Effects of uric acid-lowering therapy (ULT) on renal outcomes in CKD patients with asymptomatic hyperuricemia: a systematic review and meta-analysis.

BACKGROUND: It is well known that asymptomatic hyperuricemia and gout play an important role in patients with chronic kidney disease (CKD). However, the effect of uric acid-lowering therapy (ULT) on the prognosis of CKD patients with asymptomatic hyperuricemia remains controversial. Therefore, we aim to investigate the influence of ULT on renal outcomes in these patients. METHODS: Comprehensive searches were conducted in PubMed, EMBASE, China National Knowledge Internet (CNKI), and the Cochrane Library, up until January 2024. We included randomized controlled trials (RCTs) that evaluated the effects of ULT on renal outcomes in CKD patients with asymptomatic hyperuricemia. RESULTS: A total of 17 studies were included in the meta-analysis. Compared with placebo or no treatment, ULT preserved the loss of estimated glomerular filtrating rate (eGFR) (Weighted mean difference [WMD] and its 95% confidence intercal(CI): 2.07 [0.15,3.98] mL/min/1.73m2) at long-term subgroup. At the same time, short-term subgroup also proved the preserved loss of eGFR (WMD 5.74[2.09, 9.39] mL/min/1.73m2). Compared with placebo or no treatment, ULT also reduced the increase in serum creatinine (Scr) at short-term (WMD -44.48[-84.03,-4.92]µmol/L) subgroup and long-term (WMD -46.13[-65.64,-26.62]µmol/L) subgroup. ULT was associated with lower incidence of the events of doubling of Scr without dialysis (relative risk (RR) 0.32 [0.21, 0.49], p < 0.001). However, no difference was found for lower incidence of acute kidney injury (AKI) (p = 0.943). CONCLUSIONS: According to our study, ULT is beneficial for slowing CKD progression both in short to long-term follow-ups. Additionally, in patients younger than 60 years old, the protective effect of ULT on renal outcome is more pronounced. However, it showed no significant difference in the incidence of AKI. These findings underscore the importance of considering ULT in clinical strategies for CKD patients with asymptomatic hyperuricemia.

Associaton of Retinol Binding Protein 4 (RBP4) Levels With Hyperuricemia: A Cross-Sectional Study in a Chinese Population.

Background: There are few studies on predictive biomarkers for hyperuricemia, and the predictive value of these biomarkers tends to be poor. Additionally, no reports have described the predictive value of retinol binding protein 4 (RBP4) for hyperuricemia. Purpose: This study was performed to evaluate the value of RBP4 for predicting the risk of hyperuricemia in a general population, determine whether RBP4 could be used alone or in combination with other factors to predict the risk of hyperuricemia in the general population, and establish an optimum predictive model. Methods: We conducted a population-based cross-sectional survey in 2018, involving a questionnaire, physical examination, and laboratory testing. We enrolled 2303 individuals by stratified random sampling, and 2075 were included in the data analysis after applying the eligibility criteria. Results: Serum RBP4 level had a highly significant association with hyperuricemia (P<0.001). After adjusting for potential confounders, logistic regression indicated that the risk of hyperuricemia was highest in the highest RBP4 quartile (odds ratio: 7.9, 95% confidence interval [CI]: 4.18-14.84, compared to the lowest quartile). The area under the receiver operating characteristic (ROC) curve (AUC) for RBP4 was 0.749 (95% CI: 0.725-0.774, P<0.001), which was higher than that for all the other predictors assessed. The optimum model for predicting hyperuricemia in the general population consisted of RBP4, sex (male), body mass index, serum creatinine, high-sensitivity C-reactive protein, fasting blood glucose, insulin, and alcohol consumption. The AUC was 0.804 (95% CI: 0.782-0.826, P<0.001). Conclusions: RBP4 is strongly associated with hyperuricemia, and its predictive value was higher than that of traditional predictors.

Amelioration of Renal Injury by Resveratrol in a Rat Renal Transplantation Model via Activation of the SIRT1/NF-κB Signaling Pathway.

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-κBp65. RSV increased the expression of SIRT1 and decreased the expression of Ac-NF-κBp65. 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-κB signaling pathway.

