Effects of nicotinamide and lanthanum carbonate on serum phosphate and fibroblast growth factor-23 in CKD: The COMBINE trial

Joachim H. Ix, Tamara Isakova, Brett Larive, Kalani L. Raphael, Dominic S. Raj, Alfred K. Cheung, Stuart M. Sprague, Linda F. Fried, Jennifer J. Gassman, John P. Middleton, Michael F. Flessner, Geoffrey A. Block, Myles Wolf

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Background Higher serum phosphate and fibroblast growth factor-23 (FGF23) levels may be modifiable to prevent cardiovascular disease in CKD. Short-term studies have reported modest efficacy in phosphate and FGF23 reduction with intestinal phosphate binders in CKD. Methods To investigate effects of lanthanum carbonate (LC; a phosphate binder) and/or nicotinamide (NAM; an inhibitor of active intestinal phosphate transport) on serum phosphate and FGF23 in stage 3b/4 CKD, we conducted a randomized trial among individuals with eGFR 20–45 ml/min per 1.73 m2 to NAM (750 mg twice daily) plus LC (1000 mg thrice daily), NAM plus LC placebo, LC plus NAM placebo, or double placebo for 12 months. Dual primary end points were change from baseline in serum phosphate and intact FGF23 concentrations. Results Mean eGFR for the 205 participants was 32ml/min per 1.73 m2. At baseline, serum phosphate was 3.7 mg/dl and median FGF23 was 99 pg/ml (10th, 90th percentiles: 59, 205). Mean rates of change in phosphate increased slightly over 12 months in all groups and did not differ significantly across arms. Similarly, percent changes in FGF23 per 12 months increased for all arms except LC plus placebo, and did not differ significantly across arms. Gastrointestinal symptoms limited adherence. Adverse events rates were similar across arms. Conclusions LC and/or NAM treatment did not significantly lower serum phosphate or FGF23 in stage 3b/4 CKD over 12 months. Although these agents appeared safe, intestinal symptoms limited adherence. Reducing phosphate and FGF23 in nondialysis CKD will require new approaches.

Original languageEnglish (US)
Pages (from-to)1096-1108
Number of pages13
JournalJournal of the American Society of Nephrology
Volume30
Issue number6
DOIs
StatePublished - Jun 2019
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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