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Introduction: Inflammation plays a key role in chronic kidney disease (CKD). Monocyte-to-lymphocyte ratio (MLR) is a novel inflammatory marker. The purpose of this study was to evaluate the relationship between MLR and inflammation in CKD patients. Methods: In total, 1,809 subjects were recruited from Wanzhai Town, Zhuhai City, between December 2017 and March 2018 for a cross-sectional survey. Patients were categorized based on the absence (hypersensitive C-reactive protein [hsCRP] level ≦3 mg/L) or presence (hsCRP level >3 mg/L) of inflammation. Logistic regression models and MLR quartiles were used to explore the relationship between MLR and inflammation in CKD patients. Results: Among 1,809 subjects, 403 (22.2%) had CKD. Significant differences in systolic blood pressure, estimated glomerular filtration rate, white blood cell (WBC), neutrophil, monocyte, MLR, and interleukin-6 (IL-6) levels were observed between noninflammatory group and inflammatory group. The highest MLR quartile had higher Scr, WBC, neutrophil, monocyte, IL-6, and hsCRP values and lower eGFR and lymphocyte values. Comparing the lowest quartile of MLR, the OR (95% CI) of inflammation risk in the highest quartile was 2.30 (1.24–4.27) after adjustment for confounding factors. The area under the curve of MLR for predicting inflammation was 0.631. The cutoff point for the MLR was 0.153. Conclusion: A high MLR was significantly and independently associated with inflammation in patients with CKD, making MLR a potential marker for inflammation in this demographic. MLR may also predict the severity of CKD. [ABSTRACT FROM AUTHOR]

Retinoic acid is an active metabolite with significant physiological functions in human development, immunity, vision, and skin health. In recent years, research on retinoic acid in the field of kidney disorders has been increasing gradually. Yet, there is a lack of systematic bibliometric analysis of retinoic acid research in the kidney domain. This study included 1,368 articles published between 1998 and 2023 on treating kidney diseases with retinoic acid. Using the bibliometric analysis software VOSviewer and CiteSpace, we analyzed data on publication trends, contributing countries and institutions, journals and cocited journals, authors and cocited authors, cocited references, research hotspots, and frontiers. On the basis of the results of the bibliometric analysis, we identified the research efforts and their developmental trends, providing the groundwork for future research on retinoic acid., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Sun, Huang, Shen, Chen, Chen, Zhu, Wang, Hong, Luo, Long and Zou.)

Atherosclerosis is the most common cause of cardiovascular disease globally, associated with a high incidence of clinical events. Accumulating evidence has elucidated that long non-coding RNAs (lncRNAs) as a novel class of transcripts with critical roles in the pathophysiological processes of atherosclerosis. In this review, we summarize the recent progress of lncRNAs in the development of atherosclerosis. We mainly describe the diverse regulatory mechanisms of lncRNAs at the transcriptional and post-transcriptional levels. This study may provide helpful insights about lncRNAs as therapeutic targets or biomarkers for atherosclerosis treatment.

Purpose: The improvement of the long-term survival of patients receiving kidney transplantation remains challenging. Ischemia reperfusion injury (IRI) reduces long-term renal graft survival in the early posttransplantation phase. However, few studies have investigated the effects of IRI on the pathogenesis of chronic renal graft failure. Silent information regulator 1 (SIRT1) regulates antioxidative stress and inflammatory response and protects against IRI. This study is aimed at investigating the role of resveratrol (RSV), an SIRT1 activator, in preventing renal injury in a rat renal transplantation model., Methods: A classical F334-to-LEW orthotopic renal transplantation rat model was established. The experiment group was treated with RSV from three days prior to kidney transplantation and the treatment lasted until the day of harvest. Uninephrectomized F344 and Lewis rats were used as controls. After 12 weeks, the effects of RSV were evaluated according to renal function, histopathology, immunohistochemistry, and western blotting. The activities of oxidative stress-related markers and proinflammatory cytokines were also assessed., Results: RSV treatment significantly ameliorated renal function and histopathological lesions in kidney-transplanted rats and increased the levels of GSH, SOD, and CAT and decreased the levels of MDA and iNOS. Furthermore, RSV also inhibited the expression of proinflammatory cytokines/chemokines such as TNF- α , CD68, and IL-6 in kidney-transplanted rats. In addition, the transplant group displayed significantly lower level of SIRT1 and higher level of Ac-NF- κ Bp65. RSV increased the expression of SIRT1 and decreased the expression of Ac-NF- κ Bp65., Conclusion: SIRT1 plays an important role in the pathogenesis of chronic renal allograft dysfunction. It is a potential therapeutic agent for ameliorating inflammation and oxidative stress-induced renal injury following kidney transplantation by activating the SIRT1/NF- κ B signaling pathway., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Qin Zhou et al.)

