Effects of Lanthanum Carbonate on Whole-Body Phosphorus Balance in Patients with Stage 3b-4 CKD and Normophosphatemia

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Background: In CKD, elevated phosphorus, even within the normal range, is associated with cardiovascular disease (CVD) and mortality. However, in normophosphatemic CKD, phosphate binders do not improve vascular function, an independent predictor of CVD. Whether long-term treatment with phosphate binders affects phosphorus balance in CKD is unknown. Our objective was to determine phosphorus balance in normophosphatemic subjects with CKD 3b-4 after 12 weeks of treatment with lanthanum carbonate (LC) or placebo. Methods: A subset of 15 subjects with CKD 3b-4 and serum phosphorus within normal limits randomized to receive 12 weeks of LC or placebo investigating effects of phosphate lowering on vascular function (NCT02209636) volunteered to participate in this ancillary aim. At the end of 12 weeks, participants consumed a controlled diet (1000 mg/day phosphorus and 800 mg/day calcium) for 9 days and continued their randomly-assigned study drug (N=7 LC, N=8 placebo). Fasting morning blood samples and all stool and urine were collected during a 48-hour inpatient clinical research center stay at the end of the 9-day balance period. Phosphorus balance (mg/d) was determined by values averaged over the 48-hour period: Dietary phosphorus intake minus urine phosphorus minus fecal phosphorus. T-tests were used to compare means. Results: Mean age was 65±7y and mean eGFR was 33±6 mL/min/1.73m2. One patient randomized to LC was excluded from fecal phosphorus and phosphorus balance results due to insufficient stool. 24-hour urine phosphorus was lower with LC compared with placebo, but this did not reach statistical significance (388±60 v. 513±51, p=0.15). Fecal phosphorus was higher with LC compared with placebo (775±163 v. 259±141, p=0.03), and whole-body phosphorus balance was lower with LC compared with placebo (-131±163 v. 320±141, p=0.06). Conclusions: These results provide evidence that long-term treatment with the phosphate binder lanthanum carbonate may reduce whole-body phosphorus balance in patients with stage 3b-4 CKD and normophosphatemia. Whether this translates into beneficial clinical outcomes relevant to chronic-kidney disease-mineral and bone disorder warrants further investigation. Funding: NIDDK Support, Veterans Affairs Support

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