Responsiveness of FGF-23 and mineral metabolism to altered dietary phosphate intake in chronic kidney disease (CKD): results of a randomized trial

Sigrist, Mhairi K.; Tang, Mila; Beaulieu, Monica; Espino-Hernandez, Gabriella; Er, Lee; Djurdjev, Ognjenka; Levin, Adeera

doi:10.1093/ndt/gfs405

Cited by 74 publications

(64 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The primary source of dietary phosphorus is protein intake. In controlled research settings, it is possible to decrease dietary phosphorus intake while maintaining protein intake (17); however, this is difficult to achieve even in research settings, and recommendations to limit phosphorus intake in clinical practice will almost certainly lead to lower protein intake as well. The Modification of Diet in Renal Disease study was a randomized clinical trial evaluating dietary protein restriction in patients with CKD stage 3-4 (30).…”

Section: Discussionmentioning

confidence: 99%

24-Hour Urine Phosphorus Excretion and Mortality and Cardiovascular Events

Palomino¹,

Rifkin

Anderson

et al. 2013

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

SummaryBackground and objectives Higher morning serum phosphorus has been associated with cardiovascular disease (CVD) in patients with or without CKD. In patients with CKD and a phosphorous level .4.6 mg/dl, the Kidney Disease Improving Global Outcomes guidelines recommend dietary phosphorus restriction. However, whether phosphorus restriction influences serum phosphorus concentrations and whether dietary phosphorus is itself associated with CVD or death are uncertain.Design, setting, participants, & measurements Among 880 patients with stable CVD and normal kidney function to moderate CKD, 24-hour urine phosphorus excretion (UPE) and serum phosphorus were measured at baseline. Participants were followed for a median of 7.4 years for CVD events and all-cause mortality.Results Mean 6 SD age was 67611 years, estimated GFR (eGFR) was 71622 ml/min per 1.73 m 2 , and serum phosphorus was 3.760.6 mg/dl. Median UPE was 632 (interquartile range, 439, 853) mg/d. In models adjusted for demographic characteristics and eGFR, UPE was weakly and nonsignificantly associated with serum phosphorus (0.03 mg/dl higher phosphorus per 300 mg higher UPE; P=0.07). When adjusted for demographics, eGFR, and CVD risk factors, each 300-mg higher UPE was associated with 17% lower risk of CVD events. The association of UPE with all-cause mortality was not statistically significant (hazard ratio, 0.93; 95% confidence interval, 0.82 to 1.05). Results were similar irrespective of CKD status (P interactions . 0.87).Conclusions Among outpatients with stable CVD, the magnitude of the association of UPE with morning serum phosphorus is modest. Greater UPE is associated with lower risk for CVD events. The association was similar for all-cause mortality but was not statistically significant.

show abstract

Section: Discussionmentioning

confidence: 99%

24-Hour Urine Phosphorus Excretion and Mortality and Cardiovascular Events

Palomino¹,

Rifkin

Anderson

et al. 2013

Clinical Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…[51][52][53] Because FGF23 regulates serum phosphate levels through its endocrine effects on the kidney, gut, and parathyroid glands, FGF23 is a promising biomarker to detect responses to interventions aimed at lowering phosphate absorption. Interventional studies in healthy individuals [33][34][35] and patients with CKD [29][30][31]45,49,[54][55][56][57][58][59][60] and experimental studies in animals 39,61,62 treated with phosphate binders, nicotinamide, and low phosphate diets support FGF23 as a useful biomarker of phosphate-targeting interventions. In many, but not all, of these studies, serum phosphate was unchanged in response to interventions, but within days to weeks, FGF23 levels were reduced and found to correlate with lower urinary phosphate excretion.…”

Section: Serum Fgf23mentioning

confidence: 99%

“…29,58,59 Sources of dietary phosphate in order of increasing bioavailability are organic phosphate from plants and legumes, organic phosphate from animal and dairy sources, and inorganic phosphates that are used by the food industry as additives to enhance flavor, appearance, and shelf life of processed meats, cheeses, baked goods, and beverages. [84][85][86] Consistent with the bioavailability data, serum and urinary phosphate and FGF23 were significantly lower in uremic rats fed a grain-based versus a meat-based diet.…”

Section: Dietary Phosphate Restrictionmentioning

confidence: 99%

Rationale and Approaches to Phosphate and Fibroblast Growth Factor 23 Reduction in CKD

Isakova

Sprague

et al. 2015

Journal of the American Society of Nephrology

123

127

View full text Add to dashboard Cite

Patients with CKD often progress to ESRD and develop cardiovascular disease (CVD), yet available therapies only modestly improve clinical outcomes. Observational studies report independent associations between elevated serum phosphate and fibroblast growth factor 23 (FGF23) levels and risks of ESRD, CVD, and death. Phosphate excess induces arterial calcification, and although elevated FGF23 helps maintain serum phosphate levels in the normal range in CKD, it may contribute mechanistically to left ventricular hypertrophy (LVH). Consistent epidemiologic and experimental findings suggest the need to test therapeutic approaches that lower phosphate and FGF23 in CKD. Dietary phosphate absorption is one modifiable determinant of serum phosphate and FGF23 levels. Limited data from pilot studies in patients with CKD stages 3-4 suggest that phosphate binders, low phosphate diets, or vitamin B3 derivatives, such as niacin or nicotinamide, may reduce dietary phosphate absorption and serum phosphate and FGF23 levels. This review summarizes current knowledge regarding the deleterious systemic effects of phosphate and FGF23 excess, identifies questions that must be addressed before advancing to a full-scale clinical outcomes trial, and presents a novel therapeutic approach to lower serum phosphate and FGF23 levels that will be tested in the COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE study.

show abstract

“…The source of dietary phosphate seems to have quite a profound effect on changes in FGF23, at least in the short-term, with meat-based protein diets yielding higher levels than plant-based protein diets (despite equivalent phosphate content) (90). Dietary phosphate restriction strategies alone have yielded very modest nonsignificant reductions in FGF23 (91)(92)(93)(94), although quite extreme restriction with a very low-protein diet (,400 mg phosphate/d) has been associated with a significant reduction in circulating levels (92). Overall, reductions in FGF23 (102) did report a significant association between cFGF23 and dietary phosphate intake (assessed by food logs) in 1261 individuals enrolled in the Health Professionals follow-up study.…”

Section: Dietary Phosphate Restriction and Oral Phosphate Bindersmentioning

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

View full text Add to dashboard Cite

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.

show abstract

Responsiveness of FGF-23 and mineral metabolism to altered dietary phosphate intake in chronic kidney disease (CKD): results of a randomized trial

Abstract: FGF-23 levels appear to be responsive to changes in diet in both CKD patients and controls. Further studies are required to determine whether lowering dietary phosphate and thus FGF-23 levels are of long-term benefit in CKD patients, irrespective of sPO(4) levels.

Cited by 74 publications

References 26 publications

24-Hour Urine Phosphorus Excretion and Mortality and Cardiovascular Events

24-Hour Urine Phosphorus Excretion and Mortality and Cardiovascular Events

Rationale and Approaches to Phosphate and Fibroblast Growth Factor 23 Reduction in CKD

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

Contact Info

Product

Resources

About