Existing obesity- and lipid-related indices are inconsistent with metabolic syndrome (MetS) in chronic kidney disease (CKD) patients. We compared seven indicators, including waist circumference (WC), body mass index (BMI), visceral fat area (VFA), subcutaneous fat area (SFA), visceral adiposity index (VAI), Chinese VAI and lipid accumulation product (LAP), to evaluate their ability to predict MetS in CKD patients with and without Type 2 diabetes mellitus (T2DM) under various criteria. Multivariate logistic regression analysis was used to investigate the independent associations between the indices and metabolic syndrome among 547 non-dialysis CKD patients, aged ≥18 years. The predictive power of these indices was assessed using receiver operating characteristic (ROC) curve analysis. After adjusting for potential confounders, the correlation between VAI and MetS was strongest based on the optimal cut-off value of 1.51 (sensitivity 86.84%, specificity 91.18%) and 2.35 (sensitivity 83.54%, specificity 86.08%), with OR values of 40.585 (8.683–189.695) and 5.076 (1.247–20.657) for males and females with CKD and T2DM. In CKD patients without T2DM, based on the optimal cut-off values of 1.806 (sensitivity 98.11%, specificity 72.73%) and 3.11 (sensitivity 84.62%, specificity 83.82%), the OR values were 7.514 (3.757–15.027) and 3.008 (1.789–5.056) for males and females, respectively. The area under ROC curve (AUC) and Youden index of VAI were the highest among the seven indexes, indicating its superiority in predicting MetS in both male and female CKD patients, especially those with T2DM.

Heat stroke (HS) is the most severe heat-related emergency, and its pathophysiology remains largely unknown, especially for exertional HS (EHS), which affects younger populations, athletes, and manual workers. Herein, we performed single-cell-transcriptomics, T cell receptor sequencing, and flow cytometry of PBMCs from 9 healthy control participants, 9 patients with heat exhaustion, and 9 patients with EHS to explore complex immunological responses associated with HS pathobiology. We showcased that granzyme-positive T cells and CD56 ^dim NK cells with high cytotoxicity features and IL-1B ⁺ NLRP3 ⁺ monocytes with high inflammation and pyroptosis scores were enriched in HS, while the CD161 ⁺ T cells with innate immune-like, low cytotoxicity, and clonal expansion features were reduced in HS. Importantly, elevated granzyme-positive T and NK cells might interact with monocytes to induce pyroptosis of hepatic and renal cells and target organ injuries, and blocking the NLRP3 inflammasome pathway prior to the induction could alleviate organ injury in HS. This study offers deeper insights into the pathogenesis of HS, supporting the development of optimal treatment strategies.

Objective. It is not clear which Traditional Chinese Medicine- (TCM-) related elements affect primary IgA nephropathy (IgAN) progression. Here, we explored the risk factors, based on TCM syndrome elements, related to the prognosis of primary IgAN patients. Methods. We analyzed patients with newly diagnosed, biopsy-proven IgAN at a single institution from December 2013 to September 2021. Basic clinical and pathological characteristics were assessed at the time of renal biopsy. The study endpoint was end-stage renal disease (ESRD: eGFR 30% from baseline. Kaplan‒Meier survival analysis was used to explore the role of TCM syndrome elements in IgAN progression. Multivariate Cox regression analysis with adjustment for traditional risk factors was performed to explore TCM syndrome elements that may influence patient prognosis. The factors correlated with TCM syndrome elements in IgAN patients were further evaluated by logistic regression analysis. Results. During a median follow-up of 22.0 months, 53 (12.5%) of the 423 included IgAN patients reached the study endpoint. The main IgAN disease location elements were the kidney, liver, and spleen. The main IgAN disease nature elements were Yin-deficiency and Qi-deficiency, dampness, Yang-deficiency, phlegm, and Blood-deficiency. Kaplan‒Meier analysis identified three disease locations (liver, spleen, and kidney) and four disease natures (Qi-deficiency, Yang-deficiency, phlegm, and dampness) as elements associated with poor renal survival in IgAN patients. In multivariate Cox regression analysis, baseline Yang-deficiency was an independent risk predictor of poor prognosis in primary IgAN patients (hazard ratio 2.338; 95% confidence interval [CI]: 1.208–4.525; ) after adjustment for traditional risk factors. Furthermore, logistic regression analysis identified being female (odds ratio [OR] 2.518; 95% CI: 1.538–4.122; ), older age (OR 1.043; 95% CI: 1.022–1.065; ), low hemoglobin levels (OR 0.984; 95% CI: 0.971–0.996; ), and cellular/fibrocellular crescents (OR 1.706; 95% CI: 1.068–2.728; ) as factors affecting Yang-deficiency in IgAN patients. Conclusions. Yang-deficiency independently predicts the risk of poor prognosis in primary IgAN patients. Being female, older age, low hemoglobin levels, and cellular/fibrocellular crescents were independently associated with Yang-deficiency in IgAN patients.

