Morphometric analysis of renal arteries in patients with renal cell carcinoma

The aim of this study was to analyze morphometric parameters of renal arteries (longest diameter and tunica media thickness) in patients with renal cell carcinoma (RCC), to look into their relationship to tumor necrosis and to compare them with morphometric parameters recorded in a control group. We analyzed archival cases of RCC diagnosed in 2003 that also contained routinely sampled specimens of distal segments of renal artery. The control group consisted of specimens from both renal arteries obtained from 16 patients at routine autopsy during 2004-2005. Autopsy, as well as further histological analysis, did not disclose any malignant disease in the control group. Morphometric analysis of diameter and thickness of the renal artery tunica media was performed using Issa 3.1 software (Vamstek 2002, Zagreb, Croatia). The comparison of tunica media thickness showed that renal arteries from RCC cases were significantly thicker compared to distal parts of renal arteries in the control group (p=0.0002). Although renal artery samples from cases with necrotic tumor areas were thicker than those without tumor necrosis, the difference was not statistically significant. It is concluded that significantly thicker tunica media characterizes renal arteries in the group of patients with RCC when compared with the control group.     

Percutaneous treatment of renal cysts with OK-432 sclerosis

PURPOSE: The aim of this study was to demonstrate OK- 432 sclerotherapy efficacy for treatment of simple renal cysts. MATERIALS AND METHODS: Twenty patients with 25 symptomatic or large simple cysts were treated by ultrasonography (US)-guided percutaneous aspiration and injection of OK-432 (8 men and 12 women, mean age 63.6 years, SD 9.5). Six patients presented with flank pain, 14 presented with renal mass; renal cyst location was right, left, or bilateral sided in 9, 8, and 8 kidneys, respectively. Patients were evaluated by clinical assessment, US, or CT scan 3 months following the procedure. Complete and partial success was defined as symptom resolution with either total cyst ablation or greater than 70% reduction, respectively. Failure was defined as 30% of cyst size recurrence and/or persistent symptoms. RESULTS: Average reduction was 93.0%. Complete and partial resolution occurred in 11 (44.0%) and 13 (52.0%) cysts, respectively. One case was defined as failure, with a 64.2% size reduction from 10.9cm to 3.9cm (volume reduction rate 95.4%). Renal pain improved in all patients, regardless of complete or partial resolution. Minor complications occurred in 3 patients, 2 developed leukocytosis and 1 had mild fever (< 38.5 degrees C) following aspiration and sclerotherapy. Successful treatment was achieved with conservative measures and NSAID therapy. CONCLUSION: Percutaneous treatment of simple renal cysts with OK-432 sclerotherapy was found to be a safe, effective and minimally invasive procedure.     

Non-myeloablative mixed chimerism approaches and tolerance, a split decision

Stable mixed chimerism has been considered the most robust tolerance strategy. However, rejection of solid donor tissues by chimeras has been observed, a state termed split tolerance. Since new non-myeloablative mixed chimerism approaches are being actively pursued, we sought to determine whether they lead to full tolerance or split tolerance and to define the mechanisms involved. Fully mismatched mixed chimeras generated by induction with various lymphocyte-depleting antibodies along with either low-dose irradiation or busulfan and temporary sirolimus, maintained stable mixed chimerism but nevertheless rejected donor skin grafts. Generation of stable mixed chimerism using antibody targeting CD40L, but not depleting antibodies to CD4 and CD8, could prevent split tolerance when skin grafts were given together with donor bone marrow. Minor antigen matching abrogated the ability of effector T cells to reject donor skin grafts. A CFSE killing assay indicated that chimeras were both directly and indirectly tolerant of donor hematopoietic cell antigens, suggesting that minor mismatches triggered a tissue-specific response. Thus, split tolerance due to tissue-restricted polymorphic antigens prevents full tolerance in a number of non-myeloablative mixed chimerism protocols and a 'tolerizing' agent is required to overcome split tolerance. A model of the requirements for split tolerance is presented.     

非离子型与离子型对比剂不良反应及对肾功能指标影响观察

摘 要 目的：观察比较非离子型与离子型对比剂的不良反应及对肾功能指标变化的影响。方法：180例在我院行介入影像检查的患者随机分为两组。非离子型组90例患者使用非离子型对比剂碘普罗胺注射液,离子型组90例使用离子型对比剂76%泛影葡胺注射液。比较两组患者造影前后肾功能指标变化,评价造影剂肾病（CIN）以及造影后不良反应发生情况。结果：非离子型组发生3例轻度不良反应,不良反应发生率4.44%;显著低于离子型组的12.22%（P＜0.05）。 造影后2 d,两组患者BUN、SCr均较造影前均明显升高（P＜0.05）,而Ccr则较前明显降低（P＜0.05）,且非离子型组上述指标均优于离子型组（P＜0.05）;两组CIN分别发生3例和4例,差异无统计学意义（P>0.05）。造影后7 d,非离子型组SCr、BUN、Ccr与造影前比较无明显差异（P＞0.05）,离子型组SCr、BUN仍较造影前明显增高,Ccr则较前明显降低（P＜0.05）。两组各项指标仍有明显差异（P＜0.05）。结论：非离子型与离子型对比剂均会对患者肾功能产生一定影响,但非离子型对比剂影响较小,恢复更快;且不良反应发生较少,更为安全。     

