ArticleNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2017
Deleterious effects of phosphate on vascular and endothelial function via disruption to the nitric oxide pathway.
Article in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03594539 (The Effects of Phosphate on Microvascular Function), which is not on this map. Cited by 32 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Effects of Phosphate on Microvascular Function
Who cites it
32 citing papers in PubMed, 64 citations in OpenAlex.
- Dietary Magnesium Intake and Proteinuria: Is There a Relationship?Biological trace element research · 2024Trial
- Effect of Lanthanum Carbonate on Blood Pressure in CKD.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2021Trial
- A Controlled Increase in Dietary Phosphate Elevates BP in Healthy Human Subjects.Journal of the American Society of Nephrology : JASN · 2018Trial
- High-Phosphate-Induced Hypertension: The Pathogenic Role of Fibroblast Growth Factor 23 (FGF23) Signaling in Sympathetic Nervous System Activation.International journal of molecular sciences · 2026Review
- Hyperphosphatemia as a potential risk factor for arteriovenous fistula dysfunction: A retrospective study in hemodialysis patients.PloS one · 2025Article
- Catastrophic retinal vascular occlusion and vision loss due to crystal deposition in end-stage kidney disease treated with peritoneal dialysis.American journal of ophthalmology case reports · 2024Article
- The Doping of a Carbon Coating with Phosphorus as a Potential Way of Improving the Biological Properties of Diamond-like Carbon.Materials (Basel, Switzerland) · 2024Article
- Phosphate Control in Peritoneal Dialysis Patients: Issues, Solutions, and Open Questions.Nutrients · 2023Review
- Dysregulated phosphate metabolism in autism spectrum disorder: associations and insights for future research.Expert reviews in molecular medicine · 2023Review
- Review
- Dietary Phosphorus, Its Sources, and Mortality in Adults on Haemodialysis: The DIET-HD Study.Nutrients · 2022Article
- Pathomechanism of oxidative stress in cardiovascularrenal remodeling and therapeutic strategies.Kidney research and clinical practice · 2022Article
- Lanthanum in Dialysis, the LANDMARK Trial: A #NephJC Editorial.Kidney medicine · 2022Article
- Association between Flow-Mediated Dilation and Skin Perfusion Pressure with Peripheral Artery Disease in Hemodialysis Patients.Journal of personalized medicine · 2021Article
- Normal parathyroid hormone and non-proliferative diabetic retinopathy in patients with type 2 diabetes.Journal of diabetes investigation · 2021Article
- Calciprotein Particles: Balancing Mineral Homeostasis and Vascular Pathology.Arteriosclerosis, thrombosis, and vascular biology · 2021Review
- High-phosphorus diet controlled for sodium elevates blood pressure in healthy adults via volume expansion.Journal of clinical hypertension (Greenwich, Conn.) · 2021Article
- Uremic Toxins, Oxidative Stress, Atherosclerosis in Chronic Kidney Disease, and Kidney Transplantation.Oxidative medicine and cellular longevity · 2021Review
- Phosphate as a Signaling Molecule.Calcified tissue international · 2021Review
- Hyperphosphatemia and Cardiovascular Disease.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundHyperphosphataemia is an independent risk factor for accelerated cardiovascular disease in chronic kidney disease (CKD), although the mechanism for this is poorly understood. We investigated the effects of sustained exposure to a high-phosphate environment on endothelial function in cellular and preclinical models, as well as in human subjects.
methodsResistance vessels from rats and humans (± CKD) were incubated in a normal (1.18 mM) or high (2.5 mM) phosphate concentration solution and cells were cultured in normal- (0.5 mM) or high-phosphate (3 mM) concentration media. A single-blind crossover study was performed in healthy volunteers, receiving phosphate supplements or a phosphate binder (lanthanum), and endothelial function measured was by flow-mediated dilatation.
resultsEndothelium-dependent vasodilatation was impaired when resistance vessels were exposed to high phosphate; this could be reversed in the presence of a phosphodiesterase-5-inhibitor. Vessels from patients with CKD relaxed normally when incubated in normal-phosphate conditions, suggesting that the detrimental effects of phosphate may be reversible. Exposure to high-phosphate disrupted the whole nitric oxide pathway with reduced nitric oxide and cyclic guanosine monophosphate production and total and phospho endothelial nitric oxide synthase expression. In humans, endothelial function was reduced by chronic phosphate loading independent of serum phosphate, but was associated with higher urinary phosphate excretion and serum fibroblast growth factor 23.
conclusionsThese directly detrimental effects of phosphate, independent of other factors in the uraemic environment, may explain the increased cardiovascular risk associated with phosphate in CKD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.