J. Martín-Navarro, R. Esteras, Esmeralda Castillo, Sol Carriazo, Raul Fernandez-Prado, C. Gracia-Iguacel, Sebastián Más Fontao, A. Ortiz, E. González-Parra
Background: Reactions to dialyzers used in dialysis have been reported more frequently in recent years. Evidence, however, shows that the reaction rate has remained stable for years. Summary: One explanation for the apparent increase in publication frequency could be the lack of knowledge that dialyzer reactions may well occur with biocompatible membranes. Studies showed that the cause of these reactions is very diverse and varied, involving multiple materials. However, polyvinylpyrrolidone continues to be the main suspect, but without conclusive results. There are no differences between the different fibers, and although polysulfone is the most described, it is also the most used. Key Messages: The change to cellulose triacetate continues to be the most appropriate form of treatment. The classification of these reactions into type A and B complicates the diagnosis, and its true usefulness is in doubt.
{"title":"Reactions to Synthetic Membranes Dialyzers: Is there an Increase in Incidence?","authors":"J. Martín-Navarro, R. Esteras, Esmeralda Castillo, Sol Carriazo, Raul Fernandez-Prado, C. Gracia-Iguacel, Sebastián Más Fontao, A. Ortiz, E. González-Parra","doi":"10.1159/000501035","DOIUrl":"https://doi.org/10.1159/000501035","url":null,"abstract":"Background: Reactions to dialyzers used in dialysis have been reported more frequently in recent years. Evidence, however, shows that the reaction rate has remained stable for years. Summary: One explanation for the apparent increase in publication frequency could be the lack of knowledge that dialyzer reactions may well occur with biocompatible membranes. Studies showed that the cause of these reactions is very diverse and varied, involving multiple materials. However, polyvinylpyrrolidone continues to be the main suspect, but without conclusive results. There are no differences between the different fibers, and although polysulfone is the most described, it is also the most used. Key Messages: The change to cellulose triacetate continues to be the most appropriate form of treatment. The classification of these reactions into type A and B complicates the diagnosis, and its true usefulness is in doubt.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77268924","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}
V. Krátký, S. Kikerlová, Z. Husková, J. Sadowski, F. Kolář, L. C̆ervenka
Background/Aims: We found recently that the aortocaval fistula (ACF)-induced heart failure (HF) results in higher mortality in female than in male rats. Possibly, the development of renal dysfunction in the females, unlike in males, is associated with altered renal vascular responsiveness to angiotensin II (ANG II). Methods: Five or 20 weeks after ACF creation (compensated and decompensated HF, respectively), we assessed renal blood flow (RBF) responses to intrarenal administration of ANG II, norepinephrine (NE), and acetylcholine (Ach) in female ACF and sham-operated rats. Results: In ACF females, ANG II decreased RBF more than in healthy animals, unlike with earlier published data in male ACF rats that responded similarly. Also, NE decreased RBF more in female ACF rats, whereas Ach increased RBF to the same extent in female ACF and sham-operated rats. RBF responses to intravenous administration of NE and Ach were almost identical in female and male ACF rats. Conclusion: Female ACF rats studied at the onset of HF decompensation reveal, in contrast to male rats, enhanced renal vascular responsiveness to both NE and ANG II. When associated with the demonstrated increased intrarenal ANG II and NE concentrations, such hyperresponsiveness might promote the development of renal dysfunction and accelerate HF decompensation.
{"title":"Enhanced Renal Vascular Responsiveness to Angiotensin II and Norepinephrine: A Unique Feature of Female Rats with Congestive Heart Failure","authors":"V. Krátký, S. Kikerlová, Z. Husková, J. Sadowski, F. Kolář, L. C̆ervenka","doi":"10.1159/000502379","DOIUrl":"https://doi.org/10.1159/000502379","url":null,"abstract":"Background/Aims: We found recently that the aortocaval fistula (ACF)-induced heart failure (HF) results in higher mortality in female than in male rats. Possibly, the development of renal dysfunction in the females, unlike in males, is associated with altered renal vascular responsiveness to angiotensin II (ANG II). Methods: Five or 20 weeks after ACF creation (compensated and decompensated HF, respectively), we assessed renal blood flow (RBF) responses to intrarenal administration of ANG II, norepinephrine (NE), and acetylcholine (Ach) in female ACF and sham-operated rats. Results: In ACF females, ANG II decreased RBF more than in healthy animals, unlike with earlier published data in male ACF rats that responded similarly. Also, NE decreased RBF more in female ACF rats, whereas Ach increased RBF to the same extent in female ACF and sham-operated rats. RBF responses to intravenous administration of NE and Ach were almost identical in female and male ACF rats. Conclusion: Female ACF rats studied at the onset of HF decompensation reveal, in contrast to male rats, enhanced renal vascular responsiveness to both NE and ANG II. When associated with the demonstrated increased intrarenal ANG II and NE concentrations, such hyperresponsiveness might promote the development of renal dysfunction and accelerate HF decompensation.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86163480","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}
Mi Jung Lee, T. Chang, Joongyub Lee, Yeong‐Hoon Kim, K. Oh, S. Lee, S. Kim, J. Park, T. Yoo, Shin-Wook Kang, K. Choi, C. Ahn, S. Han
Background: Urine osmolality indicates the ability of the kidney to concentrate the urine and reflects the antidiuretic action of vasopressin. However, results about the association between urine osmolality and adverse renal outcomes in chronic kidney disease (CKD) are conflicting. We investigated the association between urine osmolality and adverse renal outcomes in a nationwide prospective CKD cohort. Methods: A total of 1,999 CKD patients were categorized into 3 groups according to their urine osmolality tertiles. Primary outcome was a composite of 50% decline in the estimated glomerular filtration rate (eGFR), initiation of dialysis, or kidney transplantation. Results: During a mean follow-up of 35.2 ± 19.0 months, primary outcome occurred in 432 (21.6%) patients; 240 (36.4%), 162 (24.3%), and 30 (4.5%) in the lowest, middle, and highest tertiles, respectively. Low urine osmolality was independently associated with a greater risk of CKD progression (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.12–2.59). This association was particularly evident in patients with CKD stages 3–4 (per 10 mosm/kg decrease; HR, 1.02; 95% CI, 1.00–1.03). Adding urine osmolality to a base model with conventional factors significantly increased the ability to predict CKD progression (C-statistics, 0.86; integrated discrimination improvement [IDI], 0.021; both p < 0.001). However, adding both urine osmolality and eGFR did not further improve the predictive ability compared with the addition of eGFR only (C-statistics, p = 0.29; IDI, p = 0.09). Conclusions: Low urine osmolality was an independent risk factor for adverse renal outcomes in CKD patients, but its predictive ability did not surpass eGFR. Thus, kidney function should be considered while interpreting the clinical significance of urine osmolality.
