OBJECTIVES:The prognostic nutritional index (PNI) is a composite indicator reflecting nutritional and immune status; however, its association with incident hyperuricemia (HUA) remains unclear. This large-scale retrospective cohort study aims to investigate the relationship between PNI and the risk of developing HUA, providing evidence for early screening and nutritional intervention strategies. METHODS:A total of 22 551 individuals who underwent baseline health examinations in 2012 were included. Participants were categorized into quartiles according to PNI levels (Q1, <52.4; Q2, 52.4-<55.1; Q3, 55.1-<57.9; Q4, ≥57.9). Cox proportional hazards models were used to evaluate the association between PNI and incident HUA, with progressive adjustment for age, sex, body mass index (BMI), hypertension, diabetes, dyslipidemia, and renal function. Using Q1 as the reference group, hazard ratios (HR) for Q2-Q4 were estimated. Restricted cubic spline models were applied to assess the dose-response relationship between continuous PNI and HUA risk. Additionally, Q1-Q3 were combined as the low-PNI group (PNI<57.9) and Q4 as the high-PNI group (PNI≥57.9) for subgroup analyses and interaction testing. RESULTS:The numbers of participants in Q1-Q4 were 5 468, 5 658, 5 680, and 5 745, respectively. During a median follow-up of 10.5 years, 5 247 incident HUA cases were identified. In the fully adjusted model, participants in Q4 had an 18.4% higher risk of HUA compared with Q1 [HR=1.184, 95% confidence interval (CI) 1.089 to 1.287, P<0.001]. When treated as a continuous variable, each 1-unit increase in PNI was associated with a 1.4% increase in HUA risk (HR=1.014, 95% CI 1.007 to 1.020, P<0.001), demonstrating a significant dose-response relationship (Ptrend<0.001). Restricted cubic spline analysis indicated a linear positive association between PNI and HUA risk after full adjustment (Ptrend<0.05). Subgroup analysis revealed that the high-PNI group had a 16.2% higher risk of HUA compared with the low-PNI group (HR=1.162, 95% CI 1.092 to 1.237, P<0.001); however, this association was attenuated among individuals with hypertension (Pinteraction=0.010). CONCLUSIONS:Elevated PNI (≥57.9) is an independent risk factor for incident HUA in a general health examination population, and this association is significantly modified by hypertension status. As a readily available composite marker, PNI may facilitate early identification of individuals at high risk for HUA and support personalized screening and intervention strategies.

The novel systemic inflammation markers are a class of indicators combining clinically common laboratory indices, reflecting the underlying immune and inflammatory status. Minimal change disease (MCD) is an important cause of idiopathic nephrotic syndrome (INS) in adults. Novel systemic inflammation markers were evaluated for their ability to predict treatment response to steroids and subsequent relapse in adult-onset MCD. This unicentric, retrospective study included the clinical data of adult-onset INS patients who were pathologically diagnosed with MCD at Xiangya Hospital of Central South University from January 2010 to December 2021 and followed up with the patients’ remission after adequate steroid treatment, starting from the time of initial complete remission to May 31, 2022, with recurrence as the end-point event. Eight common and associated novel systemic inflammation markers were collected, and univariate analysis of these markers was performed using dummy variable assignment or maximally selected rank statistics. Multivariate logistic regression and Cox regression statistics identified the independent risk factors for steroid resistance and relapse after initial remission in adult-onset MCD, respectively. A total of 121 patients were included; the median age was 22 (19,40) years, and there were 92 (76

