The future of phosphate binders: a perspective on novel therapeutics

Cernaro, Valeria; Santoro, Domenico; Lucisano, Silvia; Nicocia, Giacomo; Lacquaniti, Antonio; Buemi, Michele

doi:10.1517/13543784.2014.962652

Cited by 17 publications

(19 citation statements)

References 23 publications

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“…49 Another major problem for the nephrologist is when to start treatment of hyperphosphatemia. As hypothesized for traditional phosphate binders, 23 also iron-based binders may potentially be more effective in slowing down CKD-MBD progression if started earlier in stage 3-4 CKD. Indeed, phosphate appears not to be the ideal biomarker of calcium/phosphate imbalance since its serum levels are maintained within the normal range for a long time by the compensatory increase in parathyroid hormone and, even first, FGF23.…”

Section: Resultsmentioning

confidence: 99%

“…The consequences are the following: secondary hyperparathyroidism, altered phosphorus and calcium serum levels, increased bone remodeling, vascular calcifications, and further FGF23 production. 23 Moreover, high FGF23 is an important risk factor for cardiovascular disease since it has been associated with left ventricular hypertrophy, activation of the renin-angiotensin system, increased sodium absorption in the renal distal tubules with subsequent sodium retention and volume expansion, increased markers of inflammation, and oxidative stress. 24 The control of serum phosphate and FGF23 levels in CKD patients is therefore essential to preserve bone mineral content, prevent hyperparathyroidism, and reduce cardiovascular risk.…”

Section: Introduction To the Epidemiology And Management Issues In Ckdmentioning

confidence: 99%

“…Depending on the presence or absence of calcium in their molecular structure, phosphate binders can be classified as calcium-based and calcium-free. 23 …”

mentioning

confidence: 99%

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Phosphate binders for the treatment of chronic kidney disease: role of iron oxyhydroxide

Cernaro

Santoro

Lacquaniti

et al. 2016

IJNRD

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Chronic kidney disease-mineral bone disorder is frequent in patients with renal failure. It is characterized by abnormalities in mineral and bone metabolism with resulting hyperphosphatemia, low serum vitamin D, secondary hyperparathyroidism, altered bone morphology and strength, higher risk of bone fractures, and development of vascular or other soft tissue calcifications. Besides the recommendation to reduce phosphorus dietary intake, many drugs are currently available for the treatment of calcium/phosphate imbalance. Among them, phosphate binders represent a milestone. Calcium-based binders (calcium carbonate, calcium acetate) are effective in lowering serum phosphate, but their use has been associated with an increased risk of hypercalcemia and calcifications. Calcium-free binders (sevelamer hydrochloride, sevelamer carbonate, and lanthanum carbonate) are equally or slightly less effective than calcium-containing compounds. They would not induce an increase in calcium levels but may have relevant side effects, including gastrointestinal symptoms for sevelamer and risk of tissue accumulation for lanthanum. Accordingly, new phosphate binders are under investigation and some of them have already been approved. A promising option is sucroferric oxyhydroxide (Velphoro ® , PA21), an iron-based phosphate binder consisting of a mixture of polynuclear iron(III)-oxyhydroxide, sucrose, and starches. The present review is focused on pharmacology, mode of action, and pharmacokinetics of sucroferric oxyhydroxide, with a discussion on comparative efficacy, safety, and tolerability studies of this drug in chronic kidney disease and patient perspectives such as quality of life, satisfaction, and acceptability. Sucroferric oxyhydroxide has proven to be as effective as sevelamer in reducing phosphatemia with a similar safety profile and lower pill burden. Experimental and clinical studies have documented a minimal percentage of iron absorption without inducing toxicity. In conclusion, the overall benefit-risk balance of sucroferric oxyhydroxide is deemed to be positive, and this new drug may therefore represent a good alternative to traditional phosphate binders for the treatment of hyperphosphatemia in dialysis patients.

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Section: Resultsmentioning

confidence: 99%

Section: Introduction To the Epidemiology And Management Issues In Ckdmentioning

confidence: 99%

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Phosphate binders for the treatment of chronic kidney disease: role of iron oxyhydroxide

Cernaro

Santoro

Lacquaniti

et al. 2016

IJNRD

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“…Even though serum creatinine and SUN gradually decreased in the treatment period as a whole, this reduction was not enough to improve renal function for normalizing the serum calcium level. On the other hand, 1,25(OH) 2 D 3 , which controls serum calcium levels by promoting calcium absorption from the intestines and increasing bone resorption [26], and bone metabolism markers, which help us estimate the inflow and outflow of calcium in bone through bone metabolism, were not measured. Therefore, the reason remains unknown.…”

Section: Discussionmentioning

confidence: 99%

PA21, a novel phosphate binder, improves renal osteodystrophy in rats with chronic renal failure

et al. 2017

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The effects of PA21, a novel iron-based and non-calcium-based phosphate binder, on hyperphosphatemia and its accompanying bone abnormality in chronic kidney disease-mineral and bone disorder (CKD-MBD) were evaluated. Rats with adenine-induced chronic renal failure (CRF) were prepared by feeding them an adenine-containing diet for four weeks. They were also freely fed a diet that contained PA21 (0.5, 1.5, and 5%), sevelamer hydrochloride (0.6 and 2%) or lanthanum carbonate hydrate (0.6 and 2%) for four weeks. Blood biochemical parameters were measured and bone histomorphometry was performed for femurs, which were isolated after drug treatment. Serum phosphorus and parathyroid hormone (PTH) levels were higher in the CRF rats. Administration of phosphate binders for four weeks decreased serum phosphorus and PTH levels in a dose-dependent manner and there were significant decreases in the AUC0–28 day of these parameters in 5% PA21, 2% sevelamer hydrochloride, and 2% lanthanum carbonate hydrate groups compared with that in the CRF control group. Moreover, osteoid volume improved significantly in 5% of the PA21 group, and fibrosis volume and cortical porosity were ameliorated in 5% PA21, 2% sevelamer hydrochloride, and 2% lanthanum carbonate hydrate groups. These results suggest that PA21 is effective against hyperphosphatemia, secondary hyperparathyroidism, and bone abnormalities in CKD-MBD as sevelamer hydrochloride and lanthanum carbonate hydrate are, and that PA21 is a new potential alternative to phosphate binders.

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“…Whatever the mechanism, since pathogenesis of chronic kidney disease‐mineral bone disorder (CKD‐MBD) is not yet fully understood and this impairs the effectiveness of the currently available therapeutic strategies, it is not possible to rule out that other factors, such as semaphorin 3A, are involved in the pathophysiology of renal osteodystrophy in addition to those already known.…”

Section: Discussionmentioning

confidence: 99%

Semaphorin 3A serum levels are influenced by haemodialysis: What clinical significance?

et al. 2015

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The future of phosphate binders: a perspective on novel therapeutics

Cited by 17 publications

References 23 publications

Phosphate binders for the treatment of chronic kidney disease: role of iron oxyhydroxide

Phosphate binders for the treatment of chronic kidney disease: role of iron oxyhydroxide

PA21, a novel phosphate binder, improves renal osteodystrophy in rats with chronic renal failure

Semaphorin 3A serum levels are influenced by haemodialysis: What clinical significance?

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