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[Iron Metabolism and Iron Therapy in Chronic Renal Failure]. [慢性肾功能衰竭的铁代谢和铁治疗]。
Chiara Carla Maria Brunati, Davide Barraco, Francesco Munforte, Enrico Minetti

Iron therapy in nephropathic patients can allow optimizing treatment with EPO identifying the minimum effective dose capable of improving the patient's quality of life. The most recent studies on iron metabolism and on the interference of iron deficiency syndrome on the performance of some organs, in particular the myocardium, suggest the need to intervene very early, especially in patients with cardiomyopathy and systolic deficit. Setting up an iron therapy in nephropathic patients requires a correct diagnosis. That is particularly difficult in comorbid and inflamed patients because of the poor diagnostic reliability of the main biomarkers (ferritin and transferrin saturation). We need to spread the use of biomarkers that are not influenced by the inflammatory state, not expensive and easily accessible: reticulocyte hemoglobin could meet these requirements. The Pivotal study has delineated the optimal iron treatment in incident hemodialysis patients, treated with EPO not inflamed with classical biomarkers. It is yet to be determined, however, whether the Pivotal results are reproducible in more comorbid patients, also considering new and different therapeutic scenarios that the use of hypoxia-inducible factor-prolyl hydroxyl inhibitors may determine.

对肾病患者进行铁治疗可以优化 EPO 治疗,确定能够改善患者生活质量的最小有效剂量。有关铁代谢和缺铁综合征对某些器官(尤其是心肌)功能干扰的最新研究表明,有必要尽早进行干预,尤其是对心肌病和收缩功能不足的患者。对肾病患者进行铁剂治疗需要正确的诊断。由于主要生物标志物(铁蛋白和转铁蛋白饱和度)的诊断可靠性较差,这对于合并症和炎症患者尤其困难。我们需要推广使用不受炎症状态影响、不昂贵且容易获得的生物标志物:网状细胞血红蛋白可以满足这些要求。Pivotal 研究已经确定了血液透析患者的最佳铁治疗方法,这些患者在接受 EPO 治疗后不会出现传统生物标志物的炎症反应。不过,Pivotal 研究的结果是否能在更多合并症患者身上重现,还有待确定,同时也要考虑到缺氧诱导因子-脯氨酰羟基抑制剂的使用可能决定的新的和不同的治疗方案。
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引用次数: 0
[ACEi and ARBs: Proteinuria Containment and Nephroprotection]. [ACEi 和 ARBs:蛋白尿抑制和肾脏保护]。
Filippo Aucella, Rachele Grifa, Francesco Aucella, Giuseppe Gatta

The renin-angiotensin-aldosterone (RAAS) system plays a significant role in renal and cardiovascular pathophysiology, since its increased activity is involved in arterial hypertension, heart failure, and kidney disease. ACEIs and ARBs are essential drugs for nephroprotection: they reduce blood pressure values and albuminuria, both related to cardiovascular damage and CKD progression. The nephroprotective effects are evident in both diabetes mellitus and non-diabetic renal disease, and the initial eGFR fall, if not more than 30%, should be considered as a marker of long-term success of renal protection. To optimize the RAAS inhibition salt intake should be strictly controlled, moreover the effective antiproteinuric dose can often be higher than that used as an antihypertensive. In selected and closely monitored cases, it is also possible to consider dual RAAS blockade. Finally, it should be noted that in patients with advanced CKD RAAS inhibition should not be discontinued, either because it does not give any benefit on GFR or because it increases cardiovascular risk.

肾素-血管紧张素-醛固酮(RAAS)系统在肾脏和心血管病理生理学中发挥着重要作用,因为它的活性增加与动脉高血压、心力衰竭和肾脏疾病有关。血管紧张素转换酶抑制剂(ACEIs)和血管紧张素转换酶抑制剂(ARBs)是保护肾脏的基本药物:它们能降低血压值和白蛋白尿,而这两者都与心血管损伤和慢性肾脏病的进展有关。其肾保护作用在糖尿病和非糖尿病肾病中都很明显,最初的 eGFR 下降(如果不超过 30%)应被视为肾保护长期成功的标志。为优化 RAAS 抑制作用,应严格控制食盐摄入量,此外,有效的抗蛋白尿剂量往往高于降压药的剂量。在经过选择和密切监测的病例中,也可以考虑双重 RAAS 阻断。最后,需要注意的是,对于晚期慢性肾功能衰竭患者,不应停止 RAAS 抑制治疗,因为这对 GFR 没有任何益处,或者会增加心血管风险。
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引用次数: 0
[The Treatment of Acute Antibody-Mediated Rejection: Current State and Future Perspectives]. [急性抗体介导的排斥反应的治疗:现状与未来展望]。
Alessandra Palmisano, Ilaria Gandolfini, Micaela Gentile, Giuseppe Daniele Benigno, Marco Delsante, Marta D'angelo, Enrico Fiaccadori, Umberto Maggiore

