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Objective To compare the effects of hemodialysis (HD) and continuous renal replacement therapy on patients with uremia complicated with secondary hyperparathyroidism (SHPT) after total parathyroidectomy (TP) + parathyroid autotransplantation (AT) . Methods Sixty patients with uremia complicated with SHPT treated with TP+AT were divided into the hemodialysis group (n=30) and renal replacement group (n=30) according to the different ways of postoperative blood purification. HD treatment was given to the patients in the hemodialysis group on the first day after surgery, and heparin free anticoagulation mode was used； patients in the renal replacement group were treated with CRRT on the first day after surgery, and the citrate anticoagulation mode was used in the renal replacement group. The single chamber Kt/V (spKt/V), urea reduction rate (URR), complications, and preoperative and postoperative blood calcium, phosphorus and total parathyroid hormone (iPTH) were compared between two groups. Results Compared with the renal replacement group, the spKt/V and URR in the hemodialysis group increased (both P<0. 05) . There was no bleeding at the surgical incision in the hemodialysis group and renal replacement group. Compared with the renal replacement group, the total coagulation rate of the dialysis pipeline in the hemodialysis group was higher (P<0. 05) . Compared with the same group before surgery, the levels of blood calcium, phosphorus and iPTH in both groups decreased on the first day after surgery (all P< 0. 05) . Conclusions For uremic SHPT patients after TP+AP, the incidence of blood coagulation in the pipeline after CRRT is low, but the clearance of small molecular weight toxins is poor. HD has a stronger ability to clear small molecular weight toxins； there is a certain incidence of pipeline clotting, but there is rarely HD discontinuation caused by severe clotting. [ABSTRACT FROM AUTHOR]

Background: Uremic pruritus (UP) or chronic kidney disease-associated pruritus (CKD-aP) is one of the most intractable dermatologic symptom in patients with chronic kidney disease. Several randomized controlled trials (RCTs) have been conducted to investigate the antipruritic effects of acupuncture on UP/CKD-aP and suggested a significant therapeutic effect, while the evidence supporting the application of acupuncture is limited., Objectives: This study will assess the efficacy and safety of acupuncture for patients with UP/CKD-aP., Methods: Data Sources: RCTs will be searched in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, the Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, Wanfang Database, VIP Database, the WHO International Clinical Trials Registry Platform portal and www.ClinicalTrials.gov from inception to 31st August 2024. Study eligibility criteria: RCTs in English and Chinese conducted on UP/CKD-aP patients will be included. Participants: Adult patients diagnosed with UP/CKD-aP will be included. Interventions: All acupuncture interventions in the management of UP/CKD-aP will be included, compared with no treatment, placebo or sham acupuncture, or other treatment agents. Outcome measures: The primary outcome will be the change in the severity of itching evaluated by validated scales. Study appraisal and svnthesis methods: If necessary, a meta-analysis will be performed for the pooled therapeutic effect by Review Manager 5.3, or a qualitative descriptive analysis will be presented. The data will be transformed into the risk ratio (RR) for binary data and the mean difference (MD) or standardized MD for continuous data for analysis., Results: This review will update evidence of RCTs evaluating acupuncture for UP/CKD-aP., Limitations: Anticipated challenges contain the methodological and clinical heterogeneity in terms of evaluation tools and acupuncture interventions within included studies., Conclusion and Implications: It will benefit patients and impact health-care decision-making regarding the models of care that are feasible for patients., Trial Registration: PROSPERO CRD42021257001., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A 90-year-old patient with chronic kidney disease (stage G4) was diagnosed with pneumonia and congestive heart failure. Despite treatment with levofloxacin and furosemide, his condition deteriorated. A CT scan of the chest revealed pericardial effusion, leading to the suspicion of uremic pericarditis. Daily hemodialysis was started, resulting in significant clinical and biological improvement. Uremic pericarditis due to accumulation of uremic toxins resulting in pericardial effusion is common in end-stage renal disease. Diagnosis is guided by clinical and paraclinical findings and a high index of suspicion. Early recognition and treatment remain critical to prevent complications even in pre-end stage renal disease.

Uremic Encephalopathy results from the elevation of toxins and blood-brain barrier (BBB) disruption. Renal Ischemia/Reperfusion (I/R) injury is the principal cause of acute kidney injury and brain tissue injury. The present study was crafted to estimate the restorative impact of platelet-rich plasma (PRP) and exosome injection before the reperfusion phase on the kidney following renal I/R injury and its influence on brain tissue by tracking the histopathological, biochemical, and Doppler ultrasonography alternations in both kidney and brain tissue. Forty mature male rats were divided into five groups as follows: control, I/R, PRP, exosome, and Exosome + PRP. Renal Doppler ultrasonography was traced for all rats. Serum kidney functions and acetylcholine esterase enzyme (AchE) were evaluated. Both Gamma-aminobutyric acid (GABA) and glutamate were assessed in brain tissues. The oxidative stress (malondialdehyde), anti-oxidative (glutathione and catalase), and pro-inflammatory (Tumor necrosis factor- α and interleukin-6) markers were estimated in renal tissues. Additionally, morphometric histological examination was performed in both renal and brain tissues. Both PRP and exosome-received rats exhibited a significant improvement in both serum kidney functions and AchE compared to I/R rats. There was a 3.39-fold increase in GABA and a 2.27-fold decrease in glutamate levels in the brain tissue of PRP rats compared to the I/R rats. A significant elevation (P ≤ 0.0001) of glutathione and catalase besides a significant reduction in the expression of TNF-α and IL-6 was observed in renal tissue compared to I/R rats. A significant severe reduction (P < 0.0001) in the number of Purkinje cells, pyramidal cells in the cerebellar cortex, and the CA1 region in the hippocampus was observed in I/R rats which was significantly alleviated by both PRP and exosome. Furthermore, there was a significant improvement in Doppler parameters. PRP exerted a significant superior impact on the restoration of kidney functions and repairing uremic-induced damage in brain tissue., (© 2024. The Author(s).)

Uremic cardiomyopathy (UC) represents a complex syndrome characterized by different cardiac complications, including systolic and diastolic dysfunction, left ventricular hypertrophy, and diffuse fibrosis, potentially culminating in myocardial infarction (MI). Revascularization procedures are often necessary for MI management and can induce ischemia reperfusion injury (IR). Despite this clinical relevance, the role of fine particulate matter (PM 2.5 ) in UC pathology and the underlying subcellular mechanisms governing this pathology remains poorly understood. Hence, we investigate the impact of PM 2.5 exposure on UC susceptibility to IR injury. Using a rat model of adenine-induced chronic kidney disease (CKD), the animals were exposed to PM 2.5 at 250 µg/m 3 for 3 h daily over 21 days. Subsequently, hearts were isolated and subjected to 30 min of ischemia followed by 60 min of reperfusion to induce IR injury. UC hearts exposed to PM 2.5 followed by IR induction (Adenine + PM&#95;IR) exhibited significantly impaired cardiac function and increased cardiac injury (increased infarct size and apoptosis). Analysis at the subcellular level revealed reduced mitochondrial copy number, impaired mitochondrial bioenergetics, decreased expression of PGC1-α (a key regulator of mitochondrial biogenesis), and compromised mitochondrial quality control mechanisms. Additionally, increased mitochondrial oxidative stress and perturbation of the PI3K/AKT/AMPK signaling axis were evident. Our findings therefore collectively indicate that UC myocardium when exposed to PM 2.5 is more vulnerable to IR-induced injury, primarily due to severe mitochondrial impairment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Our understanding of the pathogenesis of uremic pruritus (also known as CKD-associated pruritus [CKD-aP]) remains elusive. Although multiple discrete changes in the immunochemical milieu of the skin of patients with CKD-aP have been described, a coherent theory of mechanism is absent. This article proposes a theoretical model of mechanism. It concentrates on the initiation phase of CKD-aP and its three parts: ( 1 ) genesis, triggered by first precipitants; ( 2 ) cascade of cytokine release that follows and the cross-talking of multiple skin cells with each other and afferent nerve fibers; and ( 3 ) enhancement. The limitation of the model will be described and ideas for future research proposed. Implications for management shall be examined., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology.)

