Serum Phosphate and Mortality in Patients with Chronic Kidney Disease

Eddington, Helen; Hoefield, Richard; Sinha, Smeeta; Chrysochou, Constantina; Lane, Beverley; Foley, Robert N.; Hegarty, Janet; New, John P.; O’Donoghue, Dónal; Middleton, Rachel; Kalra, Philip A.

doi:10.2215/cjn.00810110

Cited by 209 publications

(165 citation statements)

References 24 publications

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“…In CKD, elevated BMI is associated with reduced serum phosphate levels (18) and elevated FGF23 levels (19). Therefore, we performed formal tests for interaction between BMI and FGF23 and analyzed models stratified by BMI as lean (,25 kg/m 2 ), overweight (25 to ,30 kg/m 2 ) and obese ($30 kg/m 2 ) (20).…”

Section: Statistical Analysesmentioning

confidence: 99%

Fibroblast Growth Factor 23 and Inflammation in CKD

Mendoza

Isakova²,

Ricardo³

et al. 2012

Clinical Journal of the American Society of Nephrology

239

171

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SummaryBackground and objectives Levels of fibroblast growth factor 23 (FGF23) and inflammatory markers are commonly elevated in CKD, and each is associated with adverse clinical outcomes. This study tested the hypothesis that FGF23 is independently associated with inflammation in CKD.Design, setting, participants, & measurements The association between levels of FGF23 and the inflammatory markers IL-6, C-reactive protein (CRP), TNF-a, and fibrinogen was assessed in a cross-sectional analysis of 3879 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study between June 2003 and September 2008.Results FGF23 correlated directly with IL-6 (r=0.4), CRP (r=0.2), TNF-a (r=0.4), and fibrinogen (r=0.3; P,0.001 for each). In univariate and multivariable-adjusted linear regression analyses, natural log (ln) transformed FGF23 was significantly associated with lnIL-6, lnCRP, lnTNF-a, and fibrinogen (P,0.001 for each). Each unit higher lnFGF23 was associated with severe inflammation, defined as levels of all inflammatory markers in the highest 25th percentile, in univariate (odds ratio [OR], 2.4 [95% confidence interval (CI), 2.0-2.9]) and multivariable-adjusted (OR, 2.0 [95% CI, 1.6-2.5]) logistic regression analyses. Ascending FGF23 quartiles were independently associated with severe inflammation (OR, 5.6 for the highest versus lowest FGF23 quartile [95% CI, 2.3-13.9]; P for trend , 0.001).Conclusions Higher FGF23 levels are independently associated with higher levels of inflammatory markers in patients with CKD and with significantly greater odds of severe inflammation. Future studies should evaluate whether inflammation modifies the association between FGF23 and adverse outcomes in CKD.

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Section: Statistical Analysesmentioning

confidence: 99%

Fibroblast Growth Factor 23 and Inflammation in CKD

Mendoza

Isakova²,

Ricardo³

et al. 2012

Clinical Journal of the American Society of Nephrology

239

171

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“…However, as CKD progresses, the risk of hyperphosphatemia increases, because the limit of the ability of the kidney to excrete phosphate is reached (4)(5)(6). In patients with CKD, elevated serum phosphate is associated with vascular calcification (7,8), progression of CKD, and increased mortality (4,(9)(10)(11)(12). Consequently, the Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) (13) and the Japanese Society for Dialysis Therapy (14) recommend maintaining serum phosphate of CKD patients within the normal range.…”

Section: Introductionmentioning

confidence: 99%

Ferric Citrate Hydrate for the Treatment of Hyperphosphatemia in Nondialysis-Dependent CKD