Background: Chronic renal allograft dysfunction (CRAD) is a major condition that impedes the long-term survival of renal allografts. However, the mechanism of CRAD is obscure, and the effective strategies for controlling the progression of CRAD are lacking. The present study used a CRAD rat model to assess the effect of glycogen synthase kinase 3β (GSK-3β) inhibition on the development of CRAD., Methods: A classical F334-to-LEW orthotopic renal transplantation was performed on the CRAD group. The treatment group was treated with the GSK-3β inhibitor 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione for 12 consecutive weeks following renal transplantation. The study included uninephrectomized F344 and Lewis rats as control subjects. Twelve weeks post surgery, the rats were retrieved for analysis of renal function, urine protein levels, histological, immunohistochemical, and molecular biological parameters., Results: Administration of 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione inactivated GSK-3β and thereby improved renal function, attenuated proteinuria, and reduced renal tissue damage in CRAD rats. Besides, inactivation of GSK-3β inhibited nuclear factor-κB activation, macrophage infiltration, and expression of multiple proinflammatory cytokines/chemokines. Inhibition of GSK-3β also decreased the levels of malondialdehyde, increased superoxide dismutase levels, upregulated the expression of heme oxygenase-1 and NAD(P)H quinone oxidoreductase-1, and enhanced nuclear translocation of nuclear factor erythroid 2-related factor 2 in the kidneys of CRAD rats., Conclusions: Inhibition of GSK-3β attenuates the development of CRAD by inhibiting inflammation and oxidant stress. Thus, GSK-3β inhibition may represent a potential therapeutic strategy for the prevention and treatment of CRAD., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Urinary extracellular vesicles (uEVs) are a novel source of biomarkers. However, urinary Tamm-Horsfall Protein (THP; uromodulin) interferes with all vesicle isolation attempts, precipitates with normal urinary proteins, thus, representing an unwanted "contaminant" in urinary assays. Thus, the aim is to develop a simple method to manage THP efficiently., Experimental Design: The uEVs are isolated by hydrostatic filtration dialysis (HFD) and treated with a defined solution of urea to optimize release of uEVs from sample. Presence of uEVs is confirmed by transmission electron microscopy, Western blotting, and proteomic profiling in MS., Results: Using HFD with urea treatment for uEV isolation reduces sample complexity to a great extent. The novel simplified uEV isolation protocol allows comprehensive vesicle proteomics analysis and should be part of any urine analytics to release all sample constituents from THP trap., Conclusions and Clinical Relevance: The method brings a quick and easy protocol for THP management during uEV isolation, providing major benefits for comprehensive sample analytics., (© 2019 The Authors. Proteomics - Clinical Application published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To explore the value of detecting podocalyxin (PCX) level in urinary extracellular vesicles for the diagnosis of diabetic nephropathy., Methods: This study was conducted among 57 diabetic patients admitted during the period from March to September, 2017, including 34 with uncomplicated diabetics and 23 with diabetic nephropathy; 21 patients with other types of nephropathy and 11 healthy individuals were also included to serve as the controls. Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) were used to verify the separation of urinary extracellular vesicles. The molecular markers of extracellular vesicles (TSG101 and podocalyxin [PCX]) were detected using Western blotting. PCX levels in extracellular vesicles were also detected using ELISA., Results: TEM reveal the presence of numerous extracellular vesicles in the urine with intact morphology and different sizes, and most of them were below 300 nm in diameter as shown by NTA. TSG101 expression was detected in the samples from all the 4 groups. Positive expression of PCX was detected in the samples from patients with diabetic nephropathy but not in the other groups. In patients with diabetic nephropathy, the mean PCX levels (3.27±2.30 ng/μmol)was significantly higher than those in the healthy control group (1.22±0.36 ng/μmol), uncomplicated diabetes group (2.22±1.29 ng/μmol) and nephropathy group (1.24±0.45 ng/μmol)., Conclusions: PCX level in urinary extracellular vesicles is significantly increased in patients with diabetic nephropathy, suggesting the value of PCX as a potential marker for clinical diagnosis of diabetic nephropathy.

