Delaying Renal Aging: Metformin Holds Promise as a Potential Treatment.

Given the rapid aging of the population, age-related diseases have become an excessive burden on global health care. The kidney, a crucial metabolic organ, ages relatively quickly. While the aging process itself does not directly cause kidney damage, the physiological changes that accompany it can impair the kidney's capacity for self-repair. This makes aging kidneys more susceptible to diseases, including increased risks of chronic kidney disease and end-stage renal disease. Therefore, delaying the progression of renal aging and preserving the youthful vitality of the kidney are crucial for preventing kidney diseases. However, effective strategies against renal aging are still lacking due to the underlying mechanisms of renal aging, which have not been fully elucidated. Accumulating evidence suggests that metformin has beneficial effects in mitigating renal aging. Metformin has shown promising anti-aging results in animal models but has not been tested for this purpose yet in clinical trials. These findings indicate the potential of metformin as an anti-renal aging drug. In this review, we primarily discuss the characteristics and mechanisms of kidney aging and the potential effects of metformin against renal aging.

Association between C-reactive protein/albumin ratio and all-cause mortality in patients with stroke: Evidence from NHANES cohort study.

BACKGROUND AND AIMS: The inflammatory nutritional status is widely associated with the long-term prognosis of non-fatal stroke. The objective of this study is to examine the correlation between the C-reactive protein to albumin ratio (CAR), a new marker indicating both inflammatory and nutritional status, and the overall mortality rate among stroke patients. METHODS AND RESULTS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) database and corresponding public-use mortality data from the linked National Death Index (NDI). The study utilized maximally selected rank statistics to determine the optimal cutoff points for the CAR. Subsequently, participants were stratified into higher- and lower-CAR groups based on these cutoff points. The Kaplan-Meier survival method was used to study overall survival probability. Multivariable Cox proportional regression models were employed to calculate the Hazard Ratio (HR) and corresponding confidence interval (CI). Restricted cubic spline (RCS) model was applied to detect potential non-linear relationship between CAR and mortality risk. Furthermore, stratified and sensitive analyses were performed to examine the robustness and reliability of the results. The study, encompassing 1043 participants with an average age of 64.61 years, identified a cutoff value of 0.32 for CAR, with notable variances observed across gender and age cohorts. Over an average follow-up period of 116 months, 679 instances of all-cause mortality were documented. Kaplan-Meier survival analysis unveiled noteworthy disparities in survival probabilities between groups categorized by high and low CAR levels (p = 0.00081). Continuous CAR analysis consistently demonstrated a positive correlation between elevated CAR values and heightened risk (HR = 1.78 (1.36, 2.33)) of all-cause mortality among stroke patients. Similarly, individuals in the high CAR group exhibited adjusted HR of 1.34 (0.96, 1.89) for all-cause mortality compared to their low CAR counterparts. Subgroup and sensitive analysis consistently reinforced these findings. Smoothing curve fitting further validated CAR's significance as a prognostic indicator of all-cause mortality, indicating a linear relationship. CONCLUSION: Elevated CAR is associated with increased long-term risk of mortality for individuals who have experienced a stroke, suggesting that CAR could serve as a survival indicator.

Machine learning for the prediction of delirium in elderly intensive care unit patients.

PURPOSE: This study aims to develop and validate a prediction model for delirium in elderly ICU patients and help clinicians identify high-risk patients at the early stage. METHODS: Patients admitted to ICU for at least 24 h and using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database (76,943 ICU stays from 2008 to 2019) were considered. Patients with a positive delirium test in the first 24 h and under 65 years of age were excluded. Two prediction models, machine learning extreme gradient boosting (XGBoost) and logistic regression (LR) model, were developed and validated to predict the onset of delirium. RESULTS: Of the 18,760 patients included in the analysis, 3463(18.5%) were delirium positive. A total of 22 significant predictors were selected by LASSO regression. The XGBoost model demonstrated superior performance over the LR model, with the Area Under the Receiver Operating Characteristic (AUC) values of 0.853 (95% confidence interval [CI] 0.846-0.861) and 0.831 (95% CI 0.815-0.847) in the training and testing datasets, respectively. Moreover, the XGBoost model outperformed the LR model in both calibration and clinical utility. The top five predictors associated with the onset of delirium were sequential organ failure assessment (SOFA), infection, minimum platelets, maximum systolic blood pressure (SBP), and maximum temperature. CONCLUSION: The XGBoost model demonstrated good predictive performance for delirium among elderly ICU patients, thus assisting clinicians in identifying high-risk patients at the early stage and implementing targeted interventions to improve outcome.

[Ecological Environment Dynamical Evaluation of Hutuo River Basin Using Remote Sensing].