Metabolic Syndrome Components and Chronic Kidney Disease in a Community Population Aged 40 Years and Older in Southern China: A Cross-Sectional Study.

Purpose: To investigate the correlation between metabolic syndrome components and chronic kidney disease (CKD) among a community population aged 40 years and older in Southern China. Patients and Methods: From December 2017 to March 2018, 1969 participants (male n = 715, female n = 1254) aged 40 years and older were recruited in Southern China for a cross-sectional survey. A logistic regression model was established to analyze the correlation between metabolic syndrome components and CKD. Results: Among the 1969 subjects, 407 (20.7%) were CKD patients, including 152 males (prevalence rate 21.3%) and 255 females (prevalence rate 20.3%). Anthropometric data (waist circumference, age, systolic and diastolic blood pressure), serum/plasma data (serum creatinine, serum uric acid, fasting plasma glucose, C-reactive protein, serum triglyceride), urinary and other findings (body mass index, waist-to-hip and waist-to-height ratios, urinary albumin to creatinine ratio, homeostasis model assessment of insulin resistance) were significantly higher in patients with than without CKD (P < 0.05). Metabolic syndrome and at least some of its components were statistically significant risk factors for CKD in models with and without adjustment for diabetes, obesity and hypertension. Conclusion: Metabolic syndrome and its single or combined components are independently associated with CKD in community populations aged 40 years and older. The correlation between some components and CKD remained significant in both non-diabetic and non-obese subjects. Correlations between components of metabolic syndrome and CKD show that it is feasible and necessary to carry out targeted screening and intervention tests in people aged 40 and over.

Total Synthesis and Stereochemistry Assignment of Nucleoside Antibiotic A-94964.

A collective total synthesis of eight diastereoisomers associated with NMR analysis leads to a full stereochemistry assignment of the structurally unique nucleoside antibiotic A-94964, which features an octuronic acid uridine core decorated with an α-D-mannopyranosyl residue and an α-D-N-acylglucosaminopyranosyl residue via a phosphodiester bridge.

Potential role of anti-inflammatory HDL subclasses in metabolic unhealth/obesity.

High-density lipoprotein (HDL) particles comprising heterogeneous subclasses of different functions exert anti-inflammatory effects by interacting with immune-response cells. However, the relationship of HDL subclasses with immune-response cells in metabolic unhealth/obesity has not been defined clearly. The purpose of this study was to delineate the relational changes of HDL subclasses with immune cells and inflammatory markers in metabolic unhealth/obesity to understand the role of anti-inflammatory HDL subclasses. A total of 316 participants were classified by metabolic health. HDL subclasses were detected by microfluidic chip electrophoresis. White blood cell (WBC) counts and lymphocytes were assessed using automatic haematology analyser. Levels of high-sensitivity C-reactive protein (hs-CRP) and interleukin 6 (IL-6) were measured. In our study, not only the distribution of HDL subclasses, but also HDL-related structural proteins changed with the deterioration of metabolic disease. Moreover, lymphocytes and inflammation factors significantly gradually increased. The level of HDL2b was negatively associated with WBC, lymphocytes and hs-CRP in multivariable linear regression analysis. In multinomial logistic regression analysis, high levels of HDL3 and low levels of HDL2b increased the probability of having an unfavourable metabolic unhealth/obesity status. We supposed that HDL2b particles may play anti-inflammation by negatively regulating lymphocytes activation. HDL2b may be a therapeutic target for future metabolic disease due to the anti-inflammatory effects.

Multiple Dirac cones and Lifshitz transition in a two-dimensional Cairo lattice as a Hawking evaporation analogue.

The linear energy-momentum dispersion of Dirac cones offers a unique platform for mimicking the fantastical phenomena in high energy physics, such as Dirac fermions and black hole (BH) horizons. Three types of Dirac cones (I, III, and II) with different tilts have been proposed individually in specific materials but lack of integral lattice model. Here, we demonstrated the three types of Dirac cones inherited in aπ-conjugated Cairo lattice of double-degeneratedπandpzorbitals by means of tight-binding (TB) approach, which paves a way for the design of two-dimensional (2D) Dirac materials. From first-principles calculations, we predicted a candidate material,penta-NiSb2monolayer, to achieve these multiple Dirac cones and the Lifshitz transition between different Dirac cones driven by external biaxial strain. The coexistence of the three types of Dirac cones renderspenta-NiSb2monolayer a promising 2D fermionic analogue to simulate the event-horizon evaporation with a high Hawking temperature.

