The Enhanced Renin-Angiotensin-Aldosteron System Pharmacological Blockade - Which is the Best?

Tylicki, Leszek; Lizakowski, Sławomir; Rutkowski, Przemysław; Renke, Marcin; Sulikowska, Beata; Heleniak, Zbigniew; Donderski, Rafał; Bednarski, Rafał; Przybylska, Milena; Manitius, Jacek; Rutkowski, Bolesław

doi:10.1159/000343391

Cited by 18 publications

(13 citation statements)

References 35 publications

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“…Recent studies documented a beneficial effect of aldosterone antagonism [50,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98]. In peritoneal dialysis patients, spironolactone treatment showed protective effects on cardiac function [99].…”

Section: Aldosterone and Vascular Calcification In Ckdmentioning

confidence: 99%

Impact of Aldosterone on Osteoinductive Signaling and Vascular Calcification

et al. 2014

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Vascular calcification is frequently found already in early stages of chronic kidney disease (CKD) patients and is associated with high cardiovascular risk. The process of vascular calcification is not considered a passive phenomenon but involves, at least in part, phenotypical transformation of vascular smooth muscle cells (VSMCs). Following exposure to excessive extracellular phosphate concentrations, VSMCs undergo a reprogramming into osteo-/chondroblast-like cells. Such ‘vascular osteoinduction' is characterized by expression of osteogenic transcription factors and triggered by increased phosphate concentrations. A key role in this process is assigned to cellular phosphate transporters, most notably the type III sodium-dependent phosphate transporter Pit1. Pit1 expression is stimulated by mineralocorticoid receptor activation. Therefore, aldosterone participates in the phenotypical transformation of VSMCs. In preclinical models, aldosterone antagonism reduces vascular osteoinduction. Patients with CKD suffer from hyperphosphatemia predisposing to vascular osteogenic transformation, potentially further fostered by concomitant hyperaldosteronism. Clearly, additional research is required to define the role of aldosterone in the regulation of osteogenic signaling and the consecutive vascular calcification in CKD, but more generally also other diseases associated with excessive vascular calcification and even in individuals without overt disease.

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Section: Aldosterone and Vascular Calcification In Ckdmentioning

confidence: 99%

Impact of Aldosterone on Osteoinductive Signaling and Vascular Calcification

et al. 2014

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“…Mineralocorticoid-induced inflammation and tissue fibrosis is blunted or even reversed by inhibitors of the mineralocorticoid receptor, such as spironolactone or eplerenone [29,42,67,68,69,70,71,72,73]. At least in theory, untoward mineralocorticoid effects could be abrogated by interference with mineralocorticoid receptor-dependent signaling, such as inhibition of SGK1 [74].…”

Section: Mineralocorticoid Receptor As a Target For Anti-inflammatorymentioning

confidence: 99%

Mineralocorticoid and SGK1-Sensitive Inflammation and Tissue Fibrosis

Artunc¹,

Läng

2014

Nephron Physiol

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Effects of mineralocorticoids are not restricted to regulation of epithelial salt transport, extracellular volume and blood pressure; mineralocorticoids also influence a wide variety of seemingly unrelated functions such as inflammation and fibrosis. The present brief review addresses the role of mineralocorticoids in the orchestration of these latter processes. Mineralocorticoids foster inflammation as well as vascular, cardiac, renal and peritoneal fibrosis. Mechanisms involved in mineralocorticoid-sensitive inflammation and fibrosis include the serum- and glucocorticoid-inducible kinase 1 (SGK1), which is genomically upregulated by mineralocorticoids and transforming growth factor β (TGF-β), and stimulated by mineralocorticoid-sensitive phosphatidylinositide 3-kinase. SGK1 upregulates the inflammatory transcription factor nuclear factor-κB, which in turn stimulates the expression of diverse inflammatory mediators including connective tissue growth factor. Moreover, SGK1 inhibits the degradation of the TGF-β-dependent transcription factors Smad2/3. Mineralocorticoids foster the development of T_H17 cells, which is compromised following SGK1 deletion. Excessive SGK1 expression is observed in a wide variety of fibrosing diseases including lung fibrosis, diabetic nephropathy, glomerulonephritis, obstructive kidney disease, experimental nephrotic syndrome, obstructive nephropathy, liver cirrhosis, fibrosing pancreatitis, peritoneal fibrosis, Crohn's disease and celiac disease. The untoward inflammatory and fibrosing effects of mineralocorticoids could be blunted or even reversed by mineralocorticoid receptor blockers, which may thus be considered in the treatment of inflammatory and/or fibrosing disease.

