G. Lombardi, P. M. Ferraro, Luca Calvaruso, A. Naticchia, S. D'alonzo, G. Gambaro
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.
背景/目的:本研究的目的是描述在三级医疗中心住院的普通人群中钠血症(Na)波动与医院死亡率之间的关系。方法:我们对2010年1月至2014年12月期间在foundation polilinico a . Gemelli IRCCS医院入院的患者群体进行了回顾性观察队列研究，纳入了入院时钠值至少为2且血压正常的成年患者。根据住院期间记录的所有钠值将患者分为以下组:正常钠血症、低钠血症、高钠血症和混合钠血症。住院期间达到的最高或最低Na值与入院时读取的Na值之差用于识别最大Na波动。采用Cox比例风险模型估计钠代谢异常组和钠波动四分位数之间的院内死亡风险比(hr)。评估的协变量包括年龄、性别、最高和最低钠水平、Charlson/Deyo评分、心血管疾病、脑血管疾病、痴呆、充血性心力衰竭、严重肾脏疾病、估计肾小球滤过率和住院期间的钠测量次数。结果:46,634例患者符合纳入标准。低钠血症与住院死亡率独立相关(低钠血症:HR 3.11, 95% CI 2.53, 3.84, p < 0.001;高钠血症:HR 5.12, 95% CI 3.94, 6.65, p < 0.001;混合性钠血症:HR 4.94, 95% CI 3.08, 7.92, p < 0.001)。我们发现，钠波动的四分位数呈线性增加(p趋势<0.001)，与钠异常的严重程度无关(相对危险度2.34,95% CI 1.55, 3.54, p <0.001，钠波动最高的四分位数与最低的四分位数相比)。结论:偶发性钠血症与较高的住院死亡率相关。住院期间钠的波动是与血钠异常严重程度无关的医院死亡预后指标。
{"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}
Zechen Yan, Dahai Yu, Yamei Cai, J. Shang, R. Qin, Jing Xiao, Bin Zhao, Zhanzheng Zhao, D. Simmons
Background: Insulin resistance (IR) is increased among people with end-stage renal disease (ESRD). The Triglyceride glucose (TyG) index is a marker of IR and is also associated with the prognosis of cardiovascular disease among patients initiating peritoneal dialysis (PD). This study was aimed at examining the associations between TyG index and cardiovascular deaths in patients initiating PD. Methods and Results: Three thousand fifty-four patients initiating PD between 2007 and 2014 were included in a prospective cohort derived from Henan PD Registry, TyG index alongside other baseline characteristics were measured when ESRD patients initiated PD. Logistic regression adjusting for age, gender, and major cardiovascular risk factors estimated the association between TyG index and subsequent cardiovascular mortality within 2 years since the initiation of PD. Results: TyG index was positively associated with cardiovascular mortality: adjusted incidence rates ratio (95% CI) comparing the highest vs. lowest TyG index quartile was 2.32 (2.12–2.55) in all, 2.22 (2.01–2.46) in those with body mass index (BMI) <25 kg/m2, and 2.82 (2.24–3.54) in those with BMI ≥25 kg/m2, respectively. Linear dose-response relationships were revealed in all and by BMI. Conclusions: TyG index might be a prognostic factor in predicting cardiovascular mortality among patients initiating PD.