Introduction: Diagnosis with Western blot test (WB) may not provide clear results for certain patients, including those who are not infected with human immunodeficiency virus (HIV) but produce non-specific reactions, individuals in the HIV window period (WP), those with acute HIV infection, and advanced acquired immunodeficiency syndrome (AIDS) patients. HIV-positive individuals face an elevated risk of developing kidney disease. HIV peritoneal dialysis patients may be more susceptible to catheter-related infections. This study reports a case of HIV detected during early development of a nephrotic syndrome into uremic syndrome., Case Presentation: A 46-year-old male individual diagnosed with stage 5 chronic kidney disease was admitted to the hospital in preparation for his first renal replacement therapy. During routine check-ups, the patient was identified as having a reactive response to the HIV antigen/antibody test. The rapid detection results exhibited a weak reaction across all manufacturers, while the enzyme-linked immunosorbent assay (ELISA) test (Bio-Rad, Hercules, USA) showed a reactive response. Nonetheless, the third and fourth generation tests did not yield a response, suggesting that the patient`s internal concentration of HIV antigen or antibody was relatively low at the time. However, the confirmation test did not provide conclusive results, leading the patient to decline further renal replacement therapy. Two months later, the patient`s HIV antigen/antibody levels were measured as 95.23 in the outpatient department of our hospital., Conclusions: This case underscores the importance of actively exploring various detection strategies to enhance the efficiency of detecting acute phase HIV infection during the testing process., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Xiaowu Wang, Dong Wu; Tuantuan Li, Yong Gao.)

Objective: To compare oral pregabalin with oral sertraline for treatment of uraemic pruritus., Study Design: Randomised controlled trial. Place and Duration of the Study: Department of Nephrology, Pak Emirates Military Hospital Rawalpindi, Pakistan, from October 2023 to January 2024., Methodology: Patients with end-stage renal disease having pruritus for at least 6 weeks were included. Exclusion criteria comprised other dermatological or systemic diseases associated with pruritus, mental health issues, thrice-a-week haemodialysis schedule, and use of other treatments for uraemic pruritus. They were randomised to receive either pregabalin 75mg daily or sertraline 50mg daily for six weeks using computer-generated sequences. The Urdu version of the 5-D Itch scale was used to document the severity of pruritus at the baseline and at the end of therapy. Side effects to the treatment were also monitored., Results: There were 8 (16.67%) females and 40 (83.33%) males, with a mean age of 52.19 ± 12.19 years. The baseline 5-D Itch scale scores were equal in both groups. Mean improvement in 5-D Itch scale scores was 3.75 ± 1.26 and 2.08 ± 1.18 with pregabalin and sertraline, respectively (p <0.001). Side effects were reported by 2 (8.33%) patients on pregabalin and none using sertraline (p = 0.489)., Conclusion: Pregabalin was found to be more effective than sertraline in treating uraemic pruritus, though with a statistically insignificant trend towards a higher frequency of side effects., Key Words: Chronic renal failure, Pruritus, Renal dialysis, Selective serotonin reuptake inhibitors, Uraemia.

End-stage renal disease is a worldwide health burden, but the pathogenesis of uremia-associated cognitive impairment (CI) is poorly recognized. We hypothesized that uremia brings about deficiency of thiamin and folic acid and causes CI by inducing oxidative stress. Therefore, 24 Sprague-Dawley rats were randomly divided into two groups: a 5/6 nephrectomy group ( n  = 12) and a sham-operated group ( n  = 12). The Morris water maze was used to assess the cognitive function eight weeks post-surgery, and serum levels of thiamin, folic acid and homocysteine were detected subsequently. Brain and kidney tissues were collected for pathological examination and 8-Hydroxy-2'-deoxyguanosine (8-OHdG) immunochemistry staining. Results showed that the escape latency on training days 1-2 was longer, and the time in quadrant IV on experimental day 6 was significantly shorter in 5/6 nephrectomy group. Meanwhile, the uremic rats showed decreased thiamin, folic acid and increased homocysteine. We also found the time in quadrant IV was positively correlated with thiamin and folic acid level, while negatively correlated with the blood urea nitrogen and 8-OHdG positive cell proportion. Furthermore, in 5/6 nephrectomy group, the hippocampal neuron count was significantly reduced, and a greater proportion of 8-OHdG positive cells were detected. Pretreating LPS-stimulated rat microglial cells with thiamin or folic acid in vitro alleviated the inflammatory impairment in terms of cell viability and oxidative stress. In summary, we applied a uremic rat model and proved that uremia causes serum thiamin and folic acid deficiency, homocysteine elevation, along with neuron reduction and severe oxidative stress in hippocampus, finally leading to CI.

Background: High-quality patient-reported outcome (PRO) measures for dialysis patients with chronic pruritus are urgently needed. However, no known, well-validated multidimensional tools have been investigated to measure pruritus symptoms in dialysis patients., Objectives: To examine the psychometric properties of a multidimensional tool of chronic pruritus, the Uraemic Pruritus in Dialysis patients (UP-Dial) 14-item scale, by comparing haemodialysis and peritoneal dialysis modality., Methods: This validation study used data from the Thai Renal Outcomes Research-Uraemic Pruritus, a prospective, multicentre, longitudinal study. Data for this study were collected from 1 February 2019 to 31 May 2022. The adult sample of 226 haemodialysis and 327 peritoneal dialysis patients fulfilled the criteria of chronic pruritus based on the International Forum for the Study of Itch. Psychometric properties of the UP-Dial included validity and reliability, as measured across haemodialysis and peritoneal dialysis patients. Patients completed a set of anchor-based measurement tools, including global itching, Dermatology Life Quality Index (DLQI), EuroQoL-5 dimension-5 level (EQ-5D-5L), Kidney Disease Quality of Life-36 (KDQOL-36), Pittsburgh Sleep Quality Index (PSQI), global fatigue, Somatic Symptom Scale-8 (SSS-8) and Patient Health Questionnaire-9 (PHQ-9)., Results: From the patient's perspective, face validity was satisfactory for both dialysis samples. Psychometric analyses of the UP-Dial for each dialysis sample had good convergent validity. Spearman rho correlations indicate a positively strong correlation (0.73-0.74) with global itching, a positively moderate correlation (0.33-0.58) with DLQI, PSQI, global fatigue, SSS-8 and PHQ-9, and a negatively moderate correlation (-0.39 to -0.58) with EQ-5D-5L and KDQOL-36. The discriminant validity was satisfactory with a group of moderate and severe burden of pruritus for both dialysis samples. For scale reliability, the UP-Dial revealed excellent internal consistency (Cronbach's α = 0.89 and McDonald's ω = 0.90) and reproducibility (intraclass correlation 0.84-0.85) for both dialysis samples. Regarding psychometric properties, no statistically significant differences between dialysis samples were observed (all P > 0.05)., Conclusions: The findings reaffirm good measurement properties of the UP-Dial 14-item scale in haemodialysis and peritoneal dialysis patients with chronic pruritus. These suggest a transferability of the UP-Dial as a PRO measure in clinical trial and practice settings., Competing Interests: Conflicts of interest M.M.S. is an advisor/consultant for AstraZeneca, Bayer, GlaxoSmithKline (GSK) and Otsuka. J.A.B. is a consultant and has received research grants from Allakos, Amgen, AstraZeneca, Celldex, Escient, Genentech, GlaxoSmithKline (GSK), Jasper, Novartis and Sanofi Regeneron; has a leadership or fiduciary role in the American Academy of Allergy, Asthma & Immunology (president); Hereditary Angioedema Association (member activities board); Interasma (vice president); and the World Allergy Organization (board of directors). J.C.S. is an advisor/consultant for AbbVie, Leo Pharma, Novartis, Pfizer, Sanofi-Genzyme, Trevi, UCB and Vifor; is a speaker for AbbVie, Almirall, Eli-Lilly, Janssen-Cilag, Leo Pharma, Novartis, Pfizer and Sanofi-Genzyme; is an investigator (principal investigator in clinical trials) for AbbVie, Almirall, Amgen, AnaptysBio, BMS, Boehringer Ingelheim, Celtrion, Galapagos, Galderma, Helm AG, Incyte, InfraRX, Janssen-Cilag, Kliniksa, Leo Pharma, Medimmune, Menlo Therapeutics, Merck, Novartis, Pfizer, Regeneron, Teva, Trevi and UCB; and has a leadership or fiduciary role in the Polish Dermatological Society (president). The other authors declare that they have no relevant conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Competing Interests: The authors have no conflict of interest to declare.

