Nephrons

肾单位
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  • 文章类型: Journal Article
    目的:本研究旨在为保留肾单位手术(NSS)的不同手术方法的比较疗效提供有价值的见解,并为该领域的现有文献做出贡献。
    方法:本研究包括2016年1月至2024年3月期间因肾脏小肿块而接受NSS的患者。共97例(开放入路组41例,腹腔镜入路组中56例),带有人口学,放射学,术中,肾功能,并纳入肿瘤随访数据.三种不同的解剖评分系统(R.E.N.A.L.肾脏评分,PADUA评分和C指数)用于评估肿瘤位置并估计与肺门和收集系统的接近度。
    结果:在开放保留肾单位手术(ONSS)和腹腔镜保留肾单位手术(LNSS)组中,平均肾脏肿瘤直径(SD)分别为5.20±2.30和4.90±2.10,这在两个手术方法组中相似(p=0.061)。然而,用ONSS治疗的肿瘤具有明显更多的不良形态特征(p<0.05)。对于ONSS和LNSS组,平均R.E.N.A.L.肾脏测量评分(SD)分别为6.15±2.04和5.2±1.4(p=0.032),平均PADUA评分(SD)分别为7.46±1.14和6.8±1.0(p=0.049),C指数(SD)得分分别为1.39±0.4和1.37±0.5(p=0.062),分别。两组的平均肿瘤直径(cm)(分位数范围(IQR))分布均未发现显着差异(p=0.058)。尽管LNSS组的输血率略有增加,估计失血量(EBL),输血率,两组的住院时间相似.
    结论:尽管LNSS在术中失血方面并不明显,住院时间和输血率,它提供了与ONSS相当的长期结果。我们的研究表明,当与肾病评分相匹配时,LNSS可以实现与ONSS类似的结果。
    OBJECTIVE: This study aimed to provide valuable insights into the comparative efficacy of different surgical approaches for nephron-sparing surgery (NSS) and contribute to the existing literature in this field.
    METHODS: This study included patients who underwent NSS for small renal masses between January 2016 and March 2024. A total of 97 patients (41 in the open approach group, 56 in the laparoscopic approach group) with demographic, radiological, intraoperative, renal functional, and oncological follow-up data were included. Three different anatomical scoring systems (R.E.N.A.L. nephrometry score, PADUA score and C-index) were utilised to assess tumour location and estimate proximity to the hilum and collecting system.
    RESULTS: In the open nephron-sparing surgery (ONSS) and laparoscopic nephron-sparing surgery (LNSS) groups, the mean kidney tumour diameters (SD) were 5.20 ± 2.30 and 4.90 ± 2.10, which were similar in both surgical method groups (p = 0.061). However, tumours treated with ONSS had significantly more adverse morphometric features (p < 0.05). For ONSS and LNSS groups, the mean R.E.N.A.L. nephrometry scores (SD) were 6.15 ± 2.04 and 5.2 ± 1.4 (p = 0.032), respectively; The mean PADUA scores (SD) were 7.46 ± 1.14 and 6.8 ± 1.0 (p = 0.049), respectively; And the mean C-index (SD) scores were 1.39 ± 0.4 and 1.37 ± 0.5 (p = 0.062), respectively. No significant differences were found in the mean tumour diameter (cm) (Inter Quantile Range (IQR)) distribution of both groups (p = 0.058). Despite the slight increase in transfusion rate in the LNSS group, estimated blood loss (EBL), transfusion rates, and length of hospital stay were similar in both groups.
    CONCLUSIONS: Although LNSS does not appear superior in terms of intraoperative blood loss, length of hospital stay and transfusion rate, it provides comparable long-term outcomes to ONSS. Our study suggests that when matched with nephrometry scores, LNSS can achieve similar outcomes to ONSS.
