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Kidney Week

Abstract: PO1579

Biological Efficacy and Safety of Niacinamide in Patients with Autosomal Dominant Polycystic Kidney Disease

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic

Authors

  • El Ters, Mireille, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Zhou, Xia, University of Kansas Medical Center, Kansas City, Kansas, United States
  • Lepping, Rebecca J., University of Kansas Medical Center, Kansas City, Kansas, United States
  • Lu, Pengcheng, University of Kansas Medical Center, Kansas City, Kansas, United States
  • Mahnken, Jonathan D., University of Kansas Medical Center, Kansas City, Kansas, United States
  • Brooks, William M., University of Kansas Medical Center, Kansas City, Kansas, United States
  • Winklhofer, Franz, University of Kansas Medical Center, Kansas City, Kansas, United States
  • Li, Xiaogang, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States
  • Yu, Alan S.L., University of Kansas Medical Center, Kansas City, Kansas, United States
Background

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst enlargement,leading to kidney failure. Sirtuin-1 is upregulated in ADPKD and accelerates disease progression by deacetylating p53. Niacinamide is a dietary supplement that inhibits sirtuins at high doses.

Methods

We conducted an open-label, single arm intervention trial (Study 1, N=10),and a randomized,double blinded, placebo-controlled trial (Study 2, N=36) to assess the biological activity and safety of niacinamide. Patients with ADPKD were given 30 mg/kg oral niacinamide or placebo, for 12 months. Primary endpoint was ratio of acetylated p53 to total p53 protein in peripheral blood mononuclear cells. Secondary outcomes were change in height-adjusted total kidney volume (ht-TKV) and overall pain and quality of life scores. Other biomarkers of efficacy included serum creatinine,CRP,urine protein/creatinine and urine MCP1/creatinine ratios.

Results

There were no statistically significant differences in the baseline characteristics between treatment arms. There was no sustained effect of niacinamide on acetylated/total p53 ratio in either study. In study 1, the ratio was higher at 1 month (p= 0.003) but not at 6 and 12 months and no difference was noted between placebo and niacinamide arms in study 2 (p=0.51). There was no difference in the change of ht-TKV from baseline to 12 months between niacinamide and placebo. Ht-TKV increased slightly from 1049 to 1082 ml/m (p=0.71) with small eGFR decline from 83.6 to 81 ml/min/1.73 m2 (p=0.84) in niacinamide treated patients (combined study 1+2). Furthermore,there was no statistical difference in urine MCP1/creatinine, urine protein/creatinine and quality of life scores over time. Niacinamide was generally well-tolerated. Most common adverse effects were nausea, diarrhea, gastroesophageal reflux (combined GI symptoms:70% in study 1,78% in study 2 niacinamide treatment arm and 58% placebo), headache and acneiform rash with no difference in their incidence between niacinamide and placebo.

Conclusion

Niacinamide is safe and well-tolerated in ADPKD patients. However, we were unable to detect a sustained inhibition of sirtuin activity over 12 months of treatment, and there was no signal to suggest a beneficial effect on any efficacy measure.

Funding

  • Other NIH Support