{"title":"Triglyceride Glucose Index Predicting Cardiovascular Mortality in Chinese Initiating Peritoneal Dialysis: A Cohort Study","authors":"Zechen Yan, Dahai Yu, Yamei Cai, J. Shang, R. Qin, Jing Xiao, Bin Zhao, Zhanzheng Zhao, D. Simmons","doi":"10.1159/000500979","DOIUrl":"https://doi.org/10.1159/000500979","url":null,"abstract":"Background: Insulin resistance (IR) is increased among people with end-stage renal disease (ESRD). The Triglyceride glucose (TyG) index is a marker of IR and is also associated with the prognosis of cardiovascular disease among patients initiating peritoneal dialysis (PD). This study was aimed at examining the associations between TyG index and cardiovascular deaths in patients initiating PD. Methods and Results: Three thousand fifty-four patients initiating PD between 2007 and 2014 were included in a prospective cohort derived from Henan PD Registry, TyG index alongside other baseline characteristics were measured when ESRD patients initiated PD. Logistic regression adjusting for age, gender, and major cardiovascular risk factors estimated the association between TyG index and subsequent cardiovascular mortality within 2 years since the initiation of PD. Results: TyG index was positively associated with cardiovascular mortality: adjusted incidence rates ratio (95% CI) comparing the highest vs. lowest TyG index quartile was 2.32 (2.12–2.55) in all, 2.22 (2.01–2.46) in those with body mass index (BMI) <25 kg/m2, and 2.82 (2.24–3.54) in those with BMI ≥25 kg/m2, respectively. Linear dose-response relationships were revealed in all and by BMI. Conclusions: TyG index might be a prognostic factor in predicting cardiovascular mortality among patients initiating PD.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"305 1","pages":"669 - 678"},"PeriodicalIF":0.0,"publicationDate":"2019-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76860171","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}
Background: The cholinergic anti-inflammatory pathway, positioned at the interface of the nervous and immune systems, is the efferent limb of the “inflammatory reflex” which mainly signals through the vagus nerve. As such, the brain can modulate peripheral inflammatory responses by the activation of vagal efferent fibers. Importantly, immune cells in the spleen express most cholinergic system components such as acetylcholine (ACh), choline acetyltransferase, acetylcholinesterase, and both muscarinic and nicotinic ACh receptors, making communication between both systems possible. In general, this communication down-regulates the inflammation, achieved through different mechanisms and depending on the cells involved. Summary: With the awareness that the cholinergic anti-inflammatory pathway serves to prevent or limit inflammation in peripheral organs, vagus nerve stimulation has become a promising strategy in the treatment of several inflammatory conditions. Both pharmacological and non-pharmacological methods have been used in many studies to limit organ injury as a consequence of inflammation. Key Messages: In this review, we will highlight our current knowledge of the cholinergic anti-inflammatory pathway, with emphasis on its potential clinical use in the treatment of inflammation-triggered kidney injury.
{"title":"The Cholinergic Anti-Inflammatory Pathway as a Conceptual Framework to Treat Inflammation-Mediated Renal Injury","authors":"J. Jarczyk, B. Yard, S. Hoeger","doi":"10.1159/000500920","DOIUrl":"https://doi.org/10.1159/000500920","url":null,"abstract":"Background: The cholinergic anti-inflammatory pathway, positioned at the interface of the nervous and immune systems, is the efferent limb of the “inflammatory reflex” which mainly signals through the vagus nerve. As such, the brain can modulate peripheral inflammatory responses by the activation of vagal efferent fibers. Importantly, immune cells in the spleen express most cholinergic system components such as acetylcholine (ACh), choline acetyltransferase, acetylcholinesterase, and both muscarinic and nicotinic ACh receptors, making communication between both systems possible. In general, this communication down-regulates the inflammation, achieved through different mechanisms and depending on the cells involved. Summary: With the awareness that the cholinergic anti-inflammatory pathway serves to prevent or limit inflammation in peripheral organs, vagus nerve stimulation has become a promising strategy in the treatment of several inflammatory conditions. Both pharmacological and non-pharmacological methods have been used in many studies to limit organ injury as a consequence of inflammation. Key Messages: In this review, we will highlight our current knowledge of the cholinergic anti-inflammatory pathway, with emphasis on its potential clinical use in the treatment of inflammation-triggered kidney injury.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"152 1","pages":"435 - 448"},"PeriodicalIF":0.0,"publicationDate":"2019-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85302458","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}
S. Worawichawong, S. Worawichawong, P. Radinahamed, D. Muntham, N. Sathirapongsasuti, A. Nongnuch, M. Assanatham, C. Kitiyakara
Background/Aims: The degree of tubular atrophy and interstitial fibrosis (IFTA) is an important prognostic factor in glomerulonephritis. Imbalance between pro-inflammatory cytokines such as monocyte chemoattractant protein- 1 (MCP-1) and protective cytokines such as epidermal growth factor (EGF) likely determine IFTA severity. In separate studies, elevated MCP-1 and decreased EGF have been shown to be associated with IFTA severity. In this study, we aim to evaluate the predictive value of urinary EGF/MCP-1 ratio compared to each biomarker individually for moderate to severe IFTA in primary glomerulonephritis (GN). Methods: Urine samples were collected at biopsy from primary GN (IgA nephropathy, focal and segmental glomerulosclerosis, minimal change disease, membranous nephropathy). MCP-1 and EGF were analyzed by enzyme-linked immunosorbent assay. Results: EGF, MCP-1 and EGF/MCP-1 ratio from primary GN, all correlated with IFTA (n=58). By univariate analysis, glomerular filtration rate, EGF, and EGF/MCP-1 ratio were associated with IFTA. By multivariate analysis, only EGF/MCP-1 ratio was independently associated with IFTA. EGF/MCP-1 ratio had a sensitivity of 88% and specificity of 74 % for IFTA. EGF/MCP-1 had good discrimination for IFTA (AUC=0.85), but the improvement over EGF alone was not significant. Conclusion: EGF/MCP-1 ratio is independently associated IFTA severity in primary glomerulonephritis, but the ability of EGF/MCP-1 ratio to discriminate moderate to severe IFTA may not be much better than EGF alone.
