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Incorporation of Chest Computed Tomography Quantification to Predict Outcomes for Patients on Hemodialysis with COVID-19. 采用胸部计算机断层扫描定量法预测 COVID-19 血液透析患者的预后。
IF 3.2 4区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-06-17 eCollection Date: 2024-08-01 DOI: 10.1159/000539568
Haifan Xing, Sijie Gu, Ze Li, Xiao-Er Wei, Li He, Qiye Liu, Haoran Feng, Niansong Wang, Hengye Huang, Ying Fan

Introduction: Patients undergoing maintenance hemodialysis are vulnerable to coronavirus disease 2019 (COVID-19), exhibiting a high risk of hospitalization and mortality. Thus, early identification and intervention are important to prevent disease progression in these patients.

Methods: This was a two-center retrospective observational study of patients on hemodialysis diagnosed with COVID-19 at the Lingang and Xuhui campuses of Shanghai Sixth People's Hospital. Patients were randomized into the training (130) and validation cohorts (54), while 59 additional patients served as an independent external validation cohort. Artificial intelligence-based parameters of chest computed tomography (CT) were quantified, and a nomogram for patient outcomes at 14 and 28 days was created by screening quantitative CT measures, clinical data, and laboratory examination items, using univariate and multivariate Cox regression models.

Results: The median dialysis duration was 48 (interquartile range, 24-96) months. Age, diabetes mellitus, serum phosphorus level, lymphocyte count, and chest CT score were identified as independent prognostic indicators and included in the nomogram. The concordance index values were 0.865, 0.914, and 0.885 in the training, internal validation, and external validation cohorts, respectively. Calibration plots showed good agreement between the expected and actual outcomes.

Conclusion: This is the first study in which a reliable nomogram was developed to predict short-term outcomes and survival probabilities in patients with COVID-19 on hemodialysis. This model may be helpful to clinicians in treating COVID-19, managing serum phosphorus, and adjusting the dialysis strategies for these vulnerable patients to prevent disease progression in the context of COVID-19 and continuous emergence of novel viruses.

导言:接受维持性血液透析的患者很容易感染冠状病毒疾病2019(COVID-19),住院和死亡的风险很高。因此,早期识别和干预对预防这些患者的疾病进展非常重要:这是一项双中心回顾性观察研究,研究对象为上海市第六人民医院临港院区和徐汇院区确诊为COVID-19的血液透析患者。患者被随机分为训练组(130人)和验证组(54人),另有59名患者作为独立的外部验证组。对基于人工智能的胸部计算机断层扫描(CT)参数进行了量化,并通过筛选CT量化指标、临床数据和实验室检查项目,使用单变量和多变量Cox回归模型创建了14天和28天患者预后的提名图:透析时间的中位数为 48 个月(四分位数间距为 24-96 个月)。年龄、糖尿病、血清磷水平、淋巴细胞计数和胸部 CT 评分被确定为独立的预后指标,并被纳入提名图。训练组、内部验证组和外部验证组的一致性指数分别为 0.865、0.914 和 0.885。校准图显示,预期结果与实际结果之间的一致性良好:这是首次研究开发出可靠的提名图来预测血液透析中 COVID-19 患者的短期预后和生存概率。在 COVID-19 和新型病毒不断出现的背景下,该模型可能有助于临床医生治疗 COVID-19、管理血清磷和调整这些易感患者的透析策略,以防止疾病恶化。
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引用次数: 0
Mutation Characteristics of Primary Hyperoxaluria in the Chinese Population and Current International Diagnosis and Treatment Status. 中国人群中原发性高草酸尿症的突变特征及国际诊治现状
IF 3.2 4区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-06-17 eCollection Date: 2024-08-01 DOI: 10.1159/000539516
Xingying Zhu, Wai W Cheung, Aihua Zhang, Guixia Ding

Background: Primary hyperoxaluria (PH) is a rare autosomal recessive disorder, mainly due to the increase in endogenous oxalate production, causing a series of clinical features such as kidney stones, nephrocalcinosis, progressive impairment of renal function, and systemic oxalosis. There are three common genetic causes of glycolate metabolism anomalies. Among them, PH type 1 is the most prevalent and severe type, and early end-stage renal failure often occurs.

Summary: This review summarizes PH through pathophysiology, genotype, clinical manifestation, diagnosis, and treatment options. And explore the characteristics of Chinese PH patients.

Key messages: Diagnosis of this rare disease is based on clinical symptoms, urinary or blood oxalate concentrations, liver biopsy, and genetic testing. Currently, the main treatment is massive hydration, citrate inhibition of crystallization, dialysis, liver and kidney transplantation, and pyridoxine. Recently, RNA interference drugs have also been used. In addition, technologies such as gene editing and autologous liver cell transplantation are also being developed. C.815_816insGA and c.33_34insC mutation in the AGXT gene could be a common variant in Chinese PH1 population. Mutations at the end of exon 6 account for approximately 50% of all Chinese HOGA1 mutations. Currently, the treatment of PH in China still relies mainly on symptomatic and high-throughput dialysis, with poor prognosis (especially for PH1 patients).

