Serum P-Cresyl Sulfate Level Is an Independent Marker of Peripheral Arterial Stiffness as Assessed Using Brachial-Ankle Pulse Wave Velocity in Patients with Non-Dialysis Chronic Kidney Disease Stage 3 to 5

p-Cresyl sulfate (PCS) is a uremic toxin that causes cardiovascular injury and progression in patients with chronic kidney disease (CKD). Peripheral arterial stiffness (PAS) as measured using the brachial-ankle pulse wave velocity (baPWV) is considered a valuable predictor of cardiovascular event risk in the general population. The study investigated the correlation between serum PCS levels and PAS (baPWV > 18.0 m/s) in 160 patients with stage 3–5 CKD. Liquid chromatography–mass spectrometry was used to assay serum PCS levels. PAS was detected in 54 patients (33.8%), and it was linked to older age, a higher prevalence of hypertension, higher systolic and diastolic blood pressure, higher serum calcium–phosphorus product and PCS levels, and lower height and body weight. Multivariable logistic regression analysis for independent factors associated with PAS illustrated that, in addition to age and diastolic blood pressure, serum PCS levels exhibited an odds ratio (OR) of 1.098 (95% confidence interval = 1.029–1.171, p = 0.005). These findings demonstrated that serum PCS levels were associated with PAS among patients with stage 3–5 CKD.     

慢性肾脏病患者血管钙化的病理机制研究进展

在慢性肾脏病（chronic kidney disease,CKD）患者中,肾功能的进行性降低导致矿物质代谢紊乱、酸中毒、营养不良、炎症和尿毒症毒素积累等症状,可引起继发性甲状旁腺功能亢进、血清钙升高、磷酸盐水平升高和血清成纤维细胞生长因子-23（fibroblast growth factor-23,FGF-23）升高,由此产生CKD相关的矿物质和骨代谢紊乱,循环中过量的钙和磷酸盐也可以促进蛋白质-矿物质复合物的形成,称为钙蛋白颗粒（calpain particles,CPPs）,在CKD中,这些CPPs含有较少的钙化抑制剂,诱发炎症,并促进血管平滑肌细胞的钙化。由此促进血管钙化的发生。诸多横断面观察研究表明,血清FGF-23水平在CKD早期（1~2期）开始升高,并与肾小球滤过率呈负相关,促进血管钙化,最新的研究表明高水平脂联素对FGF-23在冠状动脉钙化的作用中起调节作用。本文综述了CKD患者血管钙化发展机制的研究进展,为进一步寻找潜在的新治疗目标指出方向。     

Reduced Expression of Metallothionein-I/II in Renal Proximal Tubules Is Associated with Advanced Chronic Kidney Disease

Chronic kidney disease (CKD) is a commonly occurring complex renal syndrome that causes overall mortality in many diseases. The clinical manifestations of CKD include renal tubulointerstitial fibrosis and loss of renal function. Metallothionein-I/II (MT-I/II) is potentially expressed in the liver and kidney, and possesses antioxidant and metal detoxification properties. However, whether MT-I/II expression is associated with the prognosis of nephropathy remains unknown. In this study, we investigated the MT-I/II level in human CKD, using immunohistochemistry. MT-I/II is located on the proximal tubules and is notably reduced in patients with CKD. MT-I/II expression was significantly correlated with the functional and histological grades of CKD. In an aristolochic acid (AAI)-induced nephropathy mouse model, MT-I/II was abundantly increased after AAI injection for 7 days, but decreased subsequently compared to that induced in the acute phase when injected with AAI for 28 days. Furthermore, we found that ammonium pyrrolidinedithiocarbamate (PDTC) restored AAI-induced MT-I/II reduction in HK2 cells. The injection of PDTC ameliorated AAI-induced renal tubulointerstitial fibrosis and reduced the concentrations of blood urea nitrogen and creatinine in mouse sera. Taken together, our results indicate that MT-I/II reduction is associated with advanced CKD, and the retention of renal MT-I/II is a potential therapeutic strategy for CKD.     