OBJECTIVES:Pyroptosis plays a critical role in tubulointerstitial lesions of diabetic kidney disease (DKD). Annexin A2 (ANXA2) is involved in cell proliferation, apoptosis, and adhesion and may be closely related to DKD, but its specific mechanism remains unclear. This study aims to investigate the role and molecular mechanism of ANXA2 in high glucose-induced pyroptosis of renal tubular epithelial cells, providing new targets for DKD prevention and treatment. METHODS:Human renal tubular epithelial HK-2 cells were divided into a normal glucose group (5.5 mmol/L), a high glucose group (30.0 mmol/L), and a osmotic control group (24.5 mmol/L mannitol+5.5 mmol/L glucose). ANXA2 expression was modulated by overexpression of plasmids and small interfering RNA (siRNA). Cell proliferation was measured by 5-ethynyl-2'-deoxyuridine (EdU) assay, apoptosis by flow cytometry, and ANXA2, p50, and p65 subcellular localization by immunofluorescence. Western blotting was employed to detect α-smooth muscle actin (α-SMA), fibronectin (FN), and collagen type IV (Col-IV). Real-time fluorescence quantitative PCR (RT-qPCR) and Western blotting were used to analyze nuclear factor-κB (NF-κB) subunits p50/p65 and the pyroptosis pathway factors NLR family Pyrin domain containing 3 (NLRP3), caspase-1, inferleukin (IL)-1β, and IL-18. Protein interactions between ANXA2 and p50/p65 were examined by co-immunoprecipitation, while chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were used to examine NF-κB binding to the ANXA2 promoter. RESULTS:High glucose upregulated ANXA2 expression and promoted its nuclear translocation (P<0.01). High glucose reduced cell proliferation, increased apoptosis, and elevated α-SMA, FN, and Col-IV expression (all P<0.05); ANXA2 overexpression aggravated these effects (all P<0.05), while ANXA2 knockdown reversed them (all P<0.05). High glucose activated NF-κB and increased NLRP3, caspase-1, L-1β, and IL-18 mRNA and protein expression (all P<0.05); ANXA2 overexpression further enhanced this, whereas knockdown suppressed NF-κB activation and downstream factors (all P<0.05). Co-immunoprecipitation confirmed ANXA2 directly binds the NF-κB subunit p65. ChIP assays revealed p65 binds specifically to ANXA2 promoter regions (ChIP-2, ChIP-4, and ChIP-6), and luciferase activity in corresponding mutant constructs (M2, M4, and M6) was significantly increased versus controls (all P<0.05), confirming positive transcriptional regulation of ANXA2 by p65. CONCLUSIONS:ANXA2 and NF-κB form a positive feedback loop that sustains NLRP3 inflammasome activation, promotes pyroptosis pathway activation, and aggravates high glucose-induced renal tubular epithelial cell injury. Targeting ANXA2 or blocking its interaction with p65 may be a novel strategy to slow DKD progression.

Kidney injury and repair are accompanied by significant disruptions in metabolic pathways, leading to renal cell dysfunction and further contributing to the progression of renal pathology. This review outlines the complex involvement of various energy production pathways in glucose, lipid, amino acid, and ketone body metabolism within the kidney. We provide a comprehensive summary of the aberrant regulation of these metabolic pathways in kidney injury and repair. After acute kidney injury (AKI), there is notable mitochondrial damage and oxygen/nutrient deprivation, leading to reduced activity in glycolysis and mitochondrial bioenergetics. Additionally, disruptions occur in the pentose phosphate pathway (PPP), amino acid metabolism, and the supply of ketone bodies. The subsequent kidney repair phase is characterized by a metabolic shift toward glycolysis, along with decreased fatty acid β-oxidation and continued disturbances in amino acid metabolism. Furthermore, the impact of metabolism dysfunction on renal cell injury, regeneration, and the development of renal fibrosis is analyzed. Finally, we discuss the potential therapeutic strategies by targeting renal metabolic regulation to ameliorate kidney injury and fibrosis and promote kidney repair.