Hutuo River Basin straddles Shanxi and Hebei provinces, and Hutuo River was once cut off due to economic development and urban expansion after 2000; however, with the national emphasis on ecological civilization and the implementation of the South-North Water Diversion Project, the ecological protection of Hutuo River Basin has been significantly improved. MODIS data, Landsat data, and night light remote sensing data were selected based on the google earth engine (GEE) platform, and a new evaluation index system was generated by combining the biological richness index, vegetation cover index, land stress index, and pollution load index in the ecological environment index (EI) and the humidity index in the remote sensing ecological index (RSEI), using the variation coefficient method and entropy weighting method to assign weights to these indices. An ecological environment evaluation model was constructed to evaluate and classify the ecological environment quality of Hutuo River Basin from 2000 to 2020, and the driving factors were interpreted by using geographic probes. The results showed that:① on a time scale, the ecological environment of Hutuo River Basin was in a decline period from 2000 to 2015 and a recovery period from 2015 to 2020. From a grid scale, the ecological environment quality in the central part of the basin showed a state of improvement year by year, and in the western and eastern parts of the basin, the ecological environment quality in the decline period decreased year by year, whereas the ecological environment quality in the recovery period improved. ② Hot spot analysis showed that the spatial distribution of the ecological environment quality in Hutuo River Basin was high in the middle and low on both sides. Cold spot regions were mainly located in major cities and towns in the eastern and southern parts and scattered in the river valley area on the west side. ③ Geodetection analysis showed that the single factor detection drivers were mainly population density, vegetation net primary productivity (NPP), fractional vegetation cover (FVC), and geomorphological type. The dominant factor of cross-detection was "geomorphological type + FVC." With the deepening of ecological civilization construction and the implementation of Hutuo River Protection Regulations, in combination with different factors such as the natural environment and social characteristics in this basin, the research on ecological environment evaluation in Hutuo River Basin can provide data support for proposing localized policies to improve the ecological environment.

Association of serum uric acid with all-cause and cardiovascular mortality in chronic kidney disease stages 3-5.

BACKGROUND AND AIMS: The role of serum uric acid (SUA) in the prognosis of chronic kidney disease (CKD) is inconclusive. To explore the association of SUA level with all-cause and cardiovascular disease (CVD) mortality in patients with CKD. METHODS AND RESULTS: Leveraging data from the National Health and Nutritional Examination Survey (NHANES) and linked national death records up to December 31 2019, we explored the association of SUA with all-cause and CVD mortality using weighted cox proportional hazards regression models and restricted cubic spline (RCS) models in patients with CKD stages 3-5. The study finally included 2644 patients with CKD stages 3-5, with a median SUA level of 6.5 mg/dL. After a median follow-up of 55 months, a total of 763 deaths were recorded, with 279 of them attributed to CVD. In the fully adjusted model, per 1 mg/dL increment in SUA concentration was found to be associated with increased HRs (95% CIs) of 1.07 (1.00, 1.14) for all-cause mortality and 1.11 (1.00, 1.24) for CVD mortality. Compared to Q2 (reference), those in Q4 had adjusted HRs of 1.72 (1.36, 2.17) for all-cause mortality and 2.17 (1.38, 3.41) for CVD mortality, while those in Q1 had adjusted HRs of 1.49 (1.19, 1.85) for all-cause mortality and 1.93 (1.26, 2.98) for CVD mortality. CONCLUSIONS: Both higher and lower SUA levels were associated with increased risks of all-cause and CVD mortality in patients with CKD stages 3-5.

Prognostic factors affecting long-term outcomes in patients with concurrent IgA nephropathy and membranous nephropathy.