Despite the advances in the immunosuppressive therapies and improvements in short term allograft survival, Antibody-mediated rejection (AMR) still represents the leading cause of late allograft failure in kidney transplant recipients. We present an insidious case of late active AMR that evolved into a severe chronic active antibody-mediated rejection, that we treated with a multidrug approach. Then, we review the current literature on the pathogenesis, diagnosis and treatment of AMR. Antibody-mediated rejection (AMR) typically occurs when anti-HLA donor-specific antibodies (DSA) bind to vascular endothelial cells of the kidney graft. DSAs may preexist to transplantation (preformed DSA) or develop after transplantation (de novo DSA). Pathogenetic mechanisms of AMR involve complement-dependent, and -independent inflammatory pathways that are variably activated depending on antigen and antibody characteristics, or on whether rejection develops early (0-6 months) or late (beyond 6 months) post-transplantation. The Banff classification system categorizes AMR rejection into active antibody-mediated rejection, chronic active antibody-mediated rejection, and chronic (inactive) antibody-mediated rejection. Currently, there are no approved therapies, treatment guidelines being based on low-quality evidence. Therefore, standard of care therapy is consensus-based. In early rejection, it is usually based on plasma exchange, intravenous immune globulin, anti-CD20 antibodies, while complement-inhibitor eculizumab is used in severe and/or refractory cases, treatments with. Recent evidence suggests that late AMR may be effectively treated with anti-CD38 therapy, which targets long lived plasma cells and NK cells.

尽管免疫抑制疗法取得了进步,短期异体移植存活率也有所提高,但抗体介导的排斥反应(AMR)仍然是肾移植受者晚期异体移植失败的主要原因。我们介绍了一个隐匿的晚期活动性AMR病例,该病例已演变为严重的慢性活动性抗体介导的排斥反应,我们采用多种药物治疗该病例。然后,我们回顾了目前有关 AMR 发病机制、诊断和治疗的文献。抗体介导的排斥反应(AMR)通常发生在抗 HLA 供体特异性抗体(DSA)与肾脏移植物的血管内皮细胞结合时。DSA可能在移植前就存在(已形成的DSA),也可能在移植后产生(新生的DSA)。AMR的致病机制涉及补体依赖性和非依赖性炎症通路,这些通路的激活程度因抗原和抗体的特性而异,或取决于排斥反应是在移植后早期(0-6个月)还是晚期(超过6个月)发生。班夫分类系统将 AMR 排斥分为活性抗体介导的排斥、慢性活性抗体介导的排斥和慢性(非活性)抗体介导的排斥。目前,还没有获得批准的疗法,治疗指南也是基于低质量的证据。因此,标准疗法是以共识为基础的。对于早期排斥反应,通常采用血浆置换、静脉注射免疫球蛋白、抗 CD20 抗体,而补体结合抑制剂 eculizumab 则用于严重和/或难治性病例。最近的证据表明,晚期AMR可通过抗CD38疗法进行有效治疗,该疗法针对的是长寿命浆细胞和NK细胞。
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引用次数: 0
[Effects of Finerenone on Proteinuria and Progression of Chronic Kidney Disease]. [非奈酮对蛋白尿和慢性肾病进展的影响]。
Antonio De Pascalis, Giuseppe Cianciolo, Alessandro Tommassetti, Stefano Bianchi

A growing body of experimental and clinical evidence confirms that aldosterone contributes, independently from its classical homeostatic effects, to the pathogenesis and progression of chronic kidney disease (CKD). In fact, the activation of the mineralocorticoid receptor (MR) in the kidney, present at the podocyte, mesangial, endothelial as well as at the tubulointerstitial levels, has been linked to podocyte damage and consequent apoptosis, proliferation of mesangial cells, inflammation of the tubulointerstitial compartment and, more generally, to the final outcome of interstitial fibrosis and glomerular sclerosis. Therefore, blockade of the MR may represent an effective treatment of CKD. Today, within the class of mineralocorticoid receptor antagonists (MRA), several molecules are available, with different pharmacokinetic and pharmacodynamic characteristics. In this brief review we will focus on the characteristics of these molecules and in particular on Finerenone, a new generation, non-steroidal MRA, characterized by minimal side effects and high pharmacological efficacy.

