BACKGROUND: Chronic kidney disease presents global health challenges, with hemodialysis as a common treatment. However, non-dialyzable uremic toxins demand further investigation for new therapeutic approaches. Renal tubular cells require scrutiny due to their vulnerability to uremic toxins.
METHODS: In this study, a systems biology approach utilized transcriptomics data from healthy renal tubular cells exposed to healthy and post-dialysis uremic plasma.
RESULTS: Differential gene expression analysis identified 983 up-regulated genes, including 70 essential proteins in the protein-protein interaction network. Modularity-based clustering revealed six clusters of essential proteins associated with 11 pathological pathways activated in response to non-dialyzable uremic toxins.
CONCLUSIONS: Notably, WNT1/11, AGT, FGF4/17/22, LMX1B, GATA4, and CXCL12 emerged as promising targets for further exploration in renal tubular pathology related to non-dialyzable uremic toxins. Understanding the molecular players and pathways linked to renal tubular dysfunction opens avenues for novel therapeutic interventions and improved clinical management of chronic kidney disease and its complications.

BACKGROUND: Consultation-liaison (CL) psychiatrists are frequently asked to consult on various abnormal movements(1). CL psychiatrists can be instrumental in aiding the primary teams to identify and manage these movement disorders. In this manuscript, we provide an illustrative case of a patient presenting with myoclonus and offer a review on this important topic. Myoclonus accompanied by delirium represents a rare post-transplant complication and can be associated with heightened morbidity and mortality. The incidence of this complication in solid organ transplant (SOT) recipients is scarcely documented, and its pathophysiology remains inadequately understood. Potential etiologies in the intensive care unit (ICU) are numerous and likely multifactorial. The literature lacks detailed descriptions of the correlation and association between myoclonus and uremia. Management of this condition requires a multimodal approach, focusing on resolving underlying metabolic disturbances and providing symptomatic treatment.
OBJECTIVE: This manuscript describes the clinical presentation of myoclonus in a liver transplant recipient accompanied by delirium and precipitated by uremia. We aim to highlight the diagnostic and therapeutic complexities, help providers distinguish myoclonus from other movement disorders, and aid appropriate management.
RESULTS: We present a case of acute myoclonus in an elderly female liver transplant recipient precipitated by uremia and improved after continuous renal replacement treatment. In addition, we conducted a systematic review utilizing EMBASSE and PubMed of reported cases of myoclonus, delirium, and/or encephalopathy accompanied by uremia. We included 12 manuscripts in our review and discussed their findings.
CONCLUSIONS: CL psychiatrists are frequently consulted for a range of movement disorders in the ICU, including myoclonus. Accurate diagnosis and identification of contributing etiologies are critical in these cases. Management typically involves addressing the underlying disorder, such as using dialysis for uremia, alongside symptomatic treatment with benzodiazepines to mitigate the frequency and amplitude of myoclonus. This approach helps to alleviate both the physical burden and psychological distress associated with the condition. This case underscores the pivotal role of the CL psychiatrist within a complex multidisciplinary team, contributing to diagnostic precision and optimization of management strategies for movement disorders.

Background/Objectives: Magnetic Resonance Imaging (MRI) is essential in diagnosing neurological conditions, offering detailed insights into brain pathology. Uremic encephalopathy (UE) is a severe neurological disorder resulting from renal failure, characterized by cognitive impairments and brain abnormalities due to the accumulation of uremic toxins (UTs). Despite extensive research on UTs, there is a significant gap in the detailed characterization of MRI findings in UE patients. This study aims to bridge this gap by conducting a comprehensive literature review of cerebral MRI findings in UE. We hypothesize that specific MRI patterns correlate with the severity and clinical manifestations of UE, thereby enhancing diagnostic accuracy and improving patient outcomes. Methods: A literature review was performed using PubMed, Cochrane Library, and Google Scholar. The search terms included \"uremic encephalopathy MRI\", \"uremia and kidney failure MRI\", and \"toxic and metabolic or acquired encephalopathies MRI\". The inclusion criteria were original articles on UE and MRI findings published in English. Results: Common MRI sequences include T1-weighted, T2-weighted, FLAIR, and DWI. Frequent MRI findings in UE are cytotoxic and vasogenic brain edema in regions such as the basal ganglia and periventricular white matter. Patterns like the \"lentiform fork sign\" and basal ganglia involvement are key indicators of UE. Conclusions: MRI plays a crucial role in diagnosing UE by identifying characteristic brain edema and specific patterns. A comprehensive diagnostic approach, incorporating clinical, laboratory, and imaging data, is essential for accurate diagnosis and management. The study calls for larger well-designed cohorts with long-term follow-up to improve the understanding and treatment of UE.

OBJECTIVE: To determine whether urea nitrogen and creatinine levels differ in lacrimal fluid (LF) and serum (SER) in nonazotemic (control) and azotemic dogs and whether there is an agreement between LF and SER.
METHODS: A prospective observational study was performed at the Auburn University Small Animal Teaching Hospital between May 2023 and March 2024. Forty control and 38 azotemic dogs were enrolled. Twenty microliters of LF per eye was collected with microcapillary tubes, and 3 mL of blood was drawn. Bland-Altman plot and intraclass correlation coefficient (ICC) were used to evaluate the agreement between LF and SER.
RESULTS: There was good agreement between LF and SER levels of urea nitrogen in the control group (Bland-Altman plot mean bias of -0.8108 ± 2.407 mg/dL; ICC of 0.874 [95% CI, 0.773 to 0.934]) and the azotemic group (Bland-Altman plot mean bias of -9.681 ± 23.89 mg/dL; ICC of 0.82 [95% CI, 0.658 to 0.906]). There was poor agreement between LF and SER concentrations for creatinine in the control and azotemic groups, with only 26 dogs with creatinine detectable in LF.
CONCLUSIONS: Lacrimal fluid and SER concentrations of urea nitrogen showed good agreement in both the control and azotemic groups, whereas poor agreement was found for creatinine in both groups.
CONCLUSIONS: Measurement of urea nitrogen in LF may provide an alternative to blood for diagnosing uremia. However, additional research is necessary before substituting LF for SER.

An arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis in uremic patients, yet its dysfunction poses a significant clinical challenge. Venous stenosis, primarily caused by venous neointimal hyperplasia, is a key factor in the failure of vascular access. During vascular access dysfunction, endothelial cells (ECs) transform mechanical stimuli into intracellular signals and interact with vascular smooth muscle cells. Tanshinone IIA, an important compound derived from Salvia miltiorrhiza, has been widely used to treat cardiovascular diseases. However, its role in modulating ECs under uremic conditions remains incompletely understood. In this research, ECs were exposed to sodium tanshinone IIA sulfonate (STS) and subjected to shear stress and uremic conditions. The results indicate that STS can reduce the suppressive effects on the expression of NF-κB p65, JNK and Collagen I in uremia-induced ECs. Moreover, the downregulation of NF-κB p65, JNK and Collagen I can be enhanced through the inhibition of ERK1/2 and the upregulation of Caveolin-1. These findings suggest that tanshinone IIA may improve EC function under uremic conditions by targeting the Caveolin-1/ERK1/2 pathway, presenting tanshinone IIA as a potential therapeutic agent against AVF immaturity caused by EC dysfunction.

BACKGROUND: Intestinal necrosis in uremic patients has been reported but is rare.
METHODS: 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.

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BACKGROUND: In males with end stage renal disease biochemical hypogonadism is a frequent finding. Testosterone and sex hormone binding globulin (SHBG) have been associated with insulin resistance, a well-known condition in uremia. The aim of the present study was to investigate in males on chronic hemodialysis the relationship of testosterone and SHBG serum levels with insulin resistance.
METHODS: In a cross-sectional study we enrolled men treated with chronic hemodialysis who did not suffer from an acute illness or other endocrinopathy, as well as primary hypogonadism, and were not hospitalised. Diabetes mellitus, diabetic nephropathy or previous transplantation were not exclusion criteria. As controls we used a community-based group of healthy males matched for age and Body Mass Index (BMI). We assessed the BMI (kg/m2) from body weight and height, the body fat content (%) by bioelectrical impedance and serum testosterone (ng/ml), SHBG (nmol/L) and estradiol (pg/ml) by standard methods. Testosterone < 3.25 ng/ml defined biochemical hypogonadism. In non-diabetic males, we calculated the homeostasis model assessment index (HOMA-R), an estimate of insulin resistance, from serum fasting insulin and glucose.
RESULTS: 27 men (age 54.4 ± 19 years) on chronic hemodialysis (treatment duration 29.1 ± 14.4 months) and 51 healthy men (age 47.1 ± 9.6 years) were included. In men on hemodialysis vs. healthy men there were increased serum levels of SHBG (40.9 ± 26.9 vs. 27.6 ± 11.9 nmol/L; p = 0.031) and a significantly enhanced frequency of biochemical hypogonadism (22.2 vs. 3.9%; p = 0.011). In cases without diabetes (n = 22) a significant correlation was observed between the HOMA-R (r = -0.586, p = 0.004) and the fasting insulin levels (r = -0.650, p = 0.001) on the one hand and the serum SHBG levels on the other.
CONCLUSIONS: Our findings confirm enhanced prevalence of biochemical hypogonadism in males on chronic hemodialysis. In non-diabetic cases the serum levels of SHBG correlated with serum insulin and insulin resistance.

BACKGROUND: Atherosclerosis is highly prevalent in people with chronic kidney disease (CKD), including those receiving peritoneal dialysis (PD). Although it is lifesaving, PD induces profound systemic inflammation, which may aggravate atherosclerosis. Therefore, the hypothesis is that this PD-induced inflammation aggravates atherosclerosis via immune cell activation.
RESULTS: ApoE-/- mice were subjected to a 5/6 nephrectomy to induce CKD. Three weeks later, mice were fed a high-cholesterol diet. Half of the nephrectomized mice then received daily peritoneal infusions of 3.86% Physioneal for 67 further days (CKD+PD) until the end of the experiment, and were compared with mice without CKD. Sham operated and PD-only mice were additional controls. CKD+PD mice displayed more severe atherosclerotic disease than control mice. Plaque area increased, and plaques were more advanced with a vulnerable phenotype typified by decreased collagen content and decreased fibrous cap thickness. Increased CD3+ T-cell numbers were present in plaques and perivascular adipose tissue of CKD and CKD+PD mice. Plaques of CKD+PD mice contained more iNOS+ immune cells. Spleens of CKD+PD mice showed more CD4+ central memory, terminally differentiated type 1 T-helper (Th1), Th17, and CX3C motif chemokine receptor 1+ (CX3CR1) CD4+ T-cells with less regulatory and effector T-cells.
CONCLUSIONS: PD-fluid exposure in uremic mice potentiates systemic and vascular T-cell-driven inflammation and aggravates atherosclerosis. PD polarized CD4+ T-cells toward an inflammatory Th1/Th17 phenotype, and increased CX3CR1+ CD4+ T-cells, which are associated with vascular homing in CKD-associated atherosclerosis. Targeting CD4+ T-cell activation and CX3CR1+ polarization has the potential to attenuate atherosclerosis in PD patients.

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