Fibroblast Growth Factor 23 and Risks of Mortality and End-Stage Renal Disease in Patients With Chronic Kidney Disease

Isakova, Tamara; Xie, Hua-Tao; Yang, Wei; Xie, Dawei; Anderson, Amanda H.; Scialla, Julia J.; Wahl, Patricia W.; Gutiérrez, Orlando M.; Steigerwalt, Susan; He, Jiang; Schwartz, Stanley; Lo, Joan C.; Ojo, Akinlolu; Sondheimer, James; Hsu, Chi-yuan; Lash, James P.; Leonard, Mary B.; Kusek, John W.; Feldman, Harold I.; Wolf, Myles

doi:10.1001/jama.2011.826

Cited by 924 publications

(798 citation statements)

References 32 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%

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%

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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“…2,5 Several cohort studies have examined the relationship between FGF-23 and renal outcomes. [10][11][12][13][14][15] In line with findings in the Chronic Renal Insufficiency Cohort cohort 11 and in the MMKD study 10 from analyses not considering the FGF-23-ADMA interaction, we confirmed that the FGF-23-CKD progression relationship was independent of (1) classic risk factors and (2) CKD-specific risk factors, such as proteinuria and the GFR, that are known to belong to the strongest predictors of CKD progression, as well as (3) major biomarkers of CKD mineral and bone disorder, including serum phosphate, 1,25(OH) 2 D, and PTH. These results further highlight the potential relevance of FGF-23 as a novel risk factor for evolution toward kidney failure in CKD.…”

Section: Discussionmentioning

confidence: 99%

“…in the United States, [11][12][13][14] as well as a large study in transplant recipients in Hungary, 15 have coherently associated high plasma FGF-23 with CKD progression toward kidney failure.…”

mentioning

confidence: 94%

Competitive Interaction Between Fibroblast Growth Factor 23 And Asymmetric Dimethylarginine in Patients With CKD

Tripepi

Kollerits

Leonardis

et al. 2015

Journal of the American Society of Nephrology

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Both fibroblast growth factor 23 (FGF-23) and asymmetric dimethylarginine (ADMA) are associated with progression of CKD. We tested the hypothesis that ADMA and FGF23 are interactive factors for CKD progression in a cohort of 758 patients with CKD in Southern Europe (mean eGFR6SD, 36613 ml/min per 1.73 m 2 ) and in a central European cohort of 173 patients with CKD (MMKD study, mean eGFR, 64639 ml/min per 1.73 m 2 ). In the first cohort, 214 patients had renal events (decrease in eGFR of .30%, dialysis, or kidney transplantation) during a 3-year follow-up. Both intact FGF-23 and ADMA predicted the incidence rate of renal events in unadjusted and adjusted analyses (P,0.001). There was a strong competitive interaction between FGF-23 and ADMA in the risk of renal events (P,0.01 in adjusted analyses); the risk associated with raised ADMA levels was highest in patients with low FGF-23 levels. These results were confirmed in the MMKD cohort, in which FGF-23 level was again an effect modifier of the relationship between plasma ADMA level and renal events (doubling of baseline serum creatinine, dialysis, or kidney transplantation) in the adjusted analyses (P,0.01). Furthermore, in the MMKD cohort there was a parallel, independent competitive interaction between symmetric dimethylarginine level and c-terminal FGF-23 level for the risk for renal events (P=0.001). These findings indicate that the association of ADMA level with the risk of CKD progression is modified by FGF-23 level and provide further evidence that dysregulation of the nitric oxide system is involved in CKD progression.

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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 Risks of Mortality and End-Stage Renal Disease in Patients With Chronic Kidney Disease

Cited by 924 publications

References 32 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

Competitive Interaction Between Fibroblast Growth Factor 23 And Asymmetric Dimethylarginine in Patients With CKD

Renal Allograft Fibrosis: Biology and Therapeutic Targets

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