背景:原发性高草酸尿症(PH)是一种罕见的常染色体隐性遗传疾病,主要是由于内源性草酸盐生成增多,引起肾结石、肾钙化、进行性肾功能损害和全身性草酸盐中毒等一系列临床特征。乙醇酸代谢异常有三种常见的遗传原因。摘要:本综述从病理生理学、基因型、临床表现、诊断和治疗方案等方面对 PH 进行了总结。并探讨了中国 PH 患者的特点:这种罕见疾病的诊断主要依据临床症状、尿液或血液草酸盐浓度、肝活检和基因检测。目前,主要治疗方法是大量补水、枸橼酸盐抑制结晶、透析、肝肾移植和吡哆醇。最近,还使用了 RNA 干扰药物。此外,基因编辑和自体肝细胞移植等技术也正在开发中。AGXT基因中的C.815_816insGA和c.33_34insC突变可能是中国PH1人群中的常见变异。第6外显子末端的突变约占中国HOGA1突变总数的50%。目前,中国的 PH 治疗仍主要依赖对症治疗和高通量透析,预后较差(尤其是 PH1 患者)。
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引用次数: 0
Effect of a Management Algorithm for Wet Contamination of Peritoneal Dialysis System on the Prevention of Peritonitis: A Prospective Observational Study. 腹膜透析系统湿污染管理算法对预防腹膜炎的影响:前瞻性观察研究。
IF 3.2 4区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-05-30 eCollection Date: 2024-08-01 DOI: 10.1159/000539582
Chunyan Yi, Wenbo Zhang, Qunying Guo, Jianxiong Lin, Wei Chen, Haiping Mao, Xiao Yang

Introduction: Wet contamination was a common problem of peritoneal dialysis (PD) system. We developed a management algorithm for wet contamination of PD system (wet contamination) on the basis of the related research literature and clinical practice experience. The purpose of this study was to observe clinical effect of the management algorithm on the prevention of peritonitis.

Methods: Patients treated wet contamination in a single PD center between October 2017 and September 2022 were included. A management algorithm was established to treat wet contamination. It comprised identification of the contamination type, addressing contaminated or aging catheters, prophylactic antibiotics, and retraining. Demographic data and clinical data about wet contamination were collected and compared.

Results: One hundred and forty-one cases of wet contamination were included in this study. The mean age was 51.7 ± 14.1 years, and 49.6% were female. The proportion of diabetic nephropathy was 9.9%. The median PD duration was 27.0 (1.7-79.7) months. Eighteen episodes (12.8%) of wet contamination-associated peritonitis developed after wet contamination. The main pathogenic bacteria of peritonitis were Gram-positive bacteria (33.3%) and Gram-negative bacteria (27.8%). The incidence of wet contamination-associated peritonitis in the compliance with the management algorithm group was significantly lower than that in the non-compliance with the management algorithm group (0.9 vs. 48.6%; p < 0.001). Non-compliance with management algorithm (OR = 185.861, p < 0.001) together with advance age (OR = 1.116, p < 0.001) and longer distance from home to hospital (OR = 1.007, p < 0.001) were independent risk factors for wet contamination-associated peritonitis.

Conclusion: The management algorithm for wet contamination of PD system could reduce the risk of peritonitis.

