BACKGROUND & AIMS: Focal and segmental sclerosed lesions in the glomeruli are found in several pathological entities and more often are found in the corticomedullary junction where renal blood flow and filtration pressure is maximal. Experimental data suggest that hyperfiltration injury results in focal and segmental glomerulosclerosis (FSGS). In keeping with this concept, malignant hypertension is a known cause of nephrotic-range proteinuria and nephrotic syndrome pathalobically represented by FSGS. We report a case of unilateral renal artery stenosis associated with nephrotic syndrome and FSGS in the contralateral kidney only. The kidney with the stenosed renal artery showed normal glomeruli with juxtaglomerular hyperplasia, suggesting that protection from hyperfiltration injury was provided by the presence of high-grade stenosis. Serum creatinine concentration, blood pressure, and proteinuria normalized after aorto-renal bypass surgery. This case shows the importance of hemodynamic factors on the pathogenesis of secondary FSGS and the progression of renal disease.

背景与目标： 肾小球的局灶性和节段性硬化性病变在几种病理实体中发现，而在肾血流量和过滤压力最大的皮质管交界处更常见。实验数据表明，超滤损伤会导致局灶性和节段性肾小球硬化 (FSGS)。与这个概念保持一致，恶性高血压是由FSGS病理代表的肾病范围蛋白尿和肾病综合征的已知原因。我们报告了仅在对侧肾脏中与肾病综合征和FSGS相关的单侧肾动脉狭窄病例。肾动脉狭窄的肾脏显示正常的肾小球并伴有近肾小球增生，这表明高级别狭窄的存在可保护高滤过损伤。主动脉-肾搭桥手术后血清肌酐浓度，血压和蛋白尿正常化。该病例显示了血流动力学因素对继发性FSGS发病机理和肾脏疾病进展的重要性。

BACKGROUND & AIMS: OBJECTIVE:To discover potential differences in known prognostic factors of renal adenocarcinoma in patients under 40 years of age. PATIENTS AND METHODS:A series of 246 patients with renal adenocarcinoma included 17 patients 40 years. Both groups were analyzed for sex, tumour size, histological characteristics and stage, examining the relative proportions within each group and looking for an association between those sets of data and age. RESULTS:No statistically significant associations were found, although it should be noted that in some cases data is incomplete. A larger proportion of low stages at least locally and a greater proportion of granule cell tumours was found in patients 40 years-old compared to those over 40. CONCLUSIONS:Existence of differences in the biological and histological characteristics of renal adenocarcinomas that develop at a younger age is not unlikely. The analysis of each factor and the survival rates in larger series should elucidate these questions, which will also be of interest to improve our understanding of the histogenesis of this type of tumours.

背景与目标：

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: OBJECTIVE:To investigate renal preservation by a novel method of perfusion using an oxygenated perfluorocarbon (PFC) emulsion via retrograde access to the kidney, as preserving renal function during urological surgery has been elusive, and the recognized technique of nephron-sparing surgery has increased its application and practice in modern urology. MATERIALS AND METHODS:After institutional review and approval, 30 New Zealand White rabbits were studied. In a solitary kidney model, each rabbit had the ureter catheterized before 40 min of renal artery occlusion. Each rabbit was randomized to one retrograde perfusion group, i.e. sham, normothermic PFC, chilled PFC, normothermic saline, and chilled saline. The rabbits were maintained for 2 weeks, during which renal function, urine output, systemic blood gases, weight and serum creatinine level were measured. After death, the kidneys were individually examined and graded by one renal pathologist unaware of the treatment. RESULTS:The rabbits treated with retrograde PFC perfusion (normothermic and chilled) had less change in their creatinine clearance, at 3.6 and 4.0 mL/min per kg, than the sham group, at 7.8 mL/min per kg, while also having significantly higher systemic venous oxygenation, at 26.3 and 10.0 mmHg, than the sham group, at 0.2 mmHg. Normothermic and chilled perfusion with PFC was also associated with less histological evidence of ischaemic damage, with mean (sd) scores of 13.0 (13.5) and 8.7 (4.5), respectively, than in the sham group, at 33.3 (16.8), while favourably matching the contralateral control kidney group, at 5.5 (2.3). The rabbits treated with saline retrograde perfusion also had better outcomes than the sham cohort. There were no adverse effects in any of the study arms or with the use of PFC. CONCLUSION:Retrograde oxygen delivery to the kidney through the urinary collecting system was successful in this pilot study. Renal function, laboratory and histological data indicate a trend towards renal preservation and even systemic oxygenation in the experimental groups compared with the sham rabbits, with no adverse effects attributed to this technique.