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  • 文章类型: Journal Article
    髓质中的肾单位环-血管逆流排列为浓缩尿液的形成提供了结构基础。迄今为止,它的形态发生以及相关的水和溶质运输尚未完全阐明。在这项研究中,对水通道蛋白(AQP)和Na-K-2Cl协同转运蛋白(NKCC2)进行免疫组织化学,以及3D可视化,在胚胎第14.5天的肾脏中,我们注意到,一旦环和血管都延伸到延髓中,就建立了两对环血管的逆流排列。一对发生在下行肢体和上行血管直肠之间,另一种发生在粗大的上行肢体和下行血管直肠之间。同时,免疫组化结果显示,表达AQP-1的肢体和血管如下降的粗细肢体和下降的直肠血管总是伴随着AQP-1阴性的上升的直肠血管或毛细血管和粗大的上升肢体,分别。此外,表达NKCC2的粗大的上升肢体与不表达NKCC2的下降直肠血管紧密接触。随着肾脏的发育,逆流排列的环形血管越来越多地延伸到髓质间质。此外,我们观察到AQP-2阳性输尿管芽及其分支通过相对较大且薄壁的静脉或毛细血管与这些对小管血管分开。因此,本研究表明,循环血管逆流排列是在肾脏发生的早期形成的,这有利于水和电解质的有效运输,以维持髓质渗透压并形成浓缩尿液。
    Nephron loop-vessel countercurrent arrangement in the medulla provides the structural basis for the formation of concentrated urine. To date, the morphogenesis of it and relevant water and solutes transportation has not been fully elucidated. In this study, with immunohistochemistry for aquaporins (AQP) and Na-K-2Cl co-transporter (NKCC2), as well as 3D visualization, we noticed in embryonic day 14.5 kidneys that the countercurrent arrangement of two pairs of loop-vessel was established as soon as the loop and vessel both extended into the medulla. One pair happened between descending limb and ascending vasa recta, the other occurred between thick ascending limb and descending vasa recta. Meanwhile, the immunohistochemical results showed that the limb and vessel expressing AQP-1 such as descending thick and thin limb and descending vasa recta was always accompanied with AQP-1 negative ascending vasa recta or capillaries and thick ascending limb, respectively. Moreover, the thick ascending limb expressing NKCC2 closely contacted with descending vasa recta without expressing NKCC2. As kidney developed, an increasing number of loop-vessels in countercurrent arrangement extended into the interstitium of the medulla. In addition, we observed that the AQP-2 positive ureteric bud and their branches were separated from those pairs of tubule-vessels by a relatively large and thin-walled veins or capillaries. Thus, the present study reveals that the loop-vessel countercurrent arrangement is formed at the early stage of nephrogenesis, which facilitates the efficient transportation of water and electrolytes to maintain the medullary osmolality and to form a concentrated urine.
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  • 文章类型: Journal Article
    肾肾单位中的ATP6AP2敲除会损害受体介导的内吞作用,增加尿白蛋白和葡萄糖排泄并损害体重增加。尿液中的非酯化脂肪酸(NEFA)与白蛋白结合,并通过megalin-cubilin复合物通过受体介导的内吞作用在近端小管中重新吸收。我们假设ATP6AP2敲除通过减少megalin增加尿NEFA排泄。对具有肾单位特异性诱导型ATP6AP2敲除和非诱导对照的10周龄雄性C57BL/6小鼠饲喂正常饮食(ND12%脂肪)或高脂肪饮食(HFD45%脂肪)6个月。ATP6AP2敲除显著增加ND和HFD饲喂小鼠的尿白蛋白:肌酸酐比率,而与各自的对照相比,ND和HFD敲除小鼠的归一化尿NEFA浓度增加489%和259%。敲除使ND和HFD的肾皮质megalinmRNA降低了47%,而megalin蛋白表达分别降低了36%和44%。同时,mTOR活性标志物增加,自噬受损.我们的结果表明,在受体介导的内吞作用受损的情况下,肾单位特异性ATP6AP2敲除会增加尿NEFA的排泄。进一步的研究应确定ATP6AP2是否有助于近端小管中肥胖相关的异位脂质沉积。
    ATP6AP2 knockout in the renal nephron impairs receptor-mediated endocytosis, increasing urinary albumin and glucose excretion and impairing weight gain. Nonesterified fatty acids (NEFA) in urine are bound to albumin and reabsorbed in the proximal tubule through receptor-mediated endocytosis by the megalin-cubilin complex. We hypothesized that ATP6AP2 knockout increases urinary NEFA excretion through a reduction in megalin. Ten-week-old male C57BL/6 mice with nephron specific inducible ATP6AP2 knockout and noninduced controls were fed either normal diet (ND 12% fat) or high fat diet (HFD 45% fat) for 6 months. ATP6AP2 knockout significantly increased urine albumin:creatinine ratio in both ND and HFD fed mice while normalized urine NEFA concentration increased 489% and 259% in ND and HFD knockout mice compared to respective controls. Knockout decreased renal cortical megalin mRNA by 47% on ND and 49% on HFD while megalin protein expression decreased by 36% and 44% respectively. At the same time, markers of mTOR activity were increased while autophagy was impaired. Our results indicate that nephron specific ATP6AP2 knockout increases urinary NEFA excretion in the setting of impaired receptor-mediated endocytosis. Further investigation should determine whether ATP6AP2 contributes to obesity related ectopic lipid deposition in the proximal tubule.