Background: Intestinal necrosis in uremic patients has been reported but is rare., Case Presentation: A 56-year-old male patient who underwent long-term regular haemodialysis was admitted to the hospital due to involuntary shaking of the limbs and nonsense speech. The patient's symptoms improved after continuous blood purification under heparin anticoagulation, rehydration, sedation, and correction of electrolyte disturbances. However, the patient experienced a sudden onset of abdominal pain and a rapid decrease in blood pressure; high-dose norepinephrine were required to maintain his blood pressure. A plain abdominal radiograph performed at bedside showed intestinal dilation. Colonoscopy revealed inflammation and oedema of the entire colon, with purulent secretions and multiple areas of patchy necrosis. The cause of intestinal ischaemia was not clear., Conclusions: Although rare, previous causes of uremic colitis have been reported. As the patient developed abdominal pain before the onset of shock and the necrosis was seen on colonoscopy, we suspect that this is a case of fulminant uremic colitis., (© 2024. The Author(s).)

Uremic pruritus, a severe complication in patients with chronic kidney disease, is associated with a high prevalence. It can cause depression and sleep disorders, and seriously affect the quality of life and the social relations of patients. Recently, there is growing evidence showing that κ-opioid receptor agonists, including nalfurafine, difelikefalin, and nalbuphine, can effectively and safely reduce itching symptoms in patients with refractory uremic pruritus. Herein, we reviewed the epidemiology, pathogenesis, clinical symptoms, and treatment strategies of uremic pruritus, and summarized in detail the progress in clinical research on the use of κ-opioid receptor agonists, including nalfurafine, difelikefalin, and nalbuphine, in the management of patients with uremic pruritus., Competing Interests: 利益冲突　所有作者均声明不存在利益冲突, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Office of Journal of Sichuan University (Medical Sciences).)

Objective: This study aimed to investigate the value of noise reduction management in the intensive care unit (ICU) in elderly patients with chronic renal failure (CRF) in the uremic phase., Methods: A retrospective study was conducted, including 150 elderly patients with CRF in the uremic phase, who were treated in the ICU ward at the First Affiliated Hospital of Soochow University between January 2021 and August 2023. Among them, 73 were in the control group (routine ICU management), and 77 were in the observation group (routine ICU management + ICU noise reduction management). Anxiety, depression, sleep treatment, quality of life, blood pressure, heart rate (HR), and cortisol (COR) levels were compared between the two groups at baseline and 10 days after admission to the ICU., Results: There was no statistical significance in the comparison of baseline data between the two groups of patients (P > 0.05). At 10 days, the sleep quality of patients in the observation group was higher than that in the control group (P < 0.05). Anxiety levels, as well as blood pressure, HR, and COR levels, were significantly lower (P < 0.05), whereas the quality of life was higher in the observation group than in the control group (P< 0.05)., Conclusion: ICU noise reduction management can effectively improve the sleep quality and quality of life of elderly patients with CRF in the uremic phase., (Copyright © 2024 Noise & Health.)

Aim: This study aimed to investigate whether computed tomography (CT)-measured erector spinae parameters (ESPs) have diagnostic, severity assessment, and prognostic predictive value in uremic sarcopenia (US)., Materials and Methods: A total of 202 uremic patients were enrolled and divided into two groups: a control group and a sarcopenia group. Sarcopenia was classified into two types: severe and nonsevere. The area, volume, and density of the erector spinae (ES) were measured using chest CT images, and the relevant ESP, including the erector spinae index (ESI), total erector spinae volume (TESV), erector spinae density (ESD), and erector spinae gauge (ESG) were calculated. The occurrence of adverse events was followed-up for 36 months. The diagnostic value and severity of US were determined using the receiver operating characteristic (ROC) curve. Survival curves diagnosed using CT were plotted and compared with the curve drawn using the gold standard. Cox regression analysis was used to identify independent risk factors associated with survival in US., Results: With an area under the curve (AUC) of 0.840 and 0.739, the combined ESP has diagnostic value and the ability to assess the severity of US. There was no significant difference in the survival curve between the combined ESP for the diagnosis of US and the gold standard (P > 0.05). ESI is a standalone predictor of survival in patients with US., Conclusion: ESP measured by CT has diagnostic values for US and its severity, as well as being a predictive value for the prognosis of US., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the efficacy and safety of ultrafiltration (UF) combined with haemodialysis (HD) sequential therapy in patients with intradialytic hypotension (IDH) and water retention., Methods: A total of 53 uraemia patients with IDH who could not tolerate dehydration and significant water and sodium retention (net weight gain of more than 4 kg) were randomly divided into control group (28 cases) and treatment group (25 cases). After adjusting dialysis parameters (blood pump speed and excessive filtration), HD was tried again in the control group, and UF combined with HD was given sequential treatment in the treatment group. Outcome measures included efficacy measures (duration of treatment, total water removal, weight loss, dyspnoea score and left ventricular ejection fraction) and safety measures (heart rate, blood pressure, IDH incidence, bleeding and thromboembolic events)., Results: In terms of efficacy indicators, In the sequential treatment group, the duration of treatment (740 ± 168 min vs . 380 ± 94 min, p  < 0.05), total water removal (5280 ± 968 mL vs. 2980 ± 765 mL, p  < 0.05) and the weight loss (2756 ± 537 g vs . 1421 ± 362 g, p  < 0.05) was significantly higher than that of control group. Postoperative dyspnoea score (1.92 ± 0.400 vs. 3.32 ± 0.476, p  < 0.05), left ventricular ejection fraction (LVEF; 49.25 ± 3.76 vs. 56.46 ± 4.42, p  < 0.05) was significantly improved compared with that before treatment, and the difference was statistically significant. In control group, dyspnoea score (1.89 ± 0.416 vs. 1.82 ± 0.390, p  > 0.05) and left ventricular ejection fraction (49.04 ± 6.72 vs. 48.61 ± 7.12, p  > 0.05) were slightly improved after treatment, but there was no statistical significance. In terms of safety indicators, patients in the control group were prone to significant blood pressure fluctuation during treatment, and the incidence of IDH was significantly higher than that in the treatment group (75% vs. 0%, p  < 0.01), the difference was statistically significant, while the other safety indicators (heart rate change, bleeding and thromboembolic events) showed no statistically significant difference between the two groups., Conclusions: Compared with conventional HD, UF combined with HD can safely and effectively reduce water retention in patients with uraemia while avoiding IDH.

