Lanthanum Carbonate Reduces Phosphorus Burden in Patients with CKD Stages 3 and 4

Sprague, Stuart M.; Abboud, Hanna E.; Qiu, Ping; Dauphin, Matthew; Zhang, Pinggao; Finn, William F.

doi:10.2215/cjn.02830608

Cited by 85 publications

(67 citation statements)

References 26 publications

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“…This contrasts with findings from prior studies of dietary phosphate restriction or phosphate binder use in CKD, which reported significant reductions in urinary phosphate excretion commensurate with the intensity of the interventions (9,13,15). Possible explanations for this lack of an effect are insufficient dietary phosphate restriction, lower doses of LC than in prior reports (15,17), withinperson variability in 24-hour urinary collections, and waning adherence with the interventions in later weeks of the study. Regardless of the mechanism, this null finding suggests that urinary phosphate may not be an ideal measure for monitoring adherence or titrating interventions aimed at reducing FGF23 levels in future interventional studies.…”

Section: Variablecontrasting

confidence: 94%

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Effects of Dietary Phosphate Restriction and Phosphate Binders on FGF23 Levels in CKD

Isakova

Barchi-Chung

Enfield

et al. 2013

Clinical Journal of the American Society of Nephrology

135

100

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SummaryBackground Elevated levels of fibroblast growth factor 23 (FGF23) are associated with increased risk of adverse outcomes in patients with CKD. Reducing dietary phosphate intake or absorption may decrease FGF23 levels, but data on the combined effects of dietary phosphate restriction and phosphate binders in CKD are limited.Design, setting, participants, & measurements In this 232 factorial, single-blinded, placebo-controlled, 3-month study, conducted between July 2009 and March 2012, 39 patients with CKD stages 3 or 4 and normal serum phosphate levels were randomly assigned to one of four groups: ad libitum diet plus lanthanum carbonate (LC) placebo (n=10), 900-mg phosphate diet plus LC placebo (n=10), ad libitum diet plus LC (n=11), or 900-mg phosphate diet plus LC (n=8). The dose of LC was 1000 mg three times daily with meals. Dietary restriction was accomplished with outpatient counseling. The primary end point was change in FGF23 levels from baseline.Results Compared with ad libitum diet, the 900-mg phosphate diet did not significantly reduce FGF23 levels (diet 3 time interaction, P=0.05). Compared with placebo, LC alone also did not significantly reduce FGF23 levels (LC 3 time interaction, P=0.21). However, the dual intervention significantly decreased FGF23 levels throughout the study period (diet 3 LC 3 time interaction, P=0.02), resulting in a 35% (95% confidence interval, 8%-62%) reduction by study end. ConclusionThe combination of LC plus counseling for a phosphate-restricted diet decreased FGF23 levels in patients with CKD stages 324 and normal serum phosphate levels.

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Section: Variablecontrasting

confidence: 94%

“…This fixed dose was chosen because it reduced urinary phosphate excretion safely and effectively in CKD stages 324 (13,15). Matching placebo was prescribed at the same frequency.…”

Section: Randomization Interventions and Adherencementioning

confidence: 99%

Effects of Dietary Phosphate Restriction and Phosphate Binders on FGF23 Levels in CKD

Isakova

Barchi-Chung

Enfield

et al. 2013

Clinical Journal of the American Society of Nephrology

135

100

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“…In physiologic studies of healthy humans, circulating FGF23 levels rose after 3-5 days of dietary phosphate loading in the absence of a significant increase in serum phosphate. [33][34][35] 40,41 Interventions that substantially lower dietary phosphate absorption typically 30,42,43 but not always 31,44 result in reductions in 24-hour urinary phosphate excretion, which may be detected even while serum phosphate levels remain unchanged. Inability to collect complete 24-hour urine collections or waning compliance with the interventions may complicate interpretation of 24-hour urinary phosphate data.…”

Section: Targeting Dietary Phosphate Absorption To Modify Phosphate Amentioning

confidence: 99%

Rationale and Approaches to Phosphate and Fibroblast Growth Factor 23 Reduction in CKD