背景:尿渗透压表明肾脏浓缩尿液的能力，反映加压素的抗利尿作用。然而，关于尿渗透压与慢性肾脏疾病(CKD)不良肾脏结局之间的关系的结果是相互矛盾的。我们在全国前瞻性CKD队列中调查了尿渗透压与不良肾脏结局之间的关系。方法:1999例慢性肾病患者按尿渗透压分型分为3组。主要结局是估计肾小球滤过率(eGFR)下降50%、开始透析或肾移植的综合结果。结果:在平均35.2±19.0个月的随访中，432例(21.6%)患者出现主要结局;最低、中、最高三分位数分别为240(36.4%)、162(24.3%)、30(4.5%)。低尿渗透压与更大的CKD进展风险独立相关(危险比[HR]， 1.71;95%可信区间[CI]， 1.12-2.59)。这种关联在CKD 3-4期患者中尤为明显(每10 mosm/kg减少;人力资源,1.02;95% ci, 1.00-1.03)。在常规因素的基础模型中加入尿渗透压可显著提高预测CKD进展的能力(C-statistics, 0.86;综合判别改进[IDI]， 0.021;p均< 0.001)。然而，与仅添加eGFR相比，同时添加尿渗透压和eGFR并没有进一步提高预测能力(C-statistics, p = 0.29;IDI, p = 0.09)。结论:低尿渗透压是CKD患者肾脏不良结局的独立危险因素，但其预测能力不超过eGFR。因此，在解释尿渗透压的临床意义时，应考虑肾功能。
{"title":"Urine Osmolality and Renal Outcome in Patients with Chronic Kidney Disease: Results from the KNOW-CKD","authors":"Mi Jung Lee, T. Chang, Joongyub Lee, Yeong‐Hoon Kim, K. Oh, S. Lee, S. Kim, J. Park, T. Yoo, Shin-Wook Kang, K. Choi, C. Ahn, S. Han","doi":"10.1159/000502291","DOIUrl":"https://doi.org/10.1159/000502291","url":null,"abstract":"Background: Urine osmolality indicates the ability of the kidney to concentrate the urine and reflects the antidiuretic action of vasopressin. However, results about the association between urine osmolality and adverse renal outcomes in chronic kidney disease (CKD) are conflicting. We investigated the association between urine osmolality and adverse renal outcomes in a nationwide prospective CKD cohort. Methods: A total of 1,999 CKD patients were categorized into 3 groups according to their urine osmolality tertiles. Primary outcome was a composite of 50% decline in the estimated glomerular filtration rate (eGFR), initiation of dialysis, or kidney transplantation. Results: During a mean follow-up of 35.2 ± 19.0 months, primary outcome occurred in 432 (21.6%) patients; 240 (36.4%), 162 (24.3%), and 30 (4.5%) in the lowest, middle, and highest tertiles, respectively. Low urine osmolality was independently associated with a greater risk of CKD progression (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.12–2.59). This association was particularly evident in patients with CKD stages 3–4 (per 10 mosm/kg decrease; HR, 1.02; 95% CI, 1.00–1.03). Adding urine osmolality to a base model with conventional factors significantly increased the ability to predict CKD progression (C-statistics, 0.86; integrated discrimination improvement [IDI], 0.021; both p < 0.001). However, adding both urine osmolality and eGFR did not further improve the predictive ability compared with the addition of eGFR only (C-statistics, p = 0.29; IDI, p = 0.09). Conclusions: Low urine osmolality was an independent risk factor for adverse renal outcomes in CKD patients, but its predictive ability did not surpass eGFR. Thus, kidney function should be considered while interpreting the clinical significance of urine osmolality.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75832492","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: Stress-induced cell senescence, which contributes to cell cycle arrest and is independent of age, plays an important role in chronic kidney disease (CKD) progression. DcR2, as a senescent marker, exclusively expressed in senescent tubular epithelia. The objective of this study was to examine whether urinary DcR2 (uDcR2) could be a potential biomarker for tubulointerstitial fibrosis (TIF) in patients with immunoglobulin A nephropathy (IgAN). Methods: This study included 210 IgAN patients and 80 healthy volunteers, with uDcR2 levels measured using enzyme-linked immunosorbent assay. We examined the relationship among uDcR2/Cr levels, renal function, and pathological parameters, using regression analysis to identify risk factors for TIF and the area under the curve (AUC) approach to predict TIF. Renal DcR2 expression was quantified by immunohistochemistry. Co-expression of DcR2 with fibrotic markers (α-smooth muscle actin [α-SMA], collagen III) was analyzed by confocal microscopy. Results: Levels of uDcR2/Cr were significantly higher in IgAN patients and in those with more severe TIF, compared with healthy controls. Serum DcR2 levels were similar across groups. The proportion of IgAN patients with stages 1–2 CKD and T0 was highest among those with uDcR2/Cr <130 ng/g. In contrast, the majority of those with uDcR2/Cr >201 ng/g had stages 4–5 CKD and T2. Levels of uDcR2/Cr were positively associated with urinary albumin to creatinine ratio (ACR), urinary N-acetyl-β-D-glucosaminidase (uNAG)/Cr, and TIF scores and negatively associated with estimated glomerular filtration rate (eGFR). uDcR2/Cr, uNAG, ACR, and eGFR were independent predictors for TIF, with AUC of 0.907 for uDcR2/Cr. This AUC value was higher than that observed for eGFR, uNAG/Cr, or ACR. The sensitivity and specificity of uDcR2/Cr in predicting TIF were 87.0 and 80.5%, respectively. Moreover, uDcR2/Cr levels were positively associated with the percentage of renal DcR2 expression. Renal DcR2 co-localized with α-SMA and collagen III in the kidneys of IgAN patients. Conclusions: Levels of uDcR2/Cr were closely associated with the severity of TIF and renal function parameters. uDcR2/Cr represents a potential biomarker for predicting TIF in IgAN patients.
