Reduction of Tissue Na+ Accumulation After Renal Transplantation

Dahlmann, Anke; Linz, Peter; Zucker, Isabelle; Haag, Viktor; Dienemann, Thomas; Nagel, Armin M.; Neubert, Patrick; Rosenhauer, Daniela; Rauh, Manfred; Horn, Stephan; Müller, Dominik N.; Schiffer, Mario; Luft, Friedrich C.; Uder, Michael; Kopp, Christoph W.

doi:10.1016/j.ekir.2021.06.022

Cited by 12 publications

(11 citation statements)

References 38 publications

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“…High salt diets (1,2), renal impairment (3)(4)(5)(6), inflammation, and infection (7)(8)(9)(10)(11) can induce Na + accumulation in skin tissues that can be simulated by addition of approximately 40 mM NaCl to standard cell culture media (= high salt condition, HS) (2,8,12,13). In addition to skin, other organs such as liver, spleen and thymus can display enhanced Na + levels [reviewed in: (14)].…”

Section: Introductionmentioning

confidence: 99%

High Na+ Environments Impair Phagocyte Oxidase-Dependent Antibacterial Activity of Neutrophils

et al. 2021

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Infection and inflammation can augment local Na+ abundance. These increases in local Na+ levels boost proinflammatory and antimicrobial macrophage activity and can favor polarization of T cells towards a proinflammatory Th17 phenotype. Although neutrophils play an important role in fighting intruding invaders, the impact of increased Na+ on the antimicrobial activity of neutrophils remains elusive. Here we show that, in neutrophils, increases in Na+ (high salt, HS) impair the ability of human and murine neutrophils to eliminate Escherichia coli and Staphylococcus aureus. High salt caused reduced spontaneous movement, degranulation and impaired production of reactive oxygen species (ROS) while leaving neutrophil viability unchanged. High salt enhanced the activity of the p38 mitogen-activated protein kinase (p38/MAPK) and increased the interleukin (IL)-8 release in a p38/MAPK-dependent manner. Whereas inhibition of p38/MAPK did not result in improved neutrophil defense, pharmacological blockade of the phagocyte oxidase (PHOX) or its genetic ablation mimicked the impaired antimicrobial activity detected under high salt conditions. Stimulation of neutrophils with phorbol-12-myristate-13-acetate (PMA) overcame high salt-induced impairment in ROS production and restored antimicrobial activity of neutrophils. Hence, we conclude that high salt-impaired PHOX activity results in diminished antimicrobial activity. Our findings suggest that increases in local Na+ represent an ionic checkpoint that prevents excessive ROS production of neutrophils, which decreases their antimicrobial potential and could potentially curtail ROS-mediated tissue damage.

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Section: Introductionmentioning

confidence: 99%

High Na+ Environments Impair Phagocyte Oxidase-Dependent Antibacterial Activity of Neutrophils

et al. 2021

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“…A recent pilot study confirmed the hypothesis that salt accumulation is increased during treatment with VEGFI [28]. This might be caused by effects on lymphangiogenesis dependent on macrophage-derived VEGF-C acting on VEGF-3 receptors [29]. VEGFI target this pathway, and thus diminished lymphangiogenesis could occur during VEGFI treatment [9].…”

Section: Discussionmentioning

confidence: 82%

Dietary sodium restriction prevents vascular endothelial growth factor inhibitor-induced hypertension

et al. 2022

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BACKGROUND: Vascular endothelial growth factor inhibitors (VEGFIs) are effective anticancer agents which often induce hypertension. VEGFI-induced hypertension is sodium-sensitive in animal studies. Therefore, the efficacy of dietary sodium restriction (DSR) to prevent VEGFI-induced hypertension in cancer patients was studied. METHODS: Cancer patients with VEGFI-induced hypertension (day mean >135/85 mmHg or a rise in systolic and/or diastolic BP ≥ 20 mmHg) were treated with DSR (aiming at <4 g salt/day). The primary endpoint was the difference in daytime mean arterial blood pressure (MAP) increase between the treatment cycle with and without DSR. RESULTS: During the first VEGFI treatment cycle without DSR, mean daytime MAP increased from 95 to 110 mmHg. During the subsequent treatment cycle with DSR, mean daytime MAP increased from 94 to 102 mmHg. Therefore, DSR attenuated the increase in mean daytime MAP by 7 mmHg (95% CI 1.3-12.0, P = 0.009). DSR prevented the rise in the endothelin-1/renin ratio that normally accompanies VEGFI-induced hypertension (P = 0.020) and prevented the onset of proteinuria: 0.15 (0.10-0.25) g/24 h with DSR versus 0.19 (0.11-0.32) g/24 h without DSR; P = 0.005. DISCUSSION: DSR significantly attenuated VEGFI induced BP rise and proteinuria and thus is an effective non-pharmacological intervention.

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“…Recent insights into the negative effects of sodium stored in the skin interstitium have renewed interest in the dialytic strategies to remove sodium by dialysis [ 16 , 24 , 29 , 30 , 31 ]. Sodium stored in the interstitial tissue is by no means unmodifiable, given that a significant reduction in interstitial sodium has been documented after a hemodialysis session [ 29 ], while a higher ultrafiltration proves to be associated with lower skin sodium in patients on PD [ 24 ].…”

Section: Volume-independent Sodium Toxicity In End-stage Kidney Diseasementioning

confidence: 99%

“…Furthermore, in hemodialysis patients, the use of low-sodium dialysate is associated with a lower sodium concentration in the skin and muscles [ 30 ]. Finally, in predialysis CKD patients, kidney transplantation caused tissue sodium accumulation to drop to the level of healthy controls [ 31 ].…”

Section: Volume-independent Sodium Toxicity In End-stage Kidney Diseasementioning

confidence: 99%

Volume-Independent Sodium Toxicity in Peritoneal Dialysis: New Insights from Bench to Bed

Borrelli

Nicola

Gregorio

et al. 2021

IJMS

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Sodium overload is common in end-stage kidney disease (ESKD) and is associated with increased cardiovascular mortality that is traditionally considered a result of extracellular volume expansion. Recently, sodium storage was detected by Na23 magnetic resonance imaging in the interstitial tissue of the skin and other tissues. This amount of sodium is osmotically active, regulated by immune cells and the lymphatic system, escapes renal control, and, more importantly, is associated with salt-sensitive hypertension. In chronic kidney disease, the interstitial sodium storage increases as the glomerular filtration rate declines and is related to cardiovascular damage, regardless of the fluid overload. This sodium accumulation in the interstitial tissues becomes more significant in ESKD, especially in older and African American patients. The possible negative effects of interstitial sodium are still under study, though a higher sodium intake might induce abnormal structural and functional changes in the peritoneal wall. Interestingly, sodium stored in the interstial tissue is not unmodifiable, since it is removable by dialysis. Nevertheless, the sodium removal by peritoneal dialysis (PD) remains challenging, and new PD solutions are desirable. In this narrative review, we carried out an update on the pathophysiological mechanisms of volume-independent sodium toxicity and possible future strategies to improve sodium removal by PD.

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Reduction of Tissue Na+ Accumulation After Renal Transplantation

Cited by 12 publications

References 38 publications

High Na+ Environments Impair Phagocyte Oxidase-Dependent Antibacterial Activity of Neutrophils

High Na+ Environments Impair Phagocyte Oxidase-Dependent Antibacterial Activity of Neutrophils

Dietary sodium restriction prevents vascular endothelial growth factor inhibitor-induced hypertension

Volume-Independent Sodium Toxicity in Peritoneal Dialysis: New Insights from Bench to Bed

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