Kidney and Blood Pressure Research最新文献

{"title":"Increased Sclerostin, but Not Dickkopf-1 Protein, Is Associated with Elevated Pulse Wave Velocity in Hemodialysis Subjects","authors":"Eirini Stavrinou, P. Sarafidis, Charalampos Koumaras, C. Loutradis, P. Giamalis, K. Tziomalos, A. Karagiannis, A. Papagianni","doi":"10.1159/000501205","DOIUrl":"https://doi.org/10.1159/000501205","url":null,"abstract":"Background: Sclerostin and Dickkopf-1 (Dkk-1) proteins are inhibitors of the canonical Wnt/β-catenin bone pathway. Pilot data suggest that sclerostin may be involved in vascular changes in chronic kidney disease (CKD), but data on the effects of Dkk-1 are scarce. This is the first study investigating simultaneously the associations of sclerostin and Dkk-1 with arterial stiffness in hemodialysis patients. Methods: A total of 80 patients on chronic hemodialysis had carotid-femoral pulse wave velocity (PWV), central blood pressure (BP), and wave reflections evaluated with applanation tonometry (Sphygmocor) on a midweek non-dialysis day. Serum levels of sclerostin and Dkk-1 were measured with ELISA. A large set of demographic, comorbid, laboratory, and drug parameters were used in the analyses. Results: Subjects with PWV >9.5 m/s (high arterial stiffness group, n = 40) were older, had higher BMI, higher prevalence of hypertension, diabetes, and coronary heart disease, and higher peripheral systolic BP, central systolic BP, C-reactive protein, and serum sclerostin (p = 0.02), but similar Dkk-1, compared to subjects with low PWV. When dichotomizing the population by sclerostin levels, those with high sclerostin had higher PWV than patients with low sclerostin levels (10.63 ± 2.71 vs. 9.77 ± 3.13, p = 0.048). Increased sclerostin (>200 pg/mL) was significantly associated with increased PWV (>9.5 m/s; HR 2.778, 95% CI 1.123–6.868 per pg/mL increase); this association remained significant after stepwise adjustment for Dkk-1, intact parathyroid hormone, and calcium × phosphate product. In contrast, no association was noted between Dkk-1 and PWV (HR 1.000, 95% CI 0.416–2.403). Conclusion: Serum sclerostin is associated with PWV independently of routine markers of CKD-MBD in hemodialysis patients. In contrast, Dkk-1 has no association with arterial stiffness and is not pathophysiologically involved in relevant vascular changes.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"18 1","pages":"679 - 689"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77680871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seven-Day Salt Loading Impairs Microvascular Endothelium-Dependent Vasodilation without Changes in Blood Pressure, Body Composition and Fluid Status in Healthy Young Humans","authors":"Lidija Barić, I. Drenjančević, A. Matić, M. Stupin, L. Kolar, Z. Mihaljević, H. Lenasi, V. Šerić, A. Stupin","doi":"10.1159/000501747","DOIUrl":"https://doi.org/10.1159/000501747","url":null,"abstract":"Objectives: We aimed to assess whether a 7-day high-salt (HS) diet affects endothelium-dependent and/or endothelium-independent microvascular function in the absence of changes in arterial blood pressure (BP), and to determine whether such microvascular changes are associated with changes in body composition and fluid status in healthy young humans. Materials and Methods: Fifty-three young healthy individuals (28 women and 25 men) were assigned to a 7-day low-salt diet (<3.5 g salt/day) followed by a 7-day HS diet (∼14 g salt/day). Skin microvascular blood flow in response to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) was assessed by laser Doppler flowmetry, and BP, heart rate (HR), plasma renin activity (PRA), serum aldosterone, serum and 24 h-urine sodium, potassium, urea and creatinine levels, together with body composition and fluid status measurement with a 4-terminal portable impedance analyzer were measured before and after diet protocols. Results: BP, HR, body composition and fluid status were unchanged, and PRA and serum aldosterone level were significantly suppressed after HS diet. ACh-induced dilation (AChID) was significantly impaired, while SNP-induced dilation was not affected by HS diet. Impaired AChID and increased salt intake, as well as impaired AChID and suppressed renin-angiotensin system were significantly positively correlated. Changes in body composition and fluid status parameters were not associated with impaired AChID. Conclusion: 7-day HS diet impairs microvascular reactivity by affecting its endothelium-dependent vasodilation in young healthy individuals. Changes are independent of BP, body composition changes or fluid retention, but are the consequences of the unique effect of HS on endothelial function.