FGF23 is independently associated with vascular calcification but not bone mineral density in patients at various CKD stages

Desjardins, Lucie; Liabeuf, Sophie; Renard, C.; Lenglet, Aurélie; Lemke, Horst‐Dieter; Choukroun, Gabriel; Drueke, Tilman B.; Massy, Ziad A.

doi:10.1007/s00198-011-1838-0

Cited by 193 publications

(151 citation statements)

References 40 publications

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“…These findings do not confirm the results of Desjardins et al (47) and Ureña et al (48) that FGF23 does not correlate with DXA BMD. This finding may be because of possible differences in patient populations and more importantly, the cross-sectional nature of these two studies.…”

Section: Discussioncontrasting

confidence: 78%

Bone Mineral Density and Serum Biochemical Predictors of Bone Loss in Patients with CKD on Dialysis

Malluche¹,

Davenport

Cantor³

et al. 2014

Clinical Journal of the American Society of Nephrology

122

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Background and objectives Use of bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) is controversial for diagnosing bone loss in CKD patients on dialysis. The alternative quantitative computed tomography (QCT) is expensive and requires high radiation exposure. This study compared the two techniques and evaluated serum biochemical parameters for prediction of bone loss.Design, setting, participants, & measurements This prospective study enrolled patients from dialysis centers throughout Kentucky. BMD of the spine and hip was measured at baseline and after 1 year by DXA and QCT. Customary and novel serum biochemical parameters were obtained at the same times, including calcium, phosphorus, whole and intact parathyroid hormone, bone-specific alkaline phosphatase, procollagen type 1 N-terminal propeptide, tartrate-resistant acid phosphatase-5b, Dickkopf-1, fibroblast growth factor, and sclerostin. Rates of detection of osteoporosis by DXA and QCT were compared. Correlations were calculated between baseline biochemical parameters and BMD at baseline and changes over 1 year. Multivariable regression was performed to adjust for age, sex, body mass index, and race.Results Eighty-one patients completed the study (mean age=52.6612.3 years, 56% men, 53% African American, and median dialysis vintage=41 months). At baseline, QCT and DXA of the spine identified similar rates of osteoporosis (13.6% and 13.6%), but at the hip, DXA identified more osteoporosis (22.2% versus 13.6%). At any site and by either method, 33.3% of the patients were osteoporotic. Baseline BMD correlated with sclerostin, intact parathyroid hormone, bone-specific alkaline phosphatase, tartrate-resistant acid phosphatase-5b, and fibroblast growth factor. At 1 year, hip QCT identified a higher number of patients experiencing bone loss (51.3%) than DXA (38.5%). After multivariable adjustment, baseline sclerostin and tartrate-resistant acid phosphatase-5b predicted bone loss measured by QCT of the hip; procollagen type 1 N-terminal propeptide predicted cortical spine bone gain by QCT.Conclusions QCT identified prospectively more bone loss at the hip than DXA. The baseline serum biochemical parameters sclerostin and tartrate-resistant acid phosphatase-5b were noninvasive independent predictors of bone loss in CKD patients on dialysis.

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Section: Discussioncontrasting

confidence: 78%

Bone Mineral Density and Serum Biochemical Predictors of Bone Loss in Patients with CKD on Dialysis

Malluche¹,

Davenport

Cantor³

et al. 2014

Clinical Journal of the American Society of Nephrology

122

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“…Furthermore, among the mineral metabolites we tested, FGF23 was most strongly correlated with each inflammatory marker, and FGF23 but not PTH or phosphate was associated with greater odds for severe inflammation in multivariable models. Given the associations between inflammation, atherosclerosis, and vascular calcification (21), and that some studies have shown association between elevated FGF23 and calcification in CKD and ESRD (22,23), these results provide new insight into another potential mechanism underlying the strong associations between elevated FGF23, cardiovascular disease, and mortality. Further studies are needed to determine whether FGF23 might contribute to atherosclerosis and vascular calcification by stimulating inflammation or whether inflammation might contribute to the development of vascular disease through effects on FGF23.…”

Section: Discussionmentioning

confidence: 82%

Fibroblast Growth Factor 23 and Inflammation in CKD

Mendoza

Isakova²,

Ricardo³

et al. 2012

Clinical Journal of the American Society of Nephrology

235

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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“…In patients with CKD, PTH and FGF-23 are increased as a compensatory response to maintain the phosphate balance from the early stages of CKD (2)(3)(4)(5). It has recently been suggested that hyperphosphatemia and FGF-23 are risks for vascular calcification, CKD progression, and death (28)(29)(30)(31)(32).…”

Section: Discussionmentioning

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

109

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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FGF23 is independently associated with vascular calcification but not bone mineral density in patients at various CKD stages

Cited by 193 publications

References 40 publications

Bone Mineral Density and Serum Biochemical Predictors of Bone Loss in Patients with CKD on Dialysis

Bone Mineral Density and Serum Biochemical Predictors of Bone Loss in Patients with CKD on Dialysis

Fibroblast Growth Factor 23 and Inflammation in CKD

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

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