简介湿污染是腹膜透析(PD)系统的常见问题。我们在相关研究文献和临床实践经验的基础上,制定了腹膜透析系统湿污染(湿污染)的管理算法。本研究旨在观察该管理算法在预防腹膜炎方面的临床效果:纳入2017年10月至2022年9月在单个PD中心接受湿性污染治疗的患者。建立了治疗湿性污染的管理算法。该算法包括识别污染类型、处理污染或老化导管、预防性抗生素和再培训。收集并比较了有关湿性污染的人口统计学数据和临床数据:本研究共纳入 141 例湿性污染病例。平均年龄为(51.7±14.1)岁,49.6%为女性。糖尿病肾病患者占 9.9%。病程中位数为 27.0 (1.7-79.7) 个月。18次(12.8%)湿污染相关性腹膜炎是在湿污染后发生的。腹膜炎的主要致病菌为革兰氏阳性菌(33.3%)和革兰氏阴性菌(27.8%)。符合管理算法组的湿污染相关腹膜炎发生率明显低于不符合管理算法组(0.9% 对 48.6%;P < 0.001)。不遵守管理算法(OR = 185.861,p < 0.001)、年龄大(OR = 1.116,p < 0.001)和从家到医院距离远(OR = 1.007,p < 0.001)是湿性污染相关性腹膜炎的独立风险因素:结论:PD系统湿污染管理算法可降低腹膜炎风险。
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引用次数: 0
Association of Estimated Glomerular Filtration Rate Trajectories with Atrial Fibrillation Risk in Populations with Normal or Mildly Impaired Renal Function 肾功能正常或轻度受损人群的估计肾小球滤过率轨迹与心房颤动风险的关系
IF 3.7 4区 医学 Pub Date : 2024-05-20 DOI: 10.1159/000539289
Chi Wang, Qian Xin, Junjuan Li, Jianli Wang, S. Yao, Miao Wang, Maoxiang Zhao, Shuohua Chen, Shouling Wu, Hao Xue
Introduction: The association between the longitudinal patterns of estimated glomerular filtration rate (eGFR) and risk of atrial fibrillation (AF) in populations with normal or mildly impaired renal function is not well-characterized. We sought to explore the eGFR trajectories in populations with normal or mildly impaired renal function and their association with AF. Methods: This prospective cohort study included 62,407 participants who were free of AF, cardiovascular diseases, and moderate to severe renal insufficiency (eGFR <60 mL/min/1.73m2) before 2010. The eGFR trajectories were developed using latent mixture modeling based on examination data in 2006, 2008, and 2010. Incident AF cases were identified in biennial electrocardiogram assessment and a review of medical insurance data and discharge registers. We used Cox regression models to estimate the hazard ratios and 95% confidence intervals (CI) for incident AF. Results: According to survey results for the range and changing pattern of eGFR during 2006 to 2010, four trajectories were identified: high-stable (range, 107.47 to 110.25 mL/min/1.73m2; n=11,719), moderate-increasing (median increase from 83.83 to 100.37 mL/min/1.73m2; n=22,634), high-decreasing (median decrease from 101.72 to 89.10 mL/min/1.73m2; n=7,943), and low-stable (range, 73.48 to 76.78 mL/min/1.73m2; n=20,111). After an average follow-up of 9.63 years, a total of 485 cases of AF were identified. Compared with the high-stable trajectory, the adjusted hazard ratios of AF were 1.70 (95% CI, 1.09–2.66) for the moderate-increasing trajectory, 1.92 (95% CI, 1.18–3.13) for the high-decreasing trajectory, and 2.28 (95% CI, 1.46–3.56) for the low-stable trajectory. The results remained consistent across a number of sensitivity analyses.Conclusions: The trajectories of eGFR were associated with subsequent AF risk in populations with normal or mildly impaired renal function.
导言:在肾功能正常或轻度受损的人群中,估计肾小球滤过率(eGFR)的纵向模式与心房颤动(AF)风险之间的关系尚未得到很好的描述。我们试图探索肾功能正常或轻度受损人群的 eGFR 轨迹及其与房颤的关系。方法:这项前瞻性队列研究共纳入了 62407 名参与者,他们在 2010 年之前没有房颤、心血管疾病和中重度肾功能不全(eGFR <60 mL/min/1.73m2)。eGFR轨迹是根据2006年、2008年和2010年的检查数据,采用潜在混合模型得出的。通过两年一次的心电图评估以及对医疗保险数据和出院登记册的审查,确定了心房颤动的发病病例。我们使用 Cox 回归模型估算了心房颤动发病的危险比和 95% 的置信区间 (CI)。结果:根据 2006 年至 2010 年期间 eGFR 范围和变化模式的调查结果,确定了四种轨迹:高度稳定(范围为 107.47 至 110.25 mL/min/1.73m2;n=11,719)、中度增加(中位数从 83.83到100.37 mL/min/1.73m2; n=22,634)、高度下降(中位数从101.72下降到89.10 mL/min/1.73m2; n=7,943)和低度稳定(范围从73.48到76.78 mL/min/1.73m2; n=20,111)。经过平均 9.63 年的随访,共发现 485 例房颤病例。与高稳定轨迹相比,中度增加轨迹的房颤调整危险比为 1.70(95% CI,1.09-2.66),高度减少轨迹的房颤调整危险比为 1.92(95% CI,1.18-3.13),低稳定轨迹的房颤调整危险比为 2.28(95% CI,1.46-3.56)。这些结果在多项敏感性分析中保持一致:在肾功能正常或轻度受损的人群中,eGFR的变化轨迹与后续房颤风险相关。
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引用次数: 0
Role of Extracellular Vesicle-Derived Noncoding RNAs in Diabetic Kidney Disease. 细胞外囊泡衍生的非编码 RNA 在糖尿病肾病中的作用
IF 3.2 4区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-04-26 eCollection Date: 2024-08-01 DOI: 10.1159/000539024
Miao Hu, Xiahong Shen, Ling Zhou

Background: Diabetic kidney disease (DKD), a metabolism-related syndrome characterized by abnormal glomerular filtration rate, proteinuria, and renal microangiopathy, is one of the most common forms of chronic kidney disease, whereas extracellular vesicles (EVs) have been recently evidenced as a novel cell communication player in DKD occurrence and progress via releasing various bioactive molecules, including proteins, lipids, and especially RNA, among which noncoding RNAs (including miRNAs, lncRNAs, and circRNAs) are the major regulators. However, the functional relevance of EV-derived ncRNAs in DKD is to be elucidated.