慢性肾脏病妊娠患者先兆子痫的危险因素探讨

目的探讨慢性肾脏病患者妊娠先兆子痫的危险因素,为预测妊娠风险和鉴别诊断提供依据。方法回顾性分析医院妊娠前已患慢性肾脏病的孕妇资料,按是否发生先兆子痫分为先兆子痛组（30例）和对照组（45例）,比较各项临床指标,用回归模型分析危险因素。结果两组间在妊娠年龄、原发病类型、妊娠前及妊娠20周后血压及蛋白尿水平、妊娠20周后血尿酸水平上有明显差别。结论非适龄妊娠、妊娠前慢性肾脏病控制欠佳以及免疫性肾小球疾病（如IgA肾病或狼疮性肾炎）是发生先兆子痫的危险因素,这类孕妇若在妊娠20周后发生2级以上的高血压和蛋白尿翻倍。且伴有血尿酸水平增加,则高度提示发生先兆子痫的可能。     

Discontinuation of Proton Pump Inhibitors in Patients With Chronic Kidney Disease

Purpose: Proton pump inhibitors (PPIs) are commonly used medications and are historically well tolerated. Recent studies have linked PPI use to the development of chronic kidney disease (CKD) and end-stage renal disease. This study investigated the impact of discontinuing PPIs on renal function in patients with CKD. Methods: We conducted a retrospective chart review of patients with established CKD, defined as 2 eGFR (estimated glomerular filtration rate) measurements of less than 60 mL/min/1.73 m² at least 90 days apart, who were on a PPI from January 1, 2014 to December 31, 2014, with a medication possession ratio greater than or equal to 70%. We compared baseline eGFR to a final eGFR after at least 6 months of discontinuation or continuation of a PPI. After power analysis, we targeted an enrollment of 200 patients (100 in each group) to achieve a power of 0.80 and an alpha of 0.05. Summary: A total of 97 patients in the PPI discontinuation group and 100 patients in the PPI continuation group met the study inclusion criteria. Baseline eGFR in the PPI continuation group was 47.9 mL/min/1.73 m² and 50.7 mL/min/1.73 m² in the discontinuation group. Final eGFR in the PPI continuation group was significantly higher than baseline at 51.1 mL/min/1.73 m² (+3.25 ± 12.8, P = .01). Final eGFR in the PPI discontinuation group was 51.8 mL/min/1.73 m² (+1.09 ± 12.8, P = .3). The average time between baseline and final eGFRs was 270 days in the PPI continuation group and 301 days in the discontinuation group. There was no statistically significant difference in the change in eGFRs between groups (95% confidence interval [CI] = −5.48-2.03, P = .37). Conclusions: Proton pump inhibitor discontinuation after prolonged continuous use in patients with CKD was not associated with a significant change in renal function after 1 year.     

Targeting Uremic Toxins to Prevent Peripheral Vascular Complications in Chronic Kidney Disease

Chronic kidney disease (CKD) exhibits progressive kidney dysfunction and leads to disturbed homeostasis, including accumulation of uremic toxins, activated renin-angiotensin system, and increased oxidative stress and proinflammatory cytokines. Patients with CKD are prone to developing the peripheral vascular disease (PVD), leading to poorer outcomes than those without CKD. Cumulative evidence has showed that the synergy of uremic milieu and PVD could exaggerate vascular complications such as limb ischemia, amputation, stenosis, or thrombosis of a dialysis vascular access, and increase mortality risk. The role of uremic toxins in the pathogenesis of vascular dysfunction in CKD has been investigated. Moreover, growing evidence has shown the promising role of uremic toxins as a therapeutic target for PVD in CKD. This review focused on uremic toxins in the pathophysiology, in vitro and animal models, and current novel clinical approaches in reducing the uremic toxin to prevent peripheral vascular complications in CKD patients.     