Background: Arterial stiffness influences the prognosis of patients with end-stage kidney disease; however, the factors that promote arterial stiffness in chronic kidney disease (CKD) patients remain unknown. We aimed to explore the clinical factors associated with arterial stiffness in CKD. Methods: Between September 2017 and September 2022, all CKD patients treated at the Department of Nephrology, General Hospital of the Chinese People’s Liberation Army, excluding dialysis patients, were screened and their medical records within the last month were collected. Arterial stiffness was measured by the augmentation index (AIx). The correlative clinical factors with arterial stiffness were explored in different linear regression models. Results: 559 patients were included in the study. AIx@75 increased as the deterioration of CKDG1–CKDG5, with values of 1 (−9, 11), 5.5 (−4, 13.25), 9 (0, 16), 12 (1.5, 23.5), and 22 (13, 28), respectively (Z = 63.03, p < 0.001). Multivariate linear regression analysis showed that AIx@75 was positively associated with female sex (β = 8.926, 95% confidence interval (CI) 6.291, 11.562, p < 0.001), age (β = 0. 485, 95% CI 0.39, 0.58, p < 0.001), mean arterial pressure (MAP) (β = 0.255, 95% CI 0.159, 0.35, p < 0.001), and was negatively associated with ACEI/ARB (β = −4.466, 95% CI −6.963, −1.969, p < 0.001) and glucocorticoid (β = −3.163, 95% CI −6.143, −0.183, p = 0.038). Smoking, eGFR, hemoglobin, and cause of disease were associated with AIx@75 in multivariate linear regression models when considering factors partly. Conclusions: Female, age, smoking, MAP, eGFR, cause of disease, ACEI/ARB, and glucocorticoid were found to be associated with atherosclerosis in CKD patients.

Diabetic kidney disease (DKD) is a common condition with few treatment options, and inflammation plays a pivotal role in its progression. Luteolin, a natural compound found in traditional Chinese herbs, is known for its anti-inflammatory properties, making it a potential treatment for DKD. But its effect and mechanisms in DKD remain incompletely elucidated. Renoprotective effects of luteolin in db/db mice were assessed with BUN, Scr, uACR, and PAS staining. Flow cytometry and extraction of total membrane proteins were conducted to examine the abundance of full-length TREM2 on the membrane of macrophages. Co-culture of differentially treated macrophages and HK2 cells evaluated luteolin's impact on efferocytosis. The molecular target of luteolin was elucidated through virtual molecular analysis, SPR, and ADAM10 activity assays. Luteolin reduced uACR, BUN, and SCr levels. Histologic analyses showed decreases in mesangial matrix, glomerular volume, GBM thickness, and foot process effacement. Tubular injury scores and KIM1 expression were lowered, while megalin and cubilin expression increased. Renal macrophage infiltration, iNOS⁺ cells, and IL-1β, IL-18, TNF-α, and MCP-1 levels were reduced. Luteolin elevated TREM2⁺ macrophages with decreased sTREM2 in vivo and in vitro. Immunofluorescence confirmed increased TREM2⁺ macrophages and enhanced full-length TREM2 on cell membrane. Luteolin exhibited dose-dependent binding to ADAM10 and inhibited its activity without affecting ADAM10 expression. In co-culture system, luteolin increased p-DAP12, p-SYK, and PHrodo⁺ cell counts. Apoptotic cells in kidney tissue decreased, while Rab5a and Rab7a expression were upregulated. Luteolin attenuates immunoinflammation and pathological injury in db/db mice by enhancing the efferocytosis of apoptotic renal tubular cells by TREM2⁺ macrophages. The potential mechanism of luteolin involves binding to ADAM10 and inhibiting its activity, which attenuates aberrant shedding of full-length TREM2 from macrophages and potentiates downstream TREM2 signaling. Collectively, luteolin provides a promising option for ameliorating immune inflammation in DKD, demonstrating strong translational potential.