Fractional Excretion of Phosphorus Modifies the Association between Fibroblast Growth Factor-23 and Outcomes

Dominguez, Julie R.; Shlipak, Michael G.; Whooley, Mary A.; Ix, Joachim H.

doi:10.1681/asn.2012090894

Cited by 81 publications

(105 citation statements)

References 31 publications

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“…Importantly, the association between FGF23 and outcomes does seem modified by a number of factors, most notably, vitamin D status and FEP (54)(55)(56). Those patients with both high FGF23 and low 25(OH)D/1,25(OH) 2 D or high FGF23 and low FEP seem to have the greatest risks of left ventricular remodeling (54), poor renal survival, and cardiovascular events (55). Thus, these measures may provide complementary information, and the use of biomarker panels may enhance risk stratification further.…”

Section: Fgf23 and Adverse Outcomes In Ckdmentioning

confidence: 99%

The Use of Fibroblast Growth Factor 23 Testing in Patients with Kidney Disease

Smith

2014

Clinical Journal of the American Society of Nephrology

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The emergence of fibroblast growth factor 23 as a potentially modifiable risk factor in CKD has led to growing interest in its measurement as a tool to assess patient risk and target therapy. This review discusses the analytical and clinical challenges faced in translating fibroblast growth factor 23 testing into routine practice. As for other bone mineral markers, agreement between commercial fibroblast growth factor 23 assays is poor, mainly because of differences in calibration, but also, these differences reflect the variable detection of hormone fragments. Direct comparison of readout from different assays is consequently limited and likely hampers setting uniform fibroblast growth factor 23-directed targets. Efforts are needed to standardize assay output to enhance clinical use. Fibroblast growth factor 23 is robustly associated with cardiovascular and renal outcomes in patients with CKD and adds value to risk assessments based on conventional risk factors. Compared with most other mineral markers, fibroblast growth factor 23 shows better intraindividual temporal stability, with minimal diurnal and week-to-week variability, but substantial interindividual variation, maximizing discriminative power for risk stratification. Conventional therapeutic interventions for the CKD-mineral bone disorder, such as dietary phosphate restriction and use of oral phosphate binders or calcimimetics, are associated with variable efficacy at modulating circulating fibroblast growth factor 23 concentrations, like they are for other mineral metabolites. Dual therapy with dietary phosphate restriction and noncalcium-based binder use achieves the most consistent fibroblast growth factor 23-lowering effect and seems best monitored using an intact assay. Additional studies are needed to evaluate whether strategies aimed at reducing levels or antagonizing its action have beneficial effects on clinical outcomes in CKD patients. Moreover, a better understanding of the mechanisms driving fibroblast growth factor 23 elevations in CKD is needed to inform the use of therapeutic interventions targeting fibroblast growth factor 23 excess. This evidence must be forthcoming to support the use of fibroblast growth factor 23 measurement and fibroblast growth factor 23-directed therapy in the clinic.

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Section: Fgf23 and Adverse Outcomes In Ckdmentioning

confidence: 99%

The Use of Fibroblast Growth Factor 23 Testing in Patients with Kidney Disease

Smith

2014

Clinical Journal of the American Society of Nephrology

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“…Recent studies suggest that high circulating FGF-23 concentrations may also be due in part to tubular FGF-23 resistance, a state of tubular dysfunction that may also increase risk of AKI (8). Although recent evidence suggests that FGF-23 is elevated at the time of AKI (9), there are no studies of which we are aware that have evaluated whether circulating levels of FGF-23 are a risk factor for AKI incidence.…”

Section: Introductionmentioning

confidence: 99%

Fibroblast Growth Factor-23 and the Long-Term Risk of Hospital-Associated AKI among Community-Dwelling Older Individuals

Brown¹,

Katz²,

Ix³

et al. 2014

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives AKI occurs frequently in older persons. Elevated circulating fibroblast growth factor-23 (FGF-23), a known marker of impaired mineral metabolism, may also reflect tubular dysfunction and risk of AKI. This study evaluated FGF-23 as well as traditional markers of kidney disease, namely urine albumin-tocreatinine ratio (UACR) and creatinine-cystatin C estimated GFR (eGFR CrCyC ), as risk factors for AKI in elderly individuals.Design, setting, participants, & measurements Plasma FGF-23, UACR, and eGFR CrCyC were measured in 3241 community-dwelling elderly individuals in the Cardiovascular Health Study. Hospitalization for AKI was defined by International Classification of Diseases, Ninth Revision, Clinical Modification codes. Associations of each biomarker with AKI were evaluated using Cox proportional hazards models adjusted for demographics, cardiovascular risk factors, and biomarkers of kidney function.Results The mean participant age was 78 years; 60% of participants were women and 16% were African Compared with the highest quartile, the lowest quartile of eGFR CrCyC (,57 ml/min per 1.73 m 2 ) was associated with AKI with an HR of 2.15 (95% CI, 1.21 to 3.82).Conclusions FGF-23 adjusted for albuminuria, cardiovascular disease risk factors, and baseline eGFR is independently associated with a higher risk of AKI hospitalizations in community-dwelling elderly individuals. Further studies to understand the nature of this association are warranted.

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“…[8][9][10][11][12][13][14][15] Furthermore, higher levels of FGF-23 are linked to kidney disease progression in persons with established CKD, although this association may not be independent of baseline eGFR and albuminuria. 11,16,17 There is limited information about the association between FGF-23 and the development of CKD in the general population.…”

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confidence: 99%

Serum Fibroblast Growth Factor-23 Is Associated with Incident Kidney Disease

Rebholz

Grams

Coresh

et al. 2015

Journal of the American Society of Nephrology

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Fibroblast growth factor-23 is a bone-derived hormone that increases urinary phosphate excretion and inhibits hydroxylation of 25-hydroxyvitamin D. Recent studies suggest that fibroblast growth factor-23 may be an early biomarker of CKD progression. However, its role in kidney function decline in the general population is unknown. We assessed the relationship between baseline (1990-1992) serum levels of intact fibroblast growth factor-23 and incident ESRD in 13,448 Atherosclerosis Risk in Communities study participants (56.1% women, 74.7% white) followed until December 31, 2010. At baseline, the mean age of participants was 56.9 years and the mean eGFR was 97 ml/min per 1.73 m 2 . During a median follow-up of 19 years, 267 participants (2.0%) developed ESRD. After adjustment for demographic characteristics, baseline eGFR, traditional CKD risk factors, and markers of mineral metabolism, the highest fibroblast growth factor-23 quintile (.54.6 pg/ml) compared with the lowest quintile (,32.0 pg/ml) was associated with risk of developing ESRD (hazard ratio, 2.10; 95% confidence interval, 1.31 to 3.36; trend P,0.001). In a large, community-based study comprising a broad range of kidney function, higher baseline fibroblast growth factor-23 levels were associated with increased risk of incident ESRD independent of the baseline level of kidney function and a number of other risk factors.

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Fractional Excretion of Phosphorus Modifies the Association between Fibroblast Growth Factor-23 and Outcomes

Cited by 81 publications

References 31 publications

The Use of Fibroblast Growth Factor 23 Testing in Patients with Kidney Disease

The Use of Fibroblast Growth Factor 23 Testing in Patients with Kidney Disease

Fibroblast Growth Factor-23 and the Long-Term Risk of Hospital-Associated AKI among Community-Dwelling Older Individuals

Serum Fibroblast Growth Factor-23 Is Associated with Incident Kidney Disease

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