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“…The effect of GA on blood pressure may have resulted from enhanced absorption of Ca 2+ , which may lower blood pressure due to stimulation of the Ca 2+ -sensingreceptor with subsequent vasodilation [26] and natriuresis due to inhibition of Na + ,K + ,2Cl - cotransport in the thick ascending limb [27]. Whatever mechanism involved, the decrease of proteinuria may delay the progression of renal disease [28], as proteinuria is an important parameter for the progression of renal disease [28,29,30,31,32,33,34,35,36,37]. …”

Section: Renal Effects Of Gum Arabicmentioning

confidence: 99%

Renal and Extrarenal Effects of Gum Arabic (Acacia Senegal) - What Can be Learned from Animal Experiments?

Nasir

2013

Kidney Blood Press Res

1,742

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Gum arabic (GA), a water-soluble dietary fiber rich in Ca²⁺, Mg²⁺ and K⁺, is used in Middle Eastern countries for the treatment of patients with chronic kidney disease. Recent animal experiments shed some light into mechanisms involved in the therapeutic action of GA. According to experiments in healthy mice, GA treatment increases creatinine clearance, enhances renal excretion of ADH, Mg²⁺ and Ca²⁺, decreases plasma phosphate concentration as well as urinary excretion of phosphate and Na⁺. In diabetic mice GA treatment increases urinary Ca²⁺ excretion, and decreases plasma phosphate concentration, plasma urea concentration, urinary flow rate, natriuresis, phosphaturia, glucosuria, proteinuria as well as blood pressure. Extrarenal effects of GA treatment in mice include decreased expression of intestinal Na⁺ coupled glucose carrier SGLT1 with subsequent delay of electrogenic intestinal glucose transport, glucose-induced hyperglycemia, hyperinsulinemia and body weight gain. GA treatment decreases colonic transcription of the angiogenetic factors angiogenin 1, angiogenin 3 and angiogenin 4, of CD38 antigen, aquaporin4, interleukin18, vav-3-oncogene, y⁺-amino acid-transporter, sulfatase1, ubiquitinD and chemokine ligand5. Moreover, GA treatment decreases angiogenin and ß-catenin protein expression. Accordingly, GA treatment counteracts the development of tumors following chemical cancerogenesis. In mouse dendritic cells, antigen-presenting cells linking innate and adaptive immunity, GA treatment modifies maturation and cytokine release. GA treatment further favourably influences the course of murine malaria. The effects of GA treatment on plasma phosphate concentration, blood pressure and proteinuria may prove beneficial in chronic renal failure and diabetic nephropathy. The effect of GA on intestinal glucose transport may be useful in the prophylaxis and treatment of obesity and diabetes, the effect of GA on angiogenin and ß-catenin expression could be exploited for the prophylaxis against colon carcinoma, the effects of GA on angiogenin expression and dendritic cells may be useful in the treatment of inflammatory disease and malaria.

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The Enhanced Renin-Angiotensin-Aldosteron System Pharmacological Blockade - Which is the Best?

Cited by 18 publications

References 35 publications

Impact of Aldosterone on Osteoinductive Signaling and Vascular Calcification

Impact of Aldosterone on Osteoinductive Signaling and Vascular Calcification

Mineralocorticoid and SGK1-Sensitive Inflammation and Tissue Fibrosis

Renal and Extrarenal Effects of Gum Arabic (Acacia Senegal) - What Can be Learned from Animal Experiments?

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