Background and Purpose: Uremic neuropathy (UN) is a disabling neuropathy in end-stage kidney disease (ESKD) affecting the majority of patients receiving long-term hemodialysis (HD). One previous nerve ultrasound study reported an increased cross-sectional area (CSA) of the median nerve in moderate UN, while another study found enlarged sural nerves in small-fiber polyneuropathy associated with ESKD. The present cohort study aims to analyze bilateral CSA of multiple nerves in UN., Methods: Ten nondiabetic ESKD patients with UN on HD for at least 2 years and 10 healthy age-matched controls underwent bilateral ultrasound examinations with CSA measurements in 13 arm and leg nerve sites. Nerve conduction studies (NCS) and the total neuropathy score (TNS) were recorded. Pearson's coefficient and the Mann-Whitney U-test were used to analyze correlations and compare groups., Results: ESKD patients presented advanced neuropathic symptoms (mean TNS 15.9). NCS showed significantly reduced motor and sensory amplitudes in the UN group compared to the control group, and a slightly reduced nerve CSA was observed in 5 of 13 nerve sites (p < .05); the other nerve sites were not enlarged. Sural nerve CSA (p < .05) and sensory amplitude (p < .01) were negatively correlated with the TNS., Conclusions: Nerve enlargement was not observed in the present study in advanced UN. A reduced nerve CSA observed in the sural nerve suggests an axonal loss associated with long-term HD in ESKD. During clinical workup of an acute disease of the peripheral nervous system in ESKD patients, nerve enlargement might be attributable to other causes than chronic UN., (© 2024 The Authors. Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

Acute kidney injury (AKI) is often accompanied by uremic encephalopathy resulting from accumulation of uremic toxins in brain possibly due to impaired blood-brain barrier (BBB) function. Anionic uremic toxins are substrates or inhibitors of organic anionic transporters (OATs). In this study we investigated the CNS behaviors and expression/function of BBB OAT3 in AKI rats and mice, which received intraperitoneal injection of cisplatin 8 and 20 mg/kg, respectively. We showed that cisplatin treatment significantly inhibited the expressions of OAT3, synaptophysin and microtubule-associated protein 2 (MAP2), impaired locomotor and exploration activities, and increased accumulation of uremic toxins in the brain of AKI rats and mice. In vitro studies showed that uremic toxins neither alter OAT3 expression in human cerebral microvascular endothelial cells, nor synaptophysin and MAP2 expressions in human neuroblastoma (SH-SY5Y) cells. In contrast, tumour necrosis factor alpha (TNFα) and the conditioned medium (CM) from RAW264.7 cells treated with indoxyl sulfate (IS) significantly impaired OAT3 expression. TNFα and CM from IS-treated BV-2 cells also inhibited synaptophysin and MAP2 expressions in SH-SY5Y cells. The alterations caused by TNFα and CMs in vitro, and by AKI and TNFα in vivo were abolished by infliximab, a monoclonal antibody designed to intercept and neutralize TNFα, suggesting that AKI impaired the expressions of OAT3, synaptophysin and MAP2 in the brain via IS-induced TNFα release from macrophages or microglia (termed as IS-TNFα axis). Treatment of mice with TNFα (0.5 mg·kg -1 ·d -1 , i.p. for 3 days) significantly increased p-p65 expression and reduced the expressions of Nrf2 and HO-1. Inhibiting NF-κB pathway, silencing p65, or activating Nrf2 and HO-1 obviously attenuated TNFα-induced downregulation of OAT3, synaptophysin and MAP2 expressions. Significantly increased p-p65 and decreased Nrf2 and HO-1 protein levels were also detected in brain of AKI mice and rats. We conclude that AKI inhibits the expressions of OAT3, synaptophysin and MAP2 due to IS-induced TNFα release from macrophages or microglia. TNFα impairs the expressions of OAT3, synaptophysin and MAP2 partly via activating NF-κB pathway and inhibiting Nrf2-HO-1 pathway., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Rationale & Objective: The toxins that contribute to uremic symptoms in patients with chronic kidney disease (CKD) are unknown. We sought to apply complementary statistical modeling approaches to data from untargeted plasma metabolomic profiling to identify solutes associated with uremic symptoms in patients with CKD., Study Design: Cross-sectional., Setting & Participants: 1,761 Chronic Renal Insufficiency Cohort (CRIC) participants with CKD not treated with dialysis., Predictors: Measurement of 448 known plasma metabolites., Outcomes: The uremic symptoms of fatigue, anorexia, pruritus, nausea, paresthesia, and pain were assessed by single items on the Kidney Disease Quality of Life-36 instrument., Analytical Approach: Multivariable adjusted linear regression, least absolute shrinkage and selection operator linear regression, and random forest models were used to identify metabolites associated with symptom severity. After adjustment for multiple comparisons, metabolites selected in at least 2 of the 3 modeling approaches were deemed "overall significant.", Results: Participant mean estimated glomerular filtration rate was 43mL/min/1.73m 2 , with 44% self-identifying as female and 41% as non-Hispanic Black. The prevalence of uremic symptoms ranged from 22% to 55%. We identified 17 metabolites for which a higher level was associated with greater severity of at least one uremic symptom and 9 metabolites inversely associated with uremic symptom severity. Many of these metabolites exhibited at least a moderate correlation with estimated glomerular filtration rate (Pearson's r≥0.5), and some were also associated with the risk of developing kidney failure or death in multivariable adjusted Cox regression models., Limitations: Lack of a second independent cohort for external validation of our findings., Conclusions: Metabolomic profiling was used to identify multiple solutes associated with uremic symptoms in adults with CKD, but future validation and mechanistic studies are needed., Plain-Language Summary: Individuals living with chronic kidney disease (CKD) often experience symptoms related to CKD, traditionally called uremic symptoms. It is likely that CKD results in alterations in the levels of numerous circulating substances that, in turn, cause uremic symptoms; however, the identity of these solutes is not known. In this study, we used metabolomic profiling in patients with CKD to gain insights into the pathophysiology of uremic symptoms. We identified 26 metabolites whose levels were significantly associated with at least one of the symptoms of fatigue, anorexia, itchiness, nausea, paresthesia, and pain. The results of this study lay the groundwork for future research into the biological causes of symptoms in patients with CKD., (Copyright © 2024 National Kidney Foundation, Inc. All rights reserved.)

Background: Uremic stomatitis is often unfamiliar to healthcare professionals. This study presents five cases of uremic stomatitis, providing a comprehensive analysis of their demographic distribution, clinicopathological features, and management strategies based on existing literature., Methods: Data were collected from centers across Brazil, Argentina, Venezuela, and Mexico. Electronic searches were conducted in five databases supplemented by manual scrutiny and gray literature., Results: The series consisted of three men and two women with a mean age of 40.2 years. Lesions mostly appeared as white plaques, particularly on the tongue (100%). The median blood urea level was 129 mg/dL. Histopathological analysis revealed epithelial changes, including acanthosis and parakeratosis, with ballooned keratinocytes in the suprabasal region. Oral lesions resolved subsequent to hemodialysis in three cases (75%). Thirty-seven studies comprising 52 cases of uremic stomatitis have been described hitherto. Most patients were male (65.4%) with a mean age of 43.6 years. Clinically, grayish-white plaques (37.3%) and ulcers/ulcerations (28.9%) were common, particularly on the tongue (30.9%). Hemodialysis was performed on 27 individuals. The resolution rate of oral lesions was 53.3%., Conclusion: Earlier recognition of uremic stomatitis, possibly associated with long-term uremia, holds the potential to improve outcomes for patients with undiagnosed chronic kidney disease., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Chronic kidney disease (CKD) patients have an increased risk for cognitive impairment compared to the general population. The risk is much higher in CKD patients who progress to end-stage kidney disease (ESKD) and require hemodialysis or peritoneal dialysis. Multiple factors may contribute to cognitive impairment in CKD patients and in patients on chronic dialysis. However, the observation that, after kidney transplantation, there is an improvement in several cognitive performance markers and that some structural and functional brain abnormalities may improve suggests that cognitive deficits in patients on dialysis may be at least partially reversible. Recent evidence supports the hypothesis that uremic toxins may disrupt the blood brain barrier and damage the brain cells. Such brain toxicity should prompt efforts to lower the burden of uremic toxins through dialytic and non-dialytic strategies., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

