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Effects of phosphate binders in moderate CKD
Geoffrey A Block1, David C Wheeler, Martha S Persky
1Denver Nephrology, 130 Rampart Way, Suite 300b, Denver, CO 80230, USA. gablock@denverneph.net
Insights
Phosphate binders lower phosphorus in CKD patients but increase vascular calcification. Their safety and efficacy for chronic kidney disease (CKD) patients remain uncertain, despite managing mineral metabolism.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Pharmacology
Background:
- Phosphate binders are proposed for chronic kidney disease (CKD) patients due to phosphorus-mortality links.
- Safety and efficacy of phosphate binders in CKD are not well-established.
Purpose of the Study:
- To assess phosphate binders' effects on mineral metabolism and vascular calcification in moderate to advanced CKD.
- Evaluate changes in serum phosphorus, parathyroid hormone, and FGF23 levels.
Main Methods:
- 148 CKD patients (eGFR 20-45 ml/min/1.73 m²) were randomized to calcium acetate, lanthanum carbonate, sevelamer carbonate, or placebo.
- Primary endpoint: change in mean serum phosphorus over 9 months.
- Secondary endpoints included urine phosphorus, PTH, FGF23, and vascular calcification.
Main Results:
- Phosphate binders slightly reduced serum phosphorus (3.9 vs 4.1 mg/dl) and significantly decreased 24-hour urine phosphorus (by 22%).
- Serum intact parathyroid hormone stabilized with binders versus increasing with placebo (P=0.002).
- Binders significantly increased coronary artery and abdominal aorta calcification (18.1% and 15.4% median increase, respectively).
Conclusions:
- Phosphate binders effectively lower phosphorus and attenuate secondary hyperparathyroidism in CKD patients with near-normal phosphorus levels.
- However, phosphate binders promote vascular calcification progression.
- The overall safety and efficacy of phosphate binders in CKD remain uncertain.
Abstract:
Some propose using phosphate binders in the CKD population given the association between higher levels of phosphorus and mortality, but their safety and efficacy in this population are not well understood. Here, we aimed to determine the effects of phosphate binders on parameters of mineral metabolism and vascular calcification among patients with moderate to advanced CKD. We randomly assigned 148 patients with estimated GFR=20-45 ml/min per 1.73 m(2) to calcium acetate, lanthanum carbonate, sevelamer carbonate, or placebo. The primary endpoint was change in mean serum phosphorus from baseline to the average of months 3, 6, and 9. Serum phosphorus decreased from a baseline mean of 4.2 mg/dl in both active and placebo arms to 3.9 mg/dl with active therapy and 4.1 mg/dl with placebo (P=0.03). Phosphate binders, but not placebo, decreased mean 24-hour urine phosphorus by 22%. Median serum intact parathyroid hormone remained stable with active therapy and increased with placebo (P=0.002). Active therapy did not significantly affect plasma C-terminal fibroblast growth factor 23 levels. Active therapy did, however, significantly increase calcification of the coronary arteries and abdominal aorta (coronary: median increases of 18.1% versus 0.6%, P=0.05; abdominal aorta: median increases of 15.4% versus 3.4%, P=0.03). In conclusion, phosphate binders significantly lower serum and urinary phosphorus and attenuate progression of secondary hyperparathyroidism among patients with CKD who have normal or near-normal levels of serum phosphorus; however, they also promote the progression of vascular calcification. The safety and efficacy of phosphate binders in CKD remain uncertain.
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