Phosphate Is a Cardiovascular Toxin

Leifheit-Nestler, Maren; Vogt, Isabel; Haffner, Dieter; Richter, Beatrice

doi:10.1007/978-3-030-91623-7_11

Cited by 6 publications

(6 citation statements)

References 261 publications

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“…Also in our study cFGF23 was proportionally higher in the CKDG3a compared to the CKDG1 group (baseline iFGF23 to cFGF23 ratio 0.72 and 0.98, respectively; P < 0.01). The altered iFGF23 to cFGF23 ratio together with lower Klotho expression potentially modulates iFGF23 sensitivity [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Alterations in regulators of the renal-bone axis, inflammation and iron status in older people with early renal impairment and the effect of vitamin D supplementation

Christodoulou,

Aspray,

Piec

et al. 2024

Age and Ageing

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Context Chronic kidney disease (CKD) leads to alterations in fibroblast growth factor 23 (FGF23) and the renal-bone axis. This may be partly driven by altered inflammation and iron status. Vitamin D supplementation may reduce inflammation. Objective and methods Older adults with early CKD (estimated glomerular filtration rate (eGFR) 30–60 ml/min/1.73 m2; CKDG3a/b; n = 35) or normal renal function (eGFR >90 ml/min/1.73 m2; CKDG1; n = 35) received 12,000, 24,000 or 48,000 IU D3/month for 1 year. Markers of the renal-bone axis, inflammation and iron status were investigated pre- and post-supplementation. Predictors of c-terminal and intact FGF23 (cFGF23; iFGF23) were identified by univariate and multivariate regression. Results Pre-supplementation, comparing CKDG3a/b to CKDG1, plasma cFGF23, iFGF23, PTH, sclerostin and TNFα were significantly higher and Klotho, 1,25-dihydroxyvitamin D and iron were lower. Post-supplementation, only cFGF23, 25(OH)D and IL6 differed between groups. The response to supplementation differed between eGFR groups. Only in the CKDG1 group, phosphate decreased, cFGF23, iFGF23 and procollagen type I N-propeptide increased. In the CKDG3a/b group, TNFα significantly decreased, and iron increased. Plasma 25(OH)D and IL10 increased, and carboxy-terminal collagen crosslinks decreased in both groups. In univariate models cFGF23 and iFGF23 were predicted by eGFR and regulators of calcium and phosphate metabolism at both time points; IL6 predicted cFGF23 (post-supplementation) and iFGF23 (pre-supplementation) in univariate models. Hepcidin predicted post-supplementation cFGF23 in multivariate models with eGFR. Conclusion Alterations in regulators of the renal-bone axis, inflammation and iron status were found in early CKD. The response to vitamin D3 supplementation differed between eGFR groups. Plasma IL6 predicted both cFGF23 and iFGF23 and hepcidin predicted cFGF23.

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Section: Discussionmentioning

confidence: 99%

Alterations in regulators of the renal-bone axis, inflammation and iron status in older people with early renal impairment and the effect of vitamin D supplementation

Christodoulou,

Aspray,

Piec

et al. 2024

Age and Ageing

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“…Major clinical problems, such as the choice of treatment for non-valvular atrial fibrillation in dialysis patients, remain unsolved and clinical nephrologists “navigate through darkness” regarding therapeutic strategy[ 9 ]. In the case of hyperphosphatemia although there is numerous scientific evidence that “phosphate is a cardiovascular toxin”[ 10 ], there has been no randomized control trial (RCT) providing evidence that “correction” will translate into tangible cardiovascular benefit, set the optimal timing of intervention, the different means or the optimal serum phosphate target[ 11 ]. Yet the patients endure an overwhelming phosphate binder pills consumption[ 12 ] with enormous economic implications for healthcare[ 13 ].…”

Section: The Problemmentioning

confidence: 99%

Redefying the therapeutic strategies against cardiorenal morbidity and mortality: Patient phenotypes

