Mineral Metabolism and Inflammation in Chronic Kidney Disease Patients

Navarro‐González, Juan F.; Mora‐Fernández, Carmen; Muros, Mercedes; Herrera, Haridian; Garcia, J.M. Mota

doi:10.2215/cjn.02420409

Cited by 93 publications

(66 citation statements)

References 52 publications

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“…The mechanisms underlying increased risk of hospitalization associated with disturbances of mineral metabolism remain uncertain. Accumulating evidence indicates that elevated levels of serum calcium-phosphorus product and disorders of calcium homeostasis may accelerate vascular calcification and induce inflammation [41,42]. Moreover, a recent study showed that higher dialysate calcium concentration is associated with increased sympathetic activity during HD, which might lead to unfavorable outcomes [43].…”

Section: Discussionmentioning

confidence: 99%

Heart Rate Variability Predicts Major Adverse Cardiovascular Events and Hospitalization in Maintenance Hemodialysis Patients

Huang

Kuo

Tsai

et al. 2017

Kidney Blood Press Res

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Background/Aims: Heart rate variability (HRV) has been linked to mortality in maintenance hemodialysis (HD) patients, but it is less clear whether HRV is associated with major adverse cardiovascular events (MACEs) and hospitalization. Methods: This study enrolled 179 maintenance HD patients. HRV was measured to assess its prognostic significance in relation to MACEs and hospitalization. Results: During the follow-up period of 33.3 ± 6.7 months, 36 (20.1%) patients had a MACE, and 98 (54.7%) experienced hospitalization. In multivariate adjusted Cox regression analysis, low very low frequency (VLF) power (hazard ratio [HR], 0.727; 95% confidence interval [CI], 0.624−0.848; p < 0.001), a history of coronary artery disease, high ultrafiltration rate, the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, and the use of beta-blockers were all significantly associated with MACEs. Low VLF power (HR, 0.873; 95% CI, 0.785−0.971; p = 0.012), low serum albumin, low serum creatinine, low Kt/V levels, and high serum calcium-phosphorus product levels significantly predicted hospitalization in maintenance HD patients. Conclusions: Reduced VLF power is linked to an increased risk of MACEs and hospitalization in maintenance HD patients. Assessing cardiac autonomic function through HRV is of pivotal prognostic significance for this patient population.

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Section: Discussionmentioning

confidence: 99%

Heart Rate Variability Predicts Major Adverse Cardiovascular Events and Hospitalization in Maintenance Hemodialysis Patients

Huang

Kuo

Tsai

et al. 2017

Kidney Blood Press Res

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“…Furthermore, increased serum phosphorus is an independent risk factor for the presence of a significant inflammatory state in CKD patients (14). In addition to the reduction of phosphorus levels, the noncalcium phosphate binder sevelamer has been associated with anti-inflammatory properties.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, serum phosphorus is direct and independently correlated with inflammatory parameters, indicating that hyperphosphatemia may be a contributing factor to inflammation (14). Therefore, adequate management of hyperphosphatemia is a critical issue in renal patients.…”

Section: Introductionmentioning

confidence: 99%

Effect of Phosphate Binders on Serum Inflammatory Profile, Soluble CD14, and Endotoxin Levels in Hemodialysis Patients

Navarro‐González¹,

Mora‐Fernández²,

Fuentes³

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Hyperphosphatemia and subclinical endotoxemia are important sources of inflammation in HD. Proinflammatory cytokines are strong correlates of soluble CD14 (sCD14) concentrations, an independent predictor of mortality in this population. We evaluated the effects of calcium acetate and sevelamer hydrochloride on serum inflammatory profile, endotoxin concentrations, and sCD14 levels in HD patients.Design, setting, participants, & measurements Prospective, randomized, open-label, parallel design trial. Fiftynine stable HD patients, 30 receiving sevelamer, and 29 receiving calcium acetate were evaluated. Serum levels of inflammatory parameters (high-sensitivity C-reactive protein [hs-CRP], TNF-␣, interleukin (IL)-1, -6, -10, and -18), as well as endotoxin and sCD14 concentrations, were measured at baseline and after 3 months of therapy.Results Serum IL-6 increased in patients receiving calcium acetate, whereas hs-CRP and IL-6 significantly decreased in subjects treated with sevelamer, with IL-10 experiencing a trend to increase (P ϭ 0.052). Serum endotoxin and sCD14 levels did not change after treatment with calcium acetate. However, these parameters decreased by 22.6% and 15.2%, respectively (P Ͻ 0.01), in patients receiving sevelamer. Multiple regression analysis showed that variation in serum endotoxin concentrations was the strongest factor associated with IL-6 change, whereas the only variables independently associated with changes in sCD14 levels were the variations in serum IL-6 and endotoxin concentrations.Conclusions Administration of the noncalcium phosphate binder sevelamer to maintenance HD patients is associated with a significant decrease in hs-CRP, IL-6, serum endotoxin levels and sCD14 concentrations.

