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Abstract: TH-PO200

Effects of Lanthanum Carbonate on Mineral Metabolism in Normophosphatemic Patients with CKD: Secondary Analysis of the COMBINE Trial

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical


  • Isakova, Tamara, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States
  • Larive, Brett, Cleveland Clinic, Cleveland, Ohio, United States
  • Gassman, Jennifer J., Cleveland Clinic, Cleveland, Ohio, United States
  • Raphael, Kalani L., VA Salt Lake City Health Care System, Salt Lake City, Utah, United States
  • Cheung, Alfred K., University of Utah, Salt Lake City, Utah, United States
  • Raj, Dominic S., GWU Medical Faculty Associates, Washington, District of Columbia, United States
  • Fried, Linda F., VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, United States
  • Middleton, John Paul, Duke University, Durham, North Carolina, United States
  • Abbott, Kevin C., The National Institutes of Health, NIDDK, Bethesda, Maryland, United States
  • Mendley, Susan R., NIDDK/NIH, Bethesda, Maryland, United States
  • Block, Geoffrey A., Colorado Kidney Care, Denver, Colorado, United States
  • Ix, Joachim H., UCSD, San Diego, California, United States
  • Wolf, Myles, Duke University, Durham, North Carolina, United States
  • Sprague, Stuart M., NorthShore University HealthSystem University of Chicago Pritzker School of Medicine, Chicago, Illinois, United States

Group or Team Name

  • CKD Optimal Management with Binders and NicotinamidE (COMBINE) Investigators

Disordered mineral metabolism is a nearly universal complication of reduced kidney function that develops early in the course of CKD and is associated with adverse clinical outcomes. Strategies aimed at reducing dietary phosphate absorption may prevent abnormalities in markers of mineral metabolism, but data from large and long-term interventional studies are lacking.


The COMBINE trial was a randomized, double-blinded, 12-month, 4-group parallel trial of nicotinamide and lanthanum carbonate vs. placebo in 205 CKD stage 3–4 patients that tested the effects of active therapies on serum phosphate and FGF23 levels and on safety and tolerability. The primary results demonstrated that compared to placebo (n=51), lanthanum carbonate (n=50), nicotinamide (n=51) or dual treatment (n=53) did not significantly lower serum phosphate or FGF23. To determine the efficacy of each individual therapy, we performed secondary analyses to test the main effects of lanthanum carbonate (treated, n=103 vs. untreated, n=102) and nicotinamide (treated, n=104 vs. untreated, n=101).


At baseline, mean eGFR was 33±7 ml/min/1.73m2, serum phosphate was 3.7±0.5 mg/dL, FGF23 was 103.6 [IQR 76.8, 145.1] pg/ml, and PTH was 96 ± 64 pg/ml. Baseline characteristics were well-balanced across comparison groups. In intention to treat analyses, the overall 12-month effect of lanthanum carbonate treatment on serum phosphate was -0.051 mg/dL (95% CI= -0.191 to 0.089, P=0.48); FGF23 was -14.0% (95% CI= -24.2 to -3.7, P=0.0077); PTH was -6.7% pg/mL (95% CI= -20.1 to 6.9, P=0.33); FEPI was -3.56 (95% CI= -5.76 to -1.36, P=0.0016); and 24 hr urine phosphate/creatinine was -0.042 mg/dL (95% CI= -0.081 to -0.003, P=0.033). No significant effects were observed with nicotinamide treatment.


In a secondary analysis of the COMBINE trial, we demonstrated that lanthanum carbonate treatment decreased urinary phosphate excretion and reduced FGF23 levels. Our findings provide support for targeting dietary phosphate absorption to modify FGF23 levels in patients with CKD stages 3-4.


  • NIDDK Support