Drug Discovery for Overcoming Chronic Kidney Disease (CKD): Development of Drugs on Endothelial Cell Protection for Overcoming CKD

Chronic kidney disease (CKD) is becoming a major public health problem worldwide. It is important to protect endothelial function in CKD treatment because injury of the endothelium is a critical event for the generation and progression of CKD. Recently, clinical studies showed that nifedipine, an antihypertensive drug, acts as a protective agent of endothelial cells (ECs). Nifedipine is reported to partially decompose to a nitrosonifedipine that has high reactivity against lipid-derived radicals in vitro. However, it is still unclear whether nitrosonifedipine is a biologically active agent against endothelial injury. We observed that nitrosonifedipine was converted to radical form by reaction with cultured ECs. The cumene hydroperoxide mediated cytotoxity was reduced by nitrosonifedipine in cultured human glomerular ECs (HGECs). Also nitrosonifedipine suppressed the expression of TNF-α–induced intercellular cell adhesion molecule-1 in HGECs. Chronic administration of N^ω-nitro-L-arginine methyl ester (L-NAME) caused systemic arterial hypertension, endotherial injury, and renal dysfunction. In L-NAME– induced hypertensive rats, nitrosonifedipine treatment improved not only the acetylcholine-induced vasodilation of the aortic rings, but also renal dysfunction such as increasing the levels of serum creatinine and urinary protein excretion. Our preliminary data suggest that nitrosonifedipine is a new and useful drug for the treatment of CKD involving ameliorating effects on EC disorder.     

慢性肾脏病基础上急性肾损伤并多脏器功能不全综合征患者CRRT的预后分析

目的探讨慢性肾脏病(CKD)美国国家基金会K/DOQI指南分期与CKD基础上急性肾损伤(AKI)合并多脏器功能不全综合征(MODS)持续肾脏替代治疗(CRRT)预后。方法选取30例CKD基础上AKI合并MODS患者,依照K/DOQI指南CKD分期分为A组(9例)、B组(15例)、C组(22例)、D组(24例),给予持续静脉血液滤过(CVVH)治疗。对比分析四组患者脏器功能恢复情况及病死率。结果 CKD1期患者4例,CRRT治疗后脏器功能均基本稳定;2期患者7例,死亡1例,病死率14.29%;3期患者12例,死亡4例,病死率33.33%;4期7例,死亡4例,病死率57.14%。P<0.05,差异有统计学意义。结论依照CKD分期,CRRT越早介入则预后效果越好。     

血肌酐与胱抑素C在慢性肾脏病诊断及评估肾功能损伤程度中的应用

目的 探讨血肌酐(serum creatinine,Scr)与胱抑素C(cystatin C,Cys-C)在慢性肾脏病(chronic kidney disease,CKD)诊断及评估肾功能损伤程度的应用价值.方法 选取咸阳市中心医院2014年6月-2016年6月收治的173例CKD患者为观察组,并选取同期体检的173例健康人为对照组.分析比较两组血清Scr与Cys-C水平,观察组Scr与Cys-C阳性率,Scr与Cys-C诊断效能,观察组不同CKD分期血清Scr与Cys-C水平.结果 观察组血清Scr和Cys-C水平均显著高于对照组(P＜0.01).观察组Cys-C阳性率显著高于Scr(P ＜0.01).ROC曲线分析显示,Cys-C的曲线下面积、特异性及比数积均明显高于Scr(P ＜0.05).观察组血清Scr和Cys-C水平均随CKD分期的增加而呈逐渐上升趋势(P＜0.01).结论 Scr与Cys-C均具有诊断CKD与评估肾功能损伤的价值,但Cys-C在特异性与准确度上更高,故可作为诊断CKD患者肾功能的可靠指标.     