Pharmacologic Targeting of BET Proteins Attenuates Hyperuricemic Nephropathy in Rats.

Hyperuricemia is an independent risk factor for renal damage and promotes the progression of chronic kidney disease. In this study, we investigated the effect of I-BET151, a small-molecule inhibitor targeting the bromodomain and extraterminal (BET) proteins, on the development of hyperuricemic nephropathy (HN), and the mechanisms involved. Expression levels of bromodomain-containing protein 2 and 4, but not 3 were increased in the kidney of rats with HN; administration of I-BET151 effectively prevented renal dysfunction, decreased urine microalbumin, and attenuated renal fibrosis as indicated by reduced activation of renal interstitial fibroblasts and expression of fibronectin and collagen I in HN rats. Mechanistic studies show that I-BET151 treatment inhibited transition of renal epithelial cells to a mesenchymal cell type as evidenced by preservation of E-cadherin and reduction of vimentin expression. This was coincident with reduced expression of TGF-ß1 and dephosphorylation of Smad3 and ERK1/2. I-BET151 was also effective in inhibiting phosphorylation of NF-κB, expression of multiple cytokines and chemokines, and infiltration of macrophages to the injured kidney. Although there were increased serum levels of uric acid and xanthine oxidase, an enzyme that catalyzes production of uric acid, and decreased expression of renal organic anion transporter 1 and 3 that promote urate excretion in the model of HN, and reduced expression levels of urine uric acid, I-BET151 treatment did not affect these responses. Collectively, our results indicate that I-BET151 alleviates HN by inhibiting epithelial to mesenchymal transition and inflammation in association with blockade of TGF-ß, ERK1/2 and NF-κB signaling.

Inhibition of Glycogen Synthase Kinase 3ß Alleviates Chronic Renal Allograft Dysfunction in Rats.

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 3ß (GSK-3ß) 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-3ß 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-3ß and thereby improved renal function, attenuated proteinuria, and reduced renal tissue damage in CRAD rats. Besides, inactivation of GSK-3ß inhibited nuclear factor-κB activation, macrophage infiltration, and expression of multiple proinflammatory cytokines/chemokines. Inhibition of GSK-3ß 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-3ß attenuates the development of CRAD by inhibiting inflammation and oxidant stress. Thus, GSK-3ß inhibition may represent a potential therapeutic strategy for the prevention and treatment of CRAD.

Comparison of Novel Metabolic Indices in Estimation of Chronic Kidney Diseases in a Southern Chinese Population.

BACKGROUND: To determine the optimal cut-off values and evaluate the associations of product of triacylglycerol and glucose (TyG), lipid accumulation product (LAPI), visceral adiposity index (VAI) with chronic kidney diseases (CKD) stratified by sex. METHODS: From January to April 2018, our team had conducted a large-scale cross-sectional survey that contained 2720 individuals on the southern coast of China. Logistic regression analysis and receiver operating characteristic (ROC) analyses were used to evaluate the optimal cut-off and value of TyG, LAPI, VAI for predicting CKD. RESULTS: A multivariate logistic regression analysis found that the TyG had the better value of prediction for the presence of CKD for the highest quartile vs the lowest quartile in both males (OR: 3.65; 95% CI, 2.04-6.52; p<0.001) and females (OR: 3.50; 95% CI, 2.20-5.56; p<0.001), followed by LAPI and VAI, when further adjusted for cofounder factors, LAPI and VAI both lost their independence, and only TyG remains its significant association with CKD in both males (OR: 2.81; 95% CI, 1.25-6.30; p<0.001) and females (OR: 3.22; 95% CI, 1.56-6.61; p<0.001). ROC curve showed that TyG had the highest AUC for predicting CKD in males (AUC: 0.618). TyG (AUC: 0.670) and LAPI (AUC: 0.670) both had the highest AUC in females. United predicted models which contain TyG were conducted for predicting CKD in males (AUC: 758) and females (AUC: 0.773) and results indicated that multivariate analysis of TyG and other traditional factors can impressively improve the accuracy of predictive probability for CKD. CONCLUSION: TyG is a priority to the other two novel indices and may become valuable makers and have strong predictive power for predicting CKD, especially in females.

