Propafenone disposition in renal insufficiency and renal failure

The pharmacokinetics of a single intravenous dose of propafenone were studied in subjects with normal renal function (n = 5), renal insufficiency (n = 5), and renal failure (n = 3). No difference in central volume of distribution, total ischemic clearance or terminal half-life existed. None of the pharmacokinetic parameters examined correlated to creatinine clearance. Within the confines of the small number of patients studied, there does not appear to be any effect of renal insufficiency or failure on single-dose propafenone disposition.     

肾动脉支架术对轻中度肾功能不全合并肾动脉狭窄患者肾功能的影响

目的研究肾动脉支架术对轻中度肾功能不全合并肾动脉狭窄患者肾功能的影响。方法选取2015年1月~2016年1月在我院已经进行过肾动脉支架手术的轻中度肾功能不全合并肾动脉狭窄的280例患者,在手术前和手术后分别对这280例患者进行血压测试、血肌酐(Scr)以及肾小球滤过率等指标进行为期1年的跟踪观察记录,分别记录患者手术前、手术后3个月、手术后6个月以及手术后1年三种不同指标的值,并对三种指标进行统计分析和检验。结果经过肾动脉支架手术后,轻中度肾功能不全合并肾动脉狭窄患者的肾功能有了明显改善,血压值恢复正常率显著高于肾动脉支架手术前,血肌酐值与手术前差异有统计学意义,肾小球滤过率也比手术前有很大的改善,这三组指标较手术前差异有统计学意义(P0.05)。结论肾动脉支架术能够有效的治疗轻中度肾功能不全合并肾动脉狭窄疾病且有显著疗效,能够使患者重新恢复到健康,在临床治疗中值得推广和应用。     

连续性肾脏替代疗法治疗急性肾功能衰竭的临床观察

目的观察连续性肾脏替代疗法（CRRT）治疗重症急性肾功能衰竭（ARF）的疗效和对预后的影响。方法对2003年以来16例ARF（伴发多器官功能障碍综合征,MODS）患者进行CRRT的临床资料回顾性分析。结果11例患者经CRRT治疗24 h后,生命指征平稳,BUN、Scr下降（P〈0.05）,二氧化碳结合力（CO2CP）正常,85-264h后进入多尿期;5例患者死于严重创伤或MODS。治疗过程中无低体温和低血压等并发症。结论CRRT治疗重症ARF患者,血液动力学稳定,溶质清除率高,有利于营养支持及清除炎性细胞因子,从而改善重症ARF患者的预后。     

New renal drug development to face chronic renal disease

Introduction: For the first time in 2012, chronic kidney diseases were added to WHO disease list because of their impact on morbidity/mortality and their substantial impact on the cost to the health care system. Although representing a clear unmet medical need and a huge business case for the pharmaceutical industry, its clinical treatment still mainly relies on drugs invented in the 1980s used for controlling blood pressure.

Areas covered: In this review, the authors aim to elucidate why renal drug development is feasible today. The article provides a particular focus on the treatments that target the pathways involved in inflammation, fibrosis and the core mechanisms driving the vicious cycle responsible for disease progression and organ function loss.

Expert opinion: Currently, it is plausible to develop effective therapeutics for renal diseases with a plethora of approaches available for their development at a preclinical and clinical level. Furthermore, the relevance of biomarkers and the use of surrogate rare disease indications as proof of mechanism for faster and/or smaller clinical development are now possible; and these developments could revolutionize the way we treat renal disease in the future.     

Enhanced renal vasoconstrictor responsiveness to vasopressin after renal denervation

Previous studies from our laboratory and others demonstrated a relative insensitivity of the renal vasculature to the vasoconstrictor influences of arginine vasopressin (AVP). Experiments were therefore conducted to identify the possible roles of renal sympathetic withdrawal and V2-vasopressinergic receptor-mediated vasodilation in this response. Renal hemodynamic responses to AVP or saline vehicle were examined in the presence or absence of either selective V1-vasopressinergic-receptor blockade or nonselective vasopressinergic-receptor antagonism in conscious intact and renal-denervated rats. Our results indicate that renal denervation profoundly augmented AVP-induced renal vasoconstriction, whereas no differences were observed in the responses to V1-receptor blockade versus combined V1, V2-receptor antagonism. These findings are consistent with a role for renal sympathoinhibition in mediating the relative insensitivity of the renal bed to the vasoconstrictor effects of AVP in conscious rats but do not support a modulatory influence of V2-receptor activity in this response.     