背景/目的:应激诱导的细胞衰老在慢性肾脏疾病(CKD)的进展中起着重要作用，它有助于细胞周期阻滞，且与年龄无关。DcR2作为衰老标志物，仅在衰老小管上皮中表达。本研究的目的是研究尿DcR2 (uDcR2)是否可以作为免疫球蛋白a肾病(IgAN)患者小管间质纤维化(TIF)的潜在生物标志物。方法:本研究纳入210例IgAN患者和80名健康志愿者，采用酶联免疫吸附法测定uDcR2水平。我们研究了uDcR2/Cr水平、肾功能和病理参数之间的关系，使用回归分析确定TIF的危险因素，并使用曲线下面积(AUC)方法预测TIF。免疫组织化学定量检测肾DcR2的表达。共聚焦显微镜观察DcR2与纤维化标志物(α-平滑肌肌动蛋白[α-SMA]、ⅲ型胶原)的共表达。结果:与健康对照相比，IgAN患者和更严重的TIF患者的uDcR2/Cr水平明显更高。各组血清DcR2水平相似。在uDcR2/Cr为201 ng/g的4-5期CKD和T2期患者中，IgAN患者1-2期CKD和T0期的比例最高。uDcR2/Cr水平与尿白蛋白/肌酐比(ACR)、尿n -乙酰-β- d -氨基葡萄糖酶(uNAG)/Cr和TIF评分呈正相关，与估计的肾小球滤过率(eGFR)负相关。uDcR2/Cr、uNAG、ACR和eGFR是TIF的独立预测因子，uDcR2/Cr的AUC为0.907。该AUC值高于eGFR、uNAG/Cr或ACR。uDcR2/Cr预测TIF的敏感性和特异性分别为87.0和80.5%。此外，uDcR2/Cr水平与肾脏DcR2表达百分比呈正相关。IgAN患者肾脏DcR2与α-SMA和胶原III共定位。结论:uDcR2/Cr水平与TIF严重程度和肾功能参数密切相关。uDcR2/Cr是预测IgAN患者TIF的潜在生物标志物。
{"title":"DCR2, a Cellular Senescent Molecule, Is a Novel Marker for Assessing Tubulointerstitial Fibrosis in Patients with Immunoglobulin A Nephropathy","authors":"Jia Chen, Wei Hu, Fei Xiao, Lirong Lin, Kehong Chen, Li-ming Wang, Xiaoyue Wang, Ya-ni He","doi":"10.1159/000502233","DOIUrl":"https://doi.org/10.1159/000502233","url":null,"abstract":"Background/Aims: Stress-induced cell senescence, which contributes to cell cycle arrest and is independent of age, plays an important role in chronic kidney disease (CKD) progression. DcR2, as a senescent marker, exclusively expressed in senescent tubular epithelia. The objective of this study was to examine whether urinary DcR2 (uDcR2) could be a potential biomarker for tubulointerstitial fibrosis (TIF) in patients with immunoglobulin A nephropathy (IgAN). Methods: This study included 210 IgAN patients and 80 healthy volunteers, with uDcR2 levels measured using enzyme-linked immunosorbent assay. We examined the relationship among uDcR2/Cr levels, renal function, and pathological parameters, using regression analysis to identify risk factors for TIF and the area under the curve (AUC) approach to predict TIF. Renal DcR2 expression was quantified by immunohistochemistry. Co-expression of DcR2 with fibrotic markers (α-smooth muscle actin [α-SMA], collagen III) was analyzed by confocal microscopy. Results: Levels of uDcR2/Cr were significantly higher in IgAN patients and in those with more severe TIF, compared with healthy controls. Serum DcR2 levels were similar across groups. The proportion of IgAN patients with stages 1–2 CKD and T0 was highest among those with uDcR2/Cr <130 ng/g. In contrast, the majority of those with uDcR2/Cr >201 ng/g had stages 4–5 CKD and T2. Levels of uDcR2/Cr were positively associated with urinary albumin to creatinine ratio (ACR), urinary N-acetyl-β-D-glucosaminidase (uNAG)/Cr, and TIF scores and negatively associated with estimated glomerular filtration rate (eGFR). uDcR2/Cr, uNAG, ACR, and eGFR were independent predictors for TIF, with AUC of 0.907 for uDcR2/Cr. This AUC value was higher than that observed for eGFR, uNAG/Cr, or ACR. The sensitivity and specificity of uDcR2/Cr in predicting TIF were 87.0 and 80.5%, respectively. Moreover, uDcR2/Cr levels were positively associated with the percentage of renal DcR2 expression. Renal DcR2 co-localized with α-SMA and collagen III in the kidneys of IgAN patients. Conclusions: Levels of uDcR2/Cr were closely associated with the severity of TIF and renal function parameters. uDcR2/Cr represents a potential biomarker for predicting TIF in IgAN patients.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88662017","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. Niizuma, Y. Iwanaga, T. Washio, T. Ashida, S. Harasawa, S. Miyazaki, N. Matsumoto