The Product of Red Blood Cells and Hematocrit Can Be Used as a Novel Indicator of Impaired Fasting Blood Glucose Status.

OBJECTIVE: To explore whether the red blood cell count multiplied by hematocrit index (RBCHct) in blood routine parameters can indicate the risk of impaired fasting blood glucose (IFG), and whether it is related to insulin resistance and inflammation. METHODS: In this cross-sectional study, previous history of diabetes was excluded, and people with normal and impaired IFG were included. We use Spearman analysis to evaluate the correlation between RBCHct index and fasting plasma glucose, insulin resistance homeostasis model assessment (HOMA-IR), and hypersensitive C-reactive protein (hs-CRP). Binary logistic regression analysis was used to evaluate the RBCHct index for assessing the potential risk of IFG, and the receiver operating characteristic (ROC) curve was used to evaluate the RBCHct index for diagnosing insulin resistance and chronic low-grade inflammatory efficacy among those with IFG. RESULTS: Correlation analysis showed that the RBCHct index and fasting plasma glucose (r=0.088, P=0.003); HOMA-IR (r=0.199, P<0.001); and hs-CRP (r=0.097, P=0.001) were positively correlated. After adjusting for confounding factors, the risk of IFG in the third and fourth quartiles of the RBCHct index increased to 1.889 and 3.048 times. The area under the ROC curve of the RBCHct index for diagnosis of insulin resistance state (HOMA-IR) was 0.695 (p<0.001), and the area under the ROC curve of the RBCHct index for the diagnosis of chronic low-inflammatory state (hs-CRP) was 0.641 (P=0.010). CONCLUSION: The RBCHct index may be a potential indicator for assessing the risk of prediabetes and is closely related to whether the body is in a state of insulin resistance and inflammation under IFG.

Synthesis of Sea Cucumber Saponins with Antitumor Activities.

Holostane glycosides are characteristic metabolites of sea cucumbers, which possess various biological activities. Here, we report the synthesis of two representative congeners, namely, pervicoside B and C, starting from lanosterol with the longest linear sequence of both 34 steps and in 0.3% overall yields. The flexible synthetic approach has enabled us to expeditiously prepare 16 analogues for preliminary studies on the key structural features influencing their antiproliferative activities against tumor cells. A simplified disaccharide is found to be as potent as natural tetrasaccharides, which can be used as a lead for future studies.

Tissue Inhibitor of Matrix Metalloproteinase 2-Loaded Polylactic Acid-Polyethylene Glycol Nanoparticles Directly Regulates Renal Tubular Epithelial Cell Proliferation via Protein Tyrosine Kinase KIT.

TIMP2 has been previously reported to be associated with acute kidney injury (AKI); however, the underlying mechanism remains unclear. Therefore, the present study investigated the regulation of TIMP2 in human tubular epithelial cells HK-2 cells. Proliferation of HK-2 cells treated by TIMP2 at normal expression level was detected. GST pulldown and mass spectrometry were performed to investigate the interacting protein of TIMP2 and immunofluorescence test was used to determine the location of the protein in HK-2 cells. Cell viability as well as the expression level of CCND1, C-FOS, MAPK1 and P-MAPK1 were detected in the samples treated by overexpressed TIMP2 and the inhibitor of the interacting protein KIT. TIMP2 significantly inhibited cell proliferation compared with the control and BB-94-treated groups (P < 0.05). KIT was identified as the interacting protein of TIMP2, and was located in both the cytoplasm and membrane of HK-2 cells. Inhibited KIT and the overexpressed of TIMP2 both significantly suppressed cell proliferation and decreased the expression levels of CCND1, MAPK1, and P-MAPK1 compared with the control (P < 0.05). No significant difference was observed in cell proliferation and the expression level of aforementioned proteins between overexpressed TIMP2 and KIT-inhibited group. The results revealed that TIMP2 regulates cell proliferation by reducing the expression levels of CCND1, MAPK1, and P-MAPK1 via KIT, indicating that TIMP2 directly regulates cell proliferation without inhibiting matrix metalloproteinases in AKI. Furthermore, PLA-PEG nanoparticles successfully transported TIMP2 to the target with no significant effect on cell proliferation.