背景与目标：

BACKGROUND & AIMS: :Left ventricular (LV) dysfunction and/or heart failure (HF) are frequent complications of hypertension and myocardial infarction (MI), placing affected patients at increased risk of significant morbidity and premature death. Given that the renin-angiotensin-aldosterone system (RAAS) is activated and of pathophysiological importance in such patients, a strong therapeutic rationale exists to target the main effector mechanism (that is, angiotensin II [Ang II]) in order to lessen the associated morbidity and mortality burden. Angiotensin-converting enzyme (ACE) inhibitors have been shown to reduce mortality and LV dysfunction and to slow disease progression in patients with HF, including high-risk, post-MI patients. However, ACE inhibitors (ACE-Is) may not provide optimal long-term RAAS blockade (a finding that is associated with a worse prognosis) and many patients are unable to tolerate such therapy (because of troublesome dry cough, for example). In contrast, Ang II receptor blockers (ARBs) may block the RAAS more completely than ACE-Is and appear to be better tolerated. Several large-scale trials gave evaluated the efficacy of ARBs in patients with LV dysfunction and/or HF (including high-risk, post-MI patients), and have confirmed their utility as an efficacious and well-tolerated alternative to ACE-Is in this setting.

背景与目标： : 左心室 (LV) 功能障碍和/或心力衰竭 (HF) 是高血压和心肌梗塞 (MI) 的常见并发症，使受影响的患者具有显着发病率和过早死亡的风险。鉴于肾素-血管紧张素-醛固酮系统 (RAAS) 在此类患者中被激活并且具有病理生理重要性，因此存在针对主要效应机制 (即血管紧张素II [Ang II]) 的强有力的治疗依据，以减轻相关的发病率和死亡率负担。血管紧张素转换酶 (ACE) 抑制剂已被证明可降低HF患者 (包括高危MI后患者) 的死亡率和LV功能障碍，并可减缓疾病进展。然而，ACE抑制剂 (ACE-Is) 可能无法提供最佳的长期RAAS阻断 (这一发现与更差的预后相关)，并且许多患者无法耐受这种治疗 (例如，由于麻烦的干咳)。相比之下，Ang II受体阻滞剂 (arb) 可能比ACE-Is更完全地阻断RAAS，并且似乎具有更好的耐受性。几项大规模试验评估了ARBs在LV功能障碍和/或HF患者 (包括高危MI后患者) 中的疗效，并已证实其作为ACE-Is的有效且耐受性良好的替代方法在这种情况下。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: OBJECTIVE:To assess whether interindividual variation in renal plasma flow or in its response to angiotensin II infusion is associated with interindividual differences in blood pressure in a population-based sample of 287 non-Hispanic whites (143 women and 144 men), aged 20-49.9 years.

METHODS:After seven days of eating a high-sodium diet (260 mmol/day), the renal plasma flow was determined by measuring the clearance of p-aminohippurate before and after infusion of 3 ng/kg per min angiotensin II. Multiple linear regression methods were used to assess whether measures of the renal plasma flow and of its response to angiotensin II infusion were predictive of systolic or diastolic blood pressures measured prior to administration of the high-sodium diet, on day 6 of the high-sodium diet, or during the renal clearance procedure on day 7 prior to angiotensin II infusion.

RESULTS:There was some evidence that measures of the renal plasma flow and of its response to angiotensin II infusion during the high-sodium diet were statistically significant predictors of measures of blood pressure in women; there was less evidence for this for blood pressures in men. Interindividual variation in measures of the renal plasma flow and of its response to angiotensin II infusion explained less than 10% of the interindividual variation in any measure of the blood pressure in both sexes.

CONCLUSION:These results suggest that interindividual variation in renal plasma flow ad in its response to angiotensin II infusion during a high-sodium diet will be of limited utility in elucidating the basis for interindividual differences in blood pressure.