Urinary extracellular vesicles (uEVs) have become a promising source for biomarkers accurately reflecting biochemical changes in kidney and urogenital diseases. Characteristically, uEVs are rich in membrane proteins associated with several cellular functions like adhesion, transport, and signaling. Hence, membrane proteins of uEVs should represent an exciting protein class with unique biological properties. In this study, we utilized uEVs to optimize the Triton X-114 detergent partitioning protocol targeted for membrane proteins and proceeded to their subsequent characterization while eliminating effects of Tamm-Horsfall protein, the most abundant interfering protein in urine. This is the first report aiming to enrich and characterize the integral transmembrane proteins present in human urinary vesicles. First, uEVs were enriched using a "hydrostatic filtration dialysis'' appliance, and then the enriched uEVs and lysates were verified by transmission electron microscopy. After using Triton X-114 phase partitioning, we generated an insoluble pellet fraction and aqueous phase (AP) and detergent phase (DP) fractions and analyzed them with LC-MS/MS. Both in- and off-gel protein digestion methods were used to reveal an increased number of membrane proteins of uEVs. After comparing with the identified proteins without phase separation as in our earlier publication, 199 different proteins were detected in DP. Prediction of transmembrane domains (TMDs) from these protein fractions showed that DP had more TMDs than other groups. The analyses of hydrophobicity revealed that the GRAVY score of DP was much higher than those of the other fractions. Furthermore, the analysis of proteins with lipid anchor revealed that DP proteins had more lipid anchors than other fractions. Additionally, KEGG pathway analysis showed that the DP proteins detected participate in endocytosis and signaling, which is consistent with the expected biological functions of membrane proteins. Finally, results of Western blotting confirmed that the membrane protein bands are found in the DP fraction instead of AP. In conclusion, our study validates the use of Triton X-114 phase partitioning protocol on uEVs for a targeted isolation of membrane proteins and to reduce sample complexity. This method successfully facilitates detection of potential biomarkers and druggable targets in uEVs.

Aim: To validate the association between visceral obesity and pathogenesis of chronic kidney disease (CKD) among individuals aged 40 years and above, and the potential of visceral adiposity index (VAI) to predict CKD., Methods: This study was based on a cross-sectional epidemiologic study in the People's Republic of China. A total of 1,581 residents aged over 40 years were included and divided into four groups based on VAI quartile intervals, namely, Groups I, II, III, and IV (eg, Group I included patients with their VAIs in the lowest quartile). Logistic regression analysis was performed., Results: VAI is positively correlated with the albumin-to-creatinine ratio and the prevalence of CKD (P<0.001), and is inversely related to estimated glomerular filtration rate (P<0.001). Using Group I as control, odds ratios (ORs) were calculated to quantify the risk of developing CKD as VAI increased (Group II 1.08 [P>0.05], Group III 1.57 [P<0.05], Group IV 2.31 [P<0.001]). Related factors like age and sex were normalized in the logistic model before calculation. ORs became 1.16 (P>0.05), 1.59 (P<0.05), and 2.14 (P<0.05), respectively, for each group after further normalization considering smoking, drinking, physical activity, education, and the history of hypertension, coronary heart disease, and diabetes. The same results were not observed after fasting blood glucose and blood pressure levels were included in the normalization. There was no significant difference in the ORs for different groups: 0.94 (P>0.05), 1.11 (P<0.05), and 1.68 (P>0.05), respectively., Conclusion: VAI is highly correlated with the prevalence of CKD in the population aged 40 years and above. It can be used to predict the pathogenesis of CKD, which is dependent on fasting blood glucose and blood pressure levels.

Objective: To investigate the value of serum IgA/C3 ratio in the diagnosis of IgA nephropathy and explore its relationship with the clinicopathological features of the patients., Methods: Sixty-six patients with IgA nephropathy, 111 with other glomerular diseases, and 40 healthy control subjects without kidney disease were tested for serum IgA and C3 levels using CRM470 adjusted standardized immune turbidimetric method, and the IgA/C3 ratio was calculated. According to Oxford and Lee's classification criteria, we analyzed the pathological grades of the renal biopsy samples from patients with IgA nephropathy. The ROC curve was used to assess the value of serum IgA and IgA/C3 ratio in predicting IgA nephropathy., Results: Patients with IgA nephropathy had an elevated serum IgA/C3 ratio than those with other glomerular diseases and the control subjects, with an area under the ROC curve of 0.776. An elevated serum IgA/C3 ratio was not found to significantly correlate with the pathological grade of renal biopsy samples in patients with IgA nephropathy., Conclusion: In the absence of renal biopsy findings, serum IgA/C3 ratio can help in the diagnosis of IgA nephropathy.

