Phosphate Binders and Clinical Outcomes in Patients with Stage 5D Chronic Kidney Disease

Zoccali, Carmine; Mallamaci, Francesca; Cannata-Andía, Jorge B.

doi:10.1111/sdi.12416

Cited by 4 publications

(2 citation statements)

References 48 publications

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“…As a consequence, at present, the treatment of hyperphosphatemia is mostly driven by clinical experience and evaluation of the individual patient. 36 Hence, even though numerous drugs are already in use in clinical practice, the "ideal" phosphate binder still does not exist. It should be effective in binding dietary phosphate with low pill burden, minimal gastrointestinal or other untoward effects, and no interaction with other medications; it should be also devoid of safety concerns and inexpensive; 37 this is the reason why new phosphate binders have been approved over recent years and others are being investigated for the treatment of phosphate imbalance in CKD.…”

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confidence: 99%

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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confidence: 99%

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

Cernaro

Santoro

Lacquaniti

et al. 2016

IJNRD

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“…It is assumed that reduced phosphate intake will benefit CKD and ESRD patients equally, though Selamet et al [1] found no relationship between 24-hour urine phosphate excretion (a surrogate for oral phosphate intake) and all cause mortality in pre-dialysis patients, suggesting that phosphate intake is not directly linked to serum phosphate levels as it is in dialysis patients. Despite widespread use of oral phosphate binding medications, no clinical trial data support benefit on bone strength, cardiovascular events or death [2]. Observational studies suggest non-calcium binders minimize vascular calcification, but again clinical trial data are lacking.…”

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confidence: 99%

Optimal management of bone mineral disorders in chronic kidney disease and end stage renal disease

Lundquist

Nigwekar

2016

Current Opinion in Nephrology and Hypertension

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Purpose of review This review summarizes recent studies on chronic kidney disease-mineral bone disorders, with a focus on new developments in disease management. Recent findings The term chronic kidney disease-mineral bone disorder has come to describe an increasingly complex network of alterations in minerals and skeletal disorders that contribute to the significant cardiovascular morbidity and mortality seen in patients with chronic kidney disease and ESRD. Clinical studies continue to suggest associations with clinical outcomes, yet current clinical trials have failed to support causality. Variability in practice exists as current guidelines for management of bone-mineral disorders are often based on weak evidence. Recent studies implicate novel pathways for therapeutic intervention in clinical trials. Summary Mineral-bone disorders in chronic kidney disease arise from alterations in a number of molecules in an increasingly complex physiological network interconnecting bone and the cardiovascular system. Despite extensive associations with improved outcomes in a number of molecules, clinical trials have yet to prove causality and there is an absence of new therapies available to improve patient outcomes. Additional clinical trials that can incorporate the complexity of mineral bone disorders and with the ability to intervene on more than one pathway are needed to advance patient care.

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The challenge of controlling phosphorus in chronic kidney disease

Cannata‐Andía

Martin

2015

Nephrol. Dial. Transplant.

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The pathogenesis and management of chronic kidney disease-mineral bone disorders (CKD-MBD) has experienced major changes, but the control of serum phosphorus at all stages of CKD still seems to be a key factor to improve clinical outcomes. High serum phosphorus is the most important uremia-related, non-traditional risk factor associated with vascular calcification in CKD patients and in the general population. Phosphorus may also be one of the key elements linking vascular calcification with low bone turnover. The main hormones and factors that contribute to the kidney regulation of phosphorus and calcium include parathyroid hormone, FGF-23, klotho and 1,25-dihydroxyvitamin D (1,25(OH)2D). Serum phosphorus did not start rising until CKD 3b in contrast with the earlier changes observed with fibroblast growth factor-23 (FGF-23), Klotho, calcitriol and parathyroid hormone (PTH). Despite FGF-23 and PTH having synergic effects regarding phosphorus removal, they have opposite effects on 1,25(OH)2D3. At the same stages of CKD in which phosphorus retention appears to occur, calcium retention also occurs. As phosphorus accumulation is associated with poor outcomes, an important question without a clear answer is at which level-range should serum phosphorus be maintained at different stages of CKD to improve clinical outcomes. There are four main strategies to manage phosphate homeostasis; phosphorus dietary intake, administration of phosphate binder agents, effective control of hyperparathyroidism and to ensure in the CKD 5D setting, an adequate scheme of dialysis. Despite all the available strategies, and the introduction of new phosphate binder agents in the market, controlling serum phosphorus remains challenging, and hyperphosphatemia continues to be extremely common in CKD 5 patients. Furthermore, despite phosphate binding agents having proved to be effective in reducing serum phosphorus, their ultimate effects on clinical outcomes remain controversial. Thus, we still need well-designed, large-scale, placebo-controlled studies to definitively prove that the reduction of serum phosphorus by phosphate binders improves clinical outcomes.

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Phosphate Binders and Clinical Outcomes in Patients with Stage 5D Chronic Kidney Disease

Cited by 4 publications

References 48 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

Optimal management of bone mineral disorders in chronic kidney disease and end stage renal disease

The challenge of controlling phosphorus in chronic kidney disease

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