Background: An increased cardiac troponin T (cTnT) level identifies a high-risk group in patients with end-stage renal disease; however, the mechanism of cTnT elevation remains unclear in such patients without acute coronary syndrome (ACS). Therefore, we explored the relationship between cTnT levels and the hemodynamic parameters and the prognostic potential of cTnT in stable patients with chronic hemodialysis (HD). Methods: We included consecutive 174 patients with HD who were referred for coronary angiography due to stable coronary artery disease (CAD), peripheral artery disease (PAD), or heart failure (HF). Hemodynamic measurement was performed, and plasma cTnT, B-type natriuretic peptide (BNP), and A-type natriuretic peptide (ANP) were measured at the same time. The potential of 3 biomarkers to predict all-cause mortality, cardiac death or hospitalized HF, and vascular event was assessed. Results: Increased log cTnT levels were correlated with increased log BNP and log ANP levels (r = 0.531, p < 0.001 and r = 0.411, p < 0.001, respectively). Not increased log cTnT, but increased log BNP and log ANP were associated with the presence of CAD and the extent of CAD. In contrast, they were all associated with the New York Heart Association functional classification and the presence of PAD and significantly correlated with left ventricular end-diastolic pressure (LVEDP) in an independent manner. Increased cTnT and BNP levels were associated with the mortality and hospitalized HF. However, increased cTnT was not associated with vascular events, unlike increased BNP. Conclusions: In patients with chronic HD without ACS, increased cTnT reflected increased LVEDP and the presence of HF or PAD independently, and it did not reflect the presence of CAD in contrast to increased BNP. cTnT and BNP were significant prognostic predictors; however, increased cTnT was associated with HF-related events, not with arteriosclerotic events.
背景:心肌肌钙蛋白T (cTnT)水平升高是终末期肾病患者的高危人群;然而，在这些无急性冠脉综合征(ACS)的患者中，cTnT升高的机制尚不清楚。因此，我们探讨了稳定型慢性血液透析(HD)患者cTnT水平与血流动力学参数的关系以及cTnT的预后潜力。方法:我们纳入了连续174例因稳定性冠状动脉疾病(CAD)、外周动脉疾病(PAD)或心力衰竭(HF)而转诊进行冠状动脉造影的HD患者。行血流动力学测定，同时测定血浆cTnT、b型利钠肽(BNP)、a型利钠肽(ANP)。评估3种生物标志物预测全因死亡率、心源性死亡或住院HF和血管事件的潜力。结果:cTnT水平升高与BNP和ANP水平升高相关(r = 0.531, p < 0.001和r = 0.411, p < 0.001)。与冠心病的存在和程度相关的不是cTnT的增加，而是BNP和ANP的增加。相比之下，它们都与纽约心脏协会功能分类和PAD的存在相关，并与左室舒张末期压(LVEDP)独立相关。cTnT和BNP水平升高与死亡率和住院HF相关。然而，与BNP升高不同，cTnT升高与血管事件无关。结论:在无ACS的慢性HD患者中，cTnT升高独立反映LVEDP升高和HF或PAD的存在，与BNP升高相反，它不反映CAD的存在。cTnT和BNP是显著的预后预测因子;然而，cTnT升高与hf相关事件相关，而与动脉硬化事件无关。
{"title":"Clinical Significance of Increased Cardiac Troponin T in Patients with Chronic Hemodialysis and Cardiovascular Disease: Comparison to B-Type Natriuretic Peptide and A-Type Natriuretic Peptide Increase","authors":"S. Niizuma, Y. Iwanaga, T. Washio, T. Ashida, S. Harasawa, S. Miyazaki, N. Matsumoto","doi":"10.1159/000502232","DOIUrl":"https://doi.org/10.1159/000502232","url":null,"abstract":"Background: An increased cardiac troponin T (cTnT) level identifies a high-risk group in patients with end-stage renal disease; however, the mechanism of cTnT elevation remains unclear in such patients without acute coronary syndrome (ACS). Therefore, we explored the relationship between cTnT levels and the hemodynamic parameters and the prognostic potential of cTnT in stable patients with chronic hemodialysis (HD). Methods: We included consecutive 174 patients with HD who were referred for coronary angiography due to stable coronary artery disease (CAD), peripheral artery disease (PAD), or heart failure (HF). Hemodynamic measurement was performed, and plasma cTnT, B-type natriuretic peptide (BNP), and A-type natriuretic peptide (ANP) were measured at the same time. The potential of 3 biomarkers to predict all-cause mortality, cardiac death or hospitalized HF, and vascular event was assessed. Results: Increased log cTnT levels were correlated with increased log BNP and log ANP levels (r = 0.531, p < 0.001 and r = 0.411, p < 0.001, respectively). Not increased log cTnT, but increased log BNP and log ANP were associated with the presence of CAD and the extent of CAD. In contrast, they were all associated with the New York Heart Association functional classification and the presence of PAD and significantly correlated with left ventricular end-diastolic pressure (LVEDP) in an independent manner. Increased cTnT and BNP levels were associated with the mortality and hospitalized HF. However, increased cTnT was not associated with vascular events, unlike increased BNP. Conclusions: In patients with chronic HD without ACS, increased cTnT reflected increased LVEDP and the presence of HF or PAD independently, and it did not reflect the presence of CAD in contrast to increased BNP. cTnT and BNP were significant prognostic predictors; however, increased cTnT was associated with HF-related events, not with arteriosclerotic events.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88913323","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}
Daisuke Uchida, R. Kido, H. Kawarazaki, Masaru Murasawa, Ayami Ando, S. Fujimoto, K. Iseki, T. Moriyama, K. Yamagata, K. Tsuruya, T. Konta, I. Narita, M. Kondo, M. Kasahara, K. Asahi, Tsuyoshi Watanabe, Y. Shibagaki
