Serum Phosphate as a Risk Factor for Cardiovascular Events in People with and without Chronic Kidney Disease: A Large Community Based Cohort Study

McGovern, Andrew; Lusignan, Simon de; Liyanage, Harshana; Tomson, Charles; Gallagher, Hugh; Rafiq, Meena; Jones, Simon

doi:10.1371/journal.pone.0074996

Cited by 115 publications

(111 citation statements)

References 42 publications

(41 reference statements)

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“…The abnormality is significantly associated with increased mortality among ESRD patients on hemodialysis [5][6][7]. Studies have also shown a strong association of hyperphosphatemia with cardiovascular morbidity and mortality in ESRD patients [8][9][10]. Consequently, adequate control of serum phosphate is a critical component in the clinical management of ESRD patients.…”

Section: Introductionmentioning

confidence: 99%

Hyperphosphatemia in End Stage Renal Disease: Prevalence and Patients Characteristics of Multiethnic Population of United Arab Emirates

Rabbani

Sathvik

Rao

et al. 2017

Int J Pharm Pharm Sci

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Objective: Hyperphosphatemia is significantly associated with increased mortality among end-stage renal disease (ESRD) patients on hemodialysis.There is a paucity of data on hyperphosphatemia in ESRD patients of the multiethnic population of United Arab Emirates (UAE). The study aimed to investigate the prevalence and characteristics of hyperphosphatemia in ESRD patients of the multiethnic population of UAE undergoing maintenance hemodialysis. Methods:Adults ESRD patients undergoing maintenance hemodialysis for more than six months at the study site were included. Demographic, clinical and biological data of the patients were collected. Patient characteristics were compared as per the serum phosphate level, between patients with or without hyperphosphatemia. Univariate and multivariate logistic regression analyses were carried out to identify the predictors of hyperphosphatemia.Results: Hyperphosphatemia was present in 73.8% of the study population, while 31.3% presented with the high calcium-phosphate product. Univariate logistic analysis revealed that hyperphosphatemia was inversely correlated with age, haemoglobin, serum calcium, and hypertensive nephropathy as the cause of renal disease, and positively correlated with female gender, expatriate status, body mass index (BMI), a higher number of comorbidities, calcium-phosphate product and parathyroid hormone (PTH). Multivariate logistic regression model revealed that only age, BMI, haemoglobin and PTH independently correlated with hyperphosphatemia. Conclusion:We report a high prevalence of hyperphosphatemia in multiethnic study population undergoing maintenance hemodialysis at a secondary care hospital in UAE. In this study population, only age, BMI, hemoglobin and PTH were identified as independent predictors of hyperphosphatemia.

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Section: Introductionmentioning

confidence: 99%

Hyperphosphatemia in End Stage Renal Disease: Prevalence and Patients Characteristics of Multiethnic Population of United Arab Emirates

Rabbani

Sathvik

Rao

et al. 2017

Int J Pharm Pharm Sci

View full text Add to dashboard Cite

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“…12,18 However, reports investigating the association of serum phosphorus level with cardiovascular outcome or mortality have shown variable results in individuals with normal kidney function. 16,[19][20][21][22][23][24][25] A possible explanation for this variability is the different distribution of serum phosphorus levels according to age, 26 sex, 20,26,27 hormonal status, 27,28 circadian variation, 29,30 and dietary phosphorus intake. Although a recent study regarding the interaction of dietary intake and diurnal variation demonstrated that fasting serum phosphorus levels are associated with all-cause mortality, 31 the study population included individuals with and without kidney disease.…”

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confidence: 99%

Sex, Age, and the Association of Serum Phosphorus With All-Cause Mortality in Adults With Normal Kidney Function

Yoo

Kang

Choi

et al. 2016

American Journal of Kidney Diseases

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“…The association is even observed in early-stage CKD and is independent of other traditional CV risk factors. 5, 6 Along with other factors, hyperphosphatemia is involved in the development of vascular calcification (VC) and endothelial dysfunction (ED), 7-9 both of which are major nontraditional CV risk factors for CKD. Phosphate is able to act either directly on these parameters or indirectly via the FGF23/Klotho and PTH axes (Figure 1).…”

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confidence: 99%

Vascular Toxicity of Phosphate in Chronic Kidney Disease

Gross

Six

Kamel

et al. 2014

Circ J

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In epidemiological studies of CKD patients and the general population, high phosphate levels are associated with CV disease (CVD). The association is even observed in early-stage CKD and is independent of other traditional CV risk factors. 5, 6 Along with other factors, hyperphosphatemia is involved in the development of vascular calcification (VC) and endothelial dysfunction (ED), 7-9 both of which are major nontraditional CV risk factors for CKD. Phosphate is able to act either directly on these parameters or indirectly via the FGF23/Klotho and PTH axes (Figure 1).We review the various effects of hyperphosphatemia on CV parameters, with a focus on its emerging role in ED. The efficacy of current therapies for improving phosphate-related CV outcomes is also discussed. Direct Effects of Phosphate on CV Calcification and ED Epidemiological and Interventional StudiesVC is deposition of calcium/phosphate, mostly as apatite, in the blood vessels, myocardium and cardiac valves. Calcification of both the intima and media occurs in CKD, 10 resulting in the stiffness of the large arteries (as evidenced by a higher pulse wave velocity) and thus promotion of CV morbidity/ mortality. The results of several epidemiological studies have highlighted an association between serum phosphate levels and VC in stage 5D CKD patients, 11,12 in early-stage CKD patients and in the general population (in whom serum phosphate levels are still within the normal range). 13, 14 Indeed, 2 elegant prospective studies of large cohorts of hosphate, principally provided by food, is involved in many physiological processes: it buffers the intracellular pH, ensures the stability of the skeleton and contributes to many essential biological functions (eg, DNA synthesis, cell membrane phospholipids, energy metabolism and intracellular signaling pathways that are regulated by phosphorylation/dephosphorylation).The physiological concentration of phosphate (0.8-1.5 mmol/L) is tightly regulated by, among others, the fibroblast growth factor 23 (FGF23)/Klotho axis, parathyroid hormone (PTH) and calcitriol (the active form of vitamin D). 1 In chronic kidney disease (CKD), the progressive loss of functional nephrons induces retention of phosphate, which in turn leads to (1) an increase in calcium/phosphate products and (2) FGF23 synthesis. With the aim of preventing hyperphosphatemia, FGF23 decreases circulating levels of calcitriol, thus inhibiting intestinal phosphate and calcium absorption. PTH, the overexpression of which is triggered by hypocalcemia, stimulates bone resorption for the primary purpose of restoring calcemia but in doing so it increases phosphatemia and thus the calcium/phosphate products. During the course of CKD, Klotho's downregulation in both the parathyroid gland and the kidney results in the loss of FGF23 being able to respectively (1) decrease PTH expression and (2) inhibit renal phosphate reabsorption. In late-stage CKD, the few remaining functional nephrons are no longer able to eliminate phosphate and a vicious circle (referred ...

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Serum Phosphate as a Risk Factor for Cardiovascular Events in People with and without Chronic Kidney Disease: A Large Community Based Cohort Study

Cited by 115 publications

References 42 publications

Hyperphosphatemia in End Stage Renal Disease: Prevalence and Patients Characteristics of Multiethnic Population of United Arab Emirates

Hyperphosphatemia in End Stage Renal Disease: Prevalence and Patients Characteristics of Multiethnic Population of United Arab Emirates

Sex, Age, and the Association of Serum Phosphorus With All-Cause Mortality in Adults With Normal Kidney Function

Vascular Toxicity of Phosphate in Chronic Kidney Disease

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