慢性肾功能不全患者肾穿刺活检的风险与价值研究

目的回顾性分析慢性肾功能不全（CRI）患者经皮肾穿刺活检（PRB）的风险与价值。方法对符合条件的50例CRI患者进行PRB,行光镜、免疫组化染色和选择性电镜检测,观察肾穿刺组织肾小球个数、病理类型、诊断以及穿刺并发症。结果肾组织标本合格率为96%。病理类型前三位为增生性肾小球硬化症21例（42%）,IgA肾病（IgAN）9例（18%）,狼疮性肾炎（LN）8例（16%）。PRB后修改诊断5例（10%）,明确病因3例（6%）,诊断修正率为16%,根据病理结果决定治疗方案16例（32%）,治疗方案修正率为26%。并发症以镜下血尿最常见,共48例（98%）,肾周小血肿11例,肾周大血肿2例,腹膜后血肿1例。结论原发性肾脏疾病肾穿后病理结果多为慢性病变,大部分患者的诊断治疗方案不受肾穿刺病理结果的影响,且肾周血肿出现机率较多且较大,偶可合并腹膜后血肿,但狼疮性肾炎表现为慢性肾衰时其肾脏病理的活动指数仍较高,少数病例肾脏病理显示新月体肾炎,仍需应用免疫抑制剂以改善预后。     

Cocaine-induced renal disease

Cocaine has anaesthetic, vasoconstrictive and CNS stimulatory effects. Presently, it is used clinically as a local anaesthetic and abused as a recreational drug. It has been implicated in both acute and chronic renal failure and has been reported to affect every aspect of the nephron. This article will review the spectrum of cocaine-induced kidney disease and attempt to give insight into the pathophysiological mechanisms involved.     

Cardiovascular and renal

A selection of World Wide Web sites relevant to papers published in this issue of Current Opinion in Pharmacology.     

肾组织肥大细胞表型特点分析研究

目的 阐明各种肾病患者肾组织肥大细胞的表型特点.方法 选取包括糖尿病肾病、IgA肾病、急性间质性肾炎、慢性间质性肾炎、过敏性紫癜性肾炎、膜性肾病和狼疮性肾炎在内的肾病患者369例,正常供肾16例,以免疫组化方法检测肾活检标本中肥大细胞类胰蛋白酶和糜蛋白酶表达情况,对其进行分型分析.结果 双连续切片分析发现,绝大多数肥大细胞表现为类胰蛋白酶和糜蛋白酶染色双阳性,仅有少数表现为类胰蛋白酶或糜蛋白酶单阳性;“双夹心”连续切片分析法显示,所谓的类胰蛋白酶或糜蛋白酶单阳性肥大细胞实际上是类胰蛋白酶和糜蛋白酶双阳性;以类胰蛋白酶为标记分子和以糜蛋白酶为标记分子检测肾组织肥大细胞的结果比较没有显著区别.结论 类胰蛋白酶糜蛋白酶亚型(MCTC亚型)是正常个体和肾病患者肾组织肥大细胞的基本亚型.     