Background/Aims: The association of diastolic blood pressure (DBP) with incidence of chronic kidney disease (CKD) in the general population is not well examined. Methods: Using national health check-up database from 2008 to 2011 in the general Japanese population aged 39–74 years, we evaluated the association between DBP and incidence of CKD 2 years later in 127,954 participants without CKD. DBP was categorized by every 5 mm Hg from the lowest (<60 mm Hg) to the highest category (>100 mm Hg) and was further stratified into those with and without antihypertensive medications (BP meds). We calculated the OR for estimating adjusted risk of incident CKD using logistic regression model. Results: Participants were 62% female and 25.9% with BP meds, mean age of 76 years with estimated glomerular filtration rate of 78.2 ± 13.4 and DBP of 76 ± 11 mm Hg. Two years later, 12,379 (9.7%) developed CKD. Compared to DBP 60–64 mm Hg without BP meds as reference, multivariate analysis showed no difference in CKD risk at any DBP category among those without BP meds. However, in those with BP meds, risk increased according to lower DBP from 95 to 60 mm Hg (p for trend 0.05) with OR 1.51 (95% CI 1.14–1.99) in DBP <60 mm Hg. In subgroup analysis within those with or without BP meds, CKD risk was lower at higher DBP (p for trend 0.02) only in those without BP meds. Conclusion: Lower DBP was associated with higher risk of incident CKD only in the general population taking antihypertensive medication.
背景/目的:在一般人群中，舒张压(DBP)与慢性肾脏疾病(CKD)发病率的关系尚未得到很好的研究。方法:利用2008年至2011年日本39-74岁普通人群的国家健康检查数据库，我们评估了127,954名无CKD的参与者2年后DBP与CKD发病率之间的关系。舒张压从最低(100毫米汞柱)开始按每5毫米汞柱分类，并进一步分为服用和不服用降压药(降压药)的患者。我们使用逻辑回归模型计算了估计CKD事件调整风险的OR。结果:参与者62%为女性，25.9%为降压药物，平均年龄76岁，估计肾小球滤过率为78.2±13.4，舒张压为76±11mmhg。两年后，12,379(9.7%)发生CKD。与未服用降压药物的舒张压60-64 mm Hg相比，多因素分析显示，未服用降压药物的患者在任何舒张压类别的CKD风险均无差异。然而，在服用降压药物的患者中，当舒张压从95到60 mm Hg时，风险增加(p为趋势0.05)，当舒张压<60 mm Hg时，OR为1.51 (95% CI 1.14-1.99)。在服用或不服用降压药物的患者中，只有在不服用降压药物的患者中，当舒张压升高时，CKD风险降低(p为趋势0.02)。结论:低舒张压仅与服用降压药的普通人群发生CKD的高风险相关。
{"title":"Lower Diastolic Blood Pressure was Associated with Higher Incidence of Chronic Kidney Disease in the General Population Only in those Using Antihypertensive Medications","authors":"Daisuke Uchida, R. Kido, H. Kawarazaki, Masaru Murasawa, Ayami Ando, S. Fujimoto, K. Iseki, T. Moriyama, K. Yamagata, K. Tsuruya, T. Konta, I. Narita, M. Kondo, M. Kasahara, K. Asahi, Tsuyoshi Watanabe, Y. Shibagaki","doi":"10.1159/000501828","DOIUrl":"https://doi.org/10.1159/000501828","url":null,"abstract":"Background/Aims: The association of diastolic blood pressure (DBP) with incidence of chronic kidney disease (CKD) in the general population is not well examined. Methods: Using national health check-up database from 2008 to 2011 in the general Japanese population aged 39–74 years, we evaluated the association between DBP and incidence of CKD 2 years later in 127,954 participants without CKD. DBP was categorized by every 5 mm Hg from the lowest (<60 mm Hg) to the highest category (>100 mm Hg) and was further stratified into those with and without antihypertensive medications (BP meds). We calculated the OR for estimating adjusted risk of incident CKD using logistic regression model. Results: Participants were 62% female and 25.9% with BP meds, mean age of 76 years with estimated glomerular filtration rate of 78.2 ± 13.4 and DBP of 76 ± 11 mm Hg. Two years later, 12,379 (9.7%) developed CKD. Compared to DBP 60–64 mm Hg without BP meds as reference, multivariate analysis showed no difference in CKD risk at any DBP category among those without BP meds. However, in those with BP meds, risk increased according to lower DBP from 95 to 60 mm Hg (p for trend 0.05) with OR 1.51 (95% CI 1.14–1.99) in DBP <60 mm Hg. In subgroup analysis within those with or without BP meds, CKD risk was lower at higher DBP (p for trend 0.02) only in those without BP meds. Conclusion: Lower DBP was associated with higher risk of incident CKD only in the general population taking antihypertensive medication.