In patients with chronic kidney disease (CKD), skeletal muscle mass and function are known to occasionally decline. However, the muscle regeneration and differentiation process in uremia has not been extensively studied. In mice with CKD induced by adenine-containing diet, the tibialis anterior muscle injured using a barium chloride injection method recovered poorly as compared to control mice. In the cultured murine skeletal myocytes, stimulation with indoxyl sulfate (IS), a representative uremic toxin, morphologically jeopardized the differentiation, which was counteracted by L-ascorbic acid (L-AsA) treatment. Transcriptome analysis of cultured myocytes identified a set of genes whose expression was down-regulated by IS stimulation but up-regulated by L-AsA treatment. Gene silencing of myomixer, one of the genes in the set, impaired myocyte fusion during differentiation. By contrast, lentiviral overexpression of myomixer compensated for a hypomorphic phenotype caused by IS treatment. The split-luciferase technique demonstrated that IS stimulation negatively affected early myofusion activity that was rescued by L-AsA treatment. Lastly, in mice with CKD compared with control mice, myomixer expression in the muscle tissue in addition to the muscle weight after the injury was reduced, both of which were restored with L-AsA treatment. Collectively, data showed that the uremic milieu impairs the expression of myomixer and impedes the myofusion process. Considering frequent musculoskeletal injuries in uremic patients, defective myocyte fusion followed by delayed muscle damage recovery could underlie their muscle loss and weakness., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: Uraemia causes a generalised encephalopathy as its most common neurological complication. Isolated brainstem uraemic encephalopathy is rare. We report a case of fatigable ptosis and complex ophthalmoplegia in brainstem uraemic encephalopathy., Case Presentation: A 22-year-old Sri Lankan man with end stage renal failure presented with acute onset diplopia and drooping of eyelids progressively worsening over one week. The patient had not complied with the prescribed renal replacement therapy which was planned to be initiated 5 months previously. On examination, his Glasgow coma scale score was 15/15, He had a fatigable asymmetrical bilateral ptosis. The ice-pack test was negative. There was a complex ophthalmoplegia with bilateral abduction failure and elevation failure of the right eye. The diplopia did not worsen with prolonged stare. The rest of the neurological examination was normal. Serum creatinine on admission was 21.81 mg/dl. The repetitive nerve stimulation did not show a decremental pattern. Magnetic resonance imaging (MRI) of the brain demonstrated diffuse midbrain and pontine oedema with T2 weighted/FLAIR hyperintensities. The patient was haemodialyzed on alternate days and his neurological deficits completely resolved by the end of the second week of dialysis. The follow up brain MRI done two weeks later demonstrated marked improvement of the brainstem oedema with residual T2 weighted/FLAIR hyperintensities in the midbrain., Conclusions: Uraemia may rarely cause an isolated brainstem encephalopathy mimicking ocular myasthenia, which resolves with correction of the uraemia., (© 2024. The Author(s).)

Background: Dialysis disequilibrium syndrome (DDS) is a rare but significant concern in adult and pediatric patients undergoing dialysis initiation with advanced uremia or if done after an interval. It is imperative to gain insights into the epidemiological patterns, pathophysiological mechanisms, and preventive strategies aimed at averting the onset of this ailment., Design: Prospective observational quality improvement initiative cohort study., Setting and Participants: A prospective single-center study involving 50 pediatric patients under 18 years recently diagnosed with chronic kidney disease stage V with blood urea ≥200 mg/dL, admitted to our tertiary care center for dialysis initiation from January 2017 to October 2023., Quality Improvement Plan: A standardized protocol was developed and followed for hemodialysis in pediatric patients with advanced uremia. This protocol included measures such as lower urea reduction ratios (targeted at 20%-30%) with shorter dialysis sessions and linear dialysate sodium profiling. Prophylactic administration of mannitol and 25% dextrose was also done to prevent the incidence of dialysis disequilibrium syndrome., Measures: Incidence of dialysis disequilibrium syndrome and severe dialysis disequilibrium syndrome, mortality, urea reduction ratios (URRs), neurological outcome at discharge, and development of complications such as infection and hypotension. Long-term outcomes were assessed at the 1-year follow-up including adherence to dialysis, renal transplantation, death, and loss to follow-up., Results: The median serum creatinine and urea levels at presentation were 7.93 and 224 mg/dL, respectively. A total of 20% of patients had neurological symptoms attributable to advanced uremia at the time of presentation. The incidence of dialysis disequilibrium syndrome was 4% (n = 2) with severe dialysis disequilibrium syndrome only 2% (n = 1). Overall mortality was 8% (n = 4) but none of the deaths were attributed to dialysis disequilibrium syndrome. The mean urea reduction ratios for the first, second, and third dialysis sessions were 23.45%, 34.56%, and 33.50%, respectively. The patients with dialysis disequilibrium syndrome were discharged with normal neurological status. Long-term outcomes showed 88% adherence to dialysis and 38% renal transplantation., Limitations: This study is characterized by a single-center design, nonrandomized approach, and limited sample size., Conclusions: Our structured protocol served as a framework for standardizing procedures contributing to low incidence rates of dialysis disequilibrium syndrome., (© 2024 International Society for Hemodialysis.)

The kidneys filter the blood to excrete waste products and excess salt from the body as urine, while reabsorbing what the body needs and keeping it in the body. For this reason, when the function of the kidneys deteriorates, urine cannot be produced, and homeostasis of electrolytes and acid-bases cannot be maintained. As a result, waste products accumulate in the body, resulting in uremia and the need for dialysis induction or kidney transplant. This paper provides an overview of the neurological complications that appear in kidney disease and their treatment.

Background: Due to the recurrent nature of uraemic pruritus among patients receiving haemodialysis, self-care can offer patients a means to ameliorate this symptom. Qualitative data on self-care of uraemic pruritus are limited., Objective: To explore how patients on haemodialysis perceive uraemic pruritus, implement self-care practice, and appraise the outcome of self-caring uraemic pruritus., Design: The Common Sense Model of Self-Regulation guided the study design., Participants and Approaches: Data were collected through face-to-face interviews with 30 patients receiving haemodialysis who were aged from 50 to 89 years and had had uraemic pruritus for more than 6 weeks. Interviews were audio recorded, and verbatim transcriptions of interviews were analysed., Findings: Our participants generally used life-related analogies to describe uraemic pruritus, which they reviewed as a momentarily controllable symptom with an endless timeline. Most participants reported limited knowledge of the aetiology and multifaceted impacts of uraemic pruritus on their daily life and emotional status. The impacts on daily life included decreased zest for activities and sleep disturbances. Physical management of uraemic pruritus involved daily substance use and interventions employed during pruritic episodes. Psychological managements involved preferences for indoor activities and a fatalistic outlook. Unsatisfactory outcomes and psychological burdens from self-care practice were reported., Conclusions: Life experiences shape symptom presentation and self-care practice in patients on haemodialysis. The modalities for self-caring for uraemic pruritus are diverse but not remarkably effective. Performing self-care tasks places a substantial burden on patients. Individualised educational programs should be developed to improve the outcome of self-care practice., (© 2022 European Dialysis and Transplant Nurses Association/European Renal Care Association.)

Background and Hypothesis: Pruritus is a common and distressing symptom that affects patients with chronic kidney disease. The concentration of protein bounded uremic toxin was associated with the uremic pruritus. The aim is to assess the efficacy of AST-120 for uremic pruritus in hemodialysis patients., Materials and Methods: The participants were enrolled and then divided into the AST-120 treatment group and control group with a ratio of 2:1. All participants underwent pre-observation screenings two weeks before the study with three visits. In the treatment phase (week 1 to week 4), the treatment group added 6g/day of AST-120 along with routine anti-pruritic treatment. Visual analog scale (VAS) and biochemical parameters were measured., Results: The VAS score began to be lower in the AST-120 treatment group after the 5th visiting ( p < 0.05). The reduction in indoxyl sulfate (IS) at 5th week along with TNF-alpha. The reduction ratio of indoxyl sulfate correlated with reduction of parathyroid hormone., Conclusion: This study has demonstrated that the four-week treatment of AST-120 decreased the severity of uremic pruritus in patients with ESRD. The concentration of IS and TNF-alpha decreased in the AST-120 treatment group. The reduction of iPTH correlated with the reduction of IS in the AST-120 treatment.