Treatment with a PPAR-γ Agonist Protects Against Hyperuricemic Nephropathy in a Rat Model.

PURPOSE: Hyperuricemia is an independent risk factor for renal damage and can promote the progression of chronic kidney disease (CKD). In the present study, we employ a rat model to investigate the effects of rosiglitazone (RGTZ), a peroxisome proliferator-activated receptor-gamma agonist, on the development of hyperuricemic nephropathy (HN), and we elucidate the mechanisms involved. METHODS: An HN rat model was established by oral administration of a mixture of adenine and potassium oxonate daily for 3 weeks. Twenty-four rats were divided into 4 groups: sham treatment, sham treatment plus RGTZ, HN, and HN treated with RGTZ. RESULTS: Administration of RGTZ effectively preserved renal function, decreased urine microalbumin, and inhibited interstitial fibrosis and macrophage infiltration in a rat HN model. RGTZ treatment also inhibited TGF-ß and NF-κB pathway activation, decreased expression of fibronectin, collagen I, α-SMA, vimentin, MCP-1, RANTES, TNF-α, and IL-1ß, and increased E-cadherin expression in the kidneys of HN rats. Furthermore, RGTZ treatment preserved expression of OAT1 and OAT3 in the kidney of HN rats. CONCLUSION: RGTZ attenuates the progression of HN through inhibiting TGF-ß signaling, suppressing epithelial-to-mesenchymal transition, reducing inflammation, and lowering serum uric acid levels by preserving expression of urate transporters.

Remote Ischemic Preconditioning Reduces the Risk of Contrast-Induced Nephropathy in Patients with Moderate Renal Impairment Undergoing Percutaneous Coronary Angiography: A Meta-Analysis.

BACKGROUND/AIMS: This meta-analysis evaluated the effects of remote ischemic preconditioning (RIPC) on the risk of contrast-induced nephropathy (CIN) in patients undergoing percutaneous coronary intervention/coronary angiography (PCI/CA). METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases were searched for randomized controlled trials (RCTs) that assessed the effect of RIPC on CIN in patients undergoing PCI/CA. The main outcomes of interest were the incidence of CIN 48-72 h after CA, the levels of serum creatinine, cystatin C, neutrophil gelatinase-associated lipocalin, and estimated glomerular filtration rate (eGFR), mortality, and requirement of hemodialysis and rehospitalization. The analysis was conducted using the random-effect model due to the expected heterogeneity among different studies. RESULTS: In total, 16 trials covering 2,048 patients were identified. By assessing the methodological quality of the included studies through the Coch-rane risk of bias, we found that of the 16 RCTs, 3 had a low risk of bias, 6 a high, and 7 an unclear risk. The application of RIPC decreased the incidence of CIN (relative risk, RR, 0.50, 95% confidence interval, CI, 0.39-0.65; p < 0.001). Subgroup analyses showed that RIPC decreased the incidence of CIN in patients with eGFR <60 mL/min/1.73 m2 (RR 0.53, 95% CI 0.38-0.75; p < 0.001) but not in patients with eGRF ≥60 mL/min/1.73 m2 (RR 0.82, 95% CI 0.35-1.94; p = 0.66) at baseline. Furthermore, the increase in serum creatinine was significantly lower in patients with RIPC compared to control patients (standardized mean difference -1.41, 95% CI -2.46 to -0.35; p = 0.009). CONCLUSIONS: Based on 16 RCTs, this meta-analysis shows that RIPC can reduce the risk of CIN in patients with moderate renal impairment undergoing PCI/CA. However, this needs to be confirmed by further high-quality evidence.

High-Sensitivity C-Reactive Protein Leads to Increased Incident Metabolic Syndrome in Women but Not in Men: A Five-Year Follow-Up Study in a Chinese Population.

