AimsThe negative effect of obesity on kidney health has been reported. The association between weight-adjusted-waist index (WWI, a newly developed adiposity index) and albuminuria has not been reported earlier.MethodsThis cross-sectional study was conducted among adults with complete data about WWI and urinary albumin-to-creatinine ratio (ACR) in 2005–2018 National Health and Nutrition Examination Survey (NHANES). WWI was calculated as waist circumference (WC) divided by the square root of weight. Weighted multivariable logistic regression and generalized additive model were employed to explore the independent relationship between WWI with albuminuria and its non-linearity. A two-piecewise linear regression model was used to calculate the threshold effect. Subgroup analysis and interaction tests were also performed.ResultsA total of 36,921 participants were enrolled with a prevalence of albuminuria of 9.32%. The prevalence of albuminuria increased with the higher WWI tertiles (Tertile 1: 5.31%, Tertile 2: 8.23%, Tertile 3: 15.65%). WWI was positively associated with a higher likelihood of albuminuria (OR = 1.28, 95% CI: 1.15–1.43), and this relationship remains stable in subgroups (all P for trend > 0.05). Non-linear positive relationships were detected in females with a breakpoint of 10.93. A positive association between WWI and albuminuria (OR = 1.39, 95% CI: 1.20–1.61) was observed on the right of the breakpoint, while the association on the left was of no statistical significance. WWI showed a stronger correlation with albuminuria (OR = 1.28) than other markers of obesity including body mass index (BMI, OR = 1.02) and WC (OR = 1.01).ConclusionWeight-adjusted-waist index levels were positively related to an increased likelihood of albuminuria in United States adults and showed a stronger relationship than BMI and WC. Our findings indicated that WWI may serve as a simple anthropometric index to predict albuminuria.

AimsWe aimed to assess the association between triglyceride–glucose (TyG) index and kidney stones in US adults.MethodsData were obtained from the 2007–2014 National Health and Nutrition Examination Survey (NHANES). Participants aged ≥18 years who were not pregnant and provided complete data about TyG index and kidney stones were included in the analysis. Weighted multivariable regression analysis and subgroup analysis were preformed to estimate the independent relationship between TyG index and nephrolithiasis and recurrence.ResultsA total of 20,972 participants were included with the mean TyG index of 8.71 ± 0.72. The prevalence rates of nephrolithiasis and recurrence were 9.30% and 3.17% overall and increased with the higher TyG index tertiles (Nephrolithiasis: Tertile 1, 6.98%; Tertile 2, 9.15%; Tertile 3, 11.98%, p < 0.01; Recurrence: Tertile 1, 1.84%; Tertile 2, 3.27%; Tertile 3, 4.50%, p < 0.01). Each unit increase in TyG index was associated with 12% and 26% higher odds of nephrolithiasis [odds ratio (OR) = 1.12; 95% CI: 1.02–1.22; p = 0.02] and recurrence (OR = 1.26; 95% CI: 1.08–1.46; p < 0.01). Interaction tests indicated no significant effect of gender, age, body mass index, hypertension, and diabetes on this association between TyG index and kidney stones.ConclusionsHigher TyG index was associated with an increased likelihood of nephrolithiasis and recurrence. Considering TyG index is a reliable indicator of insulin resistance (IR). Treatment and management of IR at a younger age may improve or alleviate the occurrence and recurrence of kidney stones.

The negative effects of obesity on the cardiovascular health have drawn much attention. Weight-adjusted-waist index (WWI) has been proved to reflect weight-independent centripetal obesity. However, the association between WWI and abdominal aortic calcification (AAC) has not been reported before. Using data from National Health and Nutrition Examination Survey 2013–2014, we aimed to determine the relationship of WWI and AAC in adults aged ≥ 40 years. WWI was determined by dividing waist circumference by the square root of weight. AAC was measured by dual-energy X-ray absorptiometry and quantified by Kauppila scores. Severe AAC (SAAC) was defined as an AAC score > 6. We utilized weighed multivariable logistic regression and generalized additive model to explore the independent association between WWI and AAC. Threshold effects were further calculated by two-piecewise linear regression model. 3082 participants were enrolled in our analysis, of which 48.2% were male. WWI was positively associated with AAC scores (β = 0.34, 95% CI 0.05–0.63) and exhibited a nonlinear relationship with SAAC. On the left of the breakpoint (WWI = 11.11), WWI and SAAC were positively associated (OR = 2.86, 95% CI 1.40–5.84), while no such relationship was found on the right (OR = 1.07, 95% CI 0.77–1.48). Our findings indicated that WWI may serve as a simple biomarker of AAC in US adults aged ≥ 40 years.

