Joachim H Ix1,2,3, Tamara Isakova4,5,6, Brett Larive7, Kalani L Raphael8,9, Dominic S Raj10, Alfred K Cheung8,9, Stuart M Sprague11, Linda F Fried12,13,14, Jennifer J Gassman7, John P Middleton15,5,16, Michael F Flessner17, Geoffrey A Block18, Myles Wolf15,5,16. 1. Division of Nephrology-Hypertension, Department of Medicine and joeix@ucsd.edu. 2. Nephrology Section, Veterans Affairs San Diego Healthcare System, La Jolla, California. 3. Division of Preventive Medicine, Department of Family Medicine and Public Health, University of California San Diego, San Diego, California. 4. Division of Nephrology and Hypertension. 5. Department of Medicine, and. 6. Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 7. Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio. 8. Salt Lake City Veterans Affairs Healthcare System and. 9. Division of Nephrology and Hypertension, University of Utah Health, Salt Lake City, Utah. 10. Division of Renal Diseases and Hypertension, George Washington University, Washington, DC. 11. Division of Nephrology, Department of Medicine, NorthShore University Health System-University of Chicago, Pritzker School of Medicine, Evanston, Illinois. 12. Renal Section. 13. Veterans Affairs Pittsburgh Healthcare System, and. 14. University of Pittsburgh School of Medicine and University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania. 15. Division of Nephrology. 16. Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina. 17. Division of Kidney, Urologic, and Hematologic Disorders, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; and. 18. Denver Nephrology, Denver, Colorado.
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 toNAM (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.
RCT Entities:
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.
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