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74130504","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: Distal renal tubular acidosis (dRTA) can be inherited or acquired. Case Presentation: Here, we describe the case of a 45-year-old female patient with non-anion gap metabolic acidosis, hypokalemia, and alkaline urine. She had a history of rheumatoid arthritis and kidney stones and failed to acidify urine upon the fludrocortisone and furosemide test. Therefore, the diagnosis of dRTA secondary to an autoimmune disease was made. A kidney biopsy was examined for markers of acid-secretory intercalated cells. Surprisingly, no obvious difference in the relative number of acid-secretory intercalated cells or in the distribution of major proteins involved in acid secretion was found. Furthermore, increasing doses of potassium citrate failed to correct the hypokalemia and acidosis. Since these findings were rather atypical for autoimmune dRTA, alternative causes of her hypokalemia and metabolic acidosis were sought. The patient was found to chronically consume laxatives, which can also cause kidney stones and may result in a false-positive urinary acidification test. Conclusion: Chronic laxative abuse may mimic dRTA and should therefore be considered in unexplained hypokalemia with non-anion gap metabolic acidosis.
{"title":"Gut It Out: Laxative Abuse Mimicking Distal Renal Tubular Acidosis","authors":"Marius Sidler, N. Mohebbi, E. Hoorn, C. Wagner","doi":"10.1159/000501855","DOIUrl":"https://doi.org/10.1159/000501855","url":null,"abstract":"Background: Distal renal tubular acidosis (dRTA) can be inherited or acquired. Case Presentation: Here, we describe the case of a 45-year-old female patient with non-anion gap metabolic acidosis, hypokalemia, and alkaline urine. She had a history of rheumatoid arthritis and kidney stones and failed to acidify urine upon the fludrocortisone and furosemide test. Therefore, the diagnosis of dRTA secondary to an autoimmune disease was made. A kidney biopsy was examined for markers of acid-secretory intercalated cells. Surprisingly, no obvious difference in the relative number of acid-secretory intercalated cells or in the distribution of major proteins involved in acid secretion was found. Furthermore, increasing doses of potassium citrate failed to correct the hypokalemia and acidosis. Since these findings were rather atypical for autoimmune dRTA, alternative causes of her hypokalemia and metabolic acidosis were sought. The patient was found to chronically consume laxatives, which can also cause kidney stones and may result in a false-positive urinary acidification test. Conclusion: Chronic laxative abuse may mimic dRTA and should therefore be considered in unexplained hypokalemia with non-anion gap metabolic acidosis.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89923001","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}
Shuwei Duan, Yan Mei, Jian Liu, Pu Chen, Ping Li, Yi-zhi Chen, Shu-peng Lin, Xue‐guang Zhang, Jiaona Liu, Xuefeng Sun, Yuansheng Xie, G. Cai, Shu-wen Liu, Jie Wu, Xiang-Mei Chen
Background/Aims: Several pathological classification systems were commonly used in clinical practice to predict the prognosis of IgA nephropathy (IgAN). However, how prognostic value differs between these systems is unclear. The aim of this study was to compare the Lee grade, the Oxford classification, and the Haas classification and to find a simplified classification. Methods: We retrospectively analyzed IgAN cases diagnosed between January 2002 and December 2007. The endpoints were progression to end-stage renal disease (ESRD) or a ≥50% decline in estimated glomerular filtration rate (eGFR). The predictive capabilities were evaluated by comparing the ability of discrimination (continuous net reclassification) and calibration (Akaike information criterion [AIC]). Results: A total of 412 IgAN patients were included in the study. The average follow-up period was 80.62 ± 23.63 months. A total of 44 (10.68%) patients progressed to ESRD, and 70 (16.99%) patients showed a ≥50% decline in eGFR. All multivariate Cox regression models had limited power for high AIC values. The prognostic values of the Lee grade and the Oxford classification were higher than those of models containing only established baseline clinical indicators for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.50, 95% CI 0.21–0.74; Oxford classification 0.48, 95% CI 0.28–0.71). The prognostic value of the Haas classification was lower than that of the other pathological classification systems for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.53, 95% CI 0.23–0.92; Oxford classification 0.59, 95% CI 0.10–0.74). The prognostic value of hierarchical classification (Beijing classification) using M and T lesion was similar to the Oxford classification. Conclusions: Both the Lee grade and the Oxford classification showed incremental prognostic values beyond established baseline clinical indicators. The Haas classification was slightly inferior to the Lee grade and the Oxford classification. The hierarchical classification (Beijing classification) using less pathological parameters does not lose predictive efficiency.
