Chronic kidney disease-associated pruritus (CKD-aP) represents a common distressing problem in patients with end-stage renal disease. This study aimed to assess the efficacy and safety of omega-3 supplementation in the treatment of CKD-aP. MEDLINE/PubMed, Cochrane Central Register of Controlled Trials, Web of Science, ProQuest, and Scopus databases were searched systematically for articles published from inception until May 21, 2024. Outcomes were pruritus severity at the end of the study or its change from baseline (primary) and intervention-related adverse effects (secondary). Results were pooled as standardized mean difference (SMD) and risk ratio (RR) for numeric and dichotomous outcomes, respectively, along with their 95% confidence intervals (CIs). Eight studies were included. Treatment with omega-3 fatty acids showed a significantly lower severity of CKD-aP at the end of treatment (pooled SMD (95% CI) = -1.03 (-1.85, -0.22), p = 0.024) and changed from baseline (pooled SMD (95% CI) = -0.93 (-1.57, -0.28), p = 0.014). Omega-3 supplementation reduced the risk of CKD-aP (pooled RR (95% CI) = 0.68 (0.12, 3.81), p = 0.661). Omega-3 fatty acid supplementation appears to be a promising effective and safe treatment for CKD-aP. However, the included studies had several limitations that warrant further high-quality studies to elucidate its effect and investigate the causes of non-response in patients who did not improve.

Regulatory T cells (Tregs) are crucial immune cells that initiate a tolerable immune response. Transforming growth factor-beta (TGFβ) is a key cytokine produced by Tregs and plays a significant role in stimulating tissue fibrosis. Systemic sclerosis, an autoimmune disease characterized by organ fibrosis, is associated with an overrepresentation of regulatory T cells. This review aims to identify Treg-dominant tolerable host immune reactions and discuss their association with scleroderma and end-stage organ failure. End-stage organ failures, including heart failure, liver cirrhosis, uremia, and pulmonary fibrosis, are frequently linked to tissue fibrosis. This suggests that TGFβ-producing Tregs are involved in the pathogenesis of these conditions. However, the exact significance of TGFβ and the mechanisms through which it induces tolerable immune reactions during end-stage organ failure remain unclear. A deeper understanding of these mechanisms could lead to improved preventive and therapeutic strategies for these severe diseases.

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.

Little is known about the prognostic value of left atrial strain by four-dimensional speckle-tracking echocardiography in end-stage renal disease patients with preserved left ventricular ejection fraction. This prospective study collected clinical and echocardiographic data from 80 stable dialysis patients (mean age 57 ± 10 years; 62.5% men). All patients underwent the dedicated four-dimensional speckle-tracking echocardiography to measure LASr (peak longitudinal strain of reservoir function), LAScd (peak longitudinal strain of conduit function), LASct (peak longitudinal strain of contractile function), LASr_c (peak circumferential strain of reservoir function), LAScd_c (peak circumferential strain of conduit function) and LASct_c (peak circumferential strain of contractile function). These patients were enrolled from August 2021 to August 2023 and followed-up for 19 months (interquartile-range 15 to 20 months). The primary outcome was a composite of all-cause mortality or major adverse cardiovascular events (MACEs). The study patients were classified into event (developed mortality or MACEs) and event-free group according to the primary outcome. Multivariate Cox regression analysis was used to investigate risk factors for all-cause mortality or MACEs. The event group had lower LASr (16.4% vs. 21.2%, P = 0.0003), LASct (8.2% vs. 11.2%, P = 0.01), LASr_c (25.2% vs. 35.0%, P = 0.0004) and LASct_c (14.9% vs. 20.9%, P = 0.001) than the event-free group. Using optimal cut-off value determined by ROC curve, the less LASr (LASr < 18.5%), LASct (LASct < 8.5%), LASr_c (LASr_c < 28.5%), and LASct_c (LASct_c < 17.5%) group had a higher mortality or MACEs rate. Multivariate cox regression analyses revealed that LASr (HR = 0.81, 95% CI [0.17; 0.91], P = 0.0005, per 1% increase) and LASr_c (HR = 0.93, 95% CI [0.87; 0.98], P = 0.01, per 1% increase) were independent predictors of all-cause mortality or MACEs. Less peak longitudinal and circumferential strains of reservoir function are predictive of poor prognosis among end-stage renal disease patients with preserved left ventricular ejection fraction.

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/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.

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.

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.

Cardiovascular disease (CVD) frequently occurs in patients with chronic kidney disease (CKD), particularly those undergoing dialysis. The mechanisms behind this may be related to traditional risk factors and CKD-specific factors that accelerate atherosclerosis and vascular calcification in CKD patients. The accumulation of uremic toxins is a significant factor in CKD-related systemic disorders. Basic research suggests that indoxyl sulfate (IS), a small protein-bound uremic toxin, is associated with macrophage dysfunctions, including increased oxidative stress, exacerbation of chronic inflammation, and abnormalities in lipid metabolism. Strategies to mitigate the toxicity of IS include optimizing gut microbiota, intervening against the abnormality of intracellular signal transduction, and using blood purification therapy with higher efficiency. Further research is needed to examine whether lowering protein-bound uremic toxins through intervention leads to a reduction in CVD in patients with CKD.