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"29 1","pages":"835 - 847"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78714315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Kynurenine Predicts Severity and Complications of Heart Failure and Associates with Established Biochemical and Clinical Markers of Disease","authors":"T. Dschietzig, K. Kellner, K. Sasse, F. Boschann, R. Klüsener, J. Ruppert, F. Armbruster, D. Bankovic, A. Meinitzer, V. Mitrović, C. Melzer","doi":"10.1159/000501483","DOIUrl":"https://doi.org/10.1159/000501483","url":null,"abstract":"Background: Kynurenine, a metabolite of the L-tryptophan pathway, plays a pivotal role in neuro-inflammation, cancer immunology, and cardiovascular inflammation, and has been shown to predict cardiovascular events. Objectives: It was our objective to increase the body of data regarding the value of kynurenine as a biomarker in chronic heart failure (CHF). Methods: We investigated the predictive value of plasma kynurenine in a CHF cohort (CHF, n = 114); in a second cohort of defibrillator carriers with CHF (AICD, n = 156), we determined clinical and biochemical determinants of the marker which was measured by enzyme immunoassay. Results: In the CHF cohort, both kynurenine and NT-proBNP increased with NYHA class. Univariate binary logistic regression showed kynurenine to predict death within a 6-month follow-up (OR 1.43, 95% CI 1.03–2.00, p = 0.033) whereas NT-proBNP did not contribute significantly. Kynurenine, like NT-proBNP, was able to discriminate at a 30% threshold of left ventricular ejection fraction (LVEF; AUC-ROC, both 0.74). Kynurenine correlated inversely with LVEF (ϱ = –0.394), glomerular filtration fraction (GFR; ϱ = –0.615), and peak VO2 (ϱ = –0.626). Moreover, there was a strong correlation of kynurenine with NT-proBNP (ϱ = 0.615). In the AICD cohort, multiple linear regression analysis demonstrated highly significant associations of kynurenine with GFR, hsCRP, and tryptophan, as well as a significant impact of age. Conclusions: This work speaks in favor of kynurenine being a new and valuable biomarker of CHF, with particular attention placed on its ability to predict mortality and reflect exercise capacity.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"39 1","pages":"765 - 776"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75101939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Protective Effect of Fluorofenidone against Cyclosporine A-Induced Nephrotoxicity","authors":"Yang Chen, Na-sui Wang, Qiongjing Yuan, Jiao Qin, Gaoyun Hu, Qianbin Li, L. Tao, Yanyun Xie, Zhang‐zhe Peng","doi":"10.1159/000500924","DOIUrl":"https://doi.org/10.1159/000500924","url":null,"abstract":"Background/Aims: Cyclosporine A (CsA) is an immunosuppressant drug that is used during organ transplants. However, its utility is limited by its nephrotoxic potential. This study aimed to investigate whether fluorofenidone (AKF-PD) could provide protection against CsA-induced nephrotoxicity. Methods: Eighty-five male Sprague-Dawley rats were divided into 5 groups: drug solvent, CsA, CsA with AKF-PD (250, 500 mg/kg/day), and CsA with pirfenidone (PFD, 250 mg/kg/day). Tubulointerstitial injury index, extracellular matrix (ECM) deposition, expression of type I and IV collagen, transforming growth factor (TGF)-β1, platelet-derived growth factor (PDGF), Fas ligand (FASL), cleaved-caspase-3, cleaved-poly(ADP-ribose) polymerase (PARP)-1, and the number of transferase-mediated nick end-labeling (TUNEL)-positive renal tubule cells were determined. In addition, levels of TGF-β1, FASL, cleaved-caspase-3, cleaved-PARP-1, and number of annexin V-positive cells were determined in rat proximal tubular epithelial cells (NRK-52E) treated with CsA (20 μmol/L), AKF-PD (400 μg/mL), PFD (400 μg/mL), and GW788388 (5 μmol/L). Results: AKF-PD (250, 500 mg/kg/day) significantly reduced tubulointerstitial injury, ECM deposition, expression of type I and IV collagen, TGF-β1, PDGF, FASL, cleaved-caspase-3, cleaved-PARP-1, and number of TUNEL-positive renal tubule cells in the CsA-treated kidneys. In addition, AKF-PD (400 μg/mL) significantly decreased TGF-β1, FASL, cleaved-caspase-3, and PARP-1 expression in NRK-52E cells and further reduced the number of annexin V-positive cells. Conclusion: AKF-PD protect kidney from fibrosis and apoptosis in CsA-induced kidney injury.