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Effects of different phosphate lowering strategies in patients with CKD on laboratory outcomes: A systematic review and NMA

BACKGROUND: Chronic kidney disease-mineral and bone disorder (CKD-MBD), a complication of chronic kidney disease, has been linked to reduced quality and length of life. High serum phosphate levels that result from CKD-MBD require phosphate-lowering agents, also known as phosphate binders. The object...

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Autores principales: Sekercioglu, Nigar, Angeliki Veroniki, Argie, Thabane, Lehana, Busse, Jason W., Akhtar-Danesh, Noori, Iorio, Alfonso, Cruz Lopes, Luciane, Guyatt, Gordon H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5331957/
https://www.ncbi.nlm.nih.gov/pubmed/28248961
http://dx.doi.org/10.1371/journal.pone.0171028
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author Sekercioglu, Nigar
Angeliki Veroniki, Argie
Thabane, Lehana
Busse, Jason W.
Akhtar-Danesh, Noori
Iorio, Alfonso
Cruz Lopes, Luciane
Guyatt, Gordon H.
author_facet Sekercioglu, Nigar
Angeliki Veroniki, Argie
Thabane, Lehana
Busse, Jason W.
Akhtar-Danesh, Noori
Iorio, Alfonso
Cruz Lopes, Luciane
Guyatt, Gordon H.
author_sort Sekercioglu, Nigar
collection PubMed
description BACKGROUND: Chronic kidney disease-mineral and bone disorder (CKD-MBD), a complication of chronic kidney disease, has been linked to reduced quality and length of life. High serum phosphate levels that result from CKD-MBD require phosphate-lowering agents, also known as phosphate binders. The objective of this systematic review is to compare the effects of available phosphate binders on laboratory outcomes in patients with CKD-MBD. METHODS: Data sources included MEDLINE and EMBASE from January 1996 to April 2016, and the Cochrane Register of Controlled Trials up to April 2016. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible randomized controlled trials (RCTs). Eligible trials enrolled patients with CKD-MBD and randomized them to receive calcium-based phosphate binders (delivered as calcium acetate, calcium citrate or calcium carbonate), non-calcium-based phosphate binders (NCBPB) (sevelamer hydrochloride, sevelamer carbonate, lanthanum carbonate, sucroferric oxyhydroxide and ferric citrate), phosphorus restricted diet (diet), placebo or no treatment and reported effects on serum levels of phosphate, calcium and parathyroid hormone. We performed Bayesian network meta-analyses (NMA) to calculate the effect estimates (mean differences) and 95% credible intervals for serum levels of phosphate, calcium and parathyroid hormone. We calculated direct, indirect and network meta-analysis estimates using random-effects models. We applied the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence for each pairwise comparison. RESULTS: Our search yielded 1108 citations; 71 RCTs were retrieved for full review and 16 proved eligible. Including an additional 13 studies from a previous review, 29 studies that enrolled 8335 participants proved eligible; 26 trials provided data for quantitative synthesis. Sevelamer, lanthanum, calcium, iron, diet and combinations of active treatments (calcium or sevelamer or lanthanum and combination of calcium and sevelamer) resulted in significantly lower serum phosphate as compared to placebo (moderate to very low quality of evidence). We found no statistically significant differences between active treatment categories in lowering serum phosphate. Sevelamer, lanthanum and diet resulted in lower serum calcium compared to calcium (moderate quality evidence for lanthanum and diet; low quality evidence for Sevelamer). Iron, sevelamer and calcium yielded lower parathyroid hormone levels as compared to lanthanum. Meta-regression analyses did not yield a statistically significant association between treatment effect and trial duration. DISCUSSION/CONCLUSIONS: We found few differences between treatments in impact on phosphate and differences in parathyroid hormone. Relative to calcium, sevelamer, lanthanum and diet showed significant reduction in serum calcium from baseline. Treatment recommendations should be based on impact on patient-important outcomes rather than on surrogate outcomes. Systematic review registration: PROSPERO CRD-42016032945