越来越多的实验和临床证据证实,醛固酮除了具有传统的平衡作用外,还有助于慢性肾脏病(CKD)的发病和进展。事实上,肾脏中存在于荚膜细胞、系膜细胞、内皮细胞以及肾小管间质水平的矿质皮质激素受体(MR)的激活与荚膜细胞损伤和随之而来的细胞凋亡、系膜细胞增殖、肾小管间质炎症以及更广泛意义上的肾小管间质纤维化和肾小球硬化的最终结果有关。因此,阻断 MR 可能是治疗慢性肾脏病的有效方法。目前,在矿质皮质激素受体拮抗剂(MRA)类别中,有几种分子具有不同的药代动力学和药效学特征。在这篇简短的综述中,我们将重点介绍这些分子的特点,尤其是非格列酮(Finerenone),它是新一代的非甾体类 MRA,具有副作用小、药效高的特点。
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引用次数: 0
[Gliflozins: Proteinuria Control and Nephroprotection]. [格列吡嗪:控制蛋白尿和保护肾脏]。
Simona Barbuto, Veronica Catalano, Marianna Pira, Giuseppe Cianciolo, Giorgia Comai, Irene Capelli, Francesco Tondolo, Federica Maritati, Gaetano La Manna

In recent years, the prevalence of chronic kidney disease (CKD) has significantly increased, with an estimated 843.6 million individuals affected in 2017 [1]. This rise is closely linked to the growing incidence of risk factors such as diabetes mellitus and obesity. Patients with diabetic kidney disease (DKD), one of the most common complications of diabetes, are characterized by high cardiovascular morbidity and mortality. Recent evidence indicates that sodium-glucose cotransporter 2 inhibitors (SGLT2i) play a crucial role in reducing the progression of both DKD and CKD, thanks to its nephroprotective and cardioprotective effects. SGLT2i work by decreasing glomerular hyperfiltration, improving tubulo-glomerular feedback, and reducing blood glucose levels.

近年来,慢性肾脏病(CKD)的发病率大幅上升,2017 年估计有 8.436 亿人受到影响[1]。这一增长与糖尿病和肥胖等风险因素的发病率不断增加密切相关。糖尿病肾病(DKD)是糖尿病最常见的并发症之一,患者的心血管疾病发病率和死亡率都很高。最近的证据表明,钠-葡萄糖共转运体 2 抑制剂(SGLT2i)具有保护肾脏和心脏的作用,在减少糖尿病肾病和慢性肾脏病的进展方面发挥着至关重要的作用。SGLT2i 通过降低肾小球高滤过率、改善肾小管-肾小球反馈和降低血糖水平发挥作用。
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引用次数: 0
[Hypoxia-Inducible Factor Prolyl Hydroxylase Enzyme Inhibitors: A Novel Therapy for Anemia Treatment in CKD Patients]. [缺氧诱导因子脯氨酰羟化酶抑制剂:治疗慢性肾脏病患者贫血的新疗法]。
Andrea Stucchi, Lorenza Magagnoli, Anila Cara, Mario Cozzolino

Anemia is a major complication of chronic kidney disease (CKD). Its prevalence increases with advancing age and progression of kidney disease. The main cause of anemia linked to CKD is represented by the reduction erythropoietin secretion. The increase in cardiovascular risk and mortality is strongly associated with the presence of anemia, and grows with the severity of the anemia, as described in numerous studies. The main therapies for the control of anemia have so far been represented by iron supplementation, the use of synthetic erythropoietin and blood transfusions. Despite the availability of adequate therapies, the prevalence of anemia in CKD continues to be significant. Drugs that inhibit the enzyme prolyl hydroxylase of hypoxia inducible factor (HIF-PHi) are able to mimic a condition of hypoxia and increase the production of endogenous erythropoietin. HIF-PHi therefore represents an important therapeutic alternative for the control of anemia linked to CKD. Numerous studies have confirmed the ability of HIF-PHi to correct anemia and maintain hemoglobin at adequate values; they also highlighted other potential beneficial pleiotropic factors on cholesterol control and iron homeostasis. Further studies are needed to confirm the safety of the drug, especially regarding cardiovascular risk, vascular thrombosis and neoplastic growth. This document highlights the mechanism of action, effects and pharmacological characteristics of HIF-PHi.

