Abstract: TH-PO511

Effect of Addition of Silybin and N-Acetylcysteine to Renin-Angiotensin System Inhibitors on Albuminuria in Type 2 Diabetic Patients with Overt Nephropathy: A Randomized Controlled Trial

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 305 CKD: Clinical Trials and Tubulointerstitial Disorders

Authors

  • Bansal, Shweta, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Hu, Shirley L, UTHealth Houston, McALlen, Texas, United States
  • Lee, Shuko, South Texas Veterans Health Care System, San Antonio, Texas, United States
  • Debnath, Subrata, University of Texas Health Science Center at San Anotonio, San Antonio, Texas, United States
  • Cunningham, Sue ED, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Velagapudi, Chakradhar, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
Background

A large proportion of patients with type 2 diabetes mellitus have diabetic nephropathy. Despite current therapies including hypertension control and renin-angiotensin system inhibitors, diabetic nephropathy progresses to end-stage renal disease in many of these patients. The aim of this study was to evaluate the efficacy of silybin and N-acetylcysteine (NAC), natural supplements with antioxidant and anti-inflammatory properties, in preventing the progression of diabetic nephropathy.

Methods

After institutional IRB and VA R&D approval, we conducted a randomized, double-blind, placebo-controlled, 5-arm parallel trial where subjects with diabetic nephropathy with albumin-creatinine ratio (ACR) of =/>150 mg/g and eGFR of 15-60 ml/min on the background of angiotensin inhibition after 1 month run-in period received either A) double placebo BID (n=16); or B) silybin placebo + NAC 600 mg BID (n=12); or C) silybin 480 mg + NAC placebo BID (n=16); or D) silybin 480 mg + NAC 600 mg BID (n=16); or E) silybin 960 mg + NAC 600 mg BID (n=15) for 3 months. Primary outcome was absolute change in urinary ACR from baseline to the end of the treatment phase.

Results

Overall, the study population was 62.97±7.48 years old, 89% male, 65% Hispanic, 27% non-Hispanic white and 7% non-Hispanic blacks, had BMI of 35.02±8.54 kg/m2, eGFR of 36.4±13.3 ml/min, and ACR of 702.8±608.5 mg/g at baseline. The baseline characteristics were similar across the treatment arms except for systolic and diastolic BP and fasting glucose. There was no difference in change in Urinary ACR in different arms (ΔUACR in B=-156±604.8, C=10.9±542.9, D=96.6±422.4 and E=353.7±732.7 mg/g) compared to placebo (ΔUACR in A=50.5±291.2, Anova p=ns). Moreover, the change in eGFR was not different in 4 treatment arms compared to placebo arm. Small sample size and short duration of the treatment phase were the major limitation of the study.

Conclusion

3-month intervention with dietary supplements silybin and NAC did not reduce urinary excretion of albumin in diabetic nephropathy patients in our study cohort.

Funding

  • Other NIH Support