PURPOSE: Metabolic syndrome (MetS), characterized by a constellation of insulin resistance, central obesity, hypertension, and hyperlipidemia, is a global health threat. High-sensitivity C-reactive protein (hs-CRP) has been shown to be associated with type 2 diabetes and cardiovascular disease; however, its association with incident MetS is less known. Therefore, the aim of this study was to examine the prospective association between hs-CRP and MetS among a Chinese population in a 5-year follow-up study. PATIENTS AND METHODS: The levels of hs-CRP were measured using serum samples collected at baseline recruitment in 2012 from 886 participants without MetS. Follow-up interviews were conducted in 2018, and MetS was diagnosed by 2017 criteria from the Chinese Diabetes Society. Multivariate logistic regression models were used to assess the overall and sex-specific associations between hs-CRP and incident MetS. The odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were computed with adjustment for demographic, socioeconomic, clinical, and lifestyle factors. RESULTS: After a mean follow-up duration of 5.40 ± 0.56 years, 116 (13.3%) participants developed MetS. In the total study population, increased hs-CRP levels were associated with a higher risk of MetS (OR comparing extreme quartiles of hs-CRP: 4.06 [95% CI: 1.91-8.65]) in the fully-adjusted model. When stratified by sex, the positive association was only observed in women (OR: 4.82 [1.89-12.3]) but not in men (OR: 3.15 [0.82-12.1]; P-interaction = 0.039). CONCLUSION: In this study of a Chinese population, a positive association between hs-CRP and incident MetS was found only in women and not in men. Sex-specific prediction and intervention of MetS using hs-CRP as a target should be further evaluated.

Association of Lipid Parameters with the Risk of Chronic Kidney Disease: A Longitudinal Study Based on Populations in Southern China.

OBJECTIVE: To investigate which plasma lipid parameters are useful for detecting chronic kidney disease (CKD) in a Chinese population without known CKD or renal impairment. METHODS: This was a prospective study. In southern Chinese cities from 2012 to 2013, a total of 1037 subjects aged ≥ 18 years old received a survey. Logistic regression and multiple linear regression analyses were performed. The lipid parameters studied included total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (nHDL-C), TG/HDL-C ratio, TC/HDL-C ratio and nHDL-C/HDL-C ratio. RESULTS: After adjusting for confounding factors, the fourth percentile of logTG/HDL-C was observed to be an independent risk factor for CKD (OR = 2.453, P < 0.001), and the highest quantile of the logTG/HDL-C ratio was associated with a higher prevalence of CKD (P < 0.05). This risk was reduced when the model was adjusted with Insulin resistance (IR) (OR = 2.034, P < 0.05). In the group of women, glucose metabolism disorders, high uric acid, and obesity, this risk was increased. Multiple regression models showed that log TG and nonHDL-C/HDL-C were negatively correlated with eGFR (P < 0.05), while log TG and TC were positively correlated with logACR (P < 0.05). The area under the curve (ROC) of lgTG/HDL was 0.623 (p < 0.001). CONCLUSION: The serum logTG/HDL-C ratio is the only suitable predictor of CKD, and IR may be the mechanism. This risk needs to be controlled in a specific population. Log TG and nonHDL-C/HDL-C were negatively correlated with eGFR, while log TG and TC were positively correlated with logACR.

Visceral Adiposity Index and Chronic Kidney Disease in a Non-Diabetic Population: A Cross-Sectional Study.

PURPOSE: To investigate the correlation between visceral obesity and pathogenesis of chronic kidney disease (CKD) among non-diabetic individuals, and to evaluate the potential of visceral adiposity index (VAI) as a predictor of CKD. PATIENTS AND METHODS: From December 2017 to March 2018, 1877 non-diabetic participants (male n=699, female n=1208) in southern China were recruited for a cross-sectional survey. Males and females were divided into four groups according to gender-specific quartiles of VAI scores. A logistic regression model was established to analyze the correlation between visceral adiposity index and CKD. RESULTS: Visceral adiposity index was positively correlated with CKD and was negatively associated with estimated glomerular filtration rate (eGFR). Using group one as the control, odds ratios (ORs) were calculated to determine the risk of developing CKD as VAI increased (male: group four 2.73 [P<0.005]; female: Group three 1.76 [P<0.05], Group four 2.88 [P<0.005]). When related factors such as history of hypertension, smoking, alcohol use, and physical inactivity were normalized in the logistic model before calculation, ORs became 2.73 (male: P<0.05), and 2.18 (female: P<0.05), respectively. The results differed after normalizing further for systolic blood pressure (SBP), diastolic blood pressure (DBP), hypersensitive c-reactive protein (hsCRP), interleukin-6 (IL-6), homocysteine (Hcy), superoxide dismutase (SOD), and retinol-binding protein (RBP). There were no significant differences in ORs among the female groups. CONCLUSION: Visceral adiposity index was significantly associated with CKD in non-diabetic individuals. It may be a good predictor of the pathogenesis of CKD and was dependent on hsCRP, IL-6, Hcy, SOD, RBP, and blood pressure levels in females and males with VAI scores of 1.41 and higher. Visceral adiposity index may be used to predict CKD in males with VAI less than 0.983.