Background: Pruritus is a common complaint in patients with end-stage renal disease. Indoxyl sulfate (IS) is a tryptophan end metabolite extremely renal excreted. Activated charcoal can interfere with IS intestinal absorption., Objectives: To evaluate the serum level of IS and the effect of activated charcoal on uremic pruritus., Materials and Methods: In all, 135 participants were divided into 2 main groups. In total, 45 normal and healthy individuals as a control group and 90 patients on regular hemodialysis; 45 of these patients had uremic pruritus and the other 45 were not complaining of uremic pruritus. Serum IS was measured. Activated charcoal was used by patients with uremic pruritus. The severity of pruritus and Dermatology Life Quality Index (DLQI) were assessed., Results: The serum IS was significantly elevated in uremic patients than in control subjects ( P  < .001) and significantly elevated in uremic patients without pruritus ( P  < .001). Furthermore, there were positive significant correlations between the serum IS and both severity of pruritus ( P  < .001) and DLQI ( P  < .001). After activated charcoal usage, there was a significant decrease in IS level with the improvement of pruritus and quality of life of patients., Conclusions: IS may play a role in uremic pruritus. Activated charcoal could be considered a treatment for uremic pruritus., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Patients with chronic kidney disease (CKD) have an increased risk of cognitive disorders, presenting as vascular dementia, compared with the general population. These cognitive disorders occur early during the course of the kidney disease and evolve in parallel with the decline in glomerular filtration rate. They affect 30 to 80 % of patients with stage 5 CKD. Kidney transplantation only partially improves cognitive impairment. In this narrative review, we summarize the epidemiology and recent clinical and experimental data on cognitive impairment in CKD and discuss the potential specific mechanisms. Among the factors associated with cognitive impairment, the accumulation of uremic toxins such as indoxyl sulfate appears to be a specific risk factor for cognitive decline. These toxins have an endothelial toxicity that can disrupt the cerebral endothelium. The rupture of the blood-brain barrier (BBB) is a mechanism implicated in several neurodegenerative pathologies and systemic diseases with cerebral tropism. Recent experimental findings in CKD indicate that disruption of the BBB appears to be an important mechanism behind cognitive impairment in CKD. In murine models of CKD, increased BBB permeability is linked to memory impairment and aryl hydrocarbon receptor activation following accumulation of circulating indoxyl sulfate. This disruption of the BBB could also have harmful consequences for stroke susceptibility and drug neurotoxicity in CKD patients.

Rationale: Wilms' tumor (WT) is the most common pediatric kidney malignancy and is rarely found in adults. Nonspecific clinical symptoms and imaging features often lead to delayed diagnosis or misdiagnosis of adult WT, resulting in poor clinical outcomes. Ultrasound (US), as an efficient and noninvasive examination method, has been widely used in clinical diagnosis and treatment. Therefore, various US evidence is meaningful to improve understanding of adult WT characteristics in ultrasound., Patient Concerns: A 45-year-old female patient with uremia (regular hemodialysis for 13 years) with painless gross hematuria was diagnosed with a right kidney tumor penetrating to the lung. Preoperatively, B-mode ultrasonography showed an ill-defined hyperechoic mass in the right kidney, which revealed an unclear border, uneven internal echoes, and calcification. Besides, the internal blood flow signal of the tumor was detected. Contrast-enhanced ultrasound (CEUS) showed an uneven hyper-enhancement in the tumor ("fast in and slow out"). Contrast-enhanced computed tomography of the kidney indicated a similar result as the CEUS. Moreover, the chest CT identified multiple pulmonary metastatic nodules., Diagnoses: An ultrasound-guided percutaneous core needle biopsy of the tumor proceeded to make a definite diagnosis of adult WT (epithelial type)., Interventions: The patient was treated with tislelizumab., Outcomes: No progress was found to date., Lessons: We report the first case in which CEUS was performed in an adult WT patient with uremia and multiple pulmonary metastases. The features obtained by the US can help in the diagnosis of adult WT and direct further diagnostic procedures., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Vascular calcification (VC) is prevalent in uremia patients, lacking effective molecular biomarkers. This study was conducted to explore the role of serum cell division cycle 42 (CDC42) in the diagnosis of uremic VC incidence and progression. We enrolled 104 uremia patients and selected arcus aortae calcification (AAC) as the outcome phenotype. Levels of CDC42, 1,25-dihydroxy vitamin D (1,25(OH) 2 -D), fibroblast growth factor-23 (FGF-23), and other laboratory parameters in the blood were measured. The receiver operator characteristic curve, the Pearson test, and the multivariate Logistic regression were used for the analysis of CDC42 diagnostic values, correlation analysis, and screening of VC risk factors, respectively. CDC42 was higher in the serum of uremia patients with VC and elevated with the increase in AAC level. Serum CDC42 level>1.025 was predictive of VC incidence with 83.58% sensitivity and 56.76% specificity, and CDC42 level>1.280 was predictive of VC progression with 73.33% sensitivity and 68.18% specificity. Serum CDC42 was positively correlated with 1,25(OH) 2 -D and FGF-23. Uremia patients with higher serum CDC42 had a higher probability of VC incidence and progression. Generally, serum CDC42 helped the diagnosis of uremic VC incidence and progression and was an independent risk factor for uremic VC progression.

Objective: To investigate the predictive value of serum d-serine level for hearing impairment (HI) in uremic patients., Methods: In this study, 30 uremic patients with HI and 30 with normal hearing were selected. The basic conditions, biochemical indicators, and serum serine levels of the two groups were compared to analyze the influencing factors of HI., Results: The age and d-serine levels were higher in the HI group, while the l-serine level was lower than uremia in the normal hearing group. Logistic regression analysis showed that d-serine level ≥10 μM and older age increased the risk of HI. The area of the receiver operating characteristic (ROC) curve drawn by the prediction probability of HI was 0.838, indicating that age, d-serine, and l-serine had predictive diagnostic values for HI ( p  < .001). Among these, the ROC curve area of d-serine in predicting HI in uremic patients was 0.822 ( p  < .001)., Conclusions: Increased d-serine and age are two risk factors for HI, while l-serine is a protective factor. d-Serine level has a predictive value for HI in uremic patients. Uremic patients are recommended hearing assessment, estimation of d-serine levels, and early intervention.

Aims: Expanded hemodialysis (HDx) therapy with improved molecular cut-off dialyzers exerts beneficial effects on lowering uremia-associated chronic systemic microinflammation, a driver of endothelial dysfunction and cardiovascular disease (CVD) in hemodialysis (HD) patients with end-stage renal disease (ESRD). However, studies on the underlying molecular mechanisms are still at an early stage. Here, we identify the (endothelial) transcription factor Krüppel-like factor 2 (KLF2) and its associated molecular signalling pathways as key targets and regulators of uremia-induced endothelial micro-inflammation in the HD/ESRD setting, which is crucial for vascular homeostasis and controlling detrimental vascular inflammation., Methods and Results: First, we found that human microvascular endothelial cells (HMECs) and other typical endothelial and kidney model cell lines (e.g. HUVECs, HREC, and HEK) exposed to uremic serum from patients treated with two different hemodialysis regimens in the Permeability Enhancement to Reduce Chronic Inflammation II (PERCI-II) crossover clinical trial - comparing High-Flux (HF) and Medium Cut-Off (MCO) membranes - exhibited strongly reduced expression of vasculoprotective KLF2 with HF dialyzers, while dialysis with MCO dialyzers led to the maintenance and restoration of physiological KLF2 levels in HMECs. Mechanistic follow-up revealed that the strong downmodulation of KLF2 in HMECs exposed to uremic serum was mediated by a dominant engagement of detrimental ERK instead of beneficial AKT signalling, with subsequent AP1-/c-FOS binding in the KLF2 promoter region, followed by the detrimental triggering of pleiotropic inflammatory mediators, while the introduction of a KLF2 overexpression plasmid could restore physiological KLF2 levels and downmodulate the detrimental vascular inflammation in a mechanistic rescue approach., Conclusion: Uremia downmodulates vasculoprotective KLF2 in endothelium, leading to detrimental vascular inflammation, while MCO dialysis with the novel improved HDx therapy approach can maintain physiological levels of vasculoprotective KLF2., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Wu, Gyamfi, Wang, Luecht, Pfefferkorn, Ashraf, Kamhieh-Milz, Witowski, Dragun, Budde, Schindler, Zickler, Moll and Catar.)