Background: The incidence of concurrent immunoglobulin A nephropathy and membranous nephropathy (cIgAN/MN) is low and rarely reported, and the prognosis of patients with cIgAN/MN remains unclear. This study was designed to compare the clinical and prognostic characteristics of cIgAN/MN with IgAN and MN and to identify crucial factors influencing the outcomes of patients with cIgAN/MN. Methods: We included biopsy-proven cIgAN/MN patients between December 2012 and December 2020 at Xijing Hospital. In the same period, propensity score matching was employed to select an equal number of IgAN and MN patients according to the following criteria: age, sex, and follow-up time. The primary endpoint was defined as a composite of eGFR decline ≥30 %, end-stage renal disease, or death. The patient survival rate was examined using Kaplan-Meier survival curves. Univariate and multivariate Cox regression analysis models were utilized to identify the risk factors affecting renal prognosis. Results: A total of 135 patients were finally included in this study and 35 (25.9 %) reached the primary endpoint. The median follow-up time of cIgAN/MN was 45.9 (24.0, 72.0) months. Compared to the IgAN group, the cIgAN/MN group exhibited a lower cumulative incidence rate of composite renal endpoints (P = 0.044), while no significant difference was found between MN and cIgAN/MN patients (P = 0.211). Univariate Cox analysis revealed that mean arterial pressure, serum potassium, blood urea nitrogen, serum IgA, segmental glomerulosclerosis (S1), and MN staging were associated with an increased risk of renal composite endpoints. The multivariate Cox regression analysis of clinical variables plus histological lesion scoring demonstrated that potassium (HR = 14.350, 95 % CI 2.637-78.090, P = 0.002), serum IgA (HR = 1.870, 95 % CI 1.109-3.153, P = 0.019), and S1 (HR = 11.965, 95 % CI 2.166-66.105, P = 0.004) were independent risk factors influencing renal outcomes in cIgAN/MN patients. Conclusion: The prognosis of cIgAN/MN patients may exhibit an intermediate pattern between IgAN and MN, leaning towards being more similar to MN in certain aspects. Within the cIgAN/MN cohort, potassium, and serum IgA may be more predictive of rapid progression of renal endpoints, and S1 may indicate a more aggressive disease course.

The protective mechanism of SIRT3 and potential therapy in acute kidney injury.

Acute kidney injury (AKI) is a complex clinical syndrome with a poor short-term prognosis, which increases the risk of the development of chronic kidney diseases and end-stage kidney disease. However, the underlying mechanism of AKI remains to be fully elucidated, and effective prevention and therapeutic strategies are still lacking. Given the enormous energy requirements for filtration and absorption, the kidneys are rich in mitochondria, which are unsurprisingly involved in the onset or progression of AKI. Accumulating evidence has recently documented that Sirtuin 3 (SIRT3), one of the most prominent deacetylases highly expressed in the mitochondria, exerts a protective effect on AKI. SIRT3 protects against AKI by regulating energy metabolism, inhibiting oxidative stress, suppressing inflammation, ameliorating apoptosis, inhibiting early-stage fibrosis and maintaining mitochondrial homeostasis. Besides, a number of SIRT3 activators have exhibited renoprotective properties both in animal models and in vitro experiments, but have not yet been applied to clinical practice, indicating a promising therapeutic approach. In this review, we unravel and summarize the recent advances in SIRT3 research and the potential therapy of SIRT3 activators in AKI.

Risk factors for mortality in brain injury patients who have severe hypernatremia and received continuous venovenous hemofiltration.

Background and objectives: The mortality rate for people with brain injuries is increased when hypernatremia is present. Patients with severe hypernatremia, who have a significant short-term mortality rate, were shown to benefit from continuous venovenous hemofiltration (CVVH), which has been indicated to be successful. Exploring the risk factors for short-term mortality in brain injury patients who underwent CVVH and had severe hypernatremia was the aim of the current study. Materials and methods: Retrospective screening was performed on patients with brain injuries who underwent CVVH at Xijing Hospital between 1 December 2010 and 31 December 2021 and who have a diagnosis of severe hypernatremia. The outcomes included 28-day patient mortality and hospital stay duration. The patient survival rate was examined using the Kaplan-Meier survival curve. To determine the risk factors for short-term death for patients, univariate and multivariate Cox regression analysis models were used. Results: Our current study included a total of 83 individuals. The included patients had a median age of 49 (IQR 35-59) years. Of the included patients, 58 patients (69.9 %) died within 28 days. The median length of hospital stay for the patient was 13 (IQR 7-21) days. The APACHE II score, SOFA score, GCS, PLT count, INR, stroke, mechanical ventilation, and vasopressor reliance were related to 28-day mortality according to the univariate Cox analysis. INR (HR = 1.004, 95 % Cl: 1.001-1.006, P = 0.008), stroke (HR = 1.971, 95 % Cl: 1.031-3.768, P = 0.04), mechanical ventilation (HR = 3.948, 95 % Cl: 1.090-14.294, P = 0.036), and vasopressor dependency (HR = 2.262, 95 % Cl: 1.099-4.655, P = 0.027) were independently associated with the risk of 28-day death rates, according to multivariate Cox regression analysis. Conclusions: Brain injuries who have severe hypernatremia requires CVVH, which has high short-term patient mortality. Mechanical ventilation, INR increase, stroke, and vasopressor dependence are independently associated with increased patient mortality risk.

Alterations of the gut microbiota in the lupus nephritis: a systematic review.