Objective: To analyze the quantity and size distribution of 24-hour urinary extracellular vesicles (uEVs) from healthy adults., Methods: The 24-hour uEVs from 9 healthy adults were isolated by hydrostatic filtration dialysis (HFD). The effectiveness of uEVs enrichment was evaluated using Western blotting and transmission electron microscopy (TEM). The quantity and size distribution of the uEVs was analyzed with BCA protein quantification, TEM, and nanoparticle tracking analysis (NTA)., Results: uEVs with different sizes and morphologies were observed under TEM. Western blotting confirmed the expression of TSG101 in all the uEV fractions from the 9 donors, ranging from 132.50 to 760.70 ng/mL. NTA results showed that the number of 24-hour uEVs amount ranged from 3.56 × 10¹² particles to 5.12 × 10¹² particles, with a CV of 14.23%. The proportion of the vesicles with a diameter <40 nm was 0.04%-0.69% with a number range of (1.80-26.49)× 10⁹ particles; the proportion of vesicles with a diameter of 40-100 nm (which is consistent with the size of exosomes)was 22.07%-42.08% with a number range of (1.00-1.77)× 10¹² particles. The proportion of vesicles with a diameter of 100-1000 nm (consistent with the size of microvesicles) was 57.88%-77.85% with a number range of (2.09-3.86)× 10¹² particles., Conclusion: The established HFD method allows efficient and convenient isolation of uEVs from a large amount of urine samples. The 24-hour uEVs from healthy adults show narrow differences between individuals and thus can be an ideal source of samples for relevant studies.

Purpose: Urinary extracellular vesicles (UEVs) are a novel source for disease biomarker discovery. However, Tamm-Horsfall protein (THP) is still a challenge for proteomic analysis since it can inhibit detection of low-abundance proteins. Here, we introduce a new approach that does not involve an ultracentrifugation step to enrich vesicles and that reduces the amount of THP to manageable levels., Experimental Design: UEVs were dialyzed and ultrafiltered after reduction and alkylation. The retained fraction was digested with trypsin to reduce the remaining THP and incubated with deoxycholate (DOC). The internal peptidome and internal proteome were analyzed by LC-ESI-MS., Results: A total of 942 different proteins and 3115 unique endogenous peptide fragments deriving from 973 different protein isoforms were identified. Around 82% of the key endosomal sorting complex required for transport components of UEVs generation could be detected from the intraluminal content., Conclusions and Clinical Relevance: Our UEVs preparation protocol provides a simplified way to investigate the intraluminal proteome and peptidome, in particular the subpopulation of UEVs of the trypsin-resistant class of exosomes (positive for tumor susceptibility gene101) and eliminates the majority of interfering proteins such as THP. This method allows the possibility to study endoproteome and endopeptidome of UEVs, thus greatly facilitating biomarker discovery., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To explore the relationship between the major allergens of 6 common allergic foods and IgA nephropathy., Methods: A sensitive sandwich enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of food-specific IgA1, IgG and IgE in 31 patients with IgA nephropathy and 80 healthy volunteers. All the patients were examined for a history of food allergy using a questionnaire., Results: Serum levels of IgA1 and IgG against the major allergens of the 6 common allergic foods were significantly higher in patients with IgA nephropathy than in healthy volunteers (P<0.05). There was no detectable food-specific IgE antibodies in the two groups. No patients had a clear history of food allergy. All the patients with increased IgG levels specific to 4 or more foods simultaneously had proteinuria., Conclusions: Some foods especially the highly allergic ones may participate in the pathogenesis and progression of IgA nephropathy.

Objective: To compare two equations for calculating glomerular filtration rate (GFR) in the evaluation of the prevalence of chronic kidney disease (CKD) and the risk factors of CKD in urban healthy population., Methods: A total of 40377 subjects (24164 males and 16213 females) participated in this study. Body height, weight and blood pressure were measured, and morning urine and venous blood samples were collected for routine urine and blood tests with measurements of blood glucose, total cholesterol, high density lipoprotein (HDL), low-density lipoprotein (LDL), creatinine and uric acid., Results and Conclusion: Using Japanese CKD Epidemiology Collaboration (J-EPI) equation and Chinese modified Modification of Diet in Renal Disease (C-MDRD) equation, the prevalence of CKD calculated was 3.9% and 6.3% in this population, respectively. The independent risk factors of CKD included an age over 60 years, high uric acid, and high blood glucose.