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"1 1","pages":"656 - 668"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89128835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of M2 Macrophages on Injury and Apoptosis of Renal Tubular Epithelial Cells Induced by Calcium Oxalate Crystals","authors":"Quan Liu, Yunlong Liu, Xiaofeng Guan, Jihua Wu, Ziqi He, Juening Kang, Z. Tao, Yao-liang Deng","doi":"10.1159/000501558","DOIUrl":"https://doi.org/10.1159/000501558","url":null,"abstract":"Background: M2 macrophages have important roles in diseases such as tumours, cardiovascular diseases and renal diseases. This study aimed to determine the effects and protective mechanism of M2 macrophages against oxidative stress injury and apoptosis induced by calcium oxalate crystals (CaOx) in renal tubular epithelial cells (HK-2) under coculture conditions. Methods: THP-1 cells were induced to differentiate into M2 macrophages by using phorbol-12-myristate-13-acetate, IL-4 and IL-13. Morphological features were observed by microscopy. Phenotypic markers were identified by reverse transcription-polymerase chain reaction, Western blot and enzyme-linked immunosorbent assay (ELISA). HK-2 cells were treated with 0.5 mg/mL CaOx crystals and co-cultured with M2 macrophages or apocynin. The viability of HK-2 cells was detected by CCK-8 assay. The lactate dehydrogenase (LDH) activity of HK-2 cells was analysed using a microplate reader. The apoptosis of HK-2 cells was examined by flow cytometry and Hoechst 33258 staining. Reactive oxygen species (ROS) expression and mitochondrial membrane potential in HK-2 cells were detected by a fluorescence microplate reader. Western blot analysis was conducted to detect the expression of p47phox, Bcl-2, cleaved caspase-3, cytochrome c, p38 MAPK, phospho-p38 MAPK, Akt and phospho-Akt. Results: The results of morphology, reverse transcription-polymerase chain reaction, Western blot and ELISA showed that THP-1 cells were successfully polarised to M2 macrophages. The results of co-culture suggested that M2 macrophages or apocynin significantly increased the cell viability and decreased the LDH activity and apoptosis rate after HK-2 cells were challenged with CaOx crystals. The expression of the p47phox protein and the concentration of ROS were reduced, the release of mitochondrial membrane potential and the expression of the Bcl-2 protein were upregulated and the protein expression of cleaved caspase-3 and cytochrome c was downregulated. The expression of the phosphorylated form of p38 MAPK increased. Under coculture conditions with M2 macrophages, the Akt protein of HK-2 cells treated with CaOx crystals was dephosphorylated, but the phosphorylated form of Akt was not reduced by apocynin. Conclusions: M2 macrophages reduced the oxidative stress injury and apoptosis of HK-2 cells by downregulating the activation of NADPH oxidase, reducing the production of ROS, inhibiting the phosphorylation of p38 MAPK and enhancing the phosphorylation of Akt. We have revealed one of the possible mechanisms by which M2 macrophages reduce the formation of kidney stones.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"32 1","pages":"777 - 791"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75576798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loop Diuretics in Acute Kidney Injury Prevention, Therapy, and Risk Stratification","authors":"D. Patschan, S. Patschan, I. Buschmann, O. Ritter","doi":"10.1159/000501315","DOIUrl":"https://doi.org/10.1159/000501315","url":null,"abstract":"Background: Loop diuretics (LD) are widely used in emergency and intensive care medicine. Summary: The substances increase the clearance of electrolytes and water; thus, they allow us to control hypervolemia and to prevent patients from pulmonary edema. LD are also frequently applied to patients with an acute decrease in glomerular filtration rate, namely, acute kidney injury (AKI). Nevertheless, volume depletion may be associated with reduced renal perfusion and possibly slower restitution or even aggravation of kidney dysfunction. Several trials on the preventive or therapeutic efficacy of LD have been published since the early 1970s. Our review article is intended to summarize the most important references related to this topic. In addition, we discuss the diagnostic value of the so-called furosemide stress test. The currently available data indicate that LD may act in a beneficial manner as long as euvolemia is maintained (matched hydration). Key Massages: LD are not beneficial for AKI treatment if kidney-related endpoints are considered. In certain situations, AKI prevention with LD can be associated with favorable outcomes as long as euvolemia is maintained. LD can help to identify AKI subjects at a higher risk of AKI progression, but the exact clinical consequences need to be determined.