{"title":"Urine Epidermal Growth Factor, Monocyte Chemoattractant Protein-1 or Their Ratio as Biomarkers for Interstitial Fibrosis and Tubular Atrophy in Primary Glomerulonephritis","authors":"S. Worawichawong, S. Worawichawong, P. Radinahamed, D. Muntham, N. Sathirapongsasuti, A. Nongnuch, M. Assanatham, C. Kitiyakara","doi":"10.1159/000452595","DOIUrl":"https://doi.org/10.1159/000452595","url":null,"abstract":"Background/Aims: The degree of tubular atrophy and interstitial fibrosis (IFTA) is an important prognostic factor in glomerulonephritis. Imbalance between pro-inflammatory cytokines such as monocyte chemoattractant protein- 1 (MCP-1) and protective cytokines such as epidermal growth factor (EGF) likely determine IFTA severity. In separate studies, elevated MCP-1 and decreased EGF have been shown to be associated with IFTA severity. In this study, we aim to evaluate the predictive value of urinary EGF/MCP-1 ratio compared to each biomarker individually for moderate to severe IFTA in primary glomerulonephritis (GN). Methods: Urine samples were collected at biopsy from primary GN (IgA nephropathy, focal and segmental glomerulosclerosis, minimal change disease, membranous nephropathy). MCP-1 and EGF were analyzed by enzyme-linked immunosorbent assay. Results: EGF, MCP-1 and EGF/MCP-1 ratio from primary GN, all correlated with IFTA (n=58). By univariate analysis, glomerular filtration rate, EGF, and EGF/MCP-1 ratio were associated with IFTA. By multivariate analysis, only EGF/MCP-1 ratio was independently associated with IFTA. EGF/MCP-1 ratio had a sensitivity of 88% and specificity of 74 % for IFTA. EGF/MCP-1 had good discrimination for IFTA (AUC=0.85), but the improvement over EGF alone was not significant. Conclusion: EGF/MCP-1 ratio is independently associated IFTA severity in primary glomerulonephritis, but the ability of EGF/MCP-1 ratio to discriminate moderate to severe IFTA may not be much better than EGF alone.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"20 1","pages":"997 - 1007"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87895712","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}
Background/Aims: Aging is associated with renal function decline and elderly patients are more vulnerable to acute kidney injury (AKI). The causes and prognosis of AKI according to new KDIGO definition that broadened the diagnosis and included more patients without dialysis dependence have not yet been compared between younger and elderly patients. Methods: In a retrospective analysis all patients with AKI admitted to a tertiary care Nephrology department (N=424) were included. Individuals were stratified by age (≤80 years, >80 years). Primary end-point was death or dialysis dependence at hospital discharge, secondary analyses addressed the need for dialysis, creatinine at discharge, mortality, and length of stay. Results: The distribution of AKI causes was different between the age groups. Circulatory AKI was the most important cause in both groups; however, septic or toxic AKI contributed relevantly in younger patients. Nevertheless, the number of patients reaching the primary end-point was similar (younger, 20.4%; older, 18.0%; OR 1.17, 95%CI, 0.703-1.948). While mortality tended to be higher in the older population, none of the secondary analyses indicated worse outcome for the older patients. Conclusion: The prognosis of AKI in elderly patients is not necessarily worse than in middle aged individuals. Nevertheless, older patients may be particularly vulnerable to circulatory or ischemic insults of the kidneys.