贫血是慢性肾脏病(CKD)的主要并发症。其发病率随着年龄的增长和肾病的进展而增加。导致慢性肾脏病贫血的主要原因是促红细胞生成素分泌减少。心血管风险和死亡率的增加与贫血的存在密切相关,并且随着贫血严重程度的增加而增加,这在许多研究中都有描述。迄今为止,控制贫血的主要疗法是补充铁剂、使用合成促红细胞生成素和输血。尽管有适当的疗法,但慢性肾脏病患者贫血的发病率仍然很高。抑制缺氧诱导因子脯氨酰羟化酶(HIF-PHi)的药物能够模拟缺氧状态,增加内源性促红细胞生成素的产生。因此,HIF-PHi 是控制与慢性肾脏病有关的贫血的一种重要治疗方法。大量研究证实,HIF-PHi 能够纠正贫血并将血红蛋白维持在适当的数值;这些研究还强调了其他潜在的对胆固醇控制和铁平衡有益的多效应因子。还需要进一步研究来确认该药物的安全性,尤其是在心血管风险、血管血栓形成和肿瘤生长方面。本文件重点介绍了 HIF-PHi 的作用机制、效果和药理特性。
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引用次数: 0
[What's New in the CKD-BMD Therapy?] [CKD-BMD疗法有何新进展?]
Piergiorgio Messa, Shanmugam Sabarinath, Carlo Maria Alfieri, Giuseppe Castellano, Simone Vettoretti

The important advances in scientific knowledge have led to a notable enrichment of therapeutic offers in the field of CKD-MBD, which have allowed better control of the related biochemical parameters compared to the past. However, this has not corresponded to a tangible improvement in the clinical outcomes, both bone and cardiovascular, associated with CKD-MBD, nor has there been a significant drop in the number of pills that nephropathic patients must take, to keep the parameters controlled biochemicals, with the therapeutic cost of these interventions remaining high. All these unsatisfied needs continue to stimulate research to find new solutions that can improve one or more of these objectives not yet achieved. In this review of the most recent literature, we have tried to summarize what has been recently proposed in the therapeutic field of CKD-MBD, underlining the possible advantages of new drugs compared to already available therapies, with particular attention to unmet needs. We have also revisited the recent acquisitions relating to drugs that have already been in use for some time, reporting the most recent evidence that could change the approach to their use.

科学知识的重大进步使 CKD-MBD 领域的治疗手段显著丰富,与过去相比,相关生化指标得到了更好的控制。然而,与此相对应的是,与 CKD-MBD 相关的骨骼和心血管方面的临床结果并没有得到明显改善,肾病患者为控制生化指标而必须服用的药物数量也没有显著减少,而这些干预措施的治疗成本仍然很高。所有这些尚未得到满足的需求都在不断激励着研究人员寻找新的解决方案,以改善其中一个或多个尚未实现的目标。在这篇最新文献综述中,我们试图总结最近在慢性肾脏病-中枢神经系统疾病治疗领域提出的建议,强调新药与现有疗法相比可能具有的优势,并特别关注尚未满足的需求。我们还重新审视了与已使用一段时间的药物有关的最新研究成果,报告了可能改变其使用方法的最新证据。
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引用次数: 0
[ADPKD and IPMN: Mere Coincidence or Double Trouble?] [ADPKD 和 IPMN:巧合还是双重麻烦?]
Q4 Medicine Pub Date : 2024-08-26 DOI: 10.69097/41-04-2024-05
Kristiana Kola, Liliana Italia De Rosa, Martina Catania, Matteo Brambilla Pisoni, Francesca Tunesi, Sara Farinone, Micaela Petrone, Paolo Manunta, Giuseppe Vezzoli, Maria Teresa Sciarrone Alibrandi

This article constitutes a review of the existing literature on the potential correlation between autosomal dominant polycystic kidney disease (ADPKD) and intraductal papillary mucinous neoplasms (IPMN) of the pancreas. Additionally, it presents a clinical case where familiarity for both pathologies was observed, derived from the direct experience of our clinic, reinforcing the hypothesis of a possible common pathogenetic pathway. The review focuses on the potential genetic correlation between these two pathologies within the realm of ciliopathies, emphasizing the importance of targeted screening and monitoring strategies to detect pancreatic complications early in patients with ADPKD. Furthermore, it highlights the complexity in the clinical management of these rare conditions and underscores the importance of early diagnosis in optimizing clinical outcomes.