Delayed administration of suramin attenuates peritoneal fibrosis in rats.

BACKGROUND: Peritoneal fibrosis is the most common complication of peritoneal dialysis, but there is currently no effective treatment. We previously reported that suramin pretreatment prevents the development of peritoneal fibrosis in a rat model of peritoneal fibrosis induced by chlorhexidine gluconate (CG). Here, we further examined the effectiveness of delayed administration of suramin on peritoneal fibrosis and the mechanism (s) involved in this process. METHODS: In the rat model of peritoneal fibrosis induced by CG, suramin or saline was administered at day 21 and 28. All rats were then sacrificed to collect peritoneal tissues for Western blot analysis and histological staining at day 35. RESULTS: Our results demonstrated that delayed administration of suramin starting at 21 days following CG injection can ameliorate peritoneal damage, with greater efficacy after two injections. Suramin also reduced the expression of α-smooth muscle actin, Collagen 1, and Fibronectin and suppressed phosphorylation of Smad-3, epidermal growth factor receptor (EGFR), signal transducers, activator of transcription 3 (STAT3) as well as extracellular signal-regulated kinases 1/2 (ERK 1/2) in the peritoneum injured with CG. Moreover, delayed administration of suramin inhibited overproduction of transforming growth factor-ß1(TGF-ß1) and expression of several pro-inflammatory cytokines, including monocyte chemoattractant protein-1, tumor necrosis factor-α, interleukin-1, and interleukin-6. CONCLUSIONS: Our results indicated that suramin can attenuate progression of peritoneal fibrosis by a mechanism involving inhibition of the TGF-ß1/Smad3 and EGFR signaling pathways as well as suppression of multiple proinflammatory cytokines. Thus, suramin may have the potential to offer an effective treatment for peritoneal fibrosis.

Lymphocyte To High-Density Lipoprotein Ratio As A New Indicator Of Inflammation And Metabolic Syndrome.

PURPOSE: Metabolic syndrome (MetS), which is a global public health problem, is a state of chronic low-grade inflammation. This study looked at the changes in hematological parameters and the predictive value of the lymphocyte to high-density lipoprotein cholesterol (HDL-C) ratio (LHR) as a new index in subjects with and without MetS in coastal cities in southern China. PATIENTS AND METHODS: In this cross-sectional study, there were 852 participants (n = 598 with MetS and n = 254 without MetS). MetS was defined in accordance with the National Cholesterol Education Program, Adult Treatment Panel III (NCEP-ATP III) criteria. RESULTS: MetS was positively correlated with white blood cell count, total lymphocyte count, neutrophil count, red blood cell count, hematocrit, hemoglobin, and high-sensitivity C-reactive protein levels (p<0.05). In addition, there was a positive correlation between LHR and the number of metabolic risk factors for MetS. In a logistic regression analysis, LHR (odds ratio: 4.117; 95% CI: 2.766-6.309; p<0.001) was an independent predictor of MetS. When a receiver operating characteristic (ROC) curve analysis was used to assess the value of LHR for predicting MetS, the area under the curve yielded a cut-off value of 1.657, with a sensitivity of 65% and a specificity of 64% (p<0.0001). CONCLUSION: In summary, MetS can involve changes in blood parameters, and LHR may be a useful marker of inflammation to assess the presence and severity of MetS.