{"title":"Clinical Course of Acute Kidney Injury in Elderly Individuals Above 80 Years","authors":"Isabell Funk, E. Seibert, S. Markau, M. Girndt","doi":"10.1159/000452599","DOIUrl":"https://doi.org/10.1159/000452599","url":null,"abstract":"Background/Aims: Aging is associated with renal function decline and elderly patients are more vulnerable to acute kidney injury (AKI). The causes and prognosis of AKI according to new KDIGO definition that broadened the diagnosis and included more patients without dialysis dependence have not yet been compared between younger and elderly patients. Methods: In a retrospective analysis all patients with AKI admitted to a tertiary care Nephrology department (N=424) were included. Individuals were stratified by age (≤80 years, >80 years). Primary end-point was death or dialysis dependence at hospital discharge, secondary analyses addressed the need for dialysis, creatinine at discharge, mortality, and length of stay. Results: The distribution of AKI causes was different between the age groups. Circulatory AKI was the most important cause in both groups; however, septic or toxic AKI contributed relevantly in younger patients. Nevertheless, the number of patients reaching the primary end-point was similar (younger, 20.4%; older, 18.0%; OR 1.17, 95%CI, 0.703-1.948). While mortality tended to be higher in the older population, none of the secondary analyses indicated worse outcome for the older patients. Conclusion: The prognosis of AKI in elderly patients is not necessarily worse than in middle aged individuals. Nevertheless, older patients may be particularly vulnerable to circulatory or ischemic insults of the kidneys.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"27 1","pages":"947 - 955"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86542966","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}
Bo Hu, Yuhong Wu, Jie Liu, Xiaohua Shen, F. Tong, Guangtao Xu, R. Shen
Background/Aims: Diabetes mellitus (DM) can lead to renal damage and dysfunction, and exacerbate renal ischemia/reperfusion injury (RI/RI). The aim of this study was to investigate the protective effect of GSK-3β inhibitor TDZD-8 against RI/RI through Nrf2/TrxR2 signaling pathway in a rat DM model. Methods: A DM rat model was established by a single injection of streptozocin. Diabetic rats were pretreated with TDZD-8 (1 mg/kg bw) or TDZD-8+auranofin (10 nmol/L, 5ml/kg bw), and then subjected to 45-min ischemia and 24-h reperfusion. Rats were equally randomized into four groups: a Sham-operated group, a RI/RI group, a TDZD-8 group, and a TDZD-8+auranofin group. Serum levels of BUN and Scr were measured. SOD activity, MDA content, and Nrf2, TrxR2 and caspase-3 expressions in rat kidney tissues were determined. Results: Renal function was improved, oxidative stress and cell apoptosis were reduced, and the expression of Nrf2 and TrxR2 was up-regulated in TDZD-8 treated rats as compared with those in auranofin treated rats. Conclusion: TDZD-8 may exert its protective effect against RI/RI by regulating the Nrf2/TrxR2 signaling pathway in the kidney tissue in DM.