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  • 文章类型: Journal Article
    RNA结合蛋白LIN28A和LIN28B有助于多种发育生物学过程。Lin28A和Lin28B表达的失调与许多类型的肿瘤有关。这项研究表明,小鼠肾单位中Lin28A的过表达导致严重的炎症和肾脏损伤,而不是肿瘤发生。值得注意的是,Lin28A过表达仅在肾单位中表达时引起炎症,但不是在肾脏的基质细胞中,突出其细胞上下文相关的性质。肾单位特异性Lin28A诱导的炎症反应不同于先前描述的Lin28B介导的炎症反馈回路,因为它是IL-6非依赖性的。相反,它与Cxcl1和Ccl2等细胞因子的快速上调有关。这些发现表明,Lin28A过表达的病理生理作用超出了细胞转化。我们的转基因小鼠模型为提高我们对急性肾损伤病理生理学的理解提供了有价值的工具。炎症是一个关键因素。
    The RNA-binding proteins LIN28A and LIN28B contribute to a variety of developmental biological processes. Dysregulation of Lin28A and Lin28B expression is associated with numerous types of tumors. This study demonstrates that Lin28A overexpression in the mouse nephrons leads to severe inflammation and kidney damage rather than to tumorigenesis. Notably, Lin28A overexpression causes inflammation only when expressed in nephrons, but not in the stromal cells of the kidneys, highlighting its cell context-dependent nature. The nephron-specific Lin28A-induced inflammatory response differs from previously described Lin28B-mediated inflammatory feedback loops as it is IL-6 independent. Instead, it is associated with the rapid upregulation of cytokines like Cxcl1 and Ccl2. These findings suggest that the pathophysiological effects of Lin28A overexpression extend beyond cell transformation. Our transgenic mouse model offers a valuable tool for advancing our understanding of the pathophysiology of acute kidney injury, where inflammation is a key factor.
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  • 文章类型: Journal Article
    目的:探讨肾部分切除术(PN)与局部复发(LR)的相关性,非转移性肾细胞癌(nmRCC)患者的以人群为基础的全国性真实世界队列研究中的远处转移性复发(DMR)和全因死亡率.
    方法:在2005-2018年期间诊断出的2751例AT或PN治疗的nmRCC肿瘤的数据,代表2701例独特患者,是从瑞典国家肾癌登记册获得的。使用Cox回归模型分析LR/DMR或有/无LR/DMR的死亡时间。
    结果:在平均4.8年的随访中,观察到111例(4.0%)肿瘤的LR,108例(3.9%)肿瘤的DMR,206例(7.5%)肿瘤无LR/DMR死亡。与PN治疗相比,AT治疗的肿瘤发生LR的风险高4.31倍(P<0.001),DMR的风险高1.91倍(P=0.018),无LR/DMR的死亡风险无显著差异。在LR/DMR后平均3.2年和2.5年的随访中,分别,24例(21.6%)LR病例和56例(51.9%)DMR病例死亡,与无LR/DMR患者的7.5%相比。在LR或DMR发生后早期死亡的风险方面,AT和PN治疗之间没有显着差异。
    结论:AT治疗nmRCC患者意味着LR和DMR的风险明显高于PN治疗。为了将LR和DMR的风险降至最低,这些结果表明,PN优先于AT作为主要治疗,支持EAU指南,主要向虚弱和/或合并症患者推荐AT。
    OBJECTIVE: To examine associations between ablative therapy (AT) and partial nephrectomy (PN) and the occurrence of local recurrence (LR), distant metastatic recurrence (DMR) and all-cause mortality in a nation-wide real-world population-based cohort of patients with nonmetastatic renal cell carcinoma (nmRCC).
    METHODS: Data on 2751 AT- or PN-treated nmRCC tumours diagnosed during 2005-2018, representing 2701 unique patients, were obtained from the National Swedish Kidney Cancer Register. Time to LR/DMR or death with/without LR/DMR was analysed using Cox regression models.
    RESULTS: During a mean of 4.8 years follow-up, LR was observed for 111 (4.0%) tumours, DMR for 108 (3.9%) tumours, and death without LR/DMR for 206 (7.5%) tumours. AT-treated tumours had a 4.31 times higher risk of LR (P < 0.001) and a 1.91 times higher risk of DMR (P = 0.018) than PN-treated, with no significant differences in risk of death without LR/DMR. During a mean of 3.2 and 2.5 years of follow-up after LR/DMR, respectively, 24 (21.6%) of the LR cases and 56 (51.9%) of the DMR cases died, compared to 7.5% in patients without LR/DMR. There were no significant differences between AT- and PN-treated regarding risks of early death after occurrence of LR or DMR.