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“…In humans, altered phosphate metabolism is associated with age-related changes, inflammation, and death in chronic kidney disease (190,300), and in young healthy subjects serum phosphorus content is associated with coronary atherosclerosis later in life (139).…”

Section: (See the Role Of Sirtuins In Cr)mentioning

confidence: 99%

Angiotensin II blockade: how its molecular targets may signal to mitochondria and slow aging. Coincidences with calorie restriction and mTOR inhibition

Cavanagh

Inserra

Ferder

2015

American Journal of Physiology-Heart and Circulatory Physiology

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de Cavanagh EM, Inserra F, Ferder L. Angiotensin II blockade: how its molecular targets may signal to mitochondria and slow aging. Coincidences with calorie restriction and mTOR inhibition. Am J Physiol Heart Circ Physiol 309: H15-H44, 2015. First published May 1, 2015; doi:10.1152/ajpheart.00459.2014, renin angiotensin system blockade (RAS-bl), and rapamycin-mediated mechanistic target of rapamycin (mTOR) inhibition increase survival and retard aging across species. Previously, we have summarized CR and RAS-bl's converging effects, and the mitochondrial function changes associated with their physiological benefits. mTOR inhibition and enhanced sirtuin and KLOTHO signaling contribute to the benefits of CR in aging. mTORC1/mTORC2 complexes contribute to cell growth and metabolic regulation. Prolonged mTORC1 activation may lead to age-related disease progression; thus, rapamycin-mediated mTOR inhibition and CR may extend lifespan and retard aging through mTORC1 interference. Sirtuins by deacetylating histone and transcription-related proteins modulate signaling and survival pathways and mitochondrial functioning. CR regulates several mammalian sirtuins favoring their role in aging regulation. KLOTHO/fibroblast growth factor 23 (FGF23) contribute to control Ca 2ϩ , phosphate, and vitamin D metabolism, and their dysregulation may participate in age-related disease. Here we review how mTOR inhibition extends lifespan, how KLOTHO functions as an aging suppressor, how sirtuins mediate longevity, how vitamin D loss may contribute to age-related disease, and how they relate to mitochondrial function. Also, we discuss how RAS-bl downregulates mTOR and upregulates KLOTHO, sirtuin, and vitamin D receptor expression, suggesting that at least some of RAS-bl benefits in aging are mediated through the modulation of mTOR, KLOTHO, and sirtuin expression and vitamin D signaling, paralleling CR actions in age retardation. Concluding, the available evidence endorses the idea that RAS-bl is among the interventions that may turn out to provide relief to the spreading issue of age-associated chronic disease. mechanistic target of rapamycin; vitamin D; caloric restriction; renin-angiotensin system EFFORTS AIMED AT DECIPHERING the mechanisms that underlie the aging process have unveiled three interventions that can increase survival and retard age-related diseases from lower organisms to mammals, i.e., caloric restriction (CR) (84,85,140,160,334), mechanistic target of rapamycin (mTOR; originally mammalian TOR) inhibition by rapamycin (173,196,281), and renin-angiotensin system blockade (RAS-bl) (20, 21, 26,63,253,284,354), although the latter has been less studied. In light of these findings, some intriguing questions come to mind: Do these interventions attenuate aging by interfering with common mechanisms? Do the mechanisms that are interfered with by CR, rapamycin, and RAS-bl mutually affect each other? Are there any pathways involved exclusively with a certain intervention?Previously (101), we have discussed the converging effects d...

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Mineral Metabolism and Inflammation in Chronic Kidney Disease Patients

Cited by 93 publications

References 52 publications

Heart Rate Variability Predicts Major Adverse Cardiovascular Events and Hospitalization in Maintenance Hemodialysis Patients

Heart Rate Variability Predicts Major Adverse Cardiovascular Events and Hospitalization in Maintenance Hemodialysis Patients

Effect of Phosphate Binders on Serum Inflammatory Profile, Soluble CD14, and Endotoxin Levels in Hemodialysis Patients

Angiotensin II blockade: how its molecular targets may signal to mitochondria and slow aging. Coincidences with calorie restriction and mTOR inhibition

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