Fibroblast Growth Factor 23 and Mortality among Patients Undergoing Hemodialysis

Gutiérrez, Orlando M.; Mannstadt, Michael; Isakova, Tamara; Rauh-Hain, Jose Alejandro; Tamez, Hector; Shah, Anand; Smith, Kelsey; Lee, Hang; Thadhani, Ravi; Jüppner, Harald; Wolf, Myles

doi:10.1056/nejmoa0706130

Cited by 1,569 publications

(1,355 citation statements)

References 38 publications

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“…FGF‐23 predicts the progression of CKD in human patients,13, 27, 28 and FGF‐23 concentrations are also well established as being independently associated with case fatality in CKD patients at the start of hemodialysis,14, 29 and in earlier stages of CKD 27, 28. At present, just as has been debated for many years concerning PTH, it is unclear whether FGF‐23 is a uremic toxin, or whether it is a surrogate marker for other causes of uremic toxicity.…”

Section: Discussionmentioning

confidence: 99%

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Relationship between Plasma Fibroblast Growth Factor‐23 Concentration and Survival Time in Cats with Chronic Kidney Disease

Geddes

Elliott

Syme

2015

Veterinary Internal Medicne

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BackgroundFibroblast growth factor‐23 (FGF‐23) and parathyroid hormone (PTH) are commonly increased in cats with azotemic chronic kidney disease (CKD). Both are predictors of survival time in human patients, but these relationships have not previously been examined in the cat.ObjectivesTo investigate the relationship between plasma FGF‐23 and PTH concentrations at diagnosis of CKD in cats with survival time and with disease progression over 12 months.Animals214 azotemic, client‐owned cats (≥9 years).Methods Retrospective study: Biochemical and urinary variables at diagnosis of azotemic CKD, including plasma FGF‐23 and PTH concentrations were assessed as predictors of survival time (all‐cause mortality) using Cox regression, and as predictors of CKD progression over 12 months using logistic regression.ResultsIn the final multivariable Cox regression model, survival was negatively associated with plasma creatinine (P = .002) and FGF‐23 concentrations (P = .014), urine protein‐to‐creatinine ratio (P < .001) and age (P < .001). Survival was positively associated with PCV (P = .004). In the final multivariable logistic regression model, independent predictors of CKD progression included logFGF‐23 and age. Neither plasma phosphate nor PTH was found to be an independent predictor of survival time or of CKD progression.Conclusions and Clinical ImportancePlasma FGF‐23 concentration is a novel prognostic indicator in cats with CKD, independent of other factors including plasma creatinine and phosphate concentrations. Further work is required to assess if FGF‐23 contributes directly to CKD progression, but regardless these findings may make FGF‐23 a useful biomarker for predicting poorer outcomes in cats with CKD.

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Section: Discussionmentioning

confidence: 99%

“…Plasma FGF‐23 concentrations in human patients are an independent predictor of progression of CKD13 and are independently associated with case fatality in patients starting haemodialysis for CKD 14. Additionally, very high levels of PTH are associated with increased risk of death in CKD patients on hemodialysis 15.…”

mentioning

confidence: 99%

Relationship between Plasma Fibroblast Growth Factor‐23 Concentration and Survival Time in Cats with Chronic Kidney Disease

Geddes

Elliott

Syme

2015

Veterinary Internal Medicne

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“…Fibroblast growth factor 23 (FGF-23) is a hormone that increases the rate of urinary excretion of phosphate and inhibits renal production of 1,25-dihydroxyvitamin D, thus helping to mitigate hyperphosphatemia in patients with kidney disease. Increased fibroblast growth factor 23 levels appear to be independently associated with mortality among patients who are beginning hemodialysis treatment (60). Because individuals with CKD have a high mortality and are at particularly high risk for cardiovascular morbidity and death, these considerations are of substantial clinical relevance (1,61).…”

Section: Discussionmentioning

confidence: 99%

Association of Dietary Phosphorus Intake and Phosphorus to Protein Ratio with Mortality in Hemodialysis Patients

Noori¹,

Kalantar-Zadeh²,

Kövesdy³

et al. 2010

Clinical Journal of the American Society of Nephrology

196

127

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Background and objectives: Epidemiologic studies show an association between higher predialysis serum phosphorus and increased death risk in maintenance hemodialysis (MHD) patients. The hypothesis that higher dietary phosphorus intake and higher phosphorus content per gram of dietary protein intake are each associated with increased mortality in MHD patients was examined.Design, setting, participants, & measurements: Food frequency questionnaires were used to conduct a cohort study to examine the survival predictability of dietary phosphorus and the ratio of phosphorus to protein intake. At the start of the cohort, Cox proportional hazard regression was used in 224 MHD patients, who were followed for up to 5 years (2001 to 2006).Results: Both higher dietary phosphorus intake and a higher dietary phosphorus to protein ratio were associated with significantly increased death hazard ratios (HR) in the unadjusted models and after incremental adjustments for case-mix, diet, serum phosphorus, malnutrition-inflammation complex syndrome, and inflammatory markers. The HR of the highest (compared with lowest) dietary phosphorus intake tertile in the fully adjusted model was 2.37. Across categories of dietary phosphorus to protein ratios of <12, 12 to <14, 14 to <16, and >16 mg/g, death HRs were 1.13, 1.00 (reference value), 1.80, and 1.99, respectively. Cubic spline models of the survival analyses showed similar incremental associations.Conclusions: Higher dietary phosphorus intake and higher dietary phosphorus to protein ratios are each associated with increased death risk in MHD patients, even after adjustments for serum phosphorus, phosphate binders and their types, and dietary protein, energy, and potassium intakes.

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“…A promising CKD biomarker is fibroblast growth factor 23 (FGF-23), which is highly increased in CKD patients and associated with cardiovascular disease and mortality (380)(381)(382). Other potentially interesting molecules include the tubular injury markers NGAL (383-385), KIM-1 (385-388), TIMP-2 (389), IGFBP7 (389) and liver-type fatty acid-binding protein (L-FABP) (390,391).…”

Section: Serum and Urine Biomarkersmentioning

confidence: 99%

Renal Allograft Fibrosis: Biology and Therapeutic Targets

Floege

2015

American Journal of Transplantation

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Fibroblast Growth Factor 23 and Mortality among Patients Undergoing Hemodialysis

Cited by 1,569 publications

References 38 publications

Relationship between Plasma Fibroblast Growth Factor‐23 Concentration and Survival Time in Cats with Chronic Kidney Disease

Relationship between Plasma Fibroblast Growth Factor‐23 Concentration and Survival Time in Cats with Chronic Kidney Disease

Association of Dietary Phosphorus Intake and Phosphorus to Protein Ratio with Mortality in Hemodialysis Patients

Renal Allograft Fibrosis: Biology and Therapeutic Targets

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