Objective:To understand the relationship between lipid accumulation product (LAP) and hyperuricemia in physical examination population.Methods:This was a cross-sectional study. The analysis was based on baseline data from a retrospective cohort study. Total of 44 294 people who received physical examination in the Health Management Center of Xiangya Hospital of Central South University from January to December 2012 were selected as subjects with whole-group sampling method. All the subjects aged ≥18 years with complete study variables. The minimum waist circumference of the subjects was calculated to determine the criteria for calculating LAP in those population. With LAP as the observed variable and hyperuricemia as the outcome variable, LAP was divided into four groups according to the interquartile interval (Q 1-Q 4 groups): group Q 1<10.56 cm·mmol/L, 10.56 cm·mmol/L≤Q 2<20.79 cm·mmol/L, 20.79 cm·mmol/L≤Q 3<38.94 cm·mmol/L, Q 4≥38.94 cm·mmol/L. Five models were constructed with logistic regression analysis. No confounding factors was adjusted in Model 1, model 2 was adjusted for age and gender; and model 3 was further adjusted for body mass index, hypertension, hyperlipidemia, creatinine and glomerular filtration rate; model 4 was further adjusted education level, occupation, health insurance, smoking, drinking, diet scores and physical exercise; model 5 was further adjusted the family history of gout, diabetes and hypertension. And the relationship between different LAP levels and hyperuricemia was analyzed. Results:In this study, the minimum waist circumference in the physical examination population was 58 cm and 53 cm for men and women, respectively. The total incidence of hyperuricemia was 13.4% in this population, 5.94% for women and 19.40% for men. When the confounding factors were not adjusted (model 1), the risk of hyperuricemia in women′s LAP Q 2 to Q 4 groups was 1.76 times (95% CI: 1.42-2.17), 5.08 times (95% CI: 4.20-6.14) and 12.58 times (95% CI: 10.43-15.18), and it was 1.68 times (95% CI: 1.43-1.96), 2.74 times (95% CI: 2.36-3.18), and 5.32 times (95% CI: 4.62-6.14) in men, respectively. After gender stratification and adjustment for confounding factors (model 5), the risk still existed, compared with that in Q 1 group of LAP, the risk of hyperuricemia in women in Q 4 group was 8.28 times higher (95% CI: 2.50-27.38) and 3.31 times higher in men (95% CI: 1.57-6.95). Conclusion:The risk of hyperuricemia in health examination population increases with LAP, especially in women.

Journal of the American Society of Nephrology 34(11S):p 834-835, November 2023. | DOI: 10.1681/ASN.20233411S1834d

Objective:To investigate the relationship between advanced glycation end products (AGEs) in the lens and type 2 diabetes mellitus.Methods:226 subjects were recruited between August 14 to September 14, 2018 from the Endocrinology Department of Central South University Xiangya Hospital, the Third Hospital of Changsha City, and the Fourth Hospital of Changsha City. The OGTT test, combined with clinical indicators, were used as the gold standard. Subjects were screened for type 2 diabetes using both the lens AGE fluorescence assay and the gold standard. Drawing the receiver operating characteristic (ROC) curve, we calculated the area under the curve (AUC) and its 95% CI and calculated the AGE for the diagnosis of type 2 diabetes. Sensitivity, specificity, Youden index, Kappa value, and its 95% CI, and the optimal cut-off value were determined according to the Youden index. Taking diabetes as the outcome indicator and AGE as the binary indicator, three logistic regression models were constructed. Stratified by age and sub-center, the differences between fasting blood glucose and 2 h postprandial blood glucose were compared between the AGE-negative and AGE-positive groups to determine the relationship between AGE and diabetes. Results:The area under the ROC curve was 0.86(95% CI: 0.81-0.91). According to the Youden index, the optimal cut-off point for AGE was 0.24. At this time, the sensitivity was 82.86(95% CI: 77.81-87.91), the specificity was 77.06(95% CI: 71.43-82.7), the Youden index was 59.92(95% CI: 53.36-66.49), the Kappa value was 79.62(95% CI: 74.22-85.02). Except for the 20-39-year-old group, the fasting blood glucose and 2 h postprandial blood glucose of the AGE-positive group in different age groups, different sub-centers, and the general population were higher than those of the AGE-negative group (all P<0.05). After adjusting for the confounding effects of age, gender, and sub-center (model 3), the relative risk of diabetes in the AGE-positive group was 11.75 times higher than the AGE-negative group (95% CI: 5.61-24.60), all with P<0.001. Conclusion:There was a high correlation between AGE in the lens and the risk of type 2 diabetes. When the cut-off point of AGE is 0.24, it had high sensitivity and specificity and could be used as a practical tool for early screening of type 2 diabetes.