Summary: Studies have reported that EV-derived ncRNAs regulate gene expression via a diverse range of regulatory mechanisms, contributing to diverse phenotypes related to DKD progression. Furthermore, there are already many potential clinical diagnostic and therapeutic studies based on these ncRNAs, which can be expected to have potential applications in clinical practice for EV-derived ncRNAs.

Key messages: In the current review, we summarized the mechanistic role of EVs in DKD according to biological function classifications, including inflammation and oxidative stress, epithelial-mesenchymal transition, cell death, and extracellular matrix deposition. In addition, we comprehensively discussed the potential applications of EV-derived ncRNAs as diagnostic biomarkers and therapeutic targets in DKD.

背景:糖尿病肾病(DKD)是一种以肾小球滤过率异常、蛋白尿和肾脏微血管病变为特征的代谢相关综合征,是最常见的慢性肾病之一、而细胞外囊泡(EVs)通过释放各种生物活性分子,包括蛋白质、脂类,尤其是 RNA,其中非编码 RNAs(包括 miRNAs、lncRNAs 和 circRNAs)是主要的调控因子,最近已被证实是 DKD 发生和发展过程中的一种新型细胞通讯方式。摘要:有研究报告称,EV衍生的ncRNA通过多种调控机制调控基因表达,导致与DKD进展相关的多种表型。此外,目前已有许多基于这些 ncRNAs 的潜在临床诊断和治疗研究,预计 EV 衍生的 ncRNAs 有可能应用于临床实践:在本综述中,我们根据炎症和氧化应激、上皮-间质转化、细胞死亡和细胞外基质沉积等生物功能分类,总结了EVs在DKD中的机理作用。此外,我们还全面讨论了 EV 衍生的 ncRNA 作为 DKD 诊断生物标志物和治疗靶点的潜在应用。
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引用次数: 0
Impact of Arterial Calcification on Cardiovascular and Renal Outcomes in Kidney Transplant Patients. 动脉钙化对肾移植患者心血管和肾脏预后的影响
IF 3.2 4区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2024-04-16 eCollection Date: 2024-08-01 DOI: 10.1159/000538929
Joohyung Ha, Jong Cheol Jeong, Jung-Hwa Ryu, Myung-Gyu Kim, Kyu Ha Huh, Kyo Won Lee, Hee-Yeon Jung, Kyung Pyo Kang, Han Ro, Seungyeup Han, Beom Seok Kim, Jaeseok Yang

Introduction: Coronary artery calcification score (CACS) and abdominal aortic calcification score (AACS) are both well-established markers of vascular stiffness, and previous studies have shown that a higher CACS is a risk factor for chronic kidney disease (CKD) progression. However, the impact of pretransplant CACS and AACS on cardiovascular and renal outcomes in kidney transplant patients has not been established.

Methods: We included 944 kidney transplant recipients from the KoreaN cohort study for Outcome in patients With Kidney Transplantation (KNOW-KT) cohort and categorized them into three groups (low, medium, and high) according to baseline CACS (0, 0 < and ≤100, >100) and AACS (0, 1-4, >4). The low (0), medium (0 < and ≤ 100), and high (>100) CACS groups each consisted of 462, 213, and 225 patients, respectively. Similarly, the low (0), medium (1-4), and high (>4) AACS groups included 638, 159, and 147 patients, respectively. The primary outcome was the occurrence of cardiovascular events. The secondary outcomes were all-cause mortality and composite kidney outcomes, which comprised of >50% decline in the estimated glomerular filtration rate and graft loss. Cox regression analysis was used to investigate the association between baseline CACS/AACS and outcomes.

Results: The high CACS group (N = 462) faced a significantly higher risk for cardiovascular outcomes (adjusted hazard ratio [aHR], 5.97; 95% confidence interval [CI], 2.01-17.7) and all-cause mortality (aHR, 2.74; 95% CI, 1.27-5.92) compared to the low CACS group (N = 225). Similarly, the high AACS group (N = 638) had an elevated risk for cardiovascular outcomes (aHR, 2.38; 95% CI, 1.16-4.88). Furthermore, the addition of CACS to prediction models improved prediction indices for cardiovascular outcomes. However, the risk of renal outcomes did not differ among CACS or AACS groups.

Conclusion: Pretransplant arterial calcification, characterized by high CACS or AACS, is an independent risk factor for cardiovascular outcomes and mortality in kidney transplant patients.