{"title":"GSK-3beta Inhibitor Induces Expression of Nrf2/TrxR2 Signaling Pathway to Protect against Renal Ischemia/Reperfusion Injury in Diabetic Rats","authors":"Bo Hu, Yuhong Wu, Jie Liu, Xiaohua Shen, F. Tong, Guangtao Xu, R. Shen","doi":"10.1159/000452598","DOIUrl":"https://doi.org/10.1159/000452598","url":null,"abstract":"Background/Aims: Diabetes mellitus (DM) can lead to renal damage and dysfunction, and exacerbate renal ischemia/reperfusion injury (RI/RI). The aim of this study was to investigate the protective effect of GSK-3β inhibitor TDZD-8 against RI/RI through Nrf2/TrxR2 signaling pathway in a rat DM model. Methods: A DM rat model was established by a single injection of streptozocin. Diabetic rats were pretreated with TDZD-8 (1 mg/kg bw) or TDZD-8+auranofin (10 nmol/L, 5ml/kg bw), and then subjected to 45-min ischemia and 24-h reperfusion. Rats were equally randomized into four groups: a Sham-operated group, a RI/RI group, a TDZD-8 group, and a TDZD-8+auranofin group. Serum levels of BUN and Scr were measured. SOD activity, MDA content, and Nrf2, TrxR2 and caspase-3 expressions in rat kidney tissues were determined. Results: Renal function was improved, oxidative stress and cell apoptosis were reduced, and the expression of Nrf2 and TrxR2 was up-regulated in TDZD-8 treated rats as compared with those in auranofin treated rats. Conclusion: TDZD-8 may exert its protective effect against RI/RI by regulating the Nrf2/TrxR2 signaling pathway in the kidney tissue in DM.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"5 1","pages":"937 - 946"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88882386","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}
Cheng-jui Lin, Chih-jen Wu, Pei-Chen Wu, C. Pan, Tuan-Jen Wang, Fang-Ju Sun, Hsuan-Liang Liu, Han-hsiang Chen, H. Yeh
Background/Aims: Indoxyl sulfate (IS) is a protein-bound uremic toxin that accumulates in patients with chronic kidney disease (CKD). We explored the effect of IS on human early endothelial progenitor cells (EPCs) and analyzed the correlation between serum IS levels and parameters of vascular function, including endothelial function in a CKD-based cohort. Methods: A cross-sectional study with 128 stable CKD patients was conducted. Flow-mediated dilation (FMD), pulse wave velocity (PWV), ankle brachial index, serum IS and other biochemical parameters were measured and analyzed. In parallel, the activity of early EPCs was also evaluated after exposure to IS. Results: In human EPCs, a concentration-dependent inhibitory effect of IS on chemotactic motility and colony formation was observed. Additionally, serum IS levels were significantly correlated with CKD stages. The total IS (T-IS) and free IS (F-IS) were strongly associated with age, hypertension, cardiovascular disease, blood pressure, PWV, blood urea nitrogen, creatine and phosphate but negatively correlated with FMD, the estimated glomerular filtration rate (eGFR), hemoglobin, hematocrit, and calcium. A multivariate linear regression analysis also showed that FMD was significantly associated with IS after adjusting for other confounding factors. Conclusions: In humans, IS impairs early EPCs and was strongly correlated with vascular dysfunction. Thus, we speculate that this adverse effect of IS may partly result from the inhibition of early EPCs.
{"title":"Indoxyl Sulfate Impairs Endothelial Progenitor Cells and Might Contribute to Vascular Dysfunction in Patients with Chronic Kidney Disease","authors":"Cheng-jui Lin, Chih-jen Wu, Pei-Chen Wu, C. Pan, Tuan-Jen Wang, Fang-Ju Sun, Hsuan-Liang Liu, Han-hsiang Chen, H. Yeh","doi":"10.1159/000452604","DOIUrl":"https://doi.org/10.1159/000452604","url":null,"abstract":"Background/Aims: Indoxyl sulfate (IS) is a protein-bound uremic toxin that accumulates in patients with chronic kidney disease (CKD). We explored the effect of IS on human early endothelial progenitor cells (EPCs) and analyzed the correlation between serum IS levels and parameters of vascular function, including endothelial function in a CKD-based cohort. Methods: A cross-sectional study with 128 stable CKD patients was conducted. Flow-mediated dilation (FMD), pulse wave velocity (PWV), ankle brachial index, serum IS and other biochemical parameters were measured and analyzed. In parallel, the