Nicole M Lioufas1,2,3, Elaine M Pascoe4, Carmel M Hawley4,5,6, Grahame J Elder7,8,9,10, Sunil V Badve11,12,4, Geoffrey A Block13, David W Johnson4,5,6, Nigel D Toussaint14,2. 1. Department of Nephrology, The Royal Melbourne Hospital, Parkville, Australia. 2. Department of Medicine, University of Melbourne, Parkville, Australia. 3. Department of Nephrology, Western Health, Melbourne, Australia. 4. Australasian Kidney Trials Network, Brisbane, Australia. 5. Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia. 6. Translational Research Institute, Brisbane, Australia. 7. Department of Nephrology, Westmead Hospital, Sydney, Australia. 8. School of Medicine, University of Notre Dame, Sydney, Australia. 9. Department of Medicine, University of Sydney, Sydney, Australia. 10. Osteoporosis and Bone Biology Division, Garvan Institute of Medical Research, Darlinghurst, Australia. 11. Department of Nephrology, St. George Hospital, Sydney, Australia. 12. Renal and Metabolic Division, the George Institute for Global Health, University of New South Wales, Sydney, Australia. 13. Reata Pharmaceuticals, Plano, Texas. 14. Department of Nephrology, The Royal Melbourne Hospital, Parkville, Australia Nigel.Toussaint@mh.org.au.
Abstract
BACKGROUND: Benefits of phosphate-lowering interventions on clinical outcomes in patients with CKD are unclear; systematic reviews have predominantly involved patients on dialysis. This study aimed to summarize evidence from randomized controlled trials (RCTs) concerning benefits and risks of noncalcium-based phosphate-lowering treatment in nondialysis CKD. METHODS: We conducted a systematic review and meta-analyses of RCTs involving noncalcium-based phosphate-lowering therapy compared with placebo, calcium-based binders, or no study medication, in adults with CKD not on dialysis or post-transplant. RCTs had ≥3 months follow-up and outcomes included biomarkers of mineral metabolism, cardiovascular parameters, and adverse events. Outcomes were meta-analyzed using the Sidik-Jonkman method for random effects. Unstandardized mean differences were used as effect sizes for continuous outcomes with common measurement units and Hedge's g standardized mean differences (SMD) otherwise. Odds ratios were used for binary outcomes. Cochrane risk of bias and GRADE assessment determined the certainty of evidence. RESULTS: In total, 20 trials involving 2498 participants (median sample size 120, median follow-up 9 months) were eligible for inclusion. Overall, risk of bias was low. Compared with placebo, noncalcium-based phosphate binders reduced serum phosphate (12 trials, weighted mean difference -0.37; 95% CI, -0.58 to -0.15 mg/dl, low certainty evidence) and urinary phosphate excretion (eight trials, SMD -0.61; 95% CI, -0.90 to -0.31, low certainty evidence), but resulted in increased constipation (nine trials, log odds ratio [OR] 0.93; 95% CI, 0.02 to 1.83, low certainty evidence) and greater vascular calcification score (three trials, SMD, 0.47; 95% CI, 0.17 to 0.77, very low certainty evidence). Data for effects of phosphate-lowering therapy on cardiovascular events (log OR, 0.51; 95% CI, -0.51 to 1.17) and death were scant. CONCLUSIONS: Noncalcium-based phosphate-lowering therapy reduced serum phosphate and urinary phosphate excretion, but there was an unclear effect on clinical outcomes and intermediate cardiovascular end points. Adequately powered RCTs are required to evaluate benefits and risks of phosphate-lowering therapy on patient-centered outcomes.
BACKGROUND: Benefits of phosphate-lowering interventions on clinical outcomes in patients with CKD are unclear; systematic reviews have predominantly involved patients on dialysis. This study aimed to summarize evidence from randomized controlled trials (RCTs) concerning benefits and risks of noncalcium-based phosphate-lowering treatment in nondialysis CKD. METHODS: We conducted a systematic review and meta-analyses of RCTs involving noncalcium-based phosphate-lowering therapy compared with placebo, calcium-based binders, or no study medication, in adults with CKD not on dialysis or post-transplant. RCTs had ≥3 months follow-up and outcomes included biomarkers of mineral metabolism, cardiovascular parameters, and adverse events. Outcomes were meta-analyzed using the Sidik-Jonkman method for random effects. Unstandardized mean differences were used as effect sizes for continuous outcomes with common measurement units and Hedge's g standardized mean differences (SMD) otherwise. Odds ratios were used for binary outcomes. Cochrane risk of bias and GRADE assessment determined the certainty of evidence. RESULTS: In total, 20 trials involving 2498 participants (median sample size 120, median follow-up 9 months) were eligible for inclusion. Overall, risk of bias was low. Compared with placebo, noncalcium-based phosphate binders reduced serum phosphate (12 trials, weighted mean difference -0.37; 95% CI, -0.58 to -0.15 mg/dl, low certainty evidence) and urinary phosphate excretion (eight trials, SMD -0.61; 95% CI, -0.90 to -0.31, low certainty evidence), but resulted in increased constipation (nine trials, log odds ratio [OR] 0.93; 95% CI, 0.02 to 1.83, low certainty evidence) and greater vascular calcification score (three trials, SMD, 0.47; 95% CI, 0.17 to 0.77, very low certainty evidence). Data for effects of phosphate-lowering therapy on cardiovascular events (log OR, 0.51; 95% CI, -0.51 to 1.17) and death were scant. CONCLUSIONS: Noncalcium-based phosphate-lowering therapy reduced serum phosphate and urinary phosphate excretion, but there was an unclear effect on clinical outcomes and intermediate cardiovascular end points. Adequately powered RCTs are required to evaluate benefits and risks of phosphate-lowering therapy on patient-centered outcomes.
Authors: Geoffrey A Block; Steven Fishbane; Mariano Rodriguez; Gerard Smits; Shay Shemesh; Pablo E Pergola; Myles Wolf; Glenn M Chertow Journal: Am J Kidney Dis Date: 2014-11-04 Impact factor: 8.860
Authors: Marcelo M Lemos; Renato Watanabe; Aluízio B Carvalho; Alessandra D B Jancikic; Fabiana M R Sanches; Dejaldo M Christofalo; Sérgio A Draibe; Maria Eugênia F Canziani Journal: Clin Nephrol Date: 2013-07 Impact factor: 0.975
Authors: Alexander Grabner; Karla Schramm; Neerupma Silswal; Matt Hendrix; Christopher Yanucil; Brian Czaya; Saurav Singh; Myles Wolf; Sven Hermann; Jörg Stypmann; Giovana Seno Di Marco; Marcus Brand; Michael J Wacker; Christian Faul Journal: Sci Rep Date: 2017-05-16 Impact factor: 4.379