Aims: We aimed to assess the association between dietary inflammation index (DII) and abdominal aortic calcification (AAC) in US adults aged ≥40 years.Methods: Data were obtained from the 2013–2014 National Health and Nutrition Examination Survey (NHANES). Participants who were <40 years old and missing the data of DII and AAC were excluded. DII was calculated based on a 24-h dietary recall interview for each participant. AAC score was quantified by assessing lateral spine images and severe AAC was defined as AAC score >6. Weighted multivariable regression analysis and subgroup analysis were preformed to estimate the independent relationship between DII with AAC score and severe AAC.Results: A total of 2,897 participants were included with the mean DII of −0.17 ± 2.80 and the mean AAC score of 1.462 ± 3.290. The prevalence of severe AAC was 7.68% overall, and participants in higher DII quartile tended to have higher rates of severe AAC (Quartile 1: 5.03%, Quartile 2: 7.44%, Quartile 3: 8.38%, Quartile 4: 10.46%, p = 0.0016). A positive association between DII and AAC score was observed (β = 0.055, 95% CI: 0.010, 0.101, p = 0.01649), and higher DII was associated with an increased risk of severe AAC (OR = 1.067, 95% CI: 1.004, 1.134, p = 0.03746). Subgroup analysis indicated that this positive association between DII and AAC was similar in population with differences in gender, age, BMI, hypertension status, and diabetes status and could be appropriate for different population settings.Conclusion: Higher pro-inflammatory diet was associated with higher AAC score and increased risk of severe AAC. Anti-inflammatory dietary management maybe beneficial to reduce the risk of AAC.

Both high mobility group box-1 (HMGB1) and histones are major damage-associated molecular patterns (DAPMs) that mediate lethal systemic inflammation, activation of the complement and coagulation system, endothelial injury and multiple organ dysfunction syndrome in critical illnesses. Although accumulating evidence collectively shows that targeting HMGB1 or histones by their specific antibodies or inhibitors could significantly mitigate aberrant immune responses in multiple critically ill animal models, routine clinical use of such agents is still not recommended by any guideline. In contrast, extracorporeal blood purification, which has been widely used to replace dysfunctional organs and remove exogenous or endogenous toxins in intensive care units, may also exert an immunomodulatory effect by eliminating inflammatory mediators such as cytokines, endotoxin, HMGB1 and histones in patients with critical illnesses. In this review, we summarize the multiple immunopathological roles of HMGB1 and histones in mediating inflammation, immune thrombosis and organ dysfunction and discuss the rationale for the removal of these DAMPs using various hemofilters. The latest preclinical and clinical evidence for the use of extracorporeal blood purification to improve the clinical outcome of critically ill patients by targeting circulating HMGB1 and histones is also gathered.

Critically ill patients with sepsis and severe COVID-19 are commonly characterized by a dysregulated immune response and an acute kidney injury. Continuous renal replacement therapy (CRRT) is now proposed as a promising adjuvant therapy to treat these critically ill patients by removing cytokines, pathogen-associated molecular patterns, and damage-associated molecular patterns from the blood. Although multiple hemofilters, including high-cutoff membranes, the oXiris hemofilter, the CytoSorb hemoadsorption device, and the Toraymyxin hemoperfusion cartridge, have been used in current clinical practice, the use of the oXiris hemofilter in critically ill patients is of particular interest because it is the only kind of hemofilter that can provide renal replacement therapy, remove endotoxins, and adsorb cytokines simultaneously. During the past five years, a growing body of literature has shown that CRRT with the oXiris hemofilter can improve hemodynamics and organ function and can decrease cytokines and endotoxins in both septic and COVID-19 patients. Here, we performed a narrative review to describe the development history of the oXiris hemofilter and to discuss the therapeutic effect of oXiris-CRRT on critically ill patients by searching the PubMed, Web of Science, and clinicaltrials.gov databases for articles published from inception to 8 September 2022 (updated on 1 November) with an English language restriction. We also summarized the current knowledge on anticoagulation techniques and safety concerns when delivering oXiris-CRRT sessions.