Diabetic nephropathy (DN) is the most important cause of end-stage renal disease with a poorer prognosis and high economic burdens of medical treatments. It is of great research value and clinical significance to explore potential gene targets of renal tubulointerstitial lesions in DN. To properly identify key genes associated with tubulointerstitial injury of DN, we initially performed a weighted gene coexpression network analysis of the dataset to screen out two nonconserved gene modules (dark orange and dark red). The regulation of oxidative stress-induced intrinsic apoptotic signaling pathway, PI3K-Akt signaling pathway, p38MAPK cascade, and Th1 and Th2 cell differentiation were primarily included in Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of these two modules. Next, 199 differentially expressed genes (DEGs) were identified via the limma package. Then, the GO annotation and KEGG pathways of the DEGs were primarily enriched in extracellular matrix (ECM) organization, epithelial cell migration, cell adhesion molecules (CAMs), NF-kappa B signaling pathway, and ECM-receptor interaction. Gene set enrichment analysis showed that in the DN group, the interaction of ECM-receptor, CAMs, the interaction of cytokine-cytokine receptor, and complement and coagulation cascade pathways were significantly activated. Eleven key genes, including ALB, ANXA1, ANXA2, C3, CCL2, CLU, EGF, FOS, PLG, TIMP1, and VCAM1, were selected by constructing a protein-protein interaction network, and expression validation, ECM-related pathways, and glomerular filtration rate correlation analysis were performed in the validated dataset. The upregulated expression of hub genes ANXA2 and FOS was verified by real-time quantitative PCR in HK-2 cells treated with high glucose. This study revealed potential regulatory mechanisms of renal tubulointerstitial damage and highlighted the crucial role of extracellular matrix in DN, which may promote the identification of new biomarkers and therapeutic targets.

Objective:To investigate the correlation between hyperuricemia and hypertension in hospital employees.Methods:A cohort was constructed from staff participating health checkups at the Xiangya Hospital of Central South University, baseline health examinations and questionnaires were conducted from February 1, 2011, to January 29, 2012; 502 participants were excluded according to the nadir criteria, and 3 525 participants were followed-up from February 1, 2012, to December 31, 2018, according to the results of annual employee checkups. The participants were divided into the normal uric acid (3 232 cases) and hyperuricemia groups (293 cases) according to the baseline examination results. The presence of hyperuricemia was used as an observation index and occurrence of hypertension within 7 years was used as an outcome indicator. Age, sex, body mass index, creatinine, LDL cholesterol, triacylglycerol, HDL cholesterol, fasting glucose, marriage, education, job position, smoking, alcohol consumption, and exercise status were used as confounding factors to construct five Cox regression models and calculate their HR values, adjusted HR values, and 95% CI to analyze the relationship between hyperuricemia and the occurrence of hypertension in the overall population and female and male populations. Results:The follow-up of the study participants was conducted for a period of (6.19±1.25) years, with a total of 21 831 person-years of follow-up. The 7-year cumulative prevalence of hypertension was 16.5% in the total population, 12.5% in the female population, 30.1% in the male population, 14.1% in the normal uric acid group, and 42.0% in the hyperuricemia group. The prevalence density of hypertension was 26.6, 19.6, 53.8, and 22.4 per 1 000 person-years in the total, female, male, and normouricemic groups, respectively. Without adjusting for any confounding variables, the risk of hypertension was higher in the total population, female population, and male population in the hyperuricemia group than in the normal uric acid group [ HR=3.86, 5.69, 1.60, (95% CI: 3.17-4.72, 4.36-7.43, 1.18-2.16)] (all P<0.05); after gradually adjusting for confounders, this correlation was only manifested in the female population [adjusted HR=1.91 (95% CI: 1.08-3.36)] (all P<0.05), and the difference was not statistically significant in the male population ( P>0.05). Conclusion:Among female hospital employees, hyperuricemia is an independent risk factor for the development of hypertension.