Yokoyama

Hirakata

Akiba

et al. 2014

Clinical Journal of the American Society of Nephrology

111

124

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Background and objectives Ferric citrate hydrate is a novel iron-based phosphate binder being developed for hyperphosphatemia in patients with CKD.Design, setting, participants, & measurements A phase 3, multicenter, randomized, double blind, placebocontrolled study investigated the efficacy and safety of ferric citrate hydrate in nondialysis-dependent patients with CKD. Starting in April of 2011, 90 CKD patients (eGFR=9.2165.72 ml/min per 1.73 m 2 ) with a serum phosphate$5.0 mg/dl were randomized 2:1 to ferric citrate hydrate or placebo for 12 weeks. The primary end point was change in serum phosphate from baseline to the end of treatment. Secondary end points included the percentage of patients achieving target serum phosphate levels (2.5-4.5 mg/dl) and change in fibroblast growth factor-23 at the end of treatment.Results The mean change in serum phosphate was 21.29 mg/dl (95% confidence interval, 21.63 to 20.96 mg/dl) in the ferric citrate hydrate group and 0.06 mg/dl (95% confidence interval, 20.20 to 0.31 mg/dl) in the placebo group (P,0.001 for difference between groups). The percentage of patients achieving target serum phosphate levels was 64.9% in the ferric citrate hydrate group and 6.9% in the placebo group (P,0.001). Fibroblast growth factor-23 concentrations were significantly lower in patients treated with ferric citrate hydrate versus placebo (change from baseline [median], 2142.0 versus 67.0 pg/ml; P,0.001). Ferric citrate hydrate significantly increased serum iron, ferritin, and transferrin saturation compared with placebo (P=0.001 or P,0.001). Five patients discontinued active treatment because of treatment-emergent adverse events with ferric citrate hydrate treatment versus one patient with placebo. Overall, adverse drug reactions were similar in patients receiving ferric citrate hydrate or placebo, with gastrointestinal disorders occurring in 30.0% of ferric citrate hydrate patients and 26.7% of patients receiving placebo. ConclusionIn patients with nondialysis-dependent CKD, 12-week treatment with ferric citrate hydrate resulted in significant reductions in serum phosphate and fibroblast growth factor-23 while simultaneously increasing serum iron parameters.

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“…Clinical evidence demonstrates that hyperphosphatemia is associated with an adverse effect on renal or cardiovascular function and an increased mortality risk, independent of other traditional risk factors. [3][4][5] The Kidney Disease Outcomes Quality Initiative (KDOQI) in the USA have recommended serum phosphorus targets of 3.5-5.5 mg/dL (1.13-1.78 mmol/L) in patients receiving dialysis. 6 Despite dietary restriction and adequate dialysis, the majority of dialysis patients suffering from hyperphosphatemia still need oral phosphate binders to control their phosphate levels and thereby reduce mortality.…”

Section: Introductionmentioning

confidence: 99%

Effects and safety of iron-based phosphate binders in dialysis patients: a systematic review and meta-analysis

Zhai

Yang

et al. 2014

Renal Failure

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Aim: To assess the effects and safety of iron-based phosphate binders in adult patients receiving dialysis. Methods: We electronically searched MEDLINE, EMBASE, CENTRAL, and CBM for randomized controlled trials about iron-based phosphate binders in adult dialysis patients. Study quality was assessed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of intervention. Meta-analysis was conducted by RevMan 5.3. Results: Eight studies with 2018 participants were eligible for our meta-analysis. Iron-based phosphate binders were superior to placebo (MD ¼ À2.43 mg/dL, 95% CI: À3.18 to À1.68, p50.00001) and as efficient as sevelamer (MD ¼ 0.04 mg/dL, 95% CI: À0.29 to 0.36, p ¼ 0.83) in reducing serum phosphorus in dialysis patients. No significant differences were found in all adverse events (OR ¼ 1.30, 95% CI: 0.77 to 2.20, p ¼ 0.32) between iron-based phosphate binders and placebo. Iron-based phosphate binders were associated with significant higher serum iron (MD ¼ 9.39 ng/mL, 95% CI 1.48 to 17.30, p ¼ 0.02), higher serum transferring saturation (MD ¼ 6.29%, 95% CI 2.72 to 9.87, p ¼ 0.0006) and lower serum total iron binding capacity (MD ¼ À23.13 mg/dL, 95% CI À35.69 to À10.58, p ¼ 0.0003) in comparison to placebo. Conclusion: Iron-based phosphate binders are as effective as sevelamer and well tolerated for hyperphosphatemia in dialysis patients. Iron-based phosphate binders appear to have a beneficial effect on renal anemia in patients receiving dialysis. Therefore, iron-based phosphate binders may represent a new treatment option for dialysis patients.

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Serum Phosphate and Mortality in Patients with Chronic Kidney Disease

Cited by 209 publications

References 24 publications

Fibroblast Growth Factor 23 and Inflammation in CKD

Fibroblast Growth Factor 23 and Inflammation in CKD

Ferric Citrate Hydrate for the Treatment of Hyperphosphatemia in Nondialysis-Dependent CKD

Effects and safety of iron-based phosphate binders in dialysis patients: a systematic review and meta-analysis

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