Abstract: PO1579
Biological Efficacy and Safety of Niacinamide in Patients with Autosomal Dominant Polycystic Kidney Disease
Session Information
- Cystic Kidney Diseases: Emerging Concepts, Biomarkers, and Clinical Trials
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
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