activity of early EPCs was also evaluated after exposure to IS. Results: In human EPCs, a concentration-dependent inhibitory effect of IS on chemotactic motility and colony formation was observed. Additionally, serum IS levels were significantly correlated with CKD stages. The total IS (T-IS) and free IS (F-IS) were strongly associated with age, hypertension, cardiovascular disease, blood pressure, PWV, blood urea nitrogen, creatine and phosphate but negatively correlated with FMD, the estimated glomerular filtration rate (eGFR), hemoglobin, hematocrit, and calcium. A multivariate linear regression analysis also showed that FMD was significantly associated with IS after adjusting for other confounding factors. Conclusions: In humans, IS impairs early EPCs and was strongly correlated with vascular dysfunction. Thus, we speculate that this adverse effect of IS may partly result from the inhibition of early EPCs.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"36 1","pages":"1025 - 1036"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86763291","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}
Liping Liu, Caili Wang, Yan Mi, Dan Liu, Li Li, Junying Fan, L. Nan, Niya Jia, Yu Du
Background/Aims: This study explored the correlation between hypertension and non-muscle myosin heavy chain 9 (MYH9) gene polymorphisms in Chinese chronic kidney disease (CKD) patients. Methods: This case-control study included 301 patients with CKD and 293 healthy controls. The E1 haplotype single nucleotide polymorphisms (SNPs) rs3752462 and rs4821480 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The association between MYH9 polymorphisms and high systolic blood pressure (SBP ≥ 140 mmHg) susceptibility in CKD patients was analysed. Results: The cases and controls had similar genotype and allele distributions at rs3752462 and rs4821480. No GG genotype at rs4821480 was observed. Patients with SBP < 140 mmHg were more likely to have the CC genotype (17.1%) than patients with SBP ≥ 140 mmHg (4.3%) (P = 0.001). Creatinine clearance (OR = 0.99, 95% CI = 0.98-0.10, P = 0.01) was associated with SBP in patients with CKD. The risk of SBP ≥ 140 mmHg was 0.24-fold greater among patients with the CC genotype than among patients with the TT genotype (P = 0.002). Conclusion: The rs3752462 polymorphism of MYH9 is associated with SBP in patients with CKD. The T allele in the dominant model was associated with an elevated risk for high SBP.
背景/目的:本研究探讨中国慢性肾脏病(CKD)患者高血压与非肌肉肌球蛋白重链9 (MYH9)基因多态性的相关性。方法:本病例-对照研究纳入301例CKD患者和293例健康对照。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法对E1单倍型单核苷酸多态性rs3752462和rs4821480进行基因分型。分析MYH9多态性与CKD患者高收缩压(收缩压≥140 mmHg)易感性之间的关系。结果:病例与对照组rs3752462和rs4821480基因型和等位基因分布相似。rs4821480位点未见GG基因型。收缩压< 140 mmHg的患者(17.1%)比收缩压≥140 mmHg的患者(4.3%)更容易发生CC基因型(P = 0.001)。CKD患者肌酐清除率(OR = 0.99, 95% CI = 0.98-0.10, P = 0.01)与收缩压相关。CC基因型患者发生收缩压≥140 mmHg的风险是TT基因型患者的0.24倍(P = 0.002)。结论:MYH9基因rs3752462多态性与CKD患者收缩压相关。显性模型中的T等位基因与高收缩压的风险升高有关。
{"title":"Association of MYH9 Polymorphisms with Hypertension in Patients with Chronic Kidney Disease in China","authors":"Liping Liu, Caili Wang, Yan Mi, Dan Liu, Li Li, Junying Fan, L. Nan, Niya Jia, Yu Du","doi":"10.1159/000452597","DOIUrl":"https://doi.org/10.1159/000452597","url":null,"abstract":"Background/Aims: This study explored the correlation between hypertension and non-muscle myosin heavy chain 9 (MYH9) gene polymorphisms in Chinese chronic kidney disease (CKD) patients. Methods: This case-control study included 301 patients with CKD and 293 healthy controls. The E1 haplotype single nucleotide polymorphisms (SNPs) rs3752462 and rs4821480 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The association between MYH9 polymorphisms and high systolic blood pressure (SBP ≥ 140 mmHg) susceptibility in CKD patients was analysed. Results: The cases and controls had similar genotype and allele distributions at rs3752462 and rs4821480. No GG genotype at rs4821480 was observed. Patients with SBP < 140 mmHg were more likely to have the CC genotype (17.1%) than patients with SBP ≥ 140 mmHg (4.3%) (P = 0.001). Creatinine clearance (OR = 0.99, 95% CI = 0.98-0.10, P = 0.01) was associated with SBP in patients with CKD. The risk of SBP ≥ 140 mmHg was 0.24-fold greater among patients with the CC genotype than among patients with the TT genotype (P = 0.002). Conclusion: The rs3752462 polymorphism of MYH9 is associated with SBP in patients with CKD. The T allele in the dominant model was associated with an elevated risk for high SBP.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"1 1","pages":"956 - 965"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76304472","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}