引言冠状动脉钙化评分(CACS)和腹主动脉钙化评分(AACS)都是公认的血管僵化标志物,以往的研究表明,较高的CACS是慢性肾脏病(CKD)进展的风险因素。然而,移植前 CACS 和 AACS 对肾移植患者心血管和肾脏预后的影响尚未确定:我们纳入了韩国肾移植患者结局队列研究(KoreaN cohort study for Outcome in patients with Kidney Transplantation,KNOW-KT)队列中的 944 名肾移植受者,并根据基线 CACS(0,0 < 和≤100,>100)和 AACS(0,1-4,>4)将他们分为三组(低、中、高)。低(0)、中(0<和≤100)和高(>100)CACS 组分别有 462、213 和 225 名患者。同样,低(0)、中(1-4)和高(>4)AACS 组分别有 638、159 和 147 名患者。主要结果是心血管事件的发生率。次要结局是全因死亡率和综合肾脏结局,包括估计肾小球滤过率下降>50%和移植物损失。Cox回归分析用于研究基线CACS/AACS与结果之间的关系:结果:与低 CACS 组(N = 225)相比,高 CACS 组(N = 462)的心血管后果风险(调整后危险比 [aHR],5.97;95% 置信区间 [CI],2.01-17.7)和全因死亡率(aHR,2.74;95% CI,1.27-5.92)明显更高。同样,高 AACS 组(N = 638)的心血管后果风险也较高(aHR,2.38;95% CI,1.16-4.88)。此外,在预测模型中加入 CACS 可改善心血管预后的预测指数。然而,CACS组和AACS组的肾脏预后风险并无差别:结论:以高 CACS 或 AACS 为特征的移植前动脉钙化是肾移植患者心血管预后和死亡率的独立风险因素。
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引用次数: 0
LRG1 contributes to the pathogenesis of multiple kidney diseases: a comprehensive review LRG1 与多种肾脏疾病的发病机制有关:全面综述
IF 3.7 4区 医学 Pub Date : 2024-04-03 DOI: 10.1159/000538443
Chunyan Chen, Jingwei Zhang, Tao Yu, Haiya Feng, Jian Liao, Yifei Jia
Background: The increasing prevalence of kidney diseases has become a significant public health issue, with a global prevalence exceeding 10%. In order to accurately identify biochemical changes and treatment outcomes associated with kidney diseases, novel methods targeting specific genes have been discovered. Among these genes, leucine-rich α-2 glycoprotein 1 (LRG1) has been identified to function as a multifunctional pathogenic signaling molecule in multiple diseases, including kidney diseases. This study aims to provide a comprehensive overview of the current evidence regarding the roles of LRG1 in different types of kidney diseases. Summary: Based on a comprehensive review, it was found that LRG1 was up-regulated in the urine, serum, or renal tissues of patients or experimental animal models with multiple kidney diseases, such as diabetic nephropathy, kidney injury, IgA nephropathy, chronic kidney diseases (CKD), clear cell renal cell carcinoma (ccRCC), end-stage renal disease, canine leishmaniosis-induced kidney disease, kidney fibrosis, and aristolochic acid nephropathy. Mechanistically, the role of LRG1 in kidney diseases is believed to be detrimental, potentially through its regulation of various genes and signaling cascades, i.e. FN1, GPR56, VEGF, VEGFR-2, DR5, GDF15, HIF-1α, SPP1, ALK1-Smad1/5/8, NLRP3-IL-1b, and TGF-β pathway. Key Messages: Further research is needed to fully comprehend the molecular mechanisms by which LRG1 contributes to the pathogenesis and pathophysiology of kidney diseases. It is anticipated that targeted treatments focusing on LRG1 will be utilized in clinical trials and implemented in clinical practice in the future.
背景:肾脏疾病的发病率越来越高,已成为一个重大的公共卫生问题,全球发病率超过 10%。为了准确鉴定与肾脏疾病相关的生化变化和治疗效果,人们发现了针对特定基因的新方法。在这些基因中,富亮氨酸α-2糖蛋白1(LRG1)已被确认在包括肾脏疾病在内的多种疾病中发挥多功能致病信号分子的作用。本研究旨在全面概述目前有关 LRG1 在不同类型肾脏疾病中作用的证据。摘要通过全面综述发现,LRG1在多种肾脏疾病患者或实验动物模型的尿液、血清或肾脏组织中上调,这些疾病包括糖尿病肾病、肾损伤、IgA肾病、慢性肾脏疾病(CKD)、透明细胞肾细胞癌(ccRCC)、终末期肾病、犬利什曼病诱导的肾病、肾纤维化和马兜铃酸肾病。从机理上讲,LRG1 在肾脏疾病中的作用被认为是有害的,可能是通过其对各种基因和信号级联(即 FN1、GPR56、VEGF、VEGFR-2、DR5、GDF15、HIF-1α、SPP1、ALK1-Smad1/5/8、NLRP3-IL-1b 和 TGF-β 通路)的调控。关键信息:要全面了解 LRG1 促成肾脏疾病发病机制和病理生理学的分子机制,还需要进一步的研究。预计针对 LRG1 的靶向治疗将被用于临床试验,并在未来应用于临床实践。
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引用次数: 0
A Klotho-based Machine Learning Model for Prediction of both Kidney and Cardiovascular Outcomes in Chronic Kidney Disease 基于 Klotho 的机器学习模型用于预测慢性肾脏病患者的肾脏和心血管预后
IF 3.7 4区 医学 Pub Date : 2024-03-25 DOI: 10.1159/000538510
Yating Wang, Yu Shi, Tangli Xiao, Xianjin Bi, Qingyu Huo, Shaobo Wang, Jiachuan Xiong, Jinghong Zhao
Background: This study aimed to develop and validate a machine learning (ML) model based on serum Klotho for predicting end-stage kidney disease (ESKD) and cardiovascular disease (CVD) in patients with chronic kidney disease (CKD).Methods: Five different ML models were trained to predict the risk of ESKD and CVD at three different time points (3, 5, and 8-year) using a cohort of 400 non-dialysis CKD patients. The dataset was divided into a training set (70%) and an internal validation set (30%). These models were informed by data comprising 47 clinical features, including serum Klotho. The best-performing model was selected and used to identify risk factors for each outcome. Model performance was assessed using various metrics.Results: The findings showed that the Lasso regression model had the highest accuracy (C-index=0.71) in predicting ESKD. The features mainly included in this model were estimated glomerular filtration rate (eGFR), 24-hour urinary microalbumin, serum albumin, phosphate, parathyroid hormone, and serum Klotho, which achieved the highest area under the curve (AUC) of 0.930 (95% CI: 0.897-0.962). In addition, for the CVD risk prediction, the Random Survival Forest (RSF) model with the highest accuracy (C-index=0.66) was selected and achieved the highest AUC of 0.782 (95% CI: 0.633-0.930). The features mainly included in this model were age, history of primary hypertension, calcium, tumor necrosis factor-alpha, and serum Klotho.Conclusion: We successfully developed and validated Klotho-based ML risk prediction models for CVD and ESKD in CKD patients with good performance, indicating their high clinical utility.
背景:本研究旨在开发和验证一种基于血清Klotho的机器学习(ML)模型,用于预测慢性肾脏病(CKD)患者的终末期肾脏病(ESKD)和心血管疾病(CVD):使用 400 名非透析 CKD 患者队列训练了五个不同的 ML 模型,以预测三个不同时间点(3 年、5 年和 8 年)的 ESKD 和 CVD 风险。数据集分为训练集(70%)和内部验证集(30%)。这些模型参考了包括血清 Klotho 在内的 47 个临床特征数据。筛选出表现最佳的模型,用于确定每种结果的风险因素。使用各种指标对模型性能进行评估:研究结果表明,Lasso 回归模型预测 ESKD 的准确率最高(C 指数=0.71)。该模型的主要特征包括估计肾小球滤过率(eGFR)、24 小时尿微量白蛋白、血清白蛋白、磷酸盐、甲状旁腺激素和血清 Klotho,其曲线下面积(AUC)最高,为 0.930(95% CI:0.897-0.962)。此外,在心血管疾病风险预测方面,随机生存森林(RSF)模型的准确度最高(C-index=0.66),AUC 最高,达到 0.782(95% CI:0.633-0.930)。该模型的主要特征包括年龄、原发性高血压病史、血钙、肿瘤坏死因子-α和血清 Klotho:我们成功开发并验证了基于 Klotho 的 CKD 患者心血管疾病和 ESKD 的 ML 风险预测模型,该模型性能良好,表明其具有很高的临床实用性。
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引用次数: 0
Roxadustat on Renal Anemia with Macroinflammation: A Retrospective Cohort Study. 罗沙司他对伴有大炎症的肾性贫血的影响:一项回顾性队列研究
IF 3.7 4区 医学 Pub Date : 2024-03-18 eCollection Date: 2024-06-01 DOI: 10.1159/000538372
Yan Tu, Zuo-Lin Li, Hong Liu, Ri-Ning Tang, Gui-Hua Wang, Lin-Li Lv, Bin Wang, Bi-Cheng Liu

