• 1 Department of Nephrology, The Royal Melbourne Hospital, Parkville, Victoria, Australia
  • 2 Department of Medicine, The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia
  • 3 Department of Nephrology, The Royal Melbourne Hospital, Parkville, Victoria, Australia
  • 4 School of Medicine, University of Notre Dame, Sydney, New South Wales, Australia
  • 5 Australasian Kidney Trials Network, The University of Queensland, Brisbane, Queensland, Australia
  • 6 St. George Hospital, Sydney, New South Wales, Australia
  • 7 Reata Pharmaceuticals, Plano, Texas
  • 8 Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
  • 9 Monash Cardiovascular Research Centre, Monash Heart, Monash Health, Clayton, Victoria, Australia
  • 10 Department of Nephrology, Princess Alexandra Hospital, Brisbane, Queensland, Australia
  • 11 Epworth Healthcare, Melbourne, Victoria, Australia
  • 12 Department of Medicine, University of Adelaide, Adelaide, South Australia, Australia
  • 13 Monash Health, Clayton, Victoria, Australia
  • 14 Concord Repatriation and General Hospital, Concord, New South Wales, Australia
  • 15 Department of Medicine, Monash University, Clayton, Victoria, Australia
  • 16 Sultanah Aminah Hospital, Johor Bahru, Malaysia
  • 17 Renal and Metabolic Division, The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia
  • 18 Kolling Institute, Royal North Shore Hospital, University of Sydney, Sydney, New South Wales, Australia
  • 19 Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
  • 20 Queen Mary Hospital, University of Hong Kong, Hong Kong
J. Am. Soc. Nephrol., 2020 Sep 11.
PMID: 32917784 DOI: 10.1681/ASN.2020040411


BACKGROUND: Hyperphosphatemia is associated with increased fibroblast growth factor 23 (FGF23), arterial calcification, and cardiovascular mortality. Effects of phosphate-lowering medication on vascular calcification and arterial stiffness in CKD remain uncertain.

METHODS: To assess the effects of non-calcium-based phosphate binders on intermediate cardiovascular markers, we conducted a multicenter, double-blind trial, randomizing 278 participants with stage 3b or 4 CKD and serum phosphate >1.00 mmol/L (3.10 mg/dl) to 500 mg lanthanum carbonate or matched placebo thrice daily for 96 weeks. We analyzed the primary outcome, carotid-femoral pulse wave velocity, using a linear mixed effects model for repeated measures. Secondary outcomes included abdominal aortic calcification and serum and urine markers of mineral metabolism.

RESULTS: A total of 138 participants received lanthanum and 140 received placebo (mean age 63.1 years; 69% male, 64% White). Mean eGFR was 26.6 ml/min per 1.73 m2; 45% of participants had diabetes and 32% had cardiovascular disease. Mean serum phosphate was 1.25 mmol/L (3.87 mg/dl), mean pulse wave velocity was 10.8 m/s, and 81.3% had abdominal aortic calcification at baseline. At 96 weeks, pulse wave velocity did not differ significantly between groups, nor did abdominal aortic calcification, serum phosphate, parathyroid hormone, FGF23, and 24-hour urinary phosphate. Serious adverse events occurred in 63 (46%) participants prescribed lanthanum and 66 (47%) prescribed placebo. Although recruitment to target was not achieved, additional analysis suggested this was unlikely to have significantly affected the principle findings.

CONCLUSIONS: In patients with stage 3b/4 CKD, treatment with lanthanum over 96 weeks did not affect arterial stiffness or aortic calcification compared with placebo. These findings do not support the role of intestinal phosphate binders to reduce cardiovascular risk in patients with CKD who have normophosphatemia.

CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Australian Clinical Trials Registry, ACTRN12610000650099.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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