Effect of Dietary Salt on Regulation of TGF-β in the Kidney

Hovater, Michael B.; Sanders, Paul W.

doi:10.1016/j.semnephrol.2012.04.006

Cited by 25 publications

(15 citation statements)

References 89 publications

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“…[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] Furthermore, impaired kidney function might amplify the adverse effects on blood pressure that can be elicited by various prescription and over-the-counter medications, such as NSAIDs. 28 In this Review we address the necessity of frequent and accurate blood pressure monitoring in patients with CKD, the current recommendations regarding blood pressure target levels, and the rationale behind these recommendations.…”

Section: Introductionmentioning

confidence: 99%

Management of hypertension in chronic kidney disease

Townsend

Taler

2015

Nat Rev Nephrol

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Hypertension is a common comorbidity in patients with impaired kidney function. The kidney exerts a marked degree of control over blood pressure through various mechanisms, such as by regulating sodium balance and hormone secretion through the activity of the renin-angiotensin system. The kidney is susceptible to injury, and if already damaged can be at risk of further loss of function as a consequence of elevated blood pressure. Once elevated blood pressure is identified, a combination of sensible lifestyle measures, such as sodium restriction and weight loss, with pharmacological intervention to reduce blood pressure will usually achieve blood pressure goals. In this Review, we outline the importance of blood pressure control for patients with chronic kidney disease (CKD), the mechanisms that affect blood pressure control, and the basis for non-drug and drug therapies. We further discuss the rationale for <140 mmHg systolic and <90 mmHg diastolic targets for blood pressure in patients with CKD, with consideration for tighter targets in the setting of proteinuria.

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Section: Introductionmentioning

confidence: 99%

Management of hypertension in chronic kidney disease

Townsend

Taler

2015

Nat Rev Nephrol

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“…Even in the absence of hypervolemia or arterial hypertension, high salt intake may increase the production of transforming growth factor-β (TGF-β) and lead to renal fibrosis [2,3]. It may also stimulate NADPH oxidases and increase the production of reactive oxygen species (ROS), resulting in enhanced NF-κB activation and the subsequent production of proinflammatory cytokines [4,5].…”

Section: Introductionmentioning

confidence: 99%

Effects of Dietary Salt Restriction on Renal Progression and Interstitial Fibrosis in Adriamycin Nephrosis

Park¹,

Kim²,

Jo³

et al. 2014

Kidney Blood Press Res

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Background/Aims: Although high salt intake is thought to accelerate renal progression in proteinuric kidney disease, it is not known whether strict dietary salt restriction could delay renal inflammation and interstitial fibrosis. Here, we sought to answer this question in a rat model of adriamycin-induced nephrotic syndrome. Methods: Adriamycin was administered via the femoral vein in a single bolus (7.5 mg/kg), and the rats were put on a sodium-deficient rodent diet. Rats with intact kidneys were studied for 5 weeks (experiment 1), and uninephrectomized rats were studied for 6 weeks (experiment 2). Results: In experiment 1, restricting salt intake improved renal tubulointerstitial histopathology in adriamycin-treated rats. Immunohistochemical and immunoblot results additionally showed that restricting dietary salt lowered adriamycin-induced expression of osteopontin, collagen III, and fibronectin. In experiment 2, salt restriction improved adriamycin-induced azotemia, although it did not affect proteinuria or blood pressure. Dietary salt restriction also reduced adriamycin-induced infiltration of ED1-positive cells and the upregulated expression of osteopontin and a-SMA. Masson's trichrome and Sirius red staining revealed that salt restriction slowed Adriamycin-induced progression of renal interstitial fibrosis. Finally, qPCR revealed that adriamycin-induced expression of TNF-a, IκB-a, gp91^phox, p47^phox, and p67^phox mRNA was blocked by salt restriction. Conclusion: Our findings demonstrate that strict dietary salt restriction delays the progress of renal inflammation and fibrosis in proteinuric kidney disease, most likely via relieving the reactive oxygen species-mediated NF-κB activation.

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“…In this context, signaling through TGF-β1 has been shown to induce tubulointerstitial fibrosis [6,7]. Most of the evidence support that TGF-β1 synthesis of extracellular matrix, collagen and fibroblast formation occur through direct actions of Ang II on the Ang II type 1 receptor [32] or aldosterone action on the mineralocorticoid receptor [33]. The collective actions of Ang II and aldosterone appear to require salt [33,34,35], and there is work to suggest that endothelial production of TGF-β1 stimulates EMT [36,37].…”

Section: Discussionmentioning

confidence: 99%

“…Most of the evidence support that TGF-β1 synthesis of extracellular matrix, collagen and fibroblast formation occur through direct actions of Ang II on the Ang II type 1 receptor [32] or aldosterone action on the mineralocorticoid receptor [33]. The collective actions of Ang II and aldosterone appear to require salt [33,34,35], and there is work to suggest that endothelial production of TGF-β1 stimulates EMT [36,37]. Thereby, our finding that 4% of salt increased TGF-β1 production along with associated periarterial and interstitial fibrosis in female SD and Ren2 rats complements prior work in this area and extends this work to suggest that there may be a role for gender.…”

Section: Discussionmentioning

confidence: 99%

Salt Loading Promotes Kidney Injury via Fibrosis in Young Female Ren2 Rats

et al. 2014

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Background/Aims: It is increasingly recognized that there is sexual dimorphism in kidney disease progression; however, this disparity is lost in the presence of diabetes where women progress at a similar rate to men. The renin-angiotensin-aldosterone system (RAAS) is known to regulate diabetes-induced kidney injury, and recent literature would suggest that gender differences exist in RAAS-dependent responses in the kidney. In this regard, these gender differences may be overcome by excessive salt intake. Thereby, we hypothesized that salt would promote proteinuria in transgenic female rats under conditions of excess tissue angiotensin (Ang) II and circulating aldosterone. Materials and Methods: We utilized young female transgenic (mRen2)27 (Ren2) rats and Sprague-Dawley (SD) littermates and fed a high-salt diet (4%) over 3 weeks. Results: Compared to SD and Ren2 controls, female Ren2 rats fed a high-salt diet displayed increases in proteinuria, periarterial and interstitial fibrosis as well as ultrastructural evidence of basement membrane thickening, loss of mitochondrial elongation, mitochondrial fragmentation and attenuation of basilar canalicular infoldings. These findings occurred temporally with increases in transforming growth factor-β but not indices of oxidant stress. Conclusions: Our current data suggest that a diet high in salt promotes progressive kidney injury as measured by proteinuria and fibrosis associated with transforming growth factor-β under conditions of excess tissue Ang II and circulating aldosterone.

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Effect of Dietary Salt on Regulation of TGF-β in the Kidney

Cited by 25 publications

References 89 publications

Management of hypertension in chronic kidney disease

Management of hypertension in chronic kidney disease

Effects of Dietary Salt Restriction on Renal Progression and Interstitial Fibrosis in Adriamycin Nephrosis

Salt Loading Promotes Kidney Injury via Fibrosis in Young Female Ren2 Rats

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