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Commentary on "Machine learning constructs a diagnostic prediction model for Calculous Pyophrosis". 关于 "机器学习构建结石性脓病诊断预测模型 "的评论。
IF 2 2区 医学 Q2 UROLOGY & NEPHROLOGY Pub Date : 2024-10-07 DOI: 10.1007/s00240-024-01646-4
Xin Chang Zou, Rong Man Yuan, Tao Zeng
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引用次数: 0
Heatwave and upper urinary tract stones morbidity: effect modification by heatwave definitions, disease subtypes, and vulnerable populations. 热浪与上尿路结石发病率:热浪定义、疾病亚型和易感人群的效应修正。
IF 2 2区 医学 Q2 UROLOGY & NEPHROLOGY Pub Date : 2024-10-03 DOI: 10.1007/s00240-024-01619-7
Chenlu Yang, Shi Li, Yunmeng Yang, Cunrui Huang, Yike Li, Chaoming Tan, Junzhe Bao

As heatwave occurs with increased frequency and intensity, the disease burden for urolithiasis, a heat-specific disease, will increase. However, heatwave effect on urolithiasis subtypes morbidity and optimal heatwave definition for urolithiasis remain unclear. Distributed lagged linear models were used to assess the associations between 32 defined heatwave and upper urinary tract stones morbidity. Relative risk (RR) and attributable fraction (AF) of upper urinary tract stone morbidity associated with heatwave of different intensities (low, middle, and high) were pooled by meta-analysis. Optimal heatwave definition was selected based on the combined score of AF, RR, and quasi-Akaike Information Criterion (QAIC) value. Stratified analyses were conducted to investigate the modification effects of gender, age, and disease subtypes. Association between heatwave and upper urinary tract stones morbidity was mainly for ureteral calculus, and AF was highest for low-intensity heatwave. This study's optimal heatwave was defined as average temperature > 93rd percentile for ≥ 2 consecutive days, with AF of 7.40% (95% CI: 2.02%, 11.27%). Heatwave was associated with ureteral calculus morbidity in males and middle-aged adults. While heatwave effect was statistically insignificant in females and other age groups. Managers should develop appropriate definitions to address heatwave based on regional characteristics and focus on heatwave effects on urolithiasis.

随着热浪出现的频率和强度的增加,泌尿系结石这种高温特异性疾病的疾病负担也会增加。然而,热浪对泌尿系结石亚型发病率的影响以及泌尿系结石的最佳热浪定义仍不清楚。我们采用分布式滞后线性模型来评估 32 个定义热浪与上尿路结石发病率之间的关系。通过荟萃分析汇集了与不同强度(低、中、高)热浪相关的上尿路结石发病率的相对风险(RR)和可归因分数(AF)。根据AF、RR和准阿卡伊克信息准则(QAIC)值的综合评分,选择了最佳热浪定义。进行了分层分析,以研究性别、年龄和疾病亚型的调节作用。热浪与上尿路结石发病率之间的关系主要与输尿管结石有关,而低强度热浪的AF值最高。本研究的最佳热浪定义为连续两天平均气温大于第93百分位数,AF为7.40%(95% CI:2.02%,11.27%)。热浪与男性和中年人的输尿管结石发病率有关。而热浪对女性和其他年龄组的影响在统计学上并不显著。管理人员应根据地区特点制定适当的热浪定义,并重点关注热浪对泌尿系结石的影响。
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引用次数: 0
Two distinct phenotypes of calcium oxalate stone formers could imply different long-term risks for renal function. 草酸钙结石形成者的两种不同表型可能意味着对肾功能的长期风险不同。
IF 2 2区 医学 Q2 UROLOGY & NEPHROLOGY Pub Date : 2024-09-28 DOI: 10.1007/s00240-024-01631-x
James C Williams, William S Bowen, James E Lingeman, Marcelino Rivera, Elaine M Worcester, Tarek M El-Achkar