低蛋白饮食联合α-酮酸对慢性肾脏病早期蛋白尿的影响研究

目的探讨早期应用低蛋白饮食联合α-酮酸能否减少蛋白尿、延缓肾脏病进展。方法将应用激素联合免疫抑制剂治疗12周后尿蛋白定量仍大于2g/d的慢性肾脏病患者分为两组:低蛋白饮食组(LPD组,蛋白0.6～0.8g.kg-1.d-1并给α-酮酸0.09g.kg-1.d-1)和正常蛋白饮食组(NPD组,蛋白1.0～1.2g.kg-1.d-1)。每月监测血压、肾功能、血清白蛋白、尿蛋白定量等指标。结果同NPD组比较,LPD组肾小球滤过率明显升高,尿蛋白定量明显下降,血清白蛋白明显升高。结论低蛋白饮食联合α-酮酸能显著减少慢性肾脏病(1～2期)蛋白尿水平,更好维持肾脏功能和营养状态。     

慢性阻塞性肺病患者的肺功能

目的了解慢性阻塞性肺病(COPD)患者肺通气功能的变化及进展规律。方法1986年至1999年,对 36例50岁以上的COPD患者,每年或隔1～2年于缓解期进行肺功能测试,计算其各项主要指标的年均下降率,并 与对照组作比较。结果13年来,COPD组肺功能的各项主要指标都下降,其中年均下降率最大的是MVV[(6.65 ±6.28)％],其次是V25/HT、MMF和FEV     

血栓弹力图评价慢性肾脏病患者高凝状态的危险因素分析

摘 要 目的：探讨血栓弹力图评价慢性肾脏病（CKD）患者高凝状态的危险因素。方法: 选取221例慢性肾脏病同时进行血栓弹力图检测的患者,根据血栓弹力图血栓最大弹力度（MA值）分为低凝组（MA＜69 mm,n=139）和高凝组（MA≥69 mm,n=82）,分析两组患者的基本情况包括性别、年龄、身高、体质量,伴发疾病如糖尿病、高脂血症、肾病综合征,用药情况如重组人促红细胞生成素、抗凝和抗血小板药物、激素等,肾功能情况如CKD1 3期和CKD4 5期,血栓弹力图中的凝血参数反应时间（R值）、凝血时间（K值）、夹角α、血栓最大弹力度（MA）,其他凝血相关指标血小板计数（Plt）等有无差异,同时采用二元逻辑回归,分析引起高凝的危险因素。结果:两组患者年龄、性别、身高、体质量等比较,差异均无统计学意义（P＞0.05）,而伴发疾病、用药情况、肾功能、部分凝血及血常规指标（包括血栓弹力图指标）比较,差异均有统计学意义（P＜0.05）。高凝的危险因素主要包括糖尿病（OR 1.895, 95%CI 1.082～3.318）、肾病综合征（OR 2.501, 95%CI 1.429～4.379）、CKD4～5期（OR 1.989,95%CI 1.136～3.483）等疾病因素,以及药物因素：重组人促红细胞生成素（OR 2.254, 95%CI 1.207～4.208）。结论:对CKD患者而言,糖尿病、肾病综合征、CKD4～5期增加患者高凝状态,肾性贫血患者使用重组人促红细胞生成素亦增加患者高凝风险。     