    CONCLUSIONS: AT treatment of patients with nmRCC implied significantly higher risks of LR and DMR compared with PN treatment. To minimize the risks of LR and DMR, these results suggest that PN is preferred over AT as primary treatment, supporting the EAU guidelines to recommended AT mainly to frail and/or comorbid patients.
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    文章类型: English Abstract
    目的:分析低恶性潜能多房性囊性肾肿瘤患者的临床病理特征及预后,并比较不同手术方式的低恶性潜能多房性囊性肾肿瘤患者的临床病理特征。
    方法:收集2010年1月至2023年9月北京大学第三医院收治的患者的临床病理资料及预后。确定了接受根治性肾切除术或保留肾单位手术并经病理诊断为低恶性潜能的多房性囊性肾肿瘤的患者。根据手术方法,将患者分为根治性肾切除术组和保留肾单位手术组。比较两组患者的临床病理特点。
    结果:本研究共纳入35例患者。诊断时的中位年龄为53.0(39.0-62.0)岁。在35名患者中,男性23人(65.7%),女性12人(34.3%)。9例患者接受根治性肾切除术(25.7%),26例患者接受了保留肾单位的手术(74.3%)。35例患者的临床T分期不超过T2a分期。中位手术时间为145.0min,估计术中失血量的中位数为20.0mL.术后住院天数中位数为6.0d,术后病理结果未见肾窦侵犯,肉瘤改变,肾上腺侵犯或淋巴结侵犯。根据手术方法,将患者分为根治性肾切除术组和保留肾单位手术组.两组患者临床病理特征差异无统计学意义。除了一名失去随访的病人,所有其他患者随访8-111个月,中位随访时间为70.5个月。只有一名患者死于非癌症特异性原因,其他患者无肿瘤转移或复发。
    结论:低恶性潜能的多房性囊性肾肿瘤患者预后良好。保留肾单位手术组和根治性肾切除术组对低恶性潜能的多房性囊性肾肿瘤患者的临床病理特征无明显差异。
    OBJECTIVE: To analyze the clinicopathological characteristics and prognosis of patients with multilocular cystic renal neoplasm of low malignant potential and compare the clinicopathological characteristics of patients with multilocular cystic renal neoplasm of low malignant potential who underwent different surgical methods.
    METHODS: Clinicopathological data and prognosis of patients admitted to Peking University Third Hospital from January 2010 to September 2023 were collected. Patients who underwent radical nephrectomy or nephron-sparing surgery and were pathologically diagnosed with multilocular cystic renal neoplasm of low malignant potential were identified. Based on the surgical methods, the patients were divided into radical nephrectomy group and nephron-sparing surgery group. The clinicopathological characteristics of the two groups were compared.
    RESULTS: A total of 35 patients were enrolled in this study. The median age at diagnosis was 53.0 (39.0-62.0) years. Among the 35 patients, 23 were males (65.7%) and 12 were females (34.3%). Nine patients underwent radical nephrectomy (25.7%), while 26 patients underwent nephron-sparing surgery (74.3%). The clinical T-stage of 35 patients did not exceed T2a stage. The median operation time was 145.0 min, and the median estimated intraoperative blood loss was 20.0 mL. The median postoperative hospitalization days was 6.0 d. The postoperative pathological results did not indicate renal sinus invasion, sarcomatous change, adrenal invasion or lymph node invasion. Based on the surgical methods, the patients were divided into a radical nephrectomy group and a nephron-sparing surgery group. There was no significant difference in clinicopathological charac-teristics between the two groups. Except for one patient who was lost to the follow-up, all the other patients were followed up for 8-111 months, with a median follow-up time of 70.5 months. Only one patient died from non-cancer-specific reasons, other patients had no tumor metastasis or recurrence.
    CONCLUSIONS: Patients with multilocular cystic renal neoplasm of low malignant potential have a good prognosis. There is no significant difference in clinicopathological characteristics of patients between nephron-sparing surgery group and radical nephrectomy group for multilocular cystic renal neoplasm of low malignant potential.