Endoscopic and biopsy findings have identified two distinct phenotypes among individuals with calcium oxalate (CaOx) kidney stones. The first type has normal renal papillae but shows interstitial mineral deposition, known as Randall's plaque. The other phenotype presents with collecting duct plugging and a higher incidence of loss of papilla tissue mass. With Randall's plaque, renal papilla injury involves the loss of small patches of calcified tissue (Randall's plaque detaching with the stone), which likely results in damage to only a few nephrons. In contrast, collecting duct mineral plugs are very large, causing obstruction to tubular flow. Since each terminal collecting duct drains thousands of nephrons, ductal plugs could lead to the degeneration of many nephrons and a significant loss of renal glomeruli. New visualization techniques for immune cells in papillary biopsies have revealed that the Randall's plaque phenotype is marked by the accumulation of macrophages around the plaque regions. In contrast, preliminary data on the plugging phenotype shows collecting duct damage with mineral plugs and increased T-lymphocytes throughout the papilla. These regions also show tubulitis, i.e., T-cell infiltration into nearby collecting duct epithelium. This suggests that while some CaOx stone formers may have some papillary inflammation but with minimal damage to nephrons, others suffer from obstruction to flow for many nephrons that may also include destructive inflammation in the renal tissue. We propose that CaOx stone formers with the plugging phenotype will have a higher long-term risk for loss of renal function.

内窥镜和活检结果发现,草酸钙(CaOx)肾结石患者有两种不同的表型。第一种表型的肾乳头正常,但出现间质矿物质沉积,即所谓的兰德尔斑块。另一种表型则表现为集合管堵塞,乳头组织肿块脱落的发生率较高。对于兰德尔斑块,肾乳头损伤包括小块钙化组织的脱落(兰德尔斑块与结石一起脱落),这可能只导致少数肾小球受损。与此相反,集合管矿物质塞非常大,会导致肾小管血流受阻。由于每个末端集合管都会引流数千个肾小球,因此导管堵塞可能会导致许多肾小球退化和肾小球的大量丧失。乳头活检中免疫细胞的新可视化技术显示,兰德尔斑块表型的特征是斑块区域周围巨噬细胞的聚集。与此相反,关于堵塞表型的初步数据显示,集合管受损,整个乳头出现矿物质堵塞和 T 淋巴细胞增多。这些区域还显示出小管炎,即 T 细胞浸润到附近的集合管上皮。这表明,一些氧化钙结石形成者可能有一些乳头炎症,但对肾小球的损害很小,而另一些结石形成者则有许多肾小球的血流受阻,可能还包括肾组织中的破坏性炎症。我们认为,具有堵塞表型的氧化钙结石形成者长期丧失肾功能的风险较高。
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引用次数: 0
Non-invasive approaches to hydration assessment: a literature review. 无创水合评估方法:文献综述。
IF 2 2区 医学 Q2 UROLOGY & NEPHROLOGY Pub Date : 2024-09-26 DOI: 10.1007/s00240-024-01630-y
Achraf Tahar, Hadil Zrour, Stéphane Dupont, Agnieszka Pozdzik

Traditional hydration assessment methods, while accurate, are often invasive and impractical for routine monitoring. In response, innovative non-invasive techniques such as bioelectrical impedance analysis (BIA), electrodermal activity (EDA), electrocardiogram (ECG) monitoring, and urine color charts have emerged, offering greater comfort and accessibility for patients. These methods use various types of sensors to capture a range of bio-signals, followed by machine learning-based classification or regression methods, providing real-time feedback on hydration status, which is crucial for effective management and prevention of urinary stones. This review explores the principles, applications, and efficacy of these non-invasive techniques, highlighting their potential to transform hydration monitoring in clinical and everyday settings. By facilitating improved patient compliance and enabling proactive hydration management, these approaches align with contemporary trends in personalized healthcare. This article presents a literature review on non-invasive approaches to hydration assessment, focusing on their significance in preventing kidney stone disease and enhancing kidney health.