Introduction: Roxadustat, the first-in-class drug for the treatment of renal anemia, has demonstrated efficacy in renal anemia with microinflammation. Additional data are needed regarding the efficacy of roxadustat on renal anemia with systemic macroinflammation.

Methods: Three cohorts of renal anemia based on the basic level of high-sensitivity CRP were included. Patients with hsCRP ≤2 mg/L were selected as non-inflammation (NI) group; 2< hsCRP ≤10 mg/L as microinflammation (MI) group; hsCRP≥10 mg/L as macroinflammation (MA) group. Patients received oral roxadustat three times per week for 52 weeks. The primary end point was the hemoglobin level over weeks 12-52. The second end point was the cumulative proportion of patients achieving hemoglobin response by the end of week 12.

Results: A total of 107 patients with chronic kidney diseases (CKDs) were enrolled. Overall, the baseline hemoglobin level of patients was 79.99 ± 11.20 g/L. Roxadustat could significantly increase the hemoglobin level in all of the three groups and did not show any significant difference (p > 0.05, respectively). Meanwhile, compared with that of the NI group, there was no significant difference in hemoglobin response rate in the MA group both at week 12 (p = 0.06; 95% confidence interval [CI], 0.9531-13.75) and week 52 (p = 0.37; 95% CI, 0.5080-7.937). Moreover, the hemoglobin response was independent of baseline hsCRP level (p = 0.72, 95% CI, -0.1139 to 0.0794). More importantly, roxadustat significantly reduced ferritin and serum iron levels and increased total iron-binding capacity in the three groups, which showed no significant differences among the three groups (p > 0.05, respectively).

