Association of combined fractional excretion of phosphate and FGF23 with heart failure and cardiovascular events in moderate and advanced renal disease

Mendonça, Luís; Vieira, Miguel Bigotte

doi:10.1007/s40620-022-01358-1

Cited by 3 publications

(5 citation statements)

References 25 publications

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“…In our analysis, the application of the panel identified by Janus et al [6] including BNP, hs-cTnT, FGF23, fibrinogen had a C-statistic of 0.80 to predict CV mortality or HHF and, therefore, performed similar to our model. Although FGF23 is an important marker of CV risk in CKD [1], assays to measure plasma levels of this hormone are not widely available, and there is also a lack of standardization among the different assay kits available [30]. Therefore, we consider that the clinical use of our 4-variable model would be simpler and easier than the use of the panel of Janus et al…”

Section: Discussionmentioning

confidence: 99%

“…The fibrinogen level and high-sensitivity C-reactive protein were quantified in EDTA plasma samples using laser-based immune-nephelometric methods on the BNII (Siemens Healthcare, Diagnostics, Deerfield, IL, USA) [13, 14]. Fibroblast growth factor 23 was measured using second-generation C-terminal ELISA (Immunotopics) [1]. High-sensitivity ELISAs (Quantikine HS; R&D Systems, Minneapolis, MN) were used to measure interleukin 6, interleukin 1-β, and tumour necrosis factor alpha [13].…”

Section: Methodsmentioning

confidence: 99%

“…Patients with chronic kidney disease (CKD) have an increased risk of ischaemic cardiovascular (CV) events, heart failure (HF), CKD progression, and mortality [1]. However, the risk of such adverse outcomes may vary among patients with CKD [2].…”

Section: Introductionmentioning

confidence: 99%

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A 4-Variable Model to Predict Cardio-Kidney Events and Mortality in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort (CRIC) Study

Mendonça,

Bigotte Vieira,

Neves

et al. 2023

Am J Nephrol

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Introduction: Current prognostic models for chronic kidney disease (CKD) are complex and were designed to predict a single outcome. We aimed to develop and validate a simple and parsimonious prognostic model to predict cardio-kidney events and mortality. Methods: Patients from the CRIC Study (n = 3,718) were randomly divided into derivation (n = 2,478) and validation (n = 1,240) cohorts. Twenty-nine candidate variables were preselected. Multivariable Cox regression models were developed using stepwise selection for various cardio-kidney endpoints, namely, (i) the primary composite outcome of 50% decline in estimated glomerular filtration rate (eGFR) from baseline, end-stage renal disease, or cardiovascular (CV) mortality; (ii) hospitalization for heart failure (HHF) or CV mortality; (iii) 3-point major CV endpoints (3P-MACE); (iv) all-cause death. Results: During a median follow-up of 9 years, the primary outcome occurred in 977 patients of the derivation cohort and 501 patients of the validation cohort. Log-transformed N-terminal pro-B-type natriuretic peptide (NT-proBNP), log-transformed high-sensitive cardiac troponin T (hs-cTnT), log-transformed albuminuria, and eGFR were the dominant predictors. The primary outcome risk score discriminated well (c-statistic = 0.83) with a proportion of events of 11.4% in the lowest tertile of risk and 91.5% in the highest tertile at 10 years. The risk model presented good discrimination for HHF or CV mortality, 3P-MACE, and all-cause death (c-statistics = 0.80, 0.75, and 0.75, respectively). The 4-variable risk model achieved similar c-statistics for all tested outcomes in the validation cohort. The discrimination of the 4-variable risk model was mostly superior to that of published models. Conclusion: The combination of NT-proBNP, hs-cTnT, albuminuria, and eGFR in a single 4-variable model provides a unique individual prognostic assessment of multiple cardio-kidney outcomes in CKD.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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A 4-Variable Model to Predict Cardio-Kidney Events and Mortality in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort (CRIC) Study

Mendonça,

Bigotte Vieira,

Neves

et al. 2023

Am J Nephrol

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“…Previous observational studies have demonstrated that the circulating concentration of FGF23 is related to heart failure (HF) (22,29,(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45), and this association appears to be stronger in patients with CKD (36,37,44,46), but is not affected by adjustment for kidney function (22,35,37,39,(41)(42)(43)(44). Some previous studies have shown significant relationships between high circulating FGF23 concentration and low ejection fraction (27,28,45,(47)(48)(49).…”

Section: Fgf23 and Heart Failurementioning

confidence: 99%

Direct and indirect effects of fibroblast growth factor 23 on the heart

2023

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Fibroblast growth factor (FGF)23 is a bone-derived phosphotropic hormone that regulates phosphate and mineral homeostasis. Recent studies have provided evidence that a high plasma concentration of FGF23 is associated with cardiac disease, including left ventricular hypertrophy (LVH), heart failure, atrial fibrillation, and cardiac death. Experimental studies have shown that FGF23 activates fibroblast growth factor receptor 4 (FGFR4)/phospholipase Cγ/calcineurin/nuclear factor of activated T-cells signaling in cardiomyocytes and induces cardiac hypertrophy in rodents. Activation of FGFR4 by FGF23 normally requires the co-receptor α-klotho, and klotho-independent signaling occurs only under conditions characterized by extremely high FGF23 concentrations. Recent studies have demonstrated that FGF23 activates the renin-angiotensin-aldosterone system (RAAS) and induces LVH, at least in part as a result of lower vitamin D activation. Moreover, crosstalk between FGF23 and RAAS results in the induction of cardiac hypertrophy and fibrosis. In this review, we summarize the results of studies regarding the relationships between FGF23 and cardiac events, and describe the potential direct and indirect mechanisms whereby FGF23 induces LVH.

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“…They found a nonlinear and positive association between serum Klotho levels and the prevalence of diabetes. Given the potential role of the Klotho and FGF23 signaling pathways on cardiovascular and renal function ( 5 , 6 ), further studies evaluating the role of Klotho across the continuum of glycemic dysfunction may offer new approaches to prevent cardio-renal complications in both prediabetes and diabetes.…”

Section: Association Of Prediabetes With Complicationsmentioning

confidence: 99%

Editorial: Prediabetes: new insights on the diagnosis, risk stratification, comorbidites, cardiovascular disease, microvascular complications, and treatment

2023

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Association of combined fractional excretion of phosphate and FGF23 with heart failure and cardiovascular events in moderate and advanced renal disease

Cited by 3 publications

References 25 publications

A 4-Variable Model to Predict Cardio-Kidney Events and Mortality in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort (CRIC) Study

A 4-Variable Model to Predict Cardio-Kidney Events and Mortality in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort (CRIC) Study

Direct and indirect effects of fibroblast growth factor 23 on the heart

Editorial: Prediabetes: new insights on the diagnosis, risk stratification, comorbidites, cardiovascular disease, microvascular complications, and treatment

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