背景与目标： 目的 : 在基于人群的287非西班牙裔白人 (143名女性和144名男性) 样本中，评估肾血浆流量或对血管紧张素II输注的反应的个体差异是否与血压的个体差异相关，年龄在20-49.9岁之间。
方法 : 在食用高钠饮食 (260 mmol/天) 7天后，通过在每分钟输注3 ng/kg血管紧张素II之前和之后测量对氨基马尿酸盐的清除率来确定肾血浆流量。使用多元线性回归方法来评估肾血浆流量及其对血管紧张素II输注的反应的测量是否可以预测高钠饮食第6天在给予高钠饮食之前测得的收缩压或舒张压。钠饮食，或在输注血管紧张素II之前第7天的肾脏清除过程中。
结果 : 有证据表明，高钠饮食期间肾脏血浆流量的测量及其对血管紧张素II输注的反应是女性血压测量的统计学显着预测指标; 男性血压的证据较少。肾血浆流量测量及其对血管紧张素II输注的反应的个体差异解释了男女血压测量中个体间差异的10%。
结论 : 这些结果表明，在高钠饮食中对血管紧张素II输注的反应中，肾血浆流量ad的个体差异在阐明血压个体差异的基础方面将是有限的。

BACKGROUND & AIMS: :Evidence suggests that gender differences exist in renin-angiotensin system (RAS) function. It was hypothesized that women may differ also in their response to RAS blockade. The renal and peripheral hemodynamic responses to incremental dosages of an angiotensin receptor blocker and the degree of angiotensin II (AngII) insensitivity achieved during 8 wk were examined in men and women. Participants were 30 young healthy men (n = 15; mean age 27 +/- 2) and women (n = 15; mean age 28 +/- 2) who were on a controlled sodium and protein diet for 1 wk before each study. The humoral, renal, and systemic response to incremental dosages of irbesartan (75 mg for 4 wk, then 150 mg for 4 wk) was assessed, as was the pressor response to AngII (3 ng/kg per min), at 2-wk intervals. AngII type 1 receptor expression in skin biopsies was assessed at baseline and after 8 wk by a real-time PCR protocol. Men and women both exhibited significant declines in BP. Women achieved significantly reduced AngII sensitivity compared with men at lower dosages, showing no pressor response at 4 wk of 75 mg/d irbesartan, whereas men continued to exhibit a pressor response at 4 wk of 150 mg/d. Receptor expression at baseline did not differ between men and women but by 8 wk was significantly decreased in women and unchanged in men. Our findings indicate that men may require larger dosages of angiotensin receptor blocker than do women and that the BP response cannot be used as a surrogate marker for adequate RAS blockade of the renal microvasculature.

背景与目标： : 证据表明，肾素-血管紧张素系统 (RAS) 功能存在性别差异。据推测，女性对RAS封锁的反应也可能有所不同。在男性和女性中检查了对血管紧张素受体阻滞剂增量剂量的肾脏和外周血液动力学反应以及在8周期间实现的血管紧张素II (AngII) 不敏感性程度。参与者是30名年轻的健康男性 (n = 15; 平均年龄27/- 2) 和女性 (n = 15; 平均年龄28/- 2)，他们在每次研究前接受钠和蛋白质饮食控制1周。评估了对递增剂量的厄贝沙坦 (75 mg，4 wk，然后150 mg，4 wk) 的体液，肾脏和全身反应，以及对AngII的升压反应 (3 ng/kg/min) 间隔2-wk。通过实时PCR方案在基线和8周后评估皮肤活检中的AngII 1型受体表达。男性和女性的血压都明显下降。与较低剂量的男性相比，女性的AngII敏感性显着降低，在4 wk 75 mg/d厄贝沙坦时没有升压反应，而男性在4 wk 150 mg/d时继续表现出升压反应。基线时，男女之间的受体表达没有差异，但到8周时，女性显着降低，而男性则没有变化。我们的发现表明，男性可能比女性需要更大剂量的血管紧张素受体阻滞剂，并且BP反应不能用作适当的RAS阻断肾微血管的替代指标。

BACKGROUND & AIMS: :In this issue of Immunity, Bezbradica et al., (2006) uncover an unsuspected role for the cytokine GM-CSF in the thymic development of invariant NKT cells, a role that licenses these cells to secrete effector cytokines upon activation in the periphery.

背景与目标： : 在本期《免疫》中，bezbratica等人 (2006) 揭示了细胞因子gm-csf在不变NKT细胞的胸腺发育中不可怀疑的作用，该作用允许这些细胞在外围激活时分泌效应细胞因子。