(1) Background: Preclinical and clinical studies on the anti-aging effect of α-Klotho are emerging. Urinary albumin excretion (UAE) is a well-known biomarker of kidney injury and generalized damage in the cardiovascular system. However, the potential relationship between α-Klotho and UAE is limited and controversial. This study aimed to quantify this relationship in the general middle-aged and elderly population from the National Health and Nutrition Survey (NHANES) 2007–2016. (2) Methods: Serum α-Klotho was measured by enzyme-linked immunosorbent assay. UAE was assessed by the albumin-to-creatinine ratio (ACR). After adjusting for several confounding variables, the relationship between α-Klotho and ACR was analyzed by weighted multivariable logistic regression, subgroup analysis, and interaction tests. A generalized additive model (GAM) with smooth functions using the two-piecewise linear regression model was used to examine the potential nonlinear relationship between α-Klotho and ACR. (3) Results: Among 13,584 participants aged 40–79 years, we observed an independent and significant negative correlation between α-Klotho and ACR (β = −12.22; 95% CI, −23.91, −0.53, p = 0.0448) by multivariable logistic regression analysis, especially in those with age ≥ 60 years, pulse pressure (PP) ≥ 60 mmHg, hypertension or diabetes. We further discovered the nonlinear relationship between α-Klotho and ACR by GAM, revealing the first negative and then positive correlations with an inflection point of 9.91 pg/mL between α-Klotho and ACR. (4) Conclusions: A dose-response relationship between α-Klotho and ACR was demonstrated, and the negative correlation therein indicated that α-Klotho has potential as a serum marker and prophylactic or therapeutic agent despite its metabolic and effective mechanisms needing to be further explored.

Vascular calcification is commonly observed in chronic kidney disease. The mechanism of how the calcification signal from endothelial cells is transmitted to vascular smooth muscle cells (VSMCs) remains unknown. The aim of the present study was to investigate whether exosomes from HUVECs (HUVEC-Exos) could regulate VSMC calcification and its potential signaling pathway. HUVEC-Exos were isolated from HUVECs under no phosphorus (NP) and high phosphorus (HP) conditions. Alizarin Red S staining and calcium (Ca) content analysis were carried out to detect calcification in VSMCs. Proteomics analysis was carried out to detect the differential expression of exosomal proteins. Protein and mRNA levels were measured by western blot analysis and reverse transcription-quantitative PCR (RT-qPCR). Exosomes derived from HP-HUVECs promoted the calcification of VSMCs, as assessed by Alizarin Red S staining, alkaline phosphatase activity assays, Ca content measurements and the increased expression of runt-related transcription factor 2 and osteopontin. Proteomic analysis detected the upregulation of STAT1 in HP-exosomes from HUVECs (HUVEC-Exos) compared with NP-HUVEC-Exos, which was also confirmed by western blot analysis and RT-qPCR. Inhibition of STAT1 expression in VSMCs using fludarabine or knockdown of STAT1 expression using small interfering RNA alleviated the calcification of VSMCs. Furthermore, lithium chloride (Wnt activator) reversed the protective effect of STAT1 inhibition on VSMC calcification, while Dickkopf-1 (Wnt inhibitor) exerted the opposite effect, suggesting that activation of the Wnt/β-catenin signaling pathway was involved in STAT1-mediated VSMC calcification. In conclusion, the present results indicated that exosomal STAT1 derived from HP-treated HUVECs could promote VSMC calcification, and activation of the Wnt/β-catenin pathway may be a potential mechanism of the VSMC calcification promoted by exosomes.