临床药师参与1例肾移植术后肺结核患者抗结核治疗的药学实践

摘 要临床药师基于循证证据,结合患者病情,与医生合作,积极参与1例肾移植术后肺结核患者的抗结核治疗,给患者提供药学服务。根据现有指南、临床研究,考虑用药经济性的基础上,临床药师对患者治疗药物的选择、药品相互作用及不良反应等方面进行合理性分析,促进合理用药。     

Physiological based pharmacokinetic modeling to estimate in vivo Ki of ketoconazole on renal P-gp using human drug-drug interaction study result of fesoterodine and ketoconazole

This study was conducted to estimate in vivo inhibition constant (Ki) of ketoconazole on renal P-glycoprotein (P-gp) using human drug-drug interaction (DDI) study result of fesoterodine and ketoconazole. Fesoterodine is a prodrug which is extensively hydrolyzed by non-specific esterases to the active metabolite 5-hydroxymethyl tolterodine (5-HMT). 5-HMT is then further metabolized via Cytochrome P450 (CYP) 2D6 and CYP3A4. It is reported that 5-HMT is a substrate of P-gp whereas fesoterodine is not. Renal clearance of 5-HMT is approximately two-times greater than renal glomerular filtration rate. This suggests the possibility that renal clearance of 5-HMT involves secretion by P-gp. Utilizing the available pharmacokinetic characteristics of fesoterodine and 5-HMT, we estimated in vivo Ki of ketoconazole on P-gp at kidney based on DDI study data using physiologically-based pharmacokinetic approach. The estimated in vivo Ki of ketoconazole for hepatic CYP3A4 (6.64 ng/mL) was consistent with the reported values. The in vivo Ki of ketoconazole for renal P-gp was successfully estimated as 2.27 ng/mL, which was notably lower than reported in vitro 50% inhibitory concentration (IC₅₀) values ranged 223–2440 ng/mL due to different condition between in vitro and in vivo.     

Tivozanib for the treatment of renal cell carcinoma

Introduction: Renal cell carcinoma (RCC) represents a heterogeneous group of cancers with distinct histological features, molecular alterations, prognosis, and response to therapy. Target agents directed against vascular endothelial growth factor and its receptor and mammalian target of rapamycin (mTOR) inhibitors have completely changed the landscape of RCC. However, the rate of complete response is still low, thus supporting the research of novel therapeutic agents.

Area covered: The authors describe the chemical features of tivozanib, its pharmacodynamic and pharmacokinetic properties, and the results obtained in human phase I–III clinical trials. Tivozanib received its first global approval in EU, Iceland, and Norway on 28 August 2017 for the first-line treatment of adult patients with advanced RCC and for adult patients who are VEGFR and mTOR inhibitor-naive following disease progression after one prior treatment with cytokines.

Expert opinion: The US Food and Drug Administration did not approve tivozanib due to the lack of a significant advantage in terms of survival compared to sorafenib. To date, the role of tivozanib in the pharmaceutical landscape of mRCC appears to be very limited. However, ongoing trials on the association between tivozanib and immunotherapy may represent a promising strategy to be assessed in future clinical trials.     

HIF-1α在重度子痫前期孕妇胎盘中的表达及与胎儿肾动脉血流的相关性

目的探讨HIF-1α在重度子痫前期孕妇胎盘中的表达及其与胎儿肾动脉血流的相关性。方法选取广州市花都区妇幼保健院2015年1月-2016年12月就诊的40例重度子痫前期孕妇为观察组,40例正常妊娠孕妇为对照组,术前48 h采用彩色多普勒超声测量胎儿肾动脉血流动力学参数,术后检测其胎盘组织中缺氧诱导因子-1α的表达,分析两者之间的相关性。结果观察组胎儿肾动脉RI(0.73±0.08)、PI(0.87±0.17)、S/D(1.90±0.22)均明显高于对照组的RI(0.45±0.06)、PI(0.62±0.11)、S/D(1.35±0.16)(P<0.05)。观察组HIF-1α蛋白阳性率85.00%,明显高于对照组的25.00%(P<0.05);观察组HIF-1αm RNA相对表达量(0.927±0.168),高于对照组的(0.534±0.132)(P<0.05);HIF-1α蛋白表达阳性组RI(0.89±0.11)、PI(0.95±0.23)、S/D(2.18±0.24),均高于HIF-1α蛋白表达阴性组RI的(0.57±0.12)、PI(0.69±0.14)、S/D(1.60±0.19)(P<0.05)。结论重度子痫前期孕妇胎盘HIF-1α呈高表达状态,同时胎儿肾动脉血流动力参数RI、PI、S/D升高。