Conclusion: Roxadustat significantly improves anemia in CKD patients with systemic macroinflammation.

简介罗沙司他是治疗肾性贫血的首创药物,对伴有微炎症的肾性贫血具有疗效。关于罗沙司他对伴有全身性大炎症的肾性贫血的疗效,还需要更多数据:方法:根据高敏 CRP 的基本水平,纳入了三组肾性贫血患者。选择 hsCRP≤2 mg/L 的患者为非炎症(NI)组;2< hsCRP≤10 mg/L 的患者为微炎症(MI)组;hsCRP≥10 mg/L 的患者为大炎症(MA)组。患者每周口服三次罗沙司他,共52周。主要终点是第12-52周的血红蛋白水平。第二个终点是在第 12 周结束时达到血红蛋白应答的患者累计比例:共有 107 名慢性肾病 (CKD) 患者入选。总体而言,患者的基线血红蛋白水平为 79.99 ± 11.20 g/L。罗沙司他能显著提高三组患者的血红蛋白水平,且无明显差异(P>0.05)。同时,与 NI 组相比,MA 组在第 12 周(P = 0.06;95% 置信区间 [CI],0.9531-13.75)和第 52 周(P = 0.37;95% CI,0.5080-7.937)的血红蛋白应答率均无显著差异。此外,血红蛋白反应与基线 hsCRP 水平无关(p = 0.72,95% CI,-0.1139 至 0.0794)。更重要的是,罗沙度他能显著降低三组的铁蛋白和血清铁水平,提高总铁结合能力,但三组间无显著差异(P分别>0.05):结论:罗沙司他能明显改善伴有全身大炎症的慢性肾脏病患者的贫血状况。
{"title":"Roxadustat on Renal Anemia with Macroinflammation: A Retrospective Cohort Study.","authors":"Yan Tu, Zuo-Lin Li, Hong Liu, Ri-Ning Tang, Gui-Hua Wang, Lin-Li Lv, Bin Wang, Bi-Cheng Liu","doi":"10.1159/000538372","DOIUrl":"10.1159/000538372","url":null,"abstract":"<p><strong>Introduction: </strong>Roxadustat, the first-in-class drug for the treatment of renal anemia, has demonstrated efficacy in renal anemia with microinflammation. Additional data are needed regarding the efficacy of roxadustat on renal anemia with systemic macroinflammation.</p><p><strong>Methods: </strong>Three cohorts of renal anemia based on the basic level of high-sensitivity CRP were included. Patients with hsCRP ≤2 mg/L were selected as non-inflammation (NI) group; 2< hsCRP ≤10 mg/L as microinflammation (MI) group; hsCRP≥10 mg/L as macroinflammation (MA) group. Patients received oral roxadustat three times per week for 52 weeks. The primary end point was the hemoglobin level over weeks 12-52. The second end point was the cumulative proportion of patients achieving hemoglobin response by the end of week 12.</p><p><strong>Results: </strong>A total of 107 patients with chronic kidney diseases (CKDs) were enrolled. Overall, the baseline hemoglobin level of patients was 79.99 ± 11.20 g/L. Roxadustat could significantly increase the hemoglobin level in all of the three groups and did not show any significant difference (<i>p</i> > 0.05, respectively). Meanwhile, compared with that of the NI group, there was no significant difference in hemoglobin response rate in the MA group both at week 12 (<i>p</i> = 0.06; 95% confidence interval [CI], 0.9531-13.75) and week 52 (<i>p</i> = 0.37; 95% CI, 0.5080-7.937). Moreover, the hemoglobin response was independent of baseline hsCRP level (<i>p</i> = 0.72, 95% CI, -0.1139 to 0.0794). More importantly, roxadustat significantly reduced ferritin and serum iron levels and increased total iron-binding capacity in the three groups, which showed no significant differences among the three groups (<i>p</i> > 0.05, respectively).</p><p><strong>Conclusion: </strong>Roxadustat significantly improves anemia in CKD patients with systemic macroinflammation.</p>","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11149990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Deep Insight into Ferroptosis in Renal Disease: Facts and Perspectives. 深入了解肾病中的铁蛋白沉积症:事实与观点。
IF 3.7 4区 医学 Pub Date : 2024-03-08 eCollection Date: 2024-06-01 DOI: 10.1159/000538106
Zhongyu Han, Yuanke Luo, Haoran Chen, Guochen Zhang, Luling You, Meiqi Zhang, Yumeng Lin, Lan Yuan, Shiyi Zhou

Background: Ferroptosis, a newly recognized form of programmed cell death, is distinguished by its reliance on reactive oxygen species and iron-mediated lipid peroxidation, setting it apart from established types like apoptosis, cell necrosis, and autophagy. Recent studies suggest its role in exacerbating or mitigating diseases by influencing metabolic and signaling pathways in conditions such as tumors and ischemic organ damage. Evidence also links ferroptosis to various kidney diseases, prompting a review of its research status and potential breakthroughs in understanding and treating these conditions.