Chronic kidney disease (CKD) is a non-reversible and progressive disease affecting the kidneys, significantly impacting global public health. One of the complications of chronic kidney disease is impaired intestinal barrier function, which may allow harmful products such as urea to enter the bloodstream and cause systemic inflammation. This study aimed to investigate whether supplementation with activated charcoal could reduce uremic toxins in patients with end-stage renal disease (ESRD). The study was a randomized clinical trial conducted at the Dialysis Center of al Diwaniyah Medical Hospital in the Diwaniyah Governorate. Eighty-two patients with ESRD on regular hemodialysis were enrolled, with 15 patients receiving oral supplementation with activated charcoal in addition to standard care and 13 patients receiving only standard care. Blood samples were collected at baseline and after eight weeks, and several biomarkers were measured, including estimated glomerular filtration rate (eGFR), creatinine, urea, phosphorus, albumin, and indoxyl sulfate. The results showed a significant reduction in both serum urea and serum phosphorus levels after eight weeks of oral-activated charcoal treatment. However, the other biomarkers were not affected by the treatment. In conclusion, the use of oral-activated charcoal for eight weeks in Iraqi patients undergoing maintenance hemodialysis improved urea and phosphorus levels., Competing Interests: The authors declare no conflict of interest., (©2023 JOURNAL of MEDICINE and LIFE.)

Background: To evaluate the clinical efficacy of supra-hemodiafiltration with endogenous reinfusion (Supra-HFR) for pruritus in uremic maintenance hemodialysis (HD) patients and explore the possible mechanism., Methods: This study prospectively included 60 patients with uremia who underwent maintenance hemodialysis and developed pruritus. Patients were randomly divided into a study group (30 cases) and a control group (30 cases). Patients in the study group underwent dialysis once a week with Supra-HFR and twice a week with HD. The group received HD dialysis 3 times a week. Visual analog scales (VAS) scores, 5-D itch scale scores, and 12-Item Pruritus Severity Scale (12-PSS) were used to evaluate the itching degree of patients. Quality of life was assessed using KDTA and SF-36 scores. Blood levels of hypersensitive C-reactive protein, calcium ion (Ca2+), phosphorus ion (P 3+ ), free parathyroid hormone (iPTH), and β2-microglobulin (β2-MG) were compared between the two groups before treatment and at follow-up 24 weeks after treatment., Results: Before treatment, there was no significant difference in VAS, 5-D itch scale, and 12-PSS score between the study group and the control group (all p > 0.05). After 24 weeks of treatment, the VAS score of the study group (2.82 ± 0.91) was significantly lower than that of the control group (7.47 ± 1.32, p < 0.001), the 5-D itch scale score of the study group (9.47 ± 2.34) was significantly lower than that of the control group (18.53 ± 4.02, p < 0.001), the 12-PSS score of the study group (11.20 ± 1.81) was significantly lower than that of the control group (16.47 ± 2.09, p < 0.001). KDTA of the study group (64.17 ± 8.07 vs. 47.83 ± 13.46, p < 0.001) and SF-36 scores (65.37 ± 6.28 vs. 55.90 ± 14.28, p = 0.002) were significantly higher than that in the control group. The levels of hs-CRP, P 3+ , iPTH, and β2-MG in the study group after treatment were lower than those before treatment, and lower than those in the control group after treatment (all p < 0.05)., Conclusions: The Supra-HFR can effectively reduce the itching symptoms of uremia patients and improve their quality of life., (© 2023 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Studies over recent years have redeveloped our understanding of uremic cardiomyopathy, defined as left ventricular hypertrophy, congestive heart failure, and associated cardiac hypertrophy plus other abnormalities that result from chronic kidney disease and are often the cause of death in affected patients. Definitions of uremic cardiomyopathy have conflicted and overlapped over the decades, complicating the body of published evidence, and making comparison difficult. New and continuing research into potential risk factors, including uremic toxins, anemia, hypervolemia, oxidative stress, inflammation, and insulin resistance, indicates the increasing interest in illuminating the pathways that lead to UC and thereby identifying potential targets for intervention. Indeed, our developing understanding of the mechanisms of UC has opened new frontiers in research, promising novel approaches to diagnosis, prognosis, treatment, and management. This educational review highlights advances in the field of uremic cardiomyopathy and how they may become applicable in practice by clinicians. Pathways to optimal treatment with current modalities (with hemodialysis and angiotensin-converting enzyme inhibitors) will be described, along with proposed steps to be taken in research to allow evidence-based integration of developing investigational therapies., (© 2023. The Author(s).)

Patients with ESRD have an increased risk of bleeding owing to platelet dysfunction associated with uremia. It is important to obtain coagulation tests and complete blood count before the surgical procedure, and abnormal values should be discussed with the patient's physician. A conservative surgical technique must be followed to decrease the risk of bleeding and infection. The dentist should ensure the availability of local hemostatic agents at the dental office to be used as needed to obtain hemostasis. Following the medical complexity status (MCS) system, the patient can be designated as MCS 2B category., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Protein energy wasting (PEW) is a common complication both in chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Of note, PEW is one of the stronger predictors of morbidity and mortality in this patient population. The pathogenesis of PEW involves several mechanisms, including anorexia, insulin resistance, acidosis and low-grade inflammation. In addition, "sterile" muscle inflammation contributes to PEW at an advanced CKD stage. Both immune and resident muscle cells can activate innate immunity; thus, they have critical roles in triggering "sterile" tissue inflammation. Toll-like receptor 4 (TLR4) can detect endogenous danger-associated molecular patterns generated or retained in blood in uremia and induce a sterile muscle inflammatory response via NF-κB in myocytes. In addition, TLR4, though the activation of the NLRP3 inflammasome, links the sensing of metabolic uremic stress in muscle to the activation of pro-inflammatory cascades, which lead to the production of IL-1β and IL-18. Finally, uremia-induced accelerated cell senescence is associated with a secretory phenotype that favors fibrosis in muscle. Targeting these innate immune pathways could lead to novel therapies for CKD-related PEW.

Chronic kidney disease-mineral and bone disorder has complex and diverse clinical manifestations, including the simplest abnormalities of calcium, phosphorus and parathyroid hormone detected in blood, abnormalities of bone transformation and mineralization in bone, and calcification of blood vessels or other soft tissues detected on imaging. Patients with CKD-MBD combined low bone mineral density and fragility fractures are referred to as CKD-MBD with low bone mineral density. Vascular calcification refers to ectopic deposition of calcium phosphate in the blood vessel walls and heart valves. The degree of vascular calcification was inversely proportional to bone mineral density. The more severe the degree of vascular calcification, the lower the bone mineral density, and the higher the risk of death, indicating that the bone-vascular axis exists. Activation and alteration of the Wnt signaling pathway are central to the treatment of vascular diseases in uremia. Vitamin D supplementation can prevent secondary hyperparathyroidism, activate osteoblasts, relieve muscle weakness and myalgia, and reduce vascular calcification. Nutritional vitamin D may improve vascular calcification in uremia patients by regulating Wnt signaling pathway., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Chronic kidney disease (CKD) is an increasing health care problem. About 10% of the general population is affected by CKD, representing the sixth cause of death in the world. Cardiovascular events are the main mortality cause in CKD, with a cardiovascular risk 10 times higher in these patients than the rate observed in healthy subjects. The gradual decline of the kidney leads to the accumulation of uremic solutes with a negative effect on every organ, especially on the cardiovascular system. Mammalian models, sharing structural and functional similarities with humans, have been widely used to study cardiovascular disease mechanisms and test new therapies, but many of them are rather expensive and difficult to manipulate. Over the last few decades, zebrafish has become a powerful non-mammalian model to study alterations associated with human disease. The high conservation of gene function, low cost, small size, rapid growth, and easiness of genetic manipulation are just some of the features of this experimental model. More specifically, embryonic cardiac development and physiological responses to exposure to numerous toxin substances are similar to those observed in mammals, making zebrafish an ideal model to study cardiac development, toxicity, and cardiovascular disease.