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  • 文章类型: Journal Article
    对正常细胞分化的破坏如何与肿瘤发生联系仍未完全了解。肾母细胞瘤,与器官发生破坏相关的胚胎性肿瘤,通常在表观遗传调节因子中存在突变,但它们在肾脏发育中的作用仍有待探索。这里,我们以单细胞分辨率显示,组蛋白乙酰化读数器ENL中的Wilms肿瘤相关突变通过重新连接基因调控格局破坏小鼠肾脏分化.突变体ENL促进肾单位祖细胞的承诺,同时通过失调转录因子如Hox簇限制其分化。它还诱导失去肾脏相关染色质同一性的异常祖细胞。此外,突变型ENL改变了基质祖细胞的转录组和染色质可及性,导致Wnt信号的过度激活。突变型ENL对肾单位和基质谱系的影响导致小鼠严重的肾脏发育缺陷和出生后死亡。值得注意的是,抑制突变体ENL的组蛋白乙酰化结合活性的小分子在很大程度上逆转了这些缺陷。这项研究提供了有关表观遗传调节因子突变如何破坏肾脏发育的见解,并提出了一种潜在的治疗方法。
    How disruptions to normal cell differentiation link to tumorigenesis remains incompletely understood. Wilms tumor, an embryonal tumor associated with disrupted organogenesis, often harbors mutations in epigenetic regulators, but their role in kidney development remains unexplored. Here, we show at single-cell resolution that a Wilms tumor-associated mutation in the histone acetylation reader ENL disrupts kidney differentiation in mice by rewiring the gene regulatory landscape. Mutant ENL promotes nephron progenitor commitment while restricting their differentiation by dysregulating transcription factors such as Hox clusters. It also induces abnormal progenitors that lose kidney-associated chromatin identity. Furthermore, mutant ENL alters the transcriptome and chromatin accessibility of stromal progenitors, resulting in hyperactivation of Wnt signaling. The impacts of mutant ENL on both nephron and stroma lineages lead to profound kidney developmental defects and postnatal mortality in mice. Notably, a small molecule inhibiting mutant ENL\'s histone acetylation binding activity largely reverses these defects. This study provides insights into how mutations in epigenetic regulators disrupt kidney development and suggests a potential therapeutic approach.
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  • 文章类型: Journal Article
    1型Bartter综合征和Gitelman综合征的特征是两个关键肾Na+转运蛋白的突变,Na-K-2Cl协同转运蛋白(NKCC2)和Na-Cl协同转运蛋白(NCC)。由于这两种转运蛋白在调节肾脏中的镁(Mg2+)和钙(Ca2+)转运中起重要作用,在1型Bartter综合征和Gitelman综合征中观察到这两种电解质的运输发生了显着变化。在这项研究中,我们使用了大鼠肾脏电解质转运的性别特异性计算模型来理解复杂的代偿机制,就管状尺寸和离子转运活动的变化而言,在这两种遗传疾病中导致Mg2和Ca2保留或浪费。鉴于肾转运蛋白模式的性二态性,我们还评估了这些改变的程度在男性和女性之间的差异。模型模拟显示,在1型Bartter综合征中,肾单位适应可防止盐浪费,有利于Mg2+保存,但不有利于Ca2+保存,而在Gitelman综合征中,这些适应有利于Ca2+保存,而不是Mg2+保存。此外,我们的模型预测,女性的肾小管尺寸和离子转运蛋白活性的补偿性改变比男性更强。
    Type 1 Bartter\'s syndrome and Gitelman\'s syndrome are characterized by mutations in two key renal Na+ transporters, Na-K-2Cl cotransporter (NKCC2) and Na-Cl cotransporter (NCC). Since these two transporters play an important role in regulating magnesium (Mg2+) and calcium (Ca2+) transport in the kidney, significant alterations in the transport of these two electrolytes are observed in type 1 Bartter\'s syndrome and Gitelman\'s syndrome. In this study, we used our sex-specific computational models of renal electrolyte transport in rats to understand the complex compensatory mechanisms, in terms of alterations in tubular dimensions and ion transporter activities, that lead to Mg2+ and Ca2+ preservation or wasting in these two genetic disorders. Given the sexual dimorphism in renal transporter patterns, we also assessed how the magnitude of these alterations may differ between males and females. Model simulations showed that in type 1 Bartter\'s syndrome, nephron adaptations prevent salt wasting and favor Mg2+ preservation but not Ca2+, whereas in Gitelman\'s syndrome, those adaptations favor Ca2+ preservation over Mg2+. In addition, our models predicted that the compensatory alterations in tubular dimensions and ion transporter activities are stronger in females than in males.NEW & NOTEWORTHY Although changes in Ca2+ excretion in type 1 Bartter\'s syndrome and Gitelman\'s syndrome are well understood, Mg2+ excretion displays an interesting paradox. This computational modeling study provides insights into how renal adaptations in these two disorders impact Ca2+ and Mg2+ transport along different nephron segments. Model simulations showed that nephron adaptations favor Mg2+ preservation over Ca2+ in Bartter\'s syndrome and Ca2+ preservation over Mg2+ in Gitelman\'s syndrome and are stronger in females than in males.
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