中介素对急性肾衰竭的肾脏保护作用

目的探讨中介素在急性肾衰竭病人血清中的表达及其对肾脏的保护机制。方法选取焦作市第二人民医院 2015年 12月至 2018年 6月间确诊的急性肾衰竭病人 45例和健康对照组 30例,采用酶联免疫吸附试验检测血清中介素水平,寻找血清中中介素水平与急性肾衰竭的相关性。另外,建立大鼠肾小管上皮细胞( NRK?52E)缺氧 /复氧模型,模拟急性肾衰竭肾脏缺血再灌注过程, MTT法检测细胞活性,流式细胞术检测细胞凋亡情况, RT?PCR和蛋白质印迹法检测自噬标志蛋白 beclin?1、微管相关蛋白轻链 3(LC3)和磷脂酰肌醇 3?激酶 /蛋白激酶 B/雷帕霉素靶蛋白( phosphatidylinositol 3?kinase/protein kinase B/mam? malian target of rapamycin,PI3K/Akt/mTOR)信号相关蛋白表达水平,以进一步探索中介素对肾脏的保护作用。结果急性肾衰竭病人血清中中介素表达水平明显高于健康对照组者。大鼠肾小管上皮细胞经过缺氧 /复氧处理后,细胞的存活率为( 45.3± 4.5)%,与对照组( 100±1.4)%相比显著下降( P＜0.05)。采用不同浓度的中介素( 2 μmol/L、4 μmol/L、6 μmol/L)对细胞进行干预后,细胞存活率分别为( 55.9±2.6)%,(75.4±3.2)%,和( 86.7±2.9)%,与缺氧 /复氧模型组相比显著上升( P＜0.05)。细胞在缺氧再复氧后发生了严重的细胞凋亡现象,凋亡率为( 42.3±3.6)%,与对照组( 10.2±1.7)%相比显著上升( P＜0.05)而经过中介素( 4 μmol/L)预孵育 4h的细胞凋亡率为( 27.6±3.1)%,与缺氧 /复氧模型组相比显著下降( P＜0.05)。随着中介浓度升高, PI3K/Akt/mTOR信号通路关键蛋白磷酸化水平显著降低( P＜0.05),beclin?1、LC3?Ⅱ/LC3?Ⅰ表达量升高,细胞自噬水平显著升高;与中介素单独处理组相比, PI3K抑制剂 LY290042与中介素( 2 μmol/L)联合用组, PI3K、Akt、mTOR磷酸化水平极显著下降(P＜0.05)beclin?1、LC3?Ⅱ/LC3?Ⅰ表达量极显著上升,细胞自噬水平极显著升高。结论中介素在急性肾衰竭病人血清中高度表达,抑制 PI3K/Akt/mTOR信号通路,上调细胞的自噬水平,实现直接保护肾脏作用。素,通过,     

Acute renal failure

Acute renal failure remains an important clinical problem with little progress made in the therapeutic approach over the past 20-30 years. The purpose of this review is to discuss possible etiologies, their diagnosis, differentiation and possible prevention. The pathophysiology of prerenal azotemia and ischemic acute renal failure are also discussed. The importance of understanding different body volume components, the urine analysis and the FE Na(+) are explained.     

ARC--augmented renal clearance

In-hospital and intensive care unit mortality rates for sepsis remain un-acceptably high, and have prompted the publication of international guidelines on best practice. Crucial to this is the application of early appropriate antibacterial therapy, in the correct dose. However, antibacterial regimes in this setting have largely been extrapolated from those in healthy volunteers, and fail to consider the unique pathophysiology and treatment provided to this population. As such, augmented renal clearance (ARC) - the enhanced renal elimination of circulating solute - is likely to be one of the more common physiological changes encountered in this setting, although to date remains largely under-appreciated. Significantly this may alter the pharmacokinetics of many routinely prescribed agents in this setting, pre-disposing to subtherapeutic levels or treatment failure. This review paper examines this phenomenon in detail, providing a summary of the likely underlying mechanisms, those patients at greatest risk, and the implications for antibacterial dosing in the critically ill.     

应用肾功能MRI技术开展肾功能评估的研究进展

肾功能MRI技术是利用肾血流灌注丰富、血氧代谢活跃、含水量丰富的特点,可以在肾大小、形态发生改变之前检测出肾功能的变化,为临床诊断提供有价值的信息。目前,采用肾功能MRI对肾血流灌注、血氧代谢水平、水分子扩散及弹性特点等方面的研究取得进展,现综述如下。