背景/目的:临床上常用几种病理分类系统来预测IgA肾病(IgAN)的预后。然而，这些系统的预后价值有何不同尚不清楚。本研究的目的是比较李氏分级，牛津分级和哈斯分级，并找到一个简化的分类。方法:回顾性分析2002年1月至2007年12月诊断的IgAN病例。终点是进展到终末期肾病(ESRD)或估计肾小球滤过率(eGFR)下降≥50%。通过比较区分(连续净重分类)和校准(赤池信息准则[AIC])的能力来评估预测能力。结果:共纳入412例IgAN患者。平均随访时间为80.62±23.63个月。44例(10.68%)患者进展为ESRD, 70例(16.99%)患者eGFR下降≥50%。所有多变量Cox回归模型对高AIC值的影响有限。Lee分级和Oxford分级的预后价值高于仅包含ESRD进展或eGFR下降≥50%的既定基线临床指标的模型(Lee分级0.50,95% CI 0.21-0.74;牛津分类0.48,95% CI 0.28-0.71)。对于进展为ESRD或eGFR下降≥50%的患者，Haas分级的预后价值低于其他病理分级(Lee分级0.53,95% CI 0.23-0.92;牛津分类0.59,95% CI 0.10-0.74)。M、T病变分级(北京分级)的预后价值与牛津分级相似。结论:Lee分级和Oxford分级均显示出超出既定基线临床指标的递增预后价值。哈斯分级略低于李氏分级和牛津分级。使用较少病理参数的分层分类(北京分类)不失去预测效率。
{"title":"Predictive Capabilities of Three Widely Used Pathology Classification Systems and a Simplified Classification (Beijing Classification) in Primary IgA Nephropathy","authors":"Shuwei Duan, Yan Mei, Jian Liu, Pu Chen, Ping Li, Yi-zhi Chen, Shu-peng Lin, Xue‐guang Zhang, Jiaona Liu, Xuefeng Sun, Yuansheng Xie, G. Cai, Shu-wen Liu, Jie Wu, Xiang-Mei Chen","doi":"10.1159/000500459","DOIUrl":"https://doi.org/10.1159/000500459","url":null,"abstract":"Background/Aims: Several pathological classification systems were commonly used in clinical practice to predict the prognosis of IgA nephropathy (IgAN). However, how prognostic value differs between these systems is unclear. The aim of this study was to compare the Lee grade, the Oxford classification, and the Haas classification and to find a simplified classification. Methods: We retrospectively analyzed IgAN cases diagnosed between January 2002 and December 2007. The endpoints were progression to end-stage renal disease (ESRD) or a ≥50% decline in estimated glomerular filtration rate (eGFR). The predictive capabilities were evaluated by comparing the ability of discrimination (continuous net reclassification) and calibration (Akaike information criterion [AIC]). Results: A total of 412 IgAN patients were included in the study. The average follow-up period was 80.62 ± 23.63 months. A total of 44 (10.68%) patients progressed to ESRD, and 70 (16.99%) patients showed a ≥50% decline in eGFR. All multivariate Cox regression models had limited power for high AIC values. The prognostic values of the Lee grade and the Oxford classification were higher than those of models containing only established baseline clinical indicators for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.50, 95% CI 0.21–0.74; Oxford classification 0.48, 95% CI 0.28–0.71). The prognostic value of the Haas classification was lower than that of the other pathological classification systems for progression to ESRD or a ≥50% decline in eGFR (Lee grade 0.53, 95% CI 0.23–0.92; Oxford classification 0.59, 95% CI 0.10–0.74). The prognostic value of hierarchical classification (Beijing classification) using M and T lesion was similar to the Oxford classification. Conclusions: Both the Lee grade and the Oxford classification showed incremental prognostic values beyond established baseline clinical indicators. The Haas classification was slightly inferior to the Lee grade and the Oxford classification. The hierarchical classification (Beijing classification) using less pathological parameters does not lose predictive efficiency.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87686407","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}
A. Rydzewska-Rosołowska, K. Kakareko, B. Naumnik, T. Hryszko
Introduction: Assessing proteinuria is of uttermost importance for a nephrologist. It is often indispensable to accurately quantify the amount of protein lost, hence complicated and time-consuming urine collections (the gold standard or “king” of methods – 24-h protein excretion rate [PER]) are often replaced by spot urinary protein to creatinine ratio (PCR). The aim of the study was to determine whether the latter can reliably compare to the gold standard and whether “timing” of a spot urine sample is essential. Methods: We performed a prospective, single-center study of 143 consecutive adult patients with glomerular proteinuria (a total of 187 cases). Protein and creatinine concentration was measured in 3 consecutive urine samples (starting with the first morning void) and a simultaneous 24-h urine collection. Agreement between 24-h PER and PCR was evaluated with Bland-Altman plots. Results: Compared to PER 3 consecutive PCRs were 0.86, 0.66, and 0.50 higher with wide limits of agreement respectively. The bias between 2 methods was influenced by sex, CKD stage, albumin concentration and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker treatment. In 24 participants, in whom at least 2 measurements at different time points were available, only 88% of differences were lower than the calculated repeatability coefficient. Conclusions: Unfortunately although random PCR correlates with 24-h protein excretion, the scatter of differences increases as 24-h proteinuria rises (without any significant effect of the sampling time). The observed lack of agreement makes PCR an unsuitable parameter to correctly quantify proteinuria; it is also not useful for monitoring the amount of daily proteinuria in the same patient. Therefore, while searching for new markers, nephrologists can only say: “long live the king!”