BACKGROUND: Emerging evidence suggests that gut microbiota dysbiosis may play a critical role in the development of lupus nephritis (LN). However, the specific characteristics of the gut microbiota in individuals with LN have not been fully clarified. METHODS: The PubMed, Web of Science, and Embase databases were systematically searched for clinical and animal studies related to the relationship between LN and gut microbiota from inception until October 1, 2023. A semiquantitative analysis was used to assess the changes in gut microbial profiles. RESULTS: A total of 15 clinical studies were selected for analysis, which included 138 LN patients, 441 systemic lupus erythematosus patients, and 1526 healthy controls (HCs). Five different types of LN mouse models were included in 5 animal studies. The alpha diversity was decreased in LN patients compared to HCs. A significant decrease in the Firmicutes/Bacteroidetes (F/B) ratio is considered a hallmark of pathological conditions. Specifically, alterations in the abundance of the phylum Proteobacteria, genera Streptococcus and Lactobacillus, and species Ruminococcus gnavus and Lactobacillus reuteri may play a critical role in the pathogenesis of LN. Remarkably, the gut taxonomic chain Bacteroidetes-Bacteroides-Bacteroides thetaiotaomicron was enriched in LN patients, which could be a crucial characteristic of LN patients. The increased level of interleukin-6, imbalance of regulatory T cells and T helper 17 cells, and decreased level of the intestinal tight junction proteins zonula occludens-1 and claudin-1 also might be related to the pathogenesis of LN. CONCLUSIONS: Specific changes in the abundance of gut microbiota such as decreased F/B ratio, and the level of inflammatory indicators, and markers of intestinal barrier dysfunction may play a crucial role in the pathogenesis of LN. These factors could be effective diagnostic and potential therapeutic targets for LN.

The Role of Tryptophan Metabolism in the Occurrence and Progression of Acute and Chronic Kidney Diseases.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are common kidney diseases in clinics with high morbidity and mortality, but their pathogenesis is intricate. Tryptophan (Trp) is a fundamental amino acid for humans, and its metabolism produces various bioactive substances involved in the pathophysiology of AKI and CKD. Metabolomic studies manifest that Trp metabolites like kynurenine (KYN), 5-hydroxyindoleacetic acid (5-HIAA), and indoxyl sulfate (IS) increase in AKI or CKD and act as biomarkers that facilitate the early identification of diseases. Meanwhile, KYN and IS act as ligands to exacerbate kidney damage by activating aryl hydrocarbon receptor (AhR) signal transduction. The reduction of renal function can cause the accumulation of Trp metabolites which in turn accelerate the progression of AKI or CKD. Besides, gut dysbiosis induces the expansion of Enterobacteriaceae family to produce excessive IS, which cannot be excreted due to the deterioration of renal function. The application of Trp metabolism as a target in AKI and CKD will also be elaborated. Thus, this study aims to elucidate Trp metabolism in the development of AKI and CKD, and explores the relative treatment strategies by targeting Trp from the perspective of metabolomics to provide a reference for their diagnosis and prevention.

[Retrospective Analysis of the Effect of Uric Acid on the Prognosis of Immunoglobulin A Nephropathy With Stage 3-4 Chronic Kidney Disease]. / å°¿é ¸æ°´å¹³å¯¹æ ¢æ€§è‚¾è„ç— 3-4期IgAè‚¾ç— é¢„åŽå½±å“çš„å›žé¡¾æ€§åˆ†æž.

Objective: To investigate the effect of uric acid on the clinicopathological characteristics and prognosis of immunoglobulin A nephropathy (IgAN) in patients with stage 3-4 chronic kidney disease (CKD). Methods: The clinical and pathological data of 263 IgAN patients who had stage 3-4 CKD and who had confrimed diagosis through renal biopsy at the First Affiliated Hospital of Air Force Medical University between December 2008 and January 2020 were retrospectively collected. According to the levels of uric acid, the patients were divided into a hyperuricemia group (n=102) and a normal uric acid group (n=161), and the clinicopathological characteristics of the two groups were compared accordingly. With progression to end-stage renal disease or death as the endpoint event, the renal survival rate of the two groups was compared by the Kaplan-Meier method and the relationship between uric acid and the prognosis was analyzed by Cox regression and LASSO regression. Results: Compared with the normal uric acid group, the hyperuricemia group had a significantly higher proportion of male patients and patients with a history of hypertension, a significantly higher level of blood urea nitrogen, and lower levels of estimated glomerular filtration rate and high-density lipoprotein. In terms of pathology, patients in the hyperuricemia group had significantly higher proportion of glomerulosclerosis, higher mesangial hypercellularity, and higher tubular atrophy/interstitial fibrosis (P<0.05). Kaplan-Meier curve showed that there was a significant difference in renal survival rate between the two groups (P<0.0001). LASSO