Silymarin