Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: an updated systematic review and meta-analysis

Jamal, Sophie A.; Vandermeer, Ben; Raggi, Paolo; Mendelssohn, David C.; Chatterley, Trish; Dorgan, Marlene; Lok, Charmaine E.; Fitchett, David; Tsuyuki, Ross T.

doi:10.1016/s0140-6736(13)60897-1

Cited by 397 publications

(280 citation statements)

References 29 publications

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“…The recent non-CBBs versus CBBs analysis by Jamal et al (9) and this meta-analysis showing lower mortality with sevelamer shift that paradigm and suggest a need to re-evaluate the recommendations of international guidelines for the management of hyperphosphatemia in CKD-MBD.…”

Section: Discussionmentioning

confidence: 91%

“…A Cochrane systematic review and meta-analysis to March of 2010 regarded data as insufficient to establish superiority of non-CBB agents over CBBs for mortality (8). However, using data to 2012, Jamal et al (9) reported significantly lower all-cause mortality with non-CBBs than CBBs and called for research to compare mortality among nonCBBs (9).…”

Section: Introductionmentioning

confidence: 99%

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Sevelamer Versus Calcium-Based Binders for Treatment of Hyperphosphatemia in CKD

Patel¹,

Bernard²,

Elder

2016

Clinical Journal of the American Society of Nephrology

154

106

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Background and objectives People with CKD stages 3-5 and on dialysis (5D) have dramatically increased mortality, which has been associated with hyperphosphatemia in many studies. Oral phosphate binders are commonly prescribed to lower serum phosphate. We conducted an updated meta-analysis of the noncalcium-based binder (non-CBB) sevelamer versus CBBs in CKD stages 3-5D.Design, setting, participants, & measurements Randomized, controlled trials comparing sevelamer with CBBs were identified through MEDLINE and the Cochrane Central Register of Controlled Trials. Patient-level outcomes included all-cause mortality, cardiovascular events and mortality, hospitalization, and adverse effects. Intermediate outcomes included vascular calcification and bone changes. Biochemical outcomes included serum phosphate, calcium, parathyroid hormone, lipids, and hypercalcemia. We conducted and reported this review according to Cochrane guidelines. ResultsWe included 25 studies to March 31, 2015 with 4770 participants (88% on hemodialysis). Patients receiving sevelamer had lower all-cause mortality (risk ratio [RR], 0.54; 95% confidence interval [95% CI], 0.32 to 0.93), no statistically significant difference in cardiovascular mortality (n=2712; RR, 0.33; 95% CI, 0.07 to 1.64), and an increase in combined gastrointestinal events of borderline statistical significance (n=384; RR, 1.42; 95% CI, 0.97 to 2.08). For biochemical outcomes, patients receiving sevelamer had lower total serum cholesterol (mean difference [MD], 220.2 mg/dl; 95% CI, 225.9 to 214.5 mg/dl), LDL-cholesterol (MD, 221.6 mg/dl; 95% CI, 227.9 to 215.4 mg/dl), and calcium (MD, 20.4 mg/dl; 95% CI, 20.6 to 20.2 mg/dl) and a reduced risk of hypercalcemia (RR, 0.30; 95% CI, 0.19 to 0.48). End of treatment intact parathyroid hormone was significantly higher for sevelamer (MD, 32.9 pg/ml; 95% CI, 0.1 to 65.7 pg/ml). Serum phosphate values showed no significant differences.Conclusions Patients with CKD stages 3-5D using sevelamer have lower all-cause mortality compared with those using CBBs. Because of a lack of placebo-controlled studies, questions remain regarding phosphate binder benefits for patients with CKD stages 3-5 and not on dialysis.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Sevelamer Versus Calcium-Based Binders for Treatment of Hyperphosphatemia in CKD

Patel¹,

Bernard²,

Elder

2016

Clinical Journal of the American Society of Nephrology

154

106

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“…These non-calcium-based phosphate binders have not shown superior phosphate or PTH reduction compared to calcium-based phosphate binders in head-to-head studies (51, 58, 59) but the studies have also focussed on 3 other outcomes; incidence of hypercalcaemia, mortality (60) and progression of vascular calcification (52,53,56,(61)(62)(63). Three systematic reviews have been published by Navaneethan et al (51) and Jamal et al (64,65) with different conclusions on whether there is a survival benefit when using non-calcium-based compared to calcium-based phosphate binders. It is unlikely that a sufficiently large study will be done to resolve this question.…”