{"title":"Comparison of Different Methods of Urinary Protein Excretion Measurement: Is the King Really Dead?","authors":"A. Rydzewska-Rosołowska, K. Kakareko, B. Naumnik, T. Hryszko","doi":"10.1159/000501884","DOIUrl":"https://doi.org/10.1159/000501884","url":null,"abstract":"Introduction: Assessing proteinuria is of uttermost importance for a nephrologist. It is often indispensable to accurately quantify the amount of protein lost, hence complicated and time-consuming urine collections (the gold standard or “king” of methods – 24-h protein excretion rate [PER]) are often replaced by spot urinary protein to creatinine ratio (PCR). The aim of the study was to determine whether the latter can reliably compare to the gold standard and whether “timing” of a spot urine sample is essential. Methods: We performed a prospective, single-center study of 143 consecutive adult patients with glomerular proteinuria (a total of 187 cases). Protein and creatinine concentration was measured in 3 consecutive urine samples (starting with the first morning void) and a simultaneous 24-h urine collection. Agreement between 24-h PER and PCR was evaluated with Bland-Altman plots. Results: Compared to PER 3 consecutive PCRs were 0.86, 0.66, and 0.50 higher with wide limits of agreement respectively. The bias between 2 methods was influenced by sex, CKD stage, albumin concentration and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker treatment. In 24 participants, in whom at least 2 measurements at different time points were available, only 88% of differences were lower than the calculated repeatability coefficient. Conclusions: Unfortunately although random PCR correlates with 24-h protein excretion, the scatter of differences increases as 24-h proteinuria rises (without any significant effect of the sampling time). The observed lack of agreement makes PCR an unsuitable parameter to correctly quantify proteinuria; it is also not useful for monitoring the amount of daily proteinuria in the same patient. Therefore, while searching for new markers, nephrologists can only say: “long live the king!”","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75529598","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}
P. Fan, Chao-xia Lu, Kun-qi Yang, P. Lu, Su-fang Hao, F. Luo, Hui‐min Zhang, L. Song, Hai-Ying Wu, Jun Cai, Xue Zhang, Xianliang Zhou
Background/Aims: Liddle syndrome (LS) is a rare autosomal dominant disease caused by mutations in genes coding for epithelial sodium channel (ENaC) subunits. The aim of this study was to identify the mutation responsible for the LS in an extended Chinese family. Methods: DNA samples from the proband with early-onset, treatment-resistant hypertension, and hypokalemia and 19 additional relatives were all sequenced for mutations in exon 13 of the β-ENaC and γ-ENaC genes, using amplification by polymerase chain reaction and direct DNA sequencing. Results: Genetic testing of exon 13 of SCNN1B revealed duplication of guanine into a string of 3 guanines located at codon 602. This frameshift mutation is predicted to generate a premature stop codon at position 607, resulting in truncated β-ENaC lacking the remaining 34 amino acids, including the crucial PY motif. Among a total of 9 participants with the identical mutation, different phenotypes were identified. Tailored treatment with amiloride was safe and effective in alleviating disease symptoms in LS. No mutation of SCNN1G was identified in any of the examined participants. Conclusions: We report here a family affected by LS harboring a frameshift mutation (c.1806dupG) with a premature stop codon deleting the PY motif of β-ENaC. Our study demonstrates that the earlier LS patients are diagnosed by genetic testing and treated with tailored medication, the greater the likelihood of preventing or minimizing complications in the vasculature and target organs.
{"title":"Truncated Epithelial Sodium Channel β Subunit Responsible for Liddle Syndrome in a Chinese Family","authors":"P. Fan, Chao-xia Lu, Kun-qi Yang, P. Lu, Su-fang Hao, F. Luo, Hui‐min Zhang, L. Song, Hai-Ying Wu, Jun Cai, Xue Zhang, Xianliang Zhou","doi":"10.1159/000500919","DOIUrl":"https://doi.org/10.1159/000500919","url":null,"abstract":"Background/Aims: Liddle syndrome (LS) is a rare autosomal dominant disease caused by mutations in genes coding for epithelial sodium channel (ENaC) subunits. The aim of this study was to identify the mutation responsible for the LS in an extended Chinese family. Methods: DNA samples from the proband with early-onset, treatment-resistant hypertension, and hypokalemia and 19 additional relatives were all sequenced for mutations in exon 13 of the β-ENaC and γ-ENaC genes, using amplification by polymerase chain reaction and direct DNA sequencing. Results: Genetic testing of exon 13 of SCNN1B revealed duplication of guanine into a string of 3 guanines located at codon 602. This frameshift mutation is predicted to generate a premature stop codon at position 607, resulting in truncated β-ENaC lacking the remaining 34 amino acids, including the crucial PY motif. Among a total of 9 participants with the identical mutation, different phenotypes were identified. Tailored treatment with amiloride was safe and effective in alleviating disease symptoms in LS. No mutation of SCNN1G was identified in any of the examined participants. Conclusions: We report here a family affected by LS harboring a frameshift mutation (c.1806dupG) with a premature stop codon deleting the PY motif of β-ENaC. Our study demonstrates that the earlier LS patients are diagnosed by genetic testing and treated with tailored medication, the greater the likelihood of preventing or minimizing complications in the vasculature and target organs.","PeriodicalId":17810,"journal":{"name":"Kidney and Blood Pressure Research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75423171","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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