BACKGROUND & AIMS: BACKGROUND/AIMS:Apoptosis has been implicated in the pathogenesis of fulminant hepatic failure (FHF) potentially involving caspases. Thus far, apoptosis in FHF has mainly been studied in animal models while human data are sparse. METHODS:Caspases-3, -8 and -9 activities and Fas expression were analyzed in correlation to TdT-mediated dUTP nick end labelling (TUNEL) positive apoptotic cells in livers of patients with FHF (n=26), chronic liver disease (CLD) (n=60) and normal controls (NC) (n=10). RESULTS:Numbers of TUNEL-positive cells were higher in FHF than in CLD and NC (P<0.001) correlating to the intrahepatic activities of caspase-3. The highest caspase-3 activities were found in fulminant hepatitis B, significantly surpassing those in FHF of any other etiology. In fulminant hepatitis B, caspase-9 activity was also higher than in controls, while caspase-8 activation was not higher than in NC. Unlike caspase-3, caspases -8 and -9 activities were not correlated to the numbers of TUNEL positive cells. Fas expression was also the highest in FHF but did not differ between hepatitis B virus-FHF and other FHF. CONCLUSIONS:Our data indicate differential activation of intrahepatic caspases in FHF depending on the underlying etiology. Massive activation of caspases in fulminant hepatitis B confirms a pivotal role of apoptotic pathways in the pathogenesis of human fulminant hepatitis B.

背景与目标：

BACKGROUND & AIMS: AIM:To identify the changes of mitochondrial protein expression in diabetic renal parenchyma and to characterize their molecular functions and biological processes in diabetes. METHODS:Mitochondrial proteins extracted from renal parenchyma mitochondria of streptozotocin-induced diabetic rats and normal rats were separated by two-dimensional polyacrylamide gel electrophoresis and identified by matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry. RESULTS:Eleven proteins from 533 visualized protein spots displayed significant different expressions in mitochondria of diabetic kidneys compared with those in normal ones. Among these altered proteins, two proteins with the most obvious changes in protein expression were identified as alpha-2u globulin (mature protein, named A2) and its proteolytically modified form (named A2-fragment) respectively. These proteins were found in mitochondria of male rat renal parenchyma and were proved to be down-regulated in diabetic rats simultaneously. CONCLUSION:Our results suggest that down-regulation of alpha-2u globulin may be associated with an abnormal β-oxidation of long-chain fatty acids during diabetes. The decreased expression of A2-fragment in renal mitochondria of diabetic nephropathy may reduce fatty acid β-oxidation, which leads to a diminished energy supply from mitochondria to kidney tissue and the deposition of a large number of fatty acids in the kidney, ultimately causing and aggravating kidney damage. In conclusion, these findings may be helpful for understanding the molecular mechanism of diabetic nephropathy.

背景与目标：

BACKGROUND & AIMS: :Statistics on treatment rates for patients with end stage renal disease (ESRD) show that the number of ESRD patients per million population in the United Kingdom has increased slowly in recent years. The British Transplantation Society issued questionnaires in 1983 and 1984 to determine the number of patients transplanted, the number of suitable patients, and the facilities needed to enable all suitable patients to receive treatment. While there is a high transplant rate, the percentage of ESRD patients on dialysis is low, and there is a "socially unacceptable deficit" with respect to treatment of diabetics and the elderly.

背景与目标： : 有关终末期肾病 (ESRD) 患者治疗率的统计数据表明，英国每百万人口中ESRD患者的数量近年来增长缓慢。英国移植学会1983年和1984发放了问卷，以确定移植的患者人数、合适的患者人数以及使所有合适的患者都能接受治疗所需的设施。尽管移植率很高，但接受透析的ESRD患者的百分比却很低，并且在糖尿病患者和老年人的治疗方面存在 “社会上不可接受的缺陷”。

