Although macrophage infiltration has been proven to increase calcified artery media in chronic kidney disease (CKD) patients, the mechanism by which macrophages are involved in vascular calcification (VC) progression remains unclear. Taking advantage of miRNA-seq, RNA-seq, dual-luciferase reporter assay, qRT-PCR, and arteries from CKD patients as well as CKD mouse models, we identified that high-phosphate-stimulated macrophage-derived exosomes (Mexo-P) suppressed let-7b-5p expression in VSMCs, which further upregulated TGFBR1. Moreover, gain-and-loss-of-function assays were used to determine the regulatory effects and downstream mechanism of let-7b-5p and TGFBR1 on VC. Mechanically, Mexo-P induced VSMC TGFBR1 upregulation by suppressing let-7b-5p, which further amplifies SMAD3/RUNX2 signaling and thereby contributes to VC. Our findings indicate that macrophage-derived exosomes promote CKD-associated VC through the let-7b-5p/TGFBR1 axis in high-phosphate conditions. Our study provides insight into macrophages associated with VC, which might be potential therapeutical targets for VC.

Background: For the coronavirus disease 2019 (COVID-19), critically ill patients had a high mortality rate. We aimed to assess the association between prolonged intermittent renal replacement therapy (PIRRT) and mortality in patients with COVID-19 undergoing invasive mechanical ventilation. Methods: In this retrospective cohort study, we included all patients with COVID-19 undergoing invasive mechanical ventilation from February 12 ^nd to March 2 ^nd , 2020. All patients were followed until death or March 28 ^th , and all survivors were followed for at least 30 days. Results: For 36 hospitalized COVID-19 patients with invasive mechanical ventilation, the mean age was 69.4 (± 10.8) years, and 30 patients (83.3%) were men. Twenty-two (61.1%) patients received PIRRT (PIRRT group) and 14 cases (38.9%) were managed with conventional strategy (non-PIRRT group). There were no differences in age, sex, comorbidities, complications, treatments and most of the laboratory findings. During median follow-up period of 9.5 (interquartile range 4.3-33.5) days, 13 of 22 (59.1%) patients in the PIRRT group and 11 of 14 (78.6%) patients in the non-PIRRT group died. Kaplan-Meier analysis demonstrated prolonged survival in patients in the PIRRT group compared with that in the non-PIRRT group (P = 0.042). The association between PIRRT and a reduced risk of mortality remained significant in three different models, with adjusted hazard ratios varying from 0.332 to 0.398. Higher levels of IL-2 receptor, TNF-α, procalcitonin, prothrombin time, and NT-proBNP were significantly associated with an increased risk of mortality in patients with PIRRT. Conclusion: PIRRT may be beneficial for the treatment of COVID-19 patients with invasive mechanical ventilation. Further prospective multicenter studies with larger sample sizes are required.

Chronic kidney disease-associated pruritus (CKD-aP) is a common and burdensome dermatologic condition in which patients can experience various symptoms. This study aimed to summarize and describe the patient-reported outcomes (PROs) and patient-reported outcome measures (PROMs) used in CKD-aP studies over the past 5 years. A total of 99 studies were identified, which included 5 different PROs and 40 different PROMs. The most frequently evaluated PRO was pruritus (n = 99), followed by health-related quality of life (HRQoL) (n = 31), sleep disturbances (n = 12), psychiatric symptoms (n = 7), and other skin symptoms (n = 5). Among the 40 different PROMs, 19 were generic, 18 were skin-specific, and 3 were CKD-specific. The most commonly used PROMs in the PROs of pruritus, HRQoL, sleeping, and psychiatric symptoms were the visual analog scale (n = 47), dermatological life quality index (n = 8), Pittsburgh sleep quality index (n = 7), and Beck depression inventory (n = 3), respectively. The PROs and PROMs are common and effective tools for evaluating CKD-aP, but more high-quality studies and guidelines are needed to reach a clear consensus on their application.

Inflammation is a key driver of diabetic kidney disease (DKD) progression, with the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome representing a promising therapeutic target. Soluble epoxide hydrolase (sEH), an enzyme that inactivates renoprotective epoxyeicosatrienoic acids into less active diols, has been implicated in renal pathophysiology. This study investigated the role of sEH in renal tubular NLRP3 inflammasome activation and its underlying mechanisms in DKD. We observed upregulated sEH expression in high glucose (HG)-stimulated human proximal tubular epithelial (HK-2) cells and diabetic kidneys. Pharmacological inhibition of sEH attenuated diabetes-induced mitochondrial damage, mitochondrial reactive oxygen species (mtROS) production, NLRP3 inflammasome activation, and renal dysfunction both in vivo and in vitro . Furthermore, sEH inhibition restored autophagy flux and enhanced PINK1/Parkin mediated-mitophagy. Activation of mitophagy by the autophagy inducer rapamycin (Rapa) alleviated HG-induced mitochondrial impairment, mtROS overproduction, and NLRP3 inflammasome activation in HK-2 cells, suggesting that the anti-inflammatory effect of sEH inhibition is mediated through mitophagy regulation. Further mechanistic studies indicated that sEH inhibition promotes mitophagy, thereby improving mitochondrial function, reducing mtROS generation, and subsequently suppressing mtROS-dependent NLRP3 inflammasome activation in DKD. In conclusion, our findings establish a novel link between sEH and NLRP3 inflammasome activation in DKD pathogenesis, highlighting sEH inhibition as a promising therapeutic strategy for DKD treatment.

The independent and domain-specific associations between physical activity (PA) and chronic kidney disease (CKD) remain underexplored. This study investigates the relationships between leisure-time, occupational, and transportation-related PA, along with sedentary behavior, and CKD prevalence in a nationally representative U.S. adult cohort. We analyzed 24,950 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2012. PA and sedentary behavior were assessed via validated questionnaires. Participants were classified based on adherence to physical activity guidelines (≥150 min/week). Multivariable logistic regression and restricted cubic splines were used to evaluate dose-response and non-linear associations. We found that meeting PA guidelines for total, leisure-time, and occupational PA was independently associated with lower odds of CKD (OR [95% CI]: 0.82 [0.73-0.93], 0.86 [0.76-0.97], and 0.85 [0.76-0.96], respectively). No significant association was observed for transportation-related PA. Sedentary behavior exceeding 6 h/day was associated with higher CKD prevalence. These associations were more pronounced in women, and dose-response patterns were evident across PA domains. This large-scale cross-sectional study identifies robust, domain-specific inverse associations between PA and CKD prevalence, particularly among women. Findings support stratified behavioral interventions targeting leisure and occupational activity domains, alongside sedentary behavior reduction, to mitigate CKD burden. Prospective studies are warranted to confirm causal pathways.