Biallelic Pathogenic GFRA1 Variants Cause Autosomal Recessive Bilateral Renal Agenesis

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Towards human ex vivo organ perfusion models to elucidate drug pharmacokinetics in health and disease

Abstract

To predict the absorption, distribution, metabolism and excretion (ADME) profile of candidate drugs a variety of preclinical models can be applied. The ADME and toxicological behavior of newly developed drugs are often investigated prior to assessment in humans, which is associated with long time-lines and high costs. Therefore, good predictions of ADME profiles earlier in the drug development process are very valuable. Good prediction of intestinal absorption and renal and biliary excretion remain especially difficult, as there is an interplay of active transport and metabolism involved. To study these processes, including enterohepatic circulation, ex vivo tissue models are highly relevant and can be regarded as the bridge between in vitro and in vivo models. In this review the current in vitro, in vivo and in more detail ex vivo models for studying pharmacokinetics in health and disease are discussed. Additionally, we propose novel models, i.e., perfused whole-organs, which we envision will generate valuable pharmacokinetic information in the future due to improved translation to the in vivo situation. These machine-perfused organ models will be particularly interesting in combination with biomarkers for assessing the functionality of transporter and CYP450 proteins.     

Management of accessory renal arteries during aneurysm repair in a patient with end-stage renal failure

The presence of accessory renal artery is a frequent anatomic variation that can challenge abdominal aortic aneurysm (AAA) repair. Here, we show an image of an abdominal aortic aneurysm extended to multiple accessory renal arteries in a patient known for an end-stage renal failure. This case raises the questions of the criteria that should be taken in consideration for an optimal management of accessory renal artery during AAA repair.     

输尿管软镜内切开引流术及后腹腔镜 下囊肿去顶术的疗效对比研究

目的 对比经尿道输尿管软镜下肾囊肿内切开引流术和后腹腔镜下肾囊肿去顶术临床疗效。方法 选取40例肾囊肿患者。年龄44~75岁，平均年龄61岁，随机分为两组，即实验组（输尿管软镜下内切开引流肾囊肿）和对照组（后腹腔镜下肾囊肿去顶术），观察两组患者治疗效果、并发症及术后随访结果。结果 两组手术均成功，对照组因为1例患者粘连比较严重而改为开放手术，术中术后均无明显的并发症，术后复查CT或者B超提示肾囊肿消失或直径缩小至术前一半以上。而术中的手术时间，术中出血量，术后疼痛分数及术后住院时间方面，实验组均优于对照组，差异均有显性（P <0.05）。随访12个月，期间，两组未发现肾囊肿复发。结论 经尿道输尿管软镜技术治疗肾囊肿（与肾集合系统毗邻的肾囊肿）具有近期微创，安全，有效，无痛苦，并发症少，住院时间短，恢复快，美容效果极佳的疗效，但远期效果需要进一步观察。     

血液回收技术中应用钠钾镁钙葡萄糖注射液对肝肾功能和血气指标的影响

目的评价钠钾镁钙葡萄糖注射液应用于血液回收技术中对患者肝肾功能和血气指标的影响。方法选择需行血液回收的神经外科手术患者60例,男31例,女29例,年龄19～67岁,BMI 21～25 kg/m~2,ASAⅠ或Ⅱ级。随机分为钠钾镁钙葡萄糖注射液组(N组)和生理盐水组(C组),每组30例。N组肝素冲管液采用低分子肝素钠25 000 IU加入钠钾镁钙葡萄糖注射液500 ml中配置,洗涤液全部应用钠钾镁钙葡萄糖注射液;C组肝素冲管液采用低分子肝素钠25 000 IU加入生理盐水500 ml中配置,洗涤液全部应用生理盐水。于血液回收前(T_0)、自体血输注完毕后(T_1)、手术后6 h(T_2)采集血样,检测ALT、AST、血清总胆红素(TBIL)、肌酐(Scr)、尿素氮(BUN)等肝肾功能指标;血氧饱和度50%时的氧分压(P_(50))、pH、血浆HCO_3~-、乳酸(Lac)、电解质(K~+、Na~+、Cl~-、Ca~(2+))、血糖(Glu)浓度等血气指标。结果与T_0时比较,T_1时C组BUN、Scr、Lac、Na~+、Cl~-、Glu浓度明显升高(P0.05),P_(50)明显升高(P0.05),pH和血浆HCO_3~-浓度以及K~+、Ca~(2+)浓度明显降低(P0.05)。与T_1时比较,T_2时C组BUN、Scr、Lac、Na~+、Cl~-、Glu浓度明显升高(P0.05),P_(50)明显升高(P0.05),pH和血浆HCO_3~-浓度以及K~+、Ca~(2+)浓度明显降低(P0.05)。与N组比较,T_1和T_2时C组BUN、Scr、Lac、Na~+、Cl~-、Glu浓度明显升高(P0.05),P_(50)明显升高(P0.05),pH和血浆HCO_3~-浓度以及K~+、Ca~(2+)浓度明显降低(P0.05)。两组不同时点AST、ALT、TBIL浓度差异无统计学意义。结论在血液回收中应用钠钾镁钙葡萄糖注射液配置肝素冲管液和洗涤液有利于减轻红细胞的损伤,改善红细胞携氧能力,维持内环境稳定和酸碱平衡,有利于保护患者肾功能,但对肝功能无明显影响。