BACKGROUND & AIMS: BACKGROUND:This retrospective study investigated overall survival (OS) and factors influencing OS in Swedish patients with metastatic renal cell carcinoma (mRCC) during the pre- (2002-2005), early (2006-2008), and late (2009-2012) targeted therapy (TT) era. METHODS:Three national Swedish registries identified patients with mRCC. Median OS was estimated using the Kaplan-Meier method. Multivariate analysis was performed using Cox proportional hazards regression. Subgroup analysis was conducted for patients with synchronous metastases (M1) and the elderly (aged≥75y). RESULTS:A total of 4,217 patients with mRCC were identified, including 1,533 patients with M1 and 1,275 elderly patients. For patients with mRCC diagnosed in 2002 to 2005, 2006 to 2008, and 2009 to 2012, median OS was 10.0, 13.0, and 18.0 months. Similarly, median OS improved in the M1 and elderly populations. Elderly patients were less likely to be prescribed TT (≥75 vs.<75y): 18.3 vs. 63.5% (in 2006-2008) and 28.6% vs. 55.9% (in 2009-2012). Diagnosis of mRCC in 2009 to 2012, nephrectomy and TT prescription were associated with improved OS in the total mRCC, M1, and elderly populations. CONCLUSION:This real-world study showed continued significant improvement in mRCC OS during the late TT era, including in M1 and elderly populations. TT should be considered for all patients with mRCC based on tolerability, regardless of age.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:Conventional hemodialysis (HD) predominates over peritoneal dialysis (PD) around the world. Prospective and comparative studies comparing the costs of these modalities are scarce. In the present prospective assessment, we describe the resources used and total patient costs for both HD and PD. ♢ METHODOLOGY:We assessed 249 patients on HD and 228 on PD. All patients were 18 years of age or older and on stable dialysis. The information was collected at three points over 1 year, using standard questionnaires. The sources for costs were the Brazilian public and private health care systems. Societal perspective was considered. ♢ STATISTICAL ANALYSIS:Core trends and dispersions were measured. Regression models assessed the impact of modality on the average total cost per patient per year. ♢ RESULTS:Of the 249 HD patients and 228 PD dialysis patients, 189 (74%) and 160 (70%) respectively completed follow-up. The mean age for women was 55.8 years; for men, it was 59.8 years (p = 0.001). The average total cost per patient-year was US$28 570 for HD and US$27 158 for PD. By category, the costs consisted of direct medical-hospital costs (82.3% for HD, 86.5% for PD), direct nonmedical costs (5.3% for HD, 3.7% for PD), and indirect costs (12.4% for HD, 9.8% for PD). Overall costs were less for PD patients than for their HD counterparts (p = 0.025). ♢ CONCLUSIONS:Maintenance dialysis represented the most important source of costs for both modalities; loss of productivity incurred significant costs. Future studies should contemplate the social consequences arising from each modality.

背景与目标：

BACKGROUND & AIMS: :Menyanthes trifoliata L. is used in Swedish traditional medicine for the treatment of inflammatory diseases of the kidney, e.g. glomerulonephritis. Earlier studies have shown that MtL increases glomerular filtration rate after renal reperfusion ischemia. This activity was suggested to be PAF-inhibitory since MtL also inhibited PAF-induced exocytosis in vitro on human neutrophils (IC(50) = 0.16 mg/ml). The present study further characterizes the anti-inflammatory properties of a rhizome decoction of this plant. MtL inhibited carrageenan-induced rat paw edema (ID(50) ≈ 1.7 g/kg p.o.) and ethyl phenylpropiolate-induced rat ear edema (32% at 2.0 g/kg p.o.) in a dose-dependent manner. Further studies revealed that MtL inhibited both fMLP-induced exocytosis (IC(50) = 0.16 mg/ml) and elastase activity (IC(50) = 0.16 mg/ml). According to these results it is likely that the activity shown in the PAF-test is at least partly due to an inhibition of elastase. MtL showed only minor hemolytic properties at the concentrations used in the PAF- and fMLP-tests, suggesting that the cells in these tests are undamaged. The decoction also inhibited the biosynthesis of LTB(4) (IC(50) ≈ 0.73 mg/ml) and prostaglandins (IC(50) = 0.37 mg/ml) in vitro in a concentration-dependent way. However, at concentrations where the decoction is active in the LTB(4)-test, it also possesses hemolytic properties.

背景与目标： : Menyanthes trifoliata L.在瑞典传统医学中用于治疗肾脏的炎症性疾病，例如肾小球肾炎。较早的研究表明，MtL会增加肾脏再灌注缺血后的肾小球滤过率。该活性被认为是PAF抑制的，因为MtL还抑制了PAF诱导的人嗜中性粒细胞的胞吐作用 (IC(50) = 0.16 mg/ml)。本研究进一步表征了该植物根茎汤的抗炎特性。MtL以剂量依赖性方式抑制角叉菜胶诱导的大鼠爪子水肿 (ID(50) ≈ 1.7g/kg p.o.) 和苯基丙醇酸乙酯诱导的大鼠耳水肿 (32% 2.0g/kg p.o.)。进一步的研究表明，MtL抑制fMLP诱导的胞吐作用 (IC(50) = 0.16 mg/ml) 和弹性蛋白酶活性 (IC(50) = 0.16 mg/ml)。根据这些结果，PAF测试中显示的活性可能至少部分归因于弹性蛋白酶的抑制。在PAF和fMLP测试中使用的浓度下，MtL仅显示出较小的溶血特性，这表明这些测试中的细胞未受损。该汤剂还以浓度依赖性方式抑制体外LTB(4) (IC(50) ≈ 0.73 mg/ml) 和前列腺素 (IC(50) = 0.37 mg/ml) 的生物合成。然而，在汤在LTB(4)-测试中具有活性的浓度下，它也具有溶血特性。