Z. Jimenez, B. C. Silva, L. Reis, M. Castro, C. D. Ramos, V. Costa-Hong, L. Bortolotto, F. Consolim-Colombo, W. Dominguez, I. Oliveira, R. Moysés, R. M. Elias
Background/Aims: Acute activation of sympathetic activation during hemodialysis is essential to maintain blood pressure (BP), albeit long-term overactivity contributes to higher mortality. Low heart rate variability (HRV), a measure of autonomic nervous system activity, and abnormal ankle-brachial index (ABI) are associated with higher mortality in patients on hemodialysis. In this study, we assessed HRV and ABI pre and post dialysis in incident patients on hemodialysis using high (1.75mmol/l) and low (1.25mmol/l) dialysate calcium concentration (DCa). Methods: HRV was measured as the ratio between low frequency and high frequency power (LF/HF). Thirty patients (age 47±16 years, 67% men) were studied in two consecutive mid-week hemodialysis sessions. Results: Mean BP variation was positive with DCa 1.75 and negative with DCa 1.25 [4.0 (-6.0, 12.2 mmHg) vs. -3.2 (-9.8, 1.3 mmHg); p=0.050]. Reduction of ABI from pre to post HD was related to higher sympathetic activity (p=0.031). The increase in LF/HF ratio was higher with DCa 1.75 (58.3% vs. 41.7% in DCa 1.75 and 1.25, respectively, RR 2.8; p=0.026). Conclusion: Although higher DCa is associated with better hemodynamic tolerability during hemodialysis, this occurs at the expense of increased sympathetic activity. Higher sympathetic activity was associated with a decrease of ABI during hemodialysis.
背景/目的:血液透析期间交感神经激活的急性激活对维持血压(BP)至关重要，尽管长期过度激活会导致更高的死亡率。低心率变异性(HRV)，一种自主神经系统活动的测量，以及异常的踝臂指数(ABI)与血液透析患者较高的死亡率相关。在这项研究中，我们使用高(1.75mmol/l)和低(1.25mmol/l)透析液钙浓度(DCa)来评估血透事件患者透析前后的HRV和ABI。方法:采用低频功率与高频功率之比(LF/HF)测定HRV。30例患者(年龄47±16岁，男性67%)进行了连续两次周中血液透析。结果:平均血压变化在DCa 1.75组为阳性，DCa 1.25组为阴性[4.0 (-6.0,12.2 mmHg) vs. -3.2 (-9.8, 1.3 mmHg)];p = 0.050)。ABI从HD前到HD后的降低与交感神经活动升高有关(p=0.031)。当DCa为1.75时，LF/HF比值的增加更高(58.3% vs. 41.7%，分别为DCa为1.75和1.25,RR为2.8;p = 0.026)。结论:虽然较高的DCa与血液透析过程中更好的血流动力学耐受性相关，但这是以增加交感神经活动为代价的。较高的交感神经活动与血液透析期间ABI的降低有关。
{"title":"High Dialysate Calcium Concentration May Cause More Sympathetic Stimulus During Hemodialysis","authors":"Z. Jimenez, B. C. Silva, L. Reis, M. Castro, C. D. Ramos, V. Costa-Hong, L. Bortolotto, F. Consolim-Colombo, W. Dominguez, I. Oliveira, R. Moysés, R. M. Elias","doi":"10.1159/000452601","DOIUrl":"https://doi.org/10.1159/000452601","url":null,"abstract":"Background/Aims: Acute activation of sympathetic activation during hemodialysis is essential to maintain blood pressure (BP), albeit long-term overactivity contributes to higher mortality. Low heart rate variability (HRV), a measure of autonomic nervous system activity, and abnormal ankle-brachial index (ABI) are associated with higher mortality in patients on hemodialysis. In this study, we assessed HRV and ABI pre and post dialysis in incident patients on hemodialysis using high (1.75mmol/l) and low (1.25mmol/l) dialysate calcium concentration (DCa). Methods: HRV was measured as the ratio between low frequency and high frequency power (LF/HF). Thirty patients (age 47±16 years, 67% men) were studied in two consecutive mid-week hemodialysis sessions. Results: Mean BP variation was positive with DCa 1.75 and negative with DCa 1.25 [4.0 (-6.0, 12.2 mmHg) vs. -3.2 (-9.8, 1.3 mmHg); p=0.050]. Reduction of ABI from pre to post HD was related to higher sympathetic activity (p=0.031). The increase in LF/HF ratio was higher with DCa 1.75 (58.3% vs. 41.7% in DCa 1.75 and 1.25, respectively, RR 2.8; p=0.026). Conclusion: Although higher DCa is associated with better hemodynamic tolerability during hemodialysis, this occurs at the expense of increased sympathetic activity. Higher sympathetic activity was associated with a decrease of ABI during hemodialysis.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"36 1","pages":"978 - 985"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79074907","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}