Section: Phosphate Bindersmentioning

confidence: 99%

Pharmacological Management of Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease

Salam

Khwaja

Wilkie

2016

Drugs

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or Article Brief (if supplied by editors): As a 'Therapy in Practice' article, we would like this to provide a succinct, up-to-date clinically orientated guide to the optimum management of secondary hyperparathyroidism in patients with chronic kidney disease. The review should include an appropriate background to the development of SHPT. It should focus primarily on pharmacological treatments but as appropriate, non-pharmacological approaches (dietary, surgical) may be discussed to fully place pharmacological therapy in context. Submission date: 31 st March 2016Word count: 4156 Compliance with Ethical StandardsFunding and conflict of interest statement from each author: Takeaway messages from the article SHPT is associated with adverse outcomes in CKD and dialysis patients  Optimum PTH level is unclear in pre-dialysis CKD and the recommended range is wide for dialysis patients.  Management of SHPT is largely pharmacological focussing on lowering PTH  PTH lowering treatment has not shown improved cardiovascular risk, fractures and mortality. AbstractSecondary hyperparathyroidism (SHPT) is a common complication of CKD and is part of the chronic kidney disease-mineral bone disorder (CKD-MBD). SHPT is associated with increased risk of fracture and mortality, thus SHPT control is recommended as kidney function declines. Effective SHPT management becomes more difficult once skeletal and cardiovascular adverse effects associated with severe SHPT have become established. However, interventional studies to lower parathyroid hormone (PTH) have so far shown inconsistent results in improving patient-centred outcomes such as mortality, cardiovascular events and fracture. Pharmacological treatment effect on PTH level is also inconsistent between predialysis CKD and dialysis patients which adds to the complexity of SHPT management. This review aims to give an overview on the pathophysiology, pharmacological and non-pharmacological treatment for SHPT in CKD including some of the limitations of current therapeutic options.

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“…On the other hand, it has been suggested that patients with CKD stages 3-5D, with known vascular or valvular calcifications, should be considered at the highest CV risk; therefore, it seems reasonable to use this information to guide the management of CKD-MBD (3,(6)(7)(8). Nevertheless, the evidence from randomized clinical trials (RCTs) in dialysis patients is limited and contradictory results have been obtained on whether treatment of laboratory abnormalities or attenuation of the progression of calcifications actually affects mortality (3,(9)(10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Clinical and Practical Use of Calcimimetics in Dialysis Patients With Secondary Hyperparathyroidism

Bover

Ureña

Ruiz-García

et al. 2016

Clinical Journal of the American Society of Nephrology

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CKD and CKD-related mineral and bone disorders (CKD-MBDs) are associated with high cardiovascular and mortality risks. In randomized clinical trials (RCTs), no single drug intervention has been shown to reduce the high mortality risk in dialysis patients, but several robust secondary analyses point toward important potential beneficial effects of controlling CKD-MBD-related factors and secondary hyperparathyroidism. The advent of cinacalcet, which has a unique mode of action at the calcium-sensing receptor, represented an important step forward in controlling CKD-MBD. In addition, new RCTs have conclusively shown that cinacalcet improves achievement of target levels for all of the metabolic abnormalities associated with CKD-MBD and may also attenuate the progression of vascular and valvular calcifications in dialysis patients. However, a final conclusion on the effect of cinacalcet on hard outcomes remains elusive. Tolerance of cinacalcet is limited by frequent secondary side effects such as nausea, vomiting, hypocalcemia and oversuppression of parathyroid hormone, which may cause some management difficulties, especially for those lacking experience with the drug. Against this background, this review aims to summarize the results of studies on cinacalcet, up to and including the publication of the recent ADVANCE and EVOLVE RCTs, as well as recent post hoc analyses, and to offer practical guidance on how to improve the clinical management of the most frequent adverse events associated with cinacalcet, based on both currently available information and personal experience. In addition, attention is drawn to less common secondary effects of cinacalcet treatment and advisable precautions.

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Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: an updated systematic review and meta-analysis

Cited by 397 publications

References 29 publications

Sevelamer Versus Calcium-Based Binders for Treatment of Hyperphosphatemia in CKD

Sevelamer Versus Calcium-Based Binders for Treatment of Hyperphosphatemia in CKD

Pharmacological Management of Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease

Clinical and Practical Use of Calcimimetics in Dialysis Patients With Secondary Hyperparathyroidism

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