〇 什么是肿瘤标志物 肿瘤标志物,是指在肿瘤发生和增殖过程中,由肿瘤细胞所产生的,存在于细胞、组织、体液或血液中可反映肿瘤存在和生长情况的一类物质,包括蛋白质、酶和多胺等.

Introduction: Transforming growth factor-β (TGF-β), a common outcome of various progressive chronic kidney diseases, can regulate and induce fibrosis. Objective: The study aimed to identify downstream targets of lncRNA ENST00000453774.1 (lnc453774.1) and outline their functions on the development of renal fibrosis. Methods: HK-2 cells were induced with 5 ng/mL TGF-β1 for 24 h to construct a renal fibrosis cell model. Differentially expressed genes (DEGs) targeted by lnc453774.1 in TGF-β1-induced renal fibrosis were identified using RNA sequencing. The dataset GSE23338 was employed to identify DEGs in 48-h TGF-β1-stimulated human kidney epithelial cells, and these DEGs were intersected with genes in the key module using weighted gene co-expression network analysis to generate key genes associated with renal fibrosis. MicroRNAs (miRs) that had targeting relationship with keys genes and lnc453774.1 were predicted by using Miranda software, and important genes were intersected with key genes that had targeting relationship with these miRs. Key target genes by lnc453774.1 were identified in a protein-protein interaction network among lnc453774.1, important genes, and reported genes related to autophagy, oxidative stress, and cell adhesion. Results: Key genes in the key module (turquoise) were intersected with DEGs in the dataset GSE23338 and yielded 20 key genes regulated by lnc453774.1 involved in renal fibrosis. Fourteen miRs had targeting relationship with lnc453774.1 and key genes, and 8 important genes targeted by these 14 miRs were identified. Fibrillin-1 (FBN1), insulin-like growth factor 1 receptor (IGF1R), and Kruppel-like factor 7 (KLF7) were identified to be involved in autophagy, oxidative stress, and cell adhesion and were elevated in the lnc453774.1-overexpressing TGF-β1-induced cells. Conclusion: These results show FBN1, IGF1R, and KLF7 serve as downstream targets of lnc453774.1, and that lnc453774.1 may protect against renal fibrosis through competing endogenous miRs which target FBN1, IGF1R, and KLF7 mRNAs.

Wang, Xiu-Fen; Xiao, Xiang-Cheng; Ge, Hui-Peng; Deng, Tian-Ci; Zhou, Qiao-Ling; Ning, Jian-Ping; Wu, Xiao-Ying; Yin, Hong-Ling; Lin, Wei; Tang, Wen-BinEditor(s): Lyu, Peng Author Information

Artificial intelligence (AI), as an advanced science technology, has been widely used in medical fields to promote medical development, mainly applied to early detections, disease diagnoses, and management.Owing to the huge number of patients, kidney disease remains a global health problem.Challenges remain in its diagnosis and treatment.AI could take individual conditions into account, produce suitable decisions and promise to make great strides in kidney disease management.Here, we review the current studies of AI applications in kidney disease in alerting systems, diagnostic assistance, guiding treatment and evaluating prognosis.Although the number of studies related to AI applications in kidney disease is small, the potential of AI in the management of kidney disease is well recognized by clinicians; AI will greatly enhance clinicians' capacity in their clinical practice in the future.