H. Pi, Yu-Feng Xu, R. Xu, Zhikai Yang, Zhen Qu, Yu-Qing Chen, Gui-ling Liu, Jie Dong
Background/Aims: Cognitive impairment and abnormal structural neuroimaging is common in chronic kidney disease patients. We aimed to explore its association with dialysis modality and the relationship between cognitive impairment and abnormal structural neuroimaging. Methods: Sixty peritoneal dialysis patients and 30 hemodialysis and 30 non-dialyzed stage 3-5 chronic kidney disease patients without history of stroke were enrolled for the study. Participants were matched for age, gender, education, diabetes status, and dialysis duration (if appropriate). Cognitive functions were measured using a battery of recognized instruments. Brain features were examined with 3-dimensional magnetic resonance imaging. Results: Cognitive impairment was significantly more severe in dialysis patients than in non-dialyzed patients. The global and specific cognitive function were not significantly different between patients on peritoneal dialysis and hemodialysis. Hemodialysis patients had more severe white matter hyperintensity, sulcal and ventricular atrophy, and SVIs than other patients. In all groups, higher white matter grade, ventricular grade, and hippocampal atrophy were significantly associated with global cognitive impairment, with hazard ratios of 1.80 (1.22-2.64), 1.67 (1.09-2.57), and 2.49 (1.07-5.77), respectively. White matter grade was also significantly associated with delayed memory (hazard ratio 1.63; 1.12-2.39). Conclusion: Dialysis modality showed no association with cognitive impairment, although hemodialysis patients had more severe neuroimaging abnormalities. For the whole group, white matter hyperintensity, and ventricular and hippocampal atrophy, were independently associated with global cognitive impairment in chronic kidney disease patients.
{"title":"Cognitive Impairment and Structural Neuroimaging Abnormalities Among Patients with Chronic Kidney Disease","authors":"H. Pi, Yu-Feng Xu, R. Xu, Zhikai Yang, Zhen Qu, Yu-Qing Chen, Gui-ling Liu, Jie Dong","doi":"10.1159/000452603","DOIUrl":"https://doi.org/10.1159/000452603","url":null,"abstract":"Background/Aims: Cognitive impairment and abnormal structural neuroimaging is common in chronic kidney disease patients. We aimed to explore its association with dialysis modality and the relationship between cognitive impairment and abnormal structural neuroimaging. Methods: Sixty peritoneal dialysis patients and 30 hemodialysis and 30 non-dialyzed stage 3-5 chronic kidney disease patients without history of stroke were enrolled for the study. Participants were matched for age, gender, education, diabetes status, and dialysis duration (if appropriate). Cognitive functions were measured using a battery of recognized instruments. Brain features were examined with 3-dimensional magnetic resonance imaging. Results: Cognitive impairment was significantly more severe in dialysis patients than in non-dialyzed patients. The global and specific cognitive function were not significantly different between patients on peritoneal dialysis and hemodialysis. Hemodialysis patients had more severe white matter hyperintensity, sulcal and ventricular atrophy, and SVIs than other patients. In all groups, higher white matter grade, ventricular grade, and hippocampal atrophy were significantly associated with global cognitive impairment, with hazard ratios of 1.80 (1.22-2.64), 1.67 (1.09-2.57), and 2.49 (1.07-5.77), respectively. White matter grade was also significantly associated with delayed memory (hazard ratio 1.63; 1.12-2.39). Conclusion: Dialysis modality showed no association with cognitive impairment, although hemodialysis patients had more severe neuroimaging abnormalities. For the whole group, white matter hyperintensity, and ventricular and hippocampal atrophy, were independently associated with global cognitive impairment in chronic kidney disease patients.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":"15 1","pages":"986 - 996"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74421674","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}
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