本文综述了常染色体显性多囊肾(ADPKD)与胰腺导管内乳头状粘液瘤(IPMN)之间潜在相关性的现有文献。此外,文章还介绍了一个临床病例,从我们临床的直接经验中观察到这两种病症的相似性,从而加强了可能存在共同发病途径的假设。综述重点讨论了纤毛虫病领域中这两种病变之间潜在的遗传相关性,强调了有针对性的筛查和监测策略对于早期发现 ADPKD 患者胰腺并发症的重要性。此外,它还强调了这些罕见疾病临床管理的复杂性,并强调了早期诊断对优化临床结果的重要性。
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引用次数: 0
[Lactobacillemia: A Rare Entity in Immunocompromised Patients. Description of a Clinical Case and Literature Review]. [乳酸菌血症:免疫力低下患者中的罕见病例。临床病例描述与文献综述]。
Q4 Medicine Pub Date : 2024-08-26 DOI: 10.69097/41-04-2024-08
Marina Cornacchiari, Anna Mudoni, Amelia Liccardo, Bianca Visciano, Maria Antonietta Rizzo, Paola Cuoccio, Luca Francesco Di Toma

Bacteremia caused by Lactobacillus is rare, data on its clinical significance are based only on case reports and a limited number of studies, often difficult to interpret. Lactobacillus species is a commensal colonizer of the mouth, gastrointestinal and genitourinary tract. Its significance as a pathogen is overlooked frequently. The diagnosis of these infections requires a mutual relationship between the physician and the microbiologist to rule out contamination risk. Most patients with Lactobacillus bacteremia are immunosuppressed or patients at increased risk of symptomatic bacteremia with comorbidities, treated with broad-spectrum antibiotics and have indwelling venous catheters. Risk factors related to Lactobacillus bacteremia include impaired host defenses and severe underlying diseases, as well as prior surgery and prolonged antibiotic therapy ineffective for lactobacilli. We describe an unusual case of a woman, on chronic hemodialysis treatment, with a sepsis due to Lactobacillus casei and review the literature.

由乳酸杆菌引起的菌血症非常罕见,有关其临床意义的数据仅基于病例报告和数量有限的研究,通常难以解释。乳酸杆菌是口腔、胃肠道和泌尿生殖道的共生菌。它作为病原体的重要性经常被忽视。这些感染的诊断需要医生和微生物学家之间的相互配合,以排除污染风险。大多数乳酸杆菌菌血症患者都是免疫抑制患者或有合并症、接受广谱抗生素治疗和留置静脉导管的无症状菌血症高危患者。与乳酸杆菌菌血症相关的风险因素包括宿主防御功能受损和严重的基础疾病,以及曾接受过手术和对乳酸杆菌无效的长期抗生素治疗。我们描述了一例长期接受血液透析治疗的妇女因酪乳杆菌引起败血症的罕见病例,并回顾了相关文献。
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引用次数: 0
[Stenotic FAV: Success of the Collaboration Between Spoke and HUB]. [Stenotic FAV:Spoke 和 HUB 之间的成功合作]。
Q4 Medicine Pub Date : 2024-08-26 DOI: 10.69097/41-04-2024-09
Ramona Nicotera, Armando Pingitore, Pietro Prunestì, Salvatore Chiarella, Cinzia Donato, Giovanni Mazzitello, Margherita Bovino, Pierpaolo Cannistrà

The arteriovenous fistula constitutes the vascular access of first choice in hemodialysis. We present three clinical cases that highlight the resolution in interventional radiology of venous stenosis, one of the major complications. Clinical monitoring and instrumental diagnostics with color Doppler ultrasound have prevented the failure of the AVF due to high risk of thrombosis. The angiographic interventions, thanks to the collaboration between Spoke and Hub, were completed without complications.

动静脉瘘是血液透析的首选血管通路。我们介绍了三例临床病例,突出说明了介入放射学解决了静脉狭窄这一主要并发症之一。临床监测和彩色多普勒超声仪器诊断避免了因血栓形成的高风险而导致 AVF 的失败。得益于 Spoke 和 Hub 的合作,血管介入手术在无并发症的情况下顺利完成。
{"title":"[Stenotic FAV: Success of the Collaboration Between Spoke and HUB].","authors":"Ramona Nicotera, Armando Pingitore, Pietro Prunestì, Salvatore Chiarella, Cinzia Donato, Giovanni Mazzitello, Margherita Bovino, Pierpaolo Cannistrà","doi":"10.69097/41-04-2024-09","DOIUrl":"https://doi.org/10.69097/41-04-2024-09","url":null,"abstract":"<p><p>The arteriovenous fistula constitutes the vascular access of first choice in hemodialysis. We present three clinical cases that highlight the resolution in interventional radiology of venous stenosis, one of the major complications. Clinical monitoring and instrumental diagnostics with color Doppler ultrasound have prevented the failure of the AVF due to high risk of thrombosis. The angiographic interventions, thanks to the collaboration between Spoke and Hub, were completed without complications.</p>","PeriodicalId":12553,"journal":{"name":"Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia","volume":"41 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia
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