Summary: In acute kidney disease (AKI), ferroptosis has been confirmed in animal kidneys after being induced by various factors such as renal ischemia-reperfusion and cisplatin, and glutathione peroxidase 4 (GPX4) is linked with AKI. Ferroptosis is associated with renal fibrosis in chronic kidney disease (CKD), TGF-β1 being crucial in this regard. In diabetic nephropathy (DN), high SLC7A11 and low nuclear receptor coactivator 4 (NCOA4) expressions are linked to disease progression. For polycystic kidney disease (PKD), ferroptosis promotes the disease by regulating ferroptosis in kidney tissue. Renal cell carcinoma (RCC) and lupus nephritis (LN) also have links to ferroptosis, with mtDNA and iron accumulation causing RCC and oxidative stress causing LN.

Key messages: Ferroptosis is a newly identified form of programmed cell death that is associated with various diseases. It targets metabolic and signaling pathways and has been linked to kidney diseases such as AKI, CKD, PKD, DN, LN, and clear cell RCC. Understanding its role in these diseases could lead to breakthroughs in their pathogenesis, etiology, and treatment.

背景:铁凋亡是一种新认识到的程序性细胞死亡形式,其特点是依赖活性氧和铁介导的脂质过氧化,使其有别于细胞凋亡、细胞坏死和自噬等既定类型。最近的研究表明,它通过影响肿瘤和缺血性器官损伤等情况下的代谢和信号通路,在加重或减轻疾病方面发挥作用。摘要:在急性肾脏病(AKI)中,经肾脏缺血再灌注和顺铂等多种因素诱导后,动物肾脏中的铁变态反应已被证实,谷胱甘肽过氧化物酶 4 (GPX4) 与 AKI 有关。铁蛋白沉积与慢性肾病(CKD)中的肾纤维化有关,而 TGF-β1 在这方面起着关键作用。在糖尿病肾病(DN)中,SLC7A11的高表达和核受体辅激活剂4(NCOA4)的低表达与疾病进展有关。对于多囊肾病(PKD),肾组织中的铁蛋白沉积会促进疾病的发生。肾细胞癌(RCC)和狼疮性肾炎(LN)也与高铁血症有关,mtDNA和铁积累导致RCC,氧化应激导致LN:铁凋亡是一种新发现的程序性细胞死亡形式,与多种疾病相关。它以新陈代谢和信号通路为目标,与肾脏疾病(如 AKI、CKD、PKD、DN、LN 和透明细胞 RCC)有关。了解它在这些疾病中的作用可能会在发病机制、病因学和治疗方面带来突破。
{"title":"A Deep Insight into Ferroptosis in Renal Disease: Facts and Perspectives.","authors":"Zhongyu Han, Yuanke Luo, Haoran Chen, Guochen Zhang, Luling You, Meiqi Zhang, Yumeng Lin, Lan Yuan, Shiyi Zhou","doi":"10.1159/000538106","DOIUrl":"10.1159/000538106","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis, a newly recognized form of programmed cell death, is distinguished by its reliance on reactive oxygen species and iron-mediated lipid peroxidation, setting it apart from established types like apoptosis, cell necrosis, and autophagy. Recent studies suggest its role in exacerbating or mitigating diseases by influencing metabolic and signaling pathways in conditions such as tumors and ischemic organ damage. Evidence also links ferroptosis to various kidney diseases, prompting a review of its research status and potential breakthroughs in understanding and treating these conditions.</p><p><strong>Summary: </strong>In acute kidney disease (AKI), ferroptosis has been confirmed in animal kidneys after being induced by various factors such as renal ischemia-reperfusion and cisplatin, and glutathione peroxidase 4 (GPX4) is linked with AKI. Ferroptosis is associated with renal fibrosis in chronic kidney disease (CKD), TGF-β1 being crucial in this regard. In diabetic nephropathy (DN), high SLC7A11 and low nuclear receptor coactivator 4 (NCOA4) expressions are linked to disease progression. For polycystic kidney disease (PKD), ferroptosis promotes the disease by regulating ferroptosis in kidney tissue. Renal cell carcinoma (RCC) and lupus nephritis (LN) also have links to ferroptosis, with mtDNA and iron accumulation causing RCC and oxidative stress causing LN.</p><p><strong>Key messages: </strong>Ferroptosis is a newly identified form of programmed cell death that is associated with various diseases. It targets metabolic and signaling pathways and has been linked to kidney diseases such as AKI, CKD, PKD, DN, LN, and clear cell RCC. Understanding its role in these diseases could lead to breakthroughs in their pathogenesis, etiology, and treatment.</p>","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11149998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Kidney Diseases
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