Cardiovascular complications are accompanied by life-threatening complications and represent the major cause of death in patients with chronic kidney disease (CKD). Magnesium is important for the physiology of cardiac function, and its deficiency is common in CKD. In the present study, we investigated the impact of oral magnesium carbonate supplementation on cardiac function in an experimental model of CKD induced in Wistar rats by an adenine diet. Echocardiographic analyses revealed restoration of impaired left ventricular cardiac function in animals with CKD. Cardiac histology and real-time PCR confirmed a high amount of elastin protein and increased collagen III expression in CKD rats supplemented with dietary magnesium as compared with CKD controls. Both structural proteins are crucial in maintaining cardiac health and physiology. Aortic calcium content increased in CKD as compared with tissue from control animals. Magnesium supplementation numerically lowered the increases in aortic calcium content as it remained statistically unchanged, compared with controls. In summary, the present study provides evidence for an improvement in cardiovascular function and aortic wall integrity in a rat model of CKD by magnesium, as evidenced by echocardiography and histology.

Introduction: In chronic kidney disease (CKD), the high morbidity and mortality risk for cardiovascular disease (CVD) are not easily explained only on the basis of traditional factors. Among nontraditional ones involved in CKD, malnutrition, inflammation, and atherosclerosis/calcification have been described as the "MIA syndrome.", Methods: In this pilot study, we evaluated the association between the variation in serum levels of 27 uremic retention solutes plus 6 indexes related to the MIA syndrome processes in a population of dialysis patients., Results: As expected, we found a direct correlation between serum albumin and both phosphate and total cholesterol (r = 0.54 and 0.37, respectively; p < 0.05). Moreover, total cholesterol and phosphate directly correlate (r = 0.40, p < 0.05). The relationship between malnutrition and inflammation is highlighted by the correlation of serum cholesterol levels with serum alpha-1 acid glycoprotein and IL-6 levels (r = -0.56, r = -0.39, respectively; p < 0.05). Moreover, the relation between inflammation and atherosclerosis/calcification is supported by the correlation of IL-6 with VEGF levels and vascular smooth muscle cell high-Pi in vitro calcification (r = 0.81, r = 0.66, respectively; p < 0.01)., Conclusion: We found significant correlations between several uremic retention solutes and malnutrition, inflammation, and atherosclerosis/calcification. Our findings support the hypothesis of a central role of the uremic milieu in the MIA syndrome and ultimately in the pathogenesis of CKD-specific CVD risk factors., (© 2022 S. Karger AG, Basel.)

Defined as the unpleasant sensation that causes the desire to scratch, pruritus is the most common skin symptom associated with uremia and appears in almost half of patients with advanced chronic kidney disease (CKD). Beyond its direct impact on quality of life, CKD-associated pruritus (CKD-aP) is an independent predictor of mortality that also has a synergistic effect with other quality of life-related symptoms, such as insomnia, depression, and anxiety. Although different mechanisms have been proposed to explain the origin of Pa-ERC, its etiopathogenesis is still not fully understood. Since new therapeutic targets have been identified and several clinical trials have recently shown promising results, our current understanding of the interrelationships has expanded significantly and the pathophysiological mechanisms underlying CKD-aP are now considered to be multifactorial. The potential triggers of pruritus in patients with CKD are discussed in this review, including hypotheses about skin xerosis, accumulation of uremic toxins, dysregulation of the immune system and systemic inflammation, uremic neuropathy, and imbalances in the endogenous opioid system. Other non-uremic causes of pruritus are also discussed, with the aim of guiding the physicians to apply an adequate aetiopathogenic approach to CKD-aP in their day-to-day clinical practice., (Copyright © 2022 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Uremic pruritus (UP) is a common and distressing symptom in patients with advanced or end-stage renal disease under hemodialysis (HD). The present multicentric study aimed to identify prevalence and determinants of severity of UP among Egyptian patients. Performed investigations included serum urea, creatinine, calcium, phosphorus, parathormone, ferritin and liver enzymes. Pruritus was evaluated using the visual analog scale. The study included 295 patients on maintenance HD. They comprised 151 patients (51.2%) with UP. Independent predictors of UP included associated hypertension (OR: 0.48, 95% CI 0.28 to 0.83, p=0.008), higher calcium levels (OR: 1.29, 95% CI 1.02 to 1.62, p=0.032), higher phosphorus levels (OR: 1.18, 95% CI 1.02 to 1.37, p=0.03) and higher high-sensitivity C-reactive protein (hsCRP) levels (OR: 1.0, 95% CI 1.0 to 1.01, p=0.049). Independent predictors of significant UP included longer HD duration (OR: 1.23, 95% CI 1.1 to 1.38, p<0.001), lack of vitamin D supplementation (OR: 3.71, 95% CI 1.03 to 13.4, p=0.045), lower albumin levels (OR: 0.32, 95% CI 0.14 to 0.74, p=0.008) and higher hsCRP levels (OR (CRP): 1.02 (1.0-1.03), p=0.011). In conclusion, UP is fairly common among Egyptian HD patients. Independent predictors of UP severity include longer HD duration, lack of vitamin D supplementation, lower albumin levels and higher hsCRP levels.

Background/aim: Uremic cardiomyopathy (UCM) is a characteristic cardiac pathology that is commonly found in patients with chronic kidney disease. This study dissected the mechanism of SPI1 in myocardial fibrosis and inflammation induced by UCM through S100A8/A9., Methods: An UCM rat model was established, followed by qRT-PCR and western blot analyses of SPI1 and S100A8/A9 expression in myocardial tissues. After alterations of SPI1 and S100A8/A9 expression in UCM rats, the blood specimens were harvested from the cardiac apex of rats. The levels of creatine phosphokinase-MB (CK-MB), blood creatinine, blood urea nitrogen (BUN), and inflammatory cytokines (interleukin [IL]-6, IL-1β, and tumor necrosis factor-α [TNF-α]) were examined in the collected blood. Collagen fibrosis was assessed by Masson staining. The expression of fibrosis markers [transforming growth factor (TGF)-β1, α-smooth muscle actin (SMA), Collagen 4a1, and Fibronectin], IL-6, IL-1β, and TNF-α was measured in myocardial tissues. Chromatin immunoprecipitation and dual-luciferase reporter gene assays were conducted to test the binding relationship between SPI1 and S100A8/A9., Results: S100A8/A9 and SPI1 were highly expressed in the myocardial tissues of UCM rats. Mechanistically, SPI1 bound to the promoter of S100A8/A9 to facilitate S100A8/A9 transcription. S100A8/A9 or SPI1 knockdown reduced myocardial fibrosis and inflammation and the levels of CK-MB, blood creatinine, and BUN, as well as the expression of TGF-β1, α-SMA, Collagen 4a1, Fibronectin, IL-6, TNF-α, and IL-1β in UCM rats., Conclusion: SPI1 knockdown diminished S100A8/A9 transcription, thus suppressing myocardial fibrosis and inflammation caused by UCM.