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"73 1","pages":"457 - 464"},"PeriodicalIF":0.0,"publicationDate":"2019-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82875513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aortic Calcification Affects Noninvasive Estimates of Central Blood Pressure in Patients with Severe Chronic Kidney Disease","authors":"R. Carlsen, S. Winther, C. Peters, E. Laugesen, D. Khatir, H. Bøtker, M. Bøttcher, P. Ivarsen, M. Svensson, N. Buus","doi":"10.1159/000501226","DOIUrl":"https://doi.org/10.1159/000501226","url":null,"abstract":"Background: Central blood pressure (BP) assessed noninvasively considerably underestimates true invasively measured aortic BP in chronic kidney disease (CKD) patients. The difference between the estimated and the true aortic BP increases with decreasing estimated glomerular filtration rates (eGFR). The present study investigated whether aortic calcification affects noninvasive estimates of central BP. Methods: Twenty-four patients with CKD stage 4–5 undergoing coronary angiography and an aortic computed tomography scan were included (63% males, age [mean ± SD ] 53 ± 11 years, and eGFR 9 ± 5 mL/min/1.73 m2). Invasive aortic BP was measured through the angiography catheter, while non-invasive central BP was obtained using radial artery tonometry with a SphygmoCor® device. The Agatston calcium score (CS) in the aorta was quantified on CT scans using the CS on CT scans. Results: The invasive aortic systolic BP (SBP) was 152 ± 23 mm Hg, while the estimated central SBP was 133 ± 20 mm Hg. Ten patients had a CS of 0 in the aorta, while 14 patients had a CS >0 in the aorta. The estimated central SBP was lower than the invasive aortic SBP in patients with aortic calcification compared to patients without (mean difference 8 mm Hg, 95% CI 0.3–16; p = 0.04). The brachial SBP was lower than the aortic SBP in patients with aortic calcification compared to patients without (mean difference 10 mm Hg, 95% CI 2–19; p = 0.02). Conclusion: In patients with advanced CKD the presence of aortic calcification is associated with a higher difference between invasively measured central aortic BP and non-invasive estimates of central BP as compared to patients without calcifications.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"88 1","pages":"704 - 714"},"PeriodicalIF":0.0,"publicationDate":"2019-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84153750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bortezomib-Based Chemotherapy with Autologous Stem Cell Transplantation for Monoclonal Gammopathy of Renal Significance: A Case Report and Literature Review","authors":"Jing Huang, Chunyan Sun, H. Su, Chun Zhang, J. Xiong","doi":"10.1159/000501314","DOIUrl":"https://doi.org/10.1159/000501314","url":null,"abstract":"Background/Aims: The term monoclonal gammopathy of renal significance (MGRS) was introduced in 2012 to emphasize kidney lesions in monoclonal gammopathy patients. Bortezomib-based chemotherapy has become the first-line treatment for MGRS. Objectives: The objective of this study was to investigate whether the strategy of combining chemotherapy with autologous stem cell transplantation (ASCT) could improve prognosis and decrease functional kidney impairment in patients with MGRS. Methods: We reported the case of a 44-year-old Asian patient who was diagnosed with MGRS and received 5 cycles of Velcade® (a trade name for bortezomib), thalidomide, and dexamethasone therapy (VTD therapy), and subsequently underwent ASCT. In addition, we performed a literature review and summarized the latest advances in the characterization, treatment, and prognosis of MGRS. Results: The patient was diagnosed with light chain deposition disease by renal biopsy. After 5 cycles of VTD therapy, the patient had a very good partial response characterized by the resolution of M-protein (20.2% before treatment vs. 2.5% after treatment), remission of the level of serum free lambda (FLAM; over 80% decline), and normalization of the serum free light chain (sFLC) ratio (κ to λ). He also had a renal response characterized by a decreased serum creatinine level (1.61 vs.1.34 mg/dL) and less severe proteinuria (6.77 g/24 h vs.1.264 g/24 h) after chemotherapy. Importantly, after ASCT, the patient achieved a complete response (CR) characterized by a negative serum immunofixation electrophoresis (IFE) result and a dramatic decrement in FLAM (over 90%). Furthermore, 6 months after ASCT, the patient still remained in stable condition with a negative IFE result, normal sFLC ratio, and low level of serum creatinine (1.31 mg/dL) and proteinuria (0.339 g/24 h). In our retrospective literature analysis, we found that MGRS patient survival time and renal outcome had been markedly improved by current therapies due to the popularization of bortezomib-based chemotherapy and ASCT. Conclusions: The patient successfully achieved CR after VTD therapy followed by ASCT. However, this treatment is controversial, and a standard therapy recommendation for MGRS has not been established. Bortezomib-based chemotherapy combined with ASCT may have prospects for the treatment of MGRS, but the exact effects of ASCT remain unclear and should be thoroughly investigated.