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spelling pubmed-53319572017-03-10 Effects of different phosphate lowering strategies in patients with CKD on laboratory outcomes: A systematic review and NMA Sekercioglu, Nigar Angeliki Veroniki, Argie Thabane, Lehana Busse, Jason W. Akhtar-Danesh, Noori Iorio, Alfonso Cruz Lopes, Luciane Guyatt, Gordon H. PLoS One Research Article BACKGROUND: Chronic kidney disease-mineral and bone disorder (CKD-MBD), a complication of chronic kidney disease, has been linked to reduced quality and length of life. High serum phosphate levels that result from CKD-MBD require phosphate-lowering agents, also known as phosphate binders. The objective of this systematic review is to compare the effects of available phosphate binders on laboratory outcomes in patients with CKD-MBD. METHODS: Data sources included MEDLINE and EMBASE from January 1996 to April 2016, and the Cochrane Register of Controlled Trials up to April 2016. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible randomized controlled trials (RCTs). Eligible trials enrolled patients with CKD-MBD and randomized them to receive calcium-based phosphate binders (delivered as calcium acetate, calcium citrate or calcium carbonate), non-calcium-based phosphate binders (NCBPB) (sevelamer hydrochloride, sevelamer carbonate, lanthanum carbonate, sucroferric oxyhydroxide and ferric citrate), phosphorus restricted diet (diet), placebo or no treatment and reported effects on serum levels of phosphate, calcium and parathyroid hormone. We performed Bayesian network meta-analyses (NMA) to calculate the effect estimates (mean differences) and 95% credible intervals for serum levels of phosphate, calcium and parathyroid hormone. We calculated direct, indirect and network meta-analysis estimates using random-effects models. We applied the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence for each pairwise comparison. RESULTS: Our search yielded 1108 citations; 71 RCTs were retrieved for full review and 16 proved eligible. Including an additional 13 studies from a previous review, 29 studies that enrolled 8335 participants proved eligible; 26 trials provided data for quantitative synthesis. Sevelamer, lanthanum, calcium, iron, diet and combinations of active treatments (calcium or sevelamer or lanthanum and combination of calcium and sevelamer) resulted in significantly lower serum phosphate as compared to placebo (moderate to very low quality of evidence). We found no statistically significant differences between active treatment categories in lowering serum phosphate. Sevelamer, lanthanum and diet resulted in lower serum calcium compared to calcium (moderate quality evidence for lanthanum and diet; low quality evidence for Sevelamer). Iron, sevelamer and calcium yielded lower parathyroid hormone levels as compared to lanthanum. Meta-regression analyses did not yield a statistically significant association between treatment effect and trial duration. DISCUSSION/CONCLUSIONS: We found few differences between treatments in impact on phosphate and differences in parathyroid hormone. Relative to calcium, sevelamer, lanthanum and diet showed significant reduction in serum calcium from baseline. Treatment recommendations should be based on impact on patient-important outcomes rather than on surrogate outcomes. Systematic review registration: PROSPERO CRD-42016032945 Public Library of Science 2017-03-01 /pmc/articles/PMC5331957/ /pubmed/28248961 http://dx.doi.org/10.1371/journal.pone.0171028 Text en © 2017 Sekercioglu et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Sekercioglu, Nigar
Angeliki Veroniki, Argie
Thabane, Lehana
Busse, Jason W.
Akhtar-Danesh, Noori
Iorio, Alfonso
Cruz Lopes, Luciane
Guyatt, Gordon H.
Effects of different phosphate lowering strategies in patients with CKD on laboratory outcomes: A systematic review and NMA
title Effects of different phosphate lowering strategies in patients with CKD on laboratory outcomes: A systematic review and NMA
title_full Effects of different phosphate lowering strategies in patients with CKD on laboratory outcomes: A systematic review and NMA
title_fullStr Effects of different phosphate lowering strategies in patients with CKD on laboratory outcomes: A systematic review and NMA
title_full_unstemmed Effects of different phosphate lowering strategies in patients with CKD on laboratory outcomes: A systematic review and NMA
title_short Effects of different phosphate lowering strategies in patients with CKD on laboratory outcomes: A systematic review and NMA
title_sort effects of different phosphate lowering strategies in patients with ckd on laboratory outcomes: a systematic review and nma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5331957/
https://www.ncbi.nlm.nih.gov/pubmed/28248961
http://dx.doi.org/10.1371/journal.pone.0171028
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