BACKGROUND Recent guidelines recommend that patients with immunoglobulin A nephropathy (IgAN) and proteinuria 0.5-1 g/d and >1 g/d be treated with long-term renin-angiotensin system blockade (RASB). This study investigated whether patients with IgAN and persistent hematuria, but without proteinuria, can benefit from RASB. MATERIAL AND METHODS IgAN patients with persistent hematuria at four centers were recruited from January 2013 to December 2018. Patients were divided into those who did and did not receive long-term RASB. The primary outcome was the appearance of proteinuria, and the secondary outcomes were the decreased percentage of hematuria, rate of decline in estimated glomerular filtration rate (eGFR) and final blood pressure. The effects of RASB on these outcomes were assessed by multivariate Cox regression models and propensity score matching. RESULTS Of the 110 eligible patients, 44 (40.0%) received RASB and 66 (60.0%) did not. Treated patients had higher diastolic pressure. The unadjusted primary outcome, the appearance of proteinuria, was significantly less frequent in individuals who were than who were not treated with RASB. Multivariate Cox regression showed that RASB reduced the risk of the primary outcome and the levels of hematuria. The rate of eGFR decline and final blood pressure did not differ in the two groups. CONCLUSIONS RASB reduced the risk of proteinuria development and increased the remission of hematuria in patients with IgAN who presented with persistent hematuria alone. RASB, however, did not affect blood pressure in patients without hypertension and did not affect the rate of eGFR decline.

Observational studies on dietary or circulating magnesium and risk of cardiovascular disease (CVD) in Chronic Kidney Disease (CKD) stage 1-4 have reported no-to-modest inverse associations. 24 h Urinary magnesium concentration (24 h UMg), an indicator of intestinal magnesium absorption, may provide better insight into the connection of CKD progression. We examined 3179 participants aged 18-74 years with CKD stage 1-4 in the Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE) study, a pro-spective population-based cohort study. Data were analysed using Spearman rank-order correlation coefficients for all comparisons. We also performed a time-to-event analysis of the data using the Kaplan-Meier survival model, Cox proportional hazard model and competing risk Fine and Gray subdistribution hazard model. During a median follow-up of 4.19 years (interquartile range, 3.43-5.09 years), when modelling end-stage renal disease (ESRD), CVD and death, 24 h UMg was associated with risk of CVD (HR, 1.612 (95% CI, 1.056-2.460)), while no significant association with ESRD and death endpoints could be detected. 24 h UMg risk variants display a modest association with CVD in CKD stage 1-4 patients. Trial registration: ClinicalTrials.gov Identifier NCT03041987. Registered January 1, 2012. (retrospectively registered) (https://www.clinicaltrials.gov/ct2/show/NCT03041987?term=Chinese+Cohort+Study+ of+Chronic+Kidney+Disease+%28C-STRIDE%29&rank=1). (c) 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Abstract Objective Renal fibrosis is the most common manifestation of chronic kidney disease (CKD). Noting that existing treatments of renal fibrosis only slow disease progression but do not cure it, there is an urgent need to identify novel therapies. Hydrogen sulfide (H2S) is a newly discovered endogenous small gas signaling molecule exerting a wide range of biologic actions in our body. This review illustrates recent experimental findings on the mechanisms underlying the therapeutic effects of H2S against renal fibrosis and highlights its potential in future clinical application. Data sources Literature was collected from PubMed until February 2019, using the search terms including “Hydrogen sulfide,” “Chronic kidney disease,” “Renal interstitial fibrosis,” “Kidney disease,” “Inflammation factor,” “Oxidative stress,” “Epithelial-to-mesenchymal transition,” “H2S donor,” “Hypertensive kidney dysfunction,” “Myofibroblasts,” “Vascular remodeling,” “transforming growth factor (TGF)-beta/Smads signaling,” and “Sulfate potassium channels.” Study selection Literature was mainly derived from English articles or articles that could be obtained with English abstracts. Article type was not limited. References were also identified from the bibliographies of identified articles and the authors’ files. Results The experimental data confirmed that H2S is widely involved in various renal pathologies by suppressing inflammation and oxidative stress, inhibiting the activation of fibrosis-related cells and their cytokine expression, ameliorating vascular remodeling and high blood pressure, stimulating tubular cell regeneration, as well as reducing apoptosis, autophagy, and hypertrophy. Therefore, H2S represents an alternative or additional therapeutic approach for renal fibrosis. Conclusions We postulate that H2S may delay the occurrence and progress of renal fibrosis, thus protecting renal function. Further experiments are required to explore the precise role of H2S in renal fibrosis and its application in clinical treatment.