Bacharaki¹,

Petrakis²,

Stylianou³

2023

World J Cardiol

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Chronic kidney disease (CKD) patients face an unacceptably high morbidity and mortality, mainly from cardiovascular diseases. Diabetes mellitus, arterial hypertension and dyslipidemia are highly prevalent in CKD patients. Established therapeutic protocols for the treatment of diabetes mellitus, arterial hypertension, and dyslipidemia are not as effective in CKD patients as in the general population. The role of non-traditional risk factors (RF) has gained interest in the last decades. These entail the deranged clinical spectrum of secondary hyperparathyroidism involving vascular and valvular calcification, under the term “CKD-mineral and bone disorder” (CKD-MBD), uremia per se , inflammation and oxidative stress. Each one of these non-traditional RF have been addressed in various study designs, but the results do not exhibit any applied clinical benefit for CKD-patients. The “crusade” against cardiorenal morbidity and mortality in CKD-patients is in some instances, derailed. We propose a therapeutic paradigm advancing from isolated treatment targets, as practiced today, to precision medicine involving patient phenotypes with distinct underlying pathophysiology. In this regard we propose two steps, based on current stratification management of corona virus disease-19 and sepsis. First, select patients who are expected to have a high mortality, i.e. , a prognostic enrichment. Second, select patients who are likely to respond to a specific therapy, i.e. , a predictive enrichment.

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“…29 Importantly, elastin-degrading enzymes, elastases, include matrix metalloproteinases (MMPs), 30 and phosphate-induced expression of MMP2 and MMP9 in VSMC calcification promotes elastin degeneration. 31 In chronic kidney disease, which is also associated with salt sensitivity, dysregulated calcium and phosphate metabolism accounts for bone mineral disorders and lower eGFR 32 and "drives vascular calcification" in CKD patients. 33 High serum phosphate levels and age of patients receiving peritoneal dialysis were independent risk factors for progression of CAC.…”

Section: Phosphate-induced Vascular Calcificationmentioning

confidence: 99%

Salt-Sensitive Hypertension: Mediation by Salt-Induced Hypervolemia and Phosphate-Induced Vascular Calcification

Brown

2023

Clin Med Insights Cardiol

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Preventing hypertension by restricting dietary salt intake, sodium chloride, is well established in public health policy, but a pathophysiological mechanism has yet to explain the controversial clinical finding that some individuals have a greater risk of hypertension from exposure to salt intake, termed salt-sensitive hypertension. The present perspective paper synthesizes interdisciplinary findings from the research literature and offers novel insights proposing that the pathogenesis of salt-sensitive hypertension is mediated by interaction of salt-induced hypervolemia and phosphate-induced vascular calcification. Arterial stiffness and blood pressure increase as calcification in the vascular media layer reduces arterial elasticity, preventing arteries from expanding to accommodate extracellular fluid overload in hypervolemia related to salt intake. Furthermore, phosphate has been found to be a direct inducer of vascular calcification. Reduction of dietary phosphate may help reduce salt-sensitive hypertension by lowering the prevalence and progression of vascular calcification. Further research should investigate the correlation of vascular calcification with salt-sensitive hypertension, and public health recommendations to prevent hypertension should encourage reductions of both sodium-induced hypervolemia and phosphate-induced vascular calcification.

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Phosphate Is a Cardiovascular Toxin

Cited by 6 publications

References 261 publications

Alterations in regulators of the renal-bone axis, inflammation and iron status in older people with early renal impairment and the effect of vitamin D supplementation

Alterations in regulators of the renal-bone axis, inflammation and iron status in older people with early renal impairment and the effect of vitamin D supplementation

Redefying the therapeutic strategies against cardiorenal morbidity and mortality: Patient phenotypes

Salt-Sensitive Hypertension: Mediation by Salt-Induced Hypervolemia and Phosphate-Induced Vascular Calcification

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