Isakova

Sprague

et al. 2015

Journal of the American Society of Nephrology

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121

127

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Patients with CKD often progress to ESRD and develop cardiovascular disease (CVD), yet available therapies only modestly improve clinical outcomes. Observational studies report independent associations between elevated serum phosphate and fibroblast growth factor 23 (FGF23) levels and risks of ESRD, CVD, and death. Phosphate excess induces arterial calcification, and although elevated FGF23 helps maintain serum phosphate levels in the normal range in CKD, it may contribute mechanistically to left ventricular hypertrophy (LVH). Consistent epidemiologic and experimental findings suggest the need to test therapeutic approaches that lower phosphate and FGF23 in CKD. Dietary phosphate absorption is one modifiable determinant of serum phosphate and FGF23 levels. Limited data from pilot studies in patients with CKD stages 3-4 suggest that phosphate binders, low phosphate diets, or vitamin B3 derivatives, such as niacin or nicotinamide, may reduce dietary phosphate absorption and serum phosphate and FGF23 levels. This review summarizes current knowledge regarding the deleterious systemic effects of phosphate and FGF23 excess, identifies questions that must be addressed before advancing to a full-scale clinical outcomes trial, and presents a novel therapeutic approach to lower serum phosphate and FGF23 levels that will be tested in the COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE study.

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“…There is a concern that calcium preparations may induce hypercalcemia and accelerate ectopic calcification, even in nondialysis-dependent CKD (15,16). The efficacy of noncalcium-containing phosphate binders, such as sevelamer and lanthanum, has been confirmed for this indication (17,18); however, sevelamer must be taken in large quantities to achieve adequate efficacy and is commonly associated with gastrointestinal side effects, such as constipation and bloating (19). Lanthanum accumulation in bone and other tissues has also been observed, although no safety issues related to tissue accumulation have been identified so far (20).…”

Section: Introductionmentioning

confidence: 99%

Ferric Citrate Hydrate for the Treatment of Hyperphosphatemia in Nondialysis-Dependent CKD

Yokoyama

Hirakata

Akiba

et al. 2014

Clinical Journal of the American Society of Nephrology

109

124

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Background and objectives Ferric citrate hydrate is a novel iron-based phosphate binder being developed for hyperphosphatemia in patients with CKD.Design, setting, participants, & measurements A phase 3, multicenter, randomized, double blind, placebocontrolled study investigated the efficacy and safety of ferric citrate hydrate in nondialysis-dependent patients with CKD. Starting in April of 2011, 90 CKD patients (eGFR=9.2165.72 ml/min per 1.73 m 2 ) with a serum phosphate$5.0 mg/dl were randomized 2:1 to ferric citrate hydrate or placebo for 12 weeks. The primary end point was change in serum phosphate from baseline to the end of treatment. Secondary end points included the percentage of patients achieving target serum phosphate levels (2.5-4.5 mg/dl) and change in fibroblast growth factor-23 at the end of treatment.Results The mean change in serum phosphate was 21.29 mg/dl (95% confidence interval, 21.63 to 20.96 mg/dl) in the ferric citrate hydrate group and 0.06 mg/dl (95% confidence interval, 20.20 to 0.31 mg/dl) in the placebo group (P,0.001 for difference between groups). The percentage of patients achieving target serum phosphate levels was 64.9% in the ferric citrate hydrate group and 6.9% in the placebo group (P,0.001). Fibroblast growth factor-23 concentrations were significantly lower in patients treated with ferric citrate hydrate versus placebo (change from baseline [median], 2142.0 versus 67.0 pg/ml; P,0.001). Ferric citrate hydrate significantly increased serum iron, ferritin, and transferrin saturation compared with placebo (P=0.001 or P,0.001). Five patients discontinued active treatment because of treatment-emergent adverse events with ferric citrate hydrate treatment versus one patient with placebo. Overall, adverse drug reactions were similar in patients receiving ferric citrate hydrate or placebo, with gastrointestinal disorders occurring in 30.0% of ferric citrate hydrate patients and 26.7% of patients receiving placebo. ConclusionIn patients with nondialysis-dependent CKD, 12-week treatment with ferric citrate hydrate resulted in significant reductions in serum phosphate and fibroblast growth factor-23 while simultaneously increasing serum iron parameters.

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Lanthanum Carbonate Reduces Phosphorus Burden in Patients with CKD Stages 3 and 4

Abstract: Background and objectives: Lanthanum carbonate (FOSRENOL

Cited by 85 publications

References 26 publications

Effects of Dietary Phosphate Restriction and Phosphate Binders on FGF23 Levels in CKD

Effects of Dietary Phosphate Restriction and Phosphate Binders on FGF23 Levels in CKD

Rationale and Approaches to Phosphate and Fibroblast Growth Factor 23 Reduction in CKD

Ferric Citrate Hydrate for the Treatment of Hyperphosphatemia in Nondialysis-Dependent CKD

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