联合检测血清PCT、CRP在细菌感染引起AECOPD患者的诊断价值

目的探讨检测血清降钙素原（procalcitonin,PCT）、C-反应蛋白（C—reactiveprotein,CRP）水平对指导细菌感染引起慢性阻塞性肺疾病急性加重期（acuteexacerbationofchronicobstructivepulmonarydisease,AECOPD）患者临床诊治中的意义。方法对AECOPD患者58例（A组）及COPD稳定期患者31例（B组）,采用免疫发光法测定其血清PCT及CRP水平,并进行诱导痰细菌定量培养;以痰中下呼吸道潜在病原菌（PPM）浓度107CFU／mL作为诊断AECOPD细菌感染的标准,将AECOPD患者分为有细菌感染组（Al组35例）、无细菌感染组（A2组23例）。结果AECOPD有细菌感染组血清PCT（0．22±0．03）ng／mL,CRP（59．79±10．23）mg／mL水平高于无细菌感染组PCT（0．11±0．02）ng／mL,CRP（18．34±3．15）mg／mL及稳定期组PCT（0．08±0．01）ng／mL,CRP（10．06±1．63）mg／mL,差异有统计学意义（P〈0．05）。COPD急性加重期无细菌感染组PCT（0．11土0．02）ng／mL水平高于稳定期组PCT（0．08±0．01）ng／mL,差异无统计学意义（P〉0．05）,急性加重期无细菌感染组CRP（18．34±3．15）mg／mL水平高于CRP（10．06±1．63）mg／mL,差异有统计学意义（P〈0．05）。结论COPD患者PCT水平升高可能与细菌感染有关、而CRP水平升高可能提示急性加重,联合检测血清PCT及CRP可以帮助了解AECOPD的细菌感染及指导抗生素应用。     

银杏叶提取物对慢性阻塞性肺疾病急性加重期患者血管内皮功能的影响

目的探讨银杏叶提取物对慢性阻塞性肺疾病急性加重期（AECOPD）患者血管内皮功能的影响。方法将60例AECOPD患者随机分为常规治疗组（CT组）,银杏叶组（GBLE组）,每组30例;并选择同期30例健康体检者作为对照组。两组常规治疗相同,GBLE组每日加用舒血宁注射液20 mL静脉滴注,连用2周。酶联免疫吸附法检测血清一氧化氮（NO）、血栓调节蛋白（TM）和血管假血友病因子（vWF）。结果两个治疗组治疗前NO,TM显著低于对照组（P〈0.01）,vWF显著高于对照组（P〈0.01）。治疗后,两组NO,TM水平较治疗前显著升高（P〈0.01）,而GBLE组升高更为显著,与CT组比较有统计学差异（P〈0.01）;两组vWF水平较治疗前显著下降（P〈0.01）,GBLE组下降较CT组更为显著（P〈0.01）。结论银杏叶提取物有显著改善AECOPD患者血管内皮细胞功能的作用,可预防血栓性疾病。     

Protein-Bound Uremic Toxins Lowering Effect of Sevelamer in Pre-Dialysis Chronic Kidney Disease Patients with Hyperphosphatemia: A Randomized Controlled Trial

P-cresyl sulfate and indoxyl sulfate are strongly associated with cardiovascular events and all-cause mortality in chronic kidney disease (CKD). This randomized controlled trial was conducted to compare the effects between sevelamer and calcium carbonate on protein-bound uremic toxins in pre-dialysis CKD patients with hyperphosphatemia. Forty pre-dialysis CKD patients with persistent hyperphosphatemia were randomly assigned to receive either 2400 mg of sevelamer daily or 1500 mg of calcium carbonate daily for 24 weeks. A significant decrease of total serum p-cresyl sulfate was observed in sevelamer therapy compared to calcium carbonate therapy (mean difference between two groups −5.61 mg/L; 95% CI −11.01 to −0.27 mg/L; p = 0.04). There was no significant difference in serum indoxyl sulfate levels (p = 0.36). Sevelamer had effects in terms of lowering fibroblast growth factor 23 (p = 0.01) and low-density lipoprotein cholesterol levels (p = 0.04). Sevelamer showed benefits in terms of retarding CKD progression. Changes in vascular stiffness were not found in this study.     

阶段性护理改善慢性阻塞性肺疾病患者疲劳的观察

目的：探讨慢性阻塞性肺疾病患者治疗中,阶段性护理改善其疲劳症状的效果。方法：将54例患者随机分为对照组和观察组2组,分别给予常规护理和阶段性护理干预,观测2组疲劳得分以及焦虑抑郁得分。结果：护理干预后,2组疲劳得分以及各维度、焦虑抑郁均有所改善,但观察组效果更加显著。结论：采用阶段性护理干预可使慢性阻塞性肺疾病患者的疲劳得到缓解,同时还可改善患者焦虑抑郁症状。