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"12 1","pages":"858 - 869"},"PeriodicalIF":0.0,"publicationDate":"2019-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90252301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA-203 Acts as a Potent Suppressor in Septic Shock by Alleviating Lung Injury via Inhibition of VNN1","authors":"L. Ling, Hai-tao Lu, Hai-feng Wang, Mei-jia Shen, Hong-bo Zhang","doi":"10.1159/000500484","DOIUrl":"https://doi.org/10.1159/000500484","url":null,"abstract":"Background: Septic shock, the most serious complication of sepsis, is a life-threatening disease that is mainly characterized by hypoperfusion and multiple organ failure. Various aberrantly expressed microRNAs (miRNAs) have been reported to be related to septic shock. We explored the regulatory effect of microRNA-203 (miR-203) on lung injury in septic shock mice. Methods: Microarray-based gene expression profiling related to septic shock identified the differentially expressed gene vanin-1 (VNN1) and potential regulatory miR-203. miR-203 was predicted to mediate VNN1 expression, thus affecting septic shock, which was investigated by treatment with miR-203 mimic, miR-203 inhibitor, and siRNA-VNN1 in septic shock mouse models. Polymorphonuclear neutrophils (PMNs) and pulmonary alveolar macrophages in bronchoalveolar lavage fluid (BALF) as well as the wet/dry ratio of the lung were also measured to assess lung injury. Additionally, the effects of miR-203 on inflammatory cytokines, oxidative stress indexes, blood biochemical indexes, serine-threonine protein kinase (AKT) signaling pathway-related factors, and apoptosis-related factors were determined. Results: VNN1 was verified to be targeted and negatively regulated by miR-203. In mouse models of septic shock, weak expression of miR-203, high expression of VNN1, and inhibition of AKT signaling pathway were identified. In response to miR-203 mimic and VNN1 gene silencing, mouse models of septic shock displayed reduced apoptosis, MDA, ALT, and AST in lung tissues, decreased levels of TNF-α, IL-1β, IFN-γ, IL-10, and IL-6, in serum, and reduced PMN and PAM levels in BALF, in addition to elevated SOD activity. Notably, the presence of miR-203 mimic led to AKT signaling pathway activation. Conclusion:This study shows that upregulating miR-203 can alleviate lung injury through activation of the AKT signaling pathway by downregulating VNN1 in septic shock.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"26 1","pages":"565 - 582"},"PeriodicalIF":0.0,"publicationDate":"2019-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84883034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium Fluctuations and Mortality in a General Hospitalized Population","authors":"G. Lombardi, P. M. Ferraro, Luca Calvaruso, A. Naticchia, S. D'alonzo, G. Gambaro","doi":"10.1159/000500916","DOIUrl":"https://doi.org/10.1159/000500916","url":null,"abstract":"Background/Aims: Aim of our study was to describe the association between natremia (Na) fluctuation and hospital mortality in a general population admitted to a tertiary medical center. Methods: We performed a retrospective observational cohort study on the patient population admitted to the Fondazione Policlinico A. Gemelli IRCCS Hospital between January 2010 and December 2014 with inclusion of adult patients with at least 2 Na values available and with a normonatremic condition at hospital admission. Patients were categorized according to all Na values recorded during hospital stay in the following groups: normonatremia, hyponatremia, hypernatremia, and mixed dysnatremia. The difference between the highest or the lowest Na value reached during hospital stay and the Na value read at hospital admission was used to identify the maximum Na fluctuation. Cox proportional hazards models were used to estimate hazard ratios (HRs) for in-hospital death in the groups with dysnatremias and across quartiles of Na fluctuation. Covariates assessed were age, sex, highest and lowest Na level, Charlson/Deyo score, cardiovascular diseases, cerebrovascular diseases, dementia, congestive heart failure, severe kidney disease, estimated glomerular filtration rate, and number of Na measurements during hospital stay. Results: 46,634 admissions matched inclusion criteria. Incident dysnatremia was independently associated with in-hospital mortality (hyponatremia: HR 3.11, 95% CI 2.53, 3.84, p < 0.001; hypernatremia: HR 5.12, 95% CI 3.94, 6.65, p < 0.001; mixed-dysnatremia: HR 4.94, 95% CI 3.08, 7.92, p < 0.001). We found a higher risk of in-hospital death by linear increase of quartile of Na fluctuation (p trend <0.001) irrespective of severity of dysnatremia (HR 2.34, 95% CI 1.55, 3.54, p < 0.001, for the highest quartile of Na fluctuation compared with the lowest). Conclusions: Incident dysnatremia is associated with higher hospital mortality. Fluctuation of Na during hospital stay is a prognostic marker for hospital death independent of dysnatremia severity.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"44 1","pages":"604 - 614"},"PeriodicalIF":0.0,"publicationDate":"2019-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73393466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}