Use of Phosphate Binders in Chronic Kidney Disease
Use of Phosphate Binders in Chronic Kidney Disease
Recently, Block et al. performed a prospective, randomized, placebo-controlled pilot study of 148 patients in CKD stages 3b and 4 assigned to either one of three phosphate binders (sevelamer, lanthanum carbonate or calcium acetate) with a follow-up of 9 months. Patients were not overtly hyperphosphatemic, but had serum phosphate levels within or just above the normal range. The intention of this pilot trial was to gain insights concerning study designs for larger outcome trials tackling early phosphate retention and its regulation, secondary hyperparathyroidism development, calcification induction or progression. Although only minor decreases of serum phosphate and no effects on serum FGF23 levels were observed, patients on phosphate binders unexpectedly showed significantly higher progression rates in vascular calcification of coronary arteries (80.6 versus 18.1%, P = 0.05) and abdominal aorta (15.4 versus 3.4%; P = 0.03) than the placebo cohort (Fig. 1). Subanalysis of the three different phosphate binder groups showed that calcium acetate was by far the most potent inducer of this effect, albeit the two calcium-free binders were still not superior to placebo; however, these subgroups were by far too small to allow sustainable interpretations.
(Enlarge Image)
Figure 1.
Results on coronary artery calcification (CAC) progression in a placebo-controlled phosphate binder pilot trial in CKD stage 3b–4 patients (a) Active: n=65, on sevelamer carbonate (n=25), lanthanum carbonate (n=18), or calcium acetate (n=22); placebo: n=41, on matching placebo. (b) Results stratified for the three different binders. With permission from [40].
In a very similar scenario concerning CKD stage 3b–4, Hill et al. investigated calcium and phosphate balance in a small cohort of patients under metabolic ward conditions (complete stool and urine collection for a total of two weeks). Patients received defined diets containing an average daily amount of approximately 1 g calcium and 1.4 g phosphate for one week. In the second week, 500 mg calcium carbonate was added to each meal of these diets (Fig. 2). The quintessence of this study was that patients with moderate-to-advanced CKD were in neutral calcium and phosphate balance even when ingesting the above-mentioned amounts of calcium and phosphate. However, addition of the phosphate binder calcium carbonate triggered a clearly positive calcium balance and, surprisingly as well, phosphate balance remained unchanged. These results appear to be in accordance to the preliminary observations by Block et al. that the use of calcium-containing phosphate binders in predialysis CKD may increase the risk of progressive vascular calcification by rendering calcium accumulation.
(Enlarge Image)
Figure 2.
Results from a randomized, placebo-controlled, cross-over design metabolic study in eight chronic kidney disease stage 3b–4 patients: participants received diets containing mean levels of 957±23mg per day calcium and 1564±52mg per day phosphorus without (1 week) or with the addition of 500mg calcium carbonate (1 week) per meal. (a) Study flowchart. (b) Calcium balance with or without addition of calcium carbonate. Phosphate balance was neutral at baseline and remained unaltered by addition of calcium carbonate. With permission from [41].
Phosphate Binders and Phosphate Balance in Early Chronic Kidney Disease
Recently, Block et al. performed a prospective, randomized, placebo-controlled pilot study of 148 patients in CKD stages 3b and 4 assigned to either one of three phosphate binders (sevelamer, lanthanum carbonate or calcium acetate) with a follow-up of 9 months. Patients were not overtly hyperphosphatemic, but had serum phosphate levels within or just above the normal range. The intention of this pilot trial was to gain insights concerning study designs for larger outcome trials tackling early phosphate retention and its regulation, secondary hyperparathyroidism development, calcification induction or progression. Although only minor decreases of serum phosphate and no effects on serum FGF23 levels were observed, patients on phosphate binders unexpectedly showed significantly higher progression rates in vascular calcification of coronary arteries (80.6 versus 18.1%, P = 0.05) and abdominal aorta (15.4 versus 3.4%; P = 0.03) than the placebo cohort (Fig. 1). Subanalysis of the three different phosphate binder groups showed that calcium acetate was by far the most potent inducer of this effect, albeit the two calcium-free binders were still not superior to placebo; however, these subgroups were by far too small to allow sustainable interpretations.
(Enlarge Image)
Figure 1.
Results on coronary artery calcification (CAC) progression in a placebo-controlled phosphate binder pilot trial in CKD stage 3b–4 patients (a) Active: n=65, on sevelamer carbonate (n=25), lanthanum carbonate (n=18), or calcium acetate (n=22); placebo: n=41, on matching placebo. (b) Results stratified for the three different binders. With permission from [40].
In a very similar scenario concerning CKD stage 3b–4, Hill et al. investigated calcium and phosphate balance in a small cohort of patients under metabolic ward conditions (complete stool and urine collection for a total of two weeks). Patients received defined diets containing an average daily amount of approximately 1 g calcium and 1.4 g phosphate for one week. In the second week, 500 mg calcium carbonate was added to each meal of these diets (Fig. 2). The quintessence of this study was that patients with moderate-to-advanced CKD were in neutral calcium and phosphate balance even when ingesting the above-mentioned amounts of calcium and phosphate. However, addition of the phosphate binder calcium carbonate triggered a clearly positive calcium balance and, surprisingly as well, phosphate balance remained unchanged. These results appear to be in accordance to the preliminary observations by Block et al. that the use of calcium-containing phosphate binders in predialysis CKD may increase the risk of progressive vascular calcification by rendering calcium accumulation.
(Enlarge Image)
Figure 2.
Results from a randomized, placebo-controlled, cross-over design metabolic study in eight chronic kidney disease stage 3b–4 patients: participants received diets containing mean levels of 957±23mg per day calcium and 1564±52mg per day phosphorus without (1 week) or with the addition of 500mg calcium carbonate (1 week) per meal. (a) Study flowchart. (b) Calcium balance with or without addition of calcium carbonate. Phosphate balance was neutral at baseline and remained unaltered by addition of calcium carbonate. With permission from [41].
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