传统的水合评估方法虽然准确,但往往具有侵入性,不适合常规监测。为此,生物电阻抗分析 (BIA)、皮肤电活动 (EDA)、心电图 (ECG) 监测和尿液色谱等创新的非侵入性技术应运而生,为患者提供了更舒适、更方便的监测。这些方法使用各种类型的传感器捕捉一系列生物信号,然后采用基于机器学习的分类或回归方法,提供有关水合状态的实时反馈,这对于有效管理和预防泌尿系统结石至关重要。本综述探讨了这些非侵入性技术的原理、应用和功效,强调了它们改变临床和日常环境中水合监测的潜力。这些方法有助于提高患者的依从性并实现主动水合管理,符合当代个性化医疗保健的发展趋势。本文对水合评估的非侵入性方法进行了文献综述,重点介绍了这些方法在预防肾结石疾病和增强肾脏健康方面的意义。
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引用次数: 0
Ultrathin semirigid retrograde ureteroscopy versus antegrade flexible ureteroscopy in treating proximal ureteric stones 1–2 cm, a prospective randomized multicenter study 超薄半刚性逆行输尿管镜与前向柔性输尿管镜在治疗 1-2 厘米输尿管近端结石中的对比,一项前瞻性随机多中心研究
IF 3.1 2区 医学 Q2 UROLOGY & NEPHROLOGY Pub Date : 2024-09-19 DOI: 10.1007/s00240-024-01626-8
Tarek Mohamed Gharib, Ibrahim Abdel-Al, Basheer N. Elmohamady, Hazem Deif, Ahmed Abdelazim Haty, Salah E. Shebl, Omar Safar, Gamal M. Hassan, Yasser M. Haggag, Adel Elatreisy

To compare the outcomes of using Ultrathin semirigid retrograde ureteroscopy and antegrade flexible ureteroscopy to treat proximal ureteric stones of sizes 1–2 cm. A prospective randomized multicenter study included patients who had proximal ureteric stones 1–2 cm, amenable for ureteroscopy and laser lithotripsy between August 2023 and February 2024. Two hundred thirty patients were divided evenly into two treatment groups. Group I included patients treated with antegrade flexible ureteroscopy and holmium laser stone fragmentation, and Group II included patients treated with retrograde ultrathin semirigid ureteroscopy. The study groups were compared in terms of patient demographics, stone access success, operation time, reoperation rates, peri-operative complications, and stone-free status. Group I included 114 patients, while Group II included 111. The mean age of the patients was 33.92 ± 10.37 years, and the size of the stones was 15.88 ± 3 mm. The study groups had comparable demographics and stone characteristics. The mean operative time was significantly longer in group I than in group II (102.55 ± 72.46 min vs. 60.98 ± 14.84 min, respectively, P < 0.001). Most reported complications were MCCS grades I and II, with no significant difference between the study groups. The stone-free rate after four weeks was 92.1% and 81.1% for groups I and II, respectively, which increased to 94.7% and 85.6% after eight weeks (P > 0.05). Antegrade flexible ureteroscopy is equivalent to retrograde ultrathin semirigid ureteroscopy in treating proximal ureteric stones regarding stone-free status and procedure-related morbidity. However, the antegrade approach has a longer operative time, greater fluoroscopy exposure, and longer hospital stays.

比较使用超薄半硬性逆行输尿管镜检查和前向柔性输尿管镜检查治疗1-2厘米大小的输尿管近端结石的效果。这项前瞻性随机多中心研究纳入了 2023 年 8 月至 2024 年 2 月间患有输尿管近端结石(1-2 厘米)、可接受输尿管镜检查和激光碎石的患者。2300 名患者被平均分为两个治疗组。I 组包括接受前行柔性输尿管镜检查和钬激光碎石治疗的患者,II 组包括接受逆行超细半硬性输尿管镜检查的患者。研究组在患者人口统计学、取石成功率、手术时间、再次手术率、围手术期并发症和无结石状态等方面进行了比较。第一组包括 114 名患者,第二组包括 111 名患者。患者的平均年龄为(33.92±10.37)岁,结石大小为(15.88±3)毫米。研究组的人口统计学和结石特征相当。第一组的平均手术时间明显长于第二组(分别为 102.55 ± 72.46 分钟对 60.98 ± 14.84 分钟,P < 0.001)。大多数报告的并发症为 MCCS I 级和 II 级,研究组之间无明显差异。I组和II组四周后的无结石率分别为92.1%和81.1%,八周后分别增至94.7%和85.6%(P > 0.05)。就无结石状态和手术相关发病率而言,前向柔性输尿管镜检查与逆行超细半硬性输尿管镜检查治疗近端输尿管结石的效果相当。不过,前向方法的手术时间更长、透视暴露更大、住院时间更长。
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引用次数: 0
Comparison of cat stone matrix and cat urine proteomes to human calcium oxalate stone matrix and urine proteomes 猫结石基质和猫尿蛋白质组与人类草酸钙结石基质和尿蛋白质组的比较
IF 3.1 2区 医学 Q2 UROLOGY & NEPHROLOGY Pub Date : 2024-09-13 DOI: 10.1007/s00240-024-01629-5
Jeffrey A. Wesson, Roman Zenka, Katherine Sherman, Jessica Eisenhauer, Jody Lulich, Carley Davis

Cat calcium oxalate monohydrate kidney stone matrix proteome showed great similarity to human calcium oxalate monohydrate stone matrix proteome, but inference of mechanistic similarity was limited by the absence of cat urine proteomic data. In this study, urine proteome distributions were measured by the same methods in 7 healthy cats for comparison to both the published human urine and cat calcium oxalate stone matrix proteomes to assess for similar enrichment patterns in both species. Furthermore, proteomic distributions were determined in cat struvite stone matrix to test for similarity to calcium oxalate monohydrate stone matrix and urine proteomes. Cat urine proteins demonstrated a similar distribution of abundance as a function of isoelectric points or net charge to human urine samples, and consequently the similarly altered patterns of protein distributions seen in calcium oxalate monohydrate stone matrix seen from both cat and human stones likely derives from the same preferential adsorption mechanism. Furthermore, the fact that protein abundance patterns seen in cat struvite stone matrix samples differ from both urine and calcium oxalate monohydrate stone matrix proteomes in systematic ways suggests that a combination of protein–protein and protein crystal interactions underly the formation of the crystal aggregates that comprise stones.

猫的一水草酸钙肾结石基质蛋白质组与人的一水草酸钙结石基质蛋白质组非常相似,但由于缺乏猫尿液蛋白质组数据,对机理相似性的推断受到了限制。本研究采用相同的方法测定了 7 只健康猫的尿液蛋白质组分布,与已发表的人类尿液蛋白质组和猫草酸钙结石基质蛋白质组进行比较,以评估这两个物种是否存在相似的富集模式。此外,还测定了猫结石基质中的蛋白质组分布,以检验与一水草酸钙结石基质和尿液蛋白质组的相似性。根据等电点或净电荷的函数,猫尿液蛋白质的丰度分布与人类尿液样本相似,因此,在猫和人类结石的一水草酸钙结石基质中看到的蛋白质分布模式的类似改变可能源自相同的优先吸附机制。此外,猫结石基质样本中的蛋白质丰度模式与尿液和一水草酸钙结石基质蛋白质组存在系统性差异,这一事实表明,结石晶体聚集体的形成是蛋白质-蛋白质和蛋白质晶体相互作用的综合结果。
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引用次数: 0
Analyzing learning curve for supine percutaneous nephrolithotomy in urology resident training programme: comparative analysis. 分析泌尿科住院医师培训课程中仰卧位经皮肾镜取石术的学习曲线:对比分析。
IF 2 2区 医学 Q2 UROLOGY & NEPHROLOGY Pub Date : 2024-09-09 DOI: 10.1007/s00240-024-01624-w
Yusuf Arıkan, Yavuz Onur Danacioğlu, Deniz Noyan Özlü, Ömer Koraş, Büşra Emir, Mehmet Zeynel Keskin

Introduction: This article attempts to provide a comprehensive review of the learning objectives and importance of the supine percutaneous nephrolithotomy (PCNL) technique.

Material method: We retrospectively reviewed the cases of Supine PCNL between January 2018 and January 2024. We divided the groups into 3: residents between 2 and 3 years (Group 1), residents between 4 and 5 years (Group 2), and endourologist (Group 3). The 2-3-year resident started to perform PCNL for the first time, while the 4-5-year resident started to perform Supine PCNL for the first time while previously performing prone PCNL.

Results: Access, fluoroscopy, and operation time were higher in Group 1, shorter in Group 2, and shortest in Group 3 (p < 0.001). Postoperative length of stay and the need for additional treatment were found to be shorter (p < 0.001), and the stone-free rate (SFR) increased (p < 0.001) from Group 1 to Group 3. The highest complication rates were observed in Group 1 (p = 0.002). SFR rate increased as the number of cases increased in Group 1 patients. Success was stable after 46-60 cases in terms of SFR. In Group 2, the SFR rate was stable after 31-45.

Cases: The most complications were observed in Group 1 and the least in Group 3.

Conclusion: In 2-3-year residents, access time and fluoroscopy time decrease with experience. In 4-5-year residents, due to their expertise in prone PCNL, the operation time and fluoroscopy time decrease with the number of cases performed. SFR is higher after 46-60 cases for 2-3-year residents and 31-45 cases for 4-5-year residents.

简介:本文试图对仰卧位经皮肾镜取石术(PCNL)技术的学习目标和重要性进行全面回顾:我们回顾性地回顾了2018年1月至2024年1月期间的仰卧位PCNL病例。我们将其分为3组:2-3年住院医师(第1组)、4-5年住院医师(第2组)和内镜医师(第3组)。2-3年住院医师首次实施 PCNL,4-5年住院医师首次实施 Supine PCNL,而之前实施的是俯卧位 PCNL:第 1 组的入路、透视和手术时间较长,第 2 组较短,第 3 组最短(P 例):结论:在 2-3 年级的住院医师中,入路时间和手术时间是最重要的:结论:对于 2-3 年的住院医师来说,随着经验的增加,入路时间和透视时间都会缩短。结论:对于 2-3 年的住院医师,入路时间和透视时间会随着经验的增加而缩短;对于 4-5 年的住院医师,由于他们擅长俯卧位 PCNL,手术时间和透视时间会随着手术例数的增加而缩短。2-3年住院医师完成46-60例手术后,SFR较高,4-5年住院医师完成31-45例手术后,SFR较高。
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引用次数: 0
Investigation of gaseous end products produced by thulium fiber laser lithotripsy of cystine, uric acid, and calcium oxalate monohydrate stones: A gas chromatographic and electron microscopic analysis. 铥纤维激光碎石术治疗胱氨酸、尿酸和一水草酸钙结石产生的气体终产物研究:气相色谱和电子显微镜分析。
IF 2 2区 医学 Q2 UROLOGY & NEPHROLOGY Pub Date : 2024-09-06 DOI: 10.1007/s00240-024-01625-9
Muzaffer Tansel Kılınç, Mehmet Serkan Özkent, Mehmet Mesut Pişkin, Yunus Emre Göger

Laser lithotripsy mechanisms can cause the chemical decomposition of stone components and the emergence of different end products. However, the potentially toxic end products formed during thulium fiber laser (TFL) lithotripsy of cystine stones have not been sufficiently investigated. The aim of our in vitro study is to analyze the chemical content of the gas products formed during the fragmentation of cystine stone with TFL. Human renal calculi consisting of 100% pure cystine, calcium oxalate monohydrate, or uric acid were fragmented separately with TFL in experimental setups and observed for gas release. After the lithotripsy, only the cystine stones showed gas formation. Gas chromatography-mass spectrometry was used to analyze the gas qualitatively, and scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDX) and X-ray diffraction was used to examine the dried cystine stone fragments. Fragmentation of the cystine stones released free cystine, sulfur, hydrogen sulfide, and carbon disulfide gas. The SEM-EDX and X-ray diffraction analyses revealed that the free cystine in the dried fragments contained 43.1% oxygen, 28.7% sulfur, 16.1% nitrogen, and 12.1% carbon atoms according to atomic weight. The detection of potentially toxic gases after lithotripsy of cystine stones with TFL indicates a risk of in vivo production. Awareness needs to be increased among healthcare professionals to prevent potential inhalation and systemic toxicity for patients and operating room personnel during TFL lithotripsy of cystine stones.

激光碎石机制可导致结石成分发生化学分解,并产生不同的最终产物。然而,铥光纤激光(TFL)碎石术治疗胱氨酸结石过程中形成的潜在毒性终产物尚未得到充分研究。我们的体外研究旨在分析铥纤维激光碎石过程中形成的气体产物的化学成分。在实验装置中,用 TFL 分别破碎由 100% 纯胱氨酸、一水草酸钙或尿酸组成的人体肾结石,并观察气体释放情况。碎石后,只有胱氨酸结石有气体形成。气相色谱-质谱法对气体进行了定性分析,扫描电子显微镜与能量色散 X 射线光谱法(SEM-EDX)和 X 射线衍射法对干燥的胱氨酸结石碎片进行了检测。胱氨酸结石碎裂后释放出游离胱氨酸、硫、硫化氢和二硫化碳气体。SEM-EDX 和 X 射线衍射分析表明,按原子量计算,干燥碎片中的游离胱氨酸含有 43.1%的氧原子、28.7% 的硫原子、16.1% 的氮原子和 12.1%的碳原子。使用 TFL 对胱氨酸结石进行碎石后检测到潜在的有毒气体,这表明体内存在产生有毒气体的风险。需要提高医护人员的认识,以防止在胱氨酸结石的TFL碎石过程中,患者和手术室人员可能吸入和全身中毒。
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引用次数: 0
Morin hydrate mitigates calcium oxalate urolithiasis by inhibiting oxalate synthesis and modulating crystal formation. 水合吗啉通过抑制草酸盐合成和调节晶体形成,缓解草酸钙性尿路结石。
IF 2 2区 医学 Q2 UROLOGY & NEPHROLOGY Pub Date : 2024-09-06 DOI: 10.1007/s00240-024-01628-6
Mounica Ponugoti, Chakravarthi Guntupalli, Narender Malothu

Calcium oxalate (CaOx) urolithiasis is a prevalent urinary disorder with significant clinical impact. This study investigates the therapeutic potential of Morin Hydrate (MH), a natural bioflavonoid, in preventing CaOx stone formation. Molecular docking studies revealed that MH binds strongly to glycolate oxidase (GO), suggesting its inhibitory effect on oxalate synthesis. In vitro assays demonstrated that MH effectively inhibits CaOx crystal nucleation, aggregation, and growth, altering crystal morphology to less stable forms. Diuretic activity studies in Wistar rats showed that MH substantially increased urine volume and ion excretion, indicating its moderate diuretic effect. In vivo experiments further supported these findings, with MH treatment improving urinary and serum markers, reducing oxidative stress, and protecting renal tissue, as evidenced by histopathological analysis. Notably, MH administration significantly decreased GO and lactate dehydrogenase activities in urolithiatic rats, indicating a reduction in oxalate production. These results suggest that MH is a promising candidate for the prevention and treatment of CaOx urolithiasis, with the potential for clinical application in reducing the risk and recurrence of kidney stones.

草酸钙(CaOx)尿路结石是一种常见的泌尿系统疾病,对临床影响很大。本研究探讨了天然生物类黄酮莫林水合物(MH)在预防草酸钙结石形成方面的治疗潜力。分子对接研究发现,MH 能与乙醇酸氧化酶(GO)紧密结合,这表明它对草酸盐的合成有抑制作用。体外试验表明,MH 能有效抑制 CaOx 晶体的成核、聚集和生长,改变晶体形态,使其变得不那么稳定。对 Wistar 大鼠进行的利尿活性研究表明,MH 可显著增加尿量和离子排泄量,这表明它具有适度的利尿作用。体内实验进一步证实了这些发现,MH 治疗可改善尿液和血清指标,减少氧化应激,保护肾组织,组织病理学分析也证明了这一点。值得注意的是,服用 MH 能明显降低尿石症大鼠的 GO 和乳酸脱氢酶活性,表明草酸盐生成减少。这些结果表明,MH 是预防和治疗 CaOx 性尿路结石的一种很有前途的候选药物,有望应用于临床,降低肾结石的风险和复发率。
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引用次数: 0
Proteome-wide mendelian randomization identifies therapeutic targets for nephrolithiasis. 全蛋白质组孟德尔随机化确定了肾炎的治疗靶点。
IF 2 2区 医学 Q2 UROLOGY & NEPHROLOGY Pub Date : 2024-09-06 DOI: 10.1007/s00240-024-01627-7
Li Wang, Kun-Peng Li, Si-Yu Chen, Shun Wan, Xiao-Ran Li, Li Yang

Kidney Stone Disease (KSD) constitutes a multifaceted disorder, emerging from a confluence of environmental and genetic determinants, and is characterized by a high frequency of occurrence and recurrence. Our objective is to elucidate potential causative proteins and identify prospective pharmacological targets within the context of KSD. This investigation harnessed the unparalleled breadth of plasma protein and KSD pooled genome-wide association study (GWAS) data, sourced from the United Kingdom Biobank Pharma Proteomics Project (UKBPPP) and the FinnGen database version R10. Through Mendelian randomization analysis, proteins exhibiting a causal influence on KSD were pinpointed. Subsequent co-localization analyses affirmed the stability of these findings, while enrichment analyses evaluated their potential for pharmacological intervention. Culminating the study, a phenome-wide association study (PheWAS) was executed, encompassing all phenotypes (2408 phenotypes) catalogued in the FinnGen database version R10. Our MR analysis identified a significant association between elevated plasma levels of proteins FKBPL, ITIH3, and SERPINC1 and increased risk of KSD based on genetic predictors. Conversely, proteins CACYBP, DAG1, ITIH1, and SEMA6C showed a protective effect against KSD, documented with statistical significance (PFDR<0.05). Co-localization analysis confirmed these seven proteins share genetic variants with KSD, signaling a shared genetic basis (PPH3 + PPH4 > 0.8). Enrichment analysis revealed key pathways including hyaluronan metabolism, collagen-rich extracellular matrix, and serine-type endopeptidase inhibition. Additionally, our PheWAS connected the associated proteins with 356 distinct diseases (PFDR<0.05), highlighting intricate disease interrelations. In conclusion, our research elucidated a causal nexus between seven plasma proteins and KSD, enriching our grasp of prospective therapeutic targets.

肾结石病(KSD)是一种由环境和遗传因素共同作用导致的多发性疾病,具有发病率高、复发率高的特点。我们的目标是阐明潜在的致病蛋白,并确定 KSD 的潜在药理靶点。这项研究利用了来自英国生物库医药蛋白质组学项目(UKBPPP)和芬兰基因数据库 R10 版的无与伦比的血浆蛋白和 KSD 全基因组关联研究(GWAS)数据。通过孟德尔随机分析,确定了对 KSD 有因果影响的蛋白质。随后的共定位分析证实了这些发现的稳定性,而富集分析则评估了这些蛋白质的药理干预潜力。最后,我们进行了一项全表型关联研究(PheWAS),涵盖了FinnGen数据库R10版收录的所有表型(2408种表型)。我们的磁共振分析发现,基于遗传预测因子,血浆中蛋白质 FKBPL、ITIH3 和 SERPINC1 水平升高与 KSD 风险增加之间存在明显关联。相反,蛋白质 CACYBP、DAG1、ITIH1 和 SEMA6C 对 KSD 有保护作用,具有统计学意义(PFDR 0.8)。富集分析揭示了关键通路,包括透明质酸代谢、富含胶原的细胞外基质和丝氨酸型内肽酶抑制。此外,我们的 PheWAS 将相关蛋白与 356 种不同的疾病联系起来(PFDR
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Urolithiasis
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