Efficacy and safety of tangshen formula on patients with type 2 diabetic kidney disease: a multicenter double-blinded randomized placebo-controlled trial

PLoS One. 2015 May 4;10(5):e0126027. doi: 10.1371/journal.pone.0126027. eCollection 2015.

Abstract

Background: Persons with diabetes are at high risk of developing diabetic kidney disease (DKD), which is associated with high morbidity and mortality. Current drug therapies for DKD, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), are not entirely satisfactory. This study aimed to evaluate the additional benefit and safety of the Chinese herbal granule Tangshen Formula (TSF) in treating DKD.

Methods: The study was designed as a six-center randomized, double-blind, placebo-controlled trial. From April 2007 through December 2009, 180 patients with DKD were enrolled. In addition to conventional treatment with ACEIs or ARBs, 122 participants were randomly assigned to receive TSF and 58 participants to receive placebo for 24 weeks. Primary outcome was urinary protein level, measured by urinary albumin excretion rate (UAER) for participants with microalbuminuria, 24-hour urinary protein (24h UP) for participants with macroalbuminuria. Secondary outcomes included renal function, serum lipids, quality of life, symptoms, and adverse events.

Findings: After 24 weeks of treatment, no statistically significant difference in UAER (TSF -19.53 μg/min compared with placebo -7.01 μg/min, with a mean difference of -12.52 μg/min; 95%CI, -68.67 to 43.63, P = 0.696) was found between TSF and placebo groups. However, TSF displayed a statistically significant decrease in 24h UP (TSF-0.21 g compared with placebo 0.36 g, with a mean difference of -0.57g; 95%CI, -1.05 to -0.09, P = 0.024). Estimated glomerular filtration rate (eGFR) was improved in both patients with microalbuminuria and macroalbuminuria, with a mean difference of 15.51 ml/min/1.73 m2 (95%CI, 3.71 to 27.31), 9.01 ml/min/1.73 m2 (95%CI, -0.10 to 18.13), respectively. Other secondary outcomes showed no statistically significant difference between groups or in the incidence of adverse events.

Conclusions: Based on conventional treatments, TSF appears to provide additional benefits compared with placebo in decreasing proteinuria and improving eGFR in DKD patients with macroalbuminuria. Nevertheless, further study is needed to evaluate TSF treating patients with microalbuminuria.

Trial registration: Chinese Clinical Trial Registry ChiCTR-TRC-10000843.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Diabetic Nephropathies / diagnosis
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / physiopathology
  • Drug Therapy, Combination
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / adverse effects
  • Drugs, Chinese Herbal / therapeutic use*
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Male
  • Medicine, Chinese Traditional
  • Middle Aged
  • Proteinuria / drug therapy
  • Proteinuria / urine
  • Treatment Outcome

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Drugs, Chinese Herbal

Grants and funding

This work was supported by a grant from the Major State Basic Research Development Program of China (973 Program) (No. 2005CB523503), the China International Science and Technology Cooperation (No.2006DFB31480), the China International Science and Technology Cooperation (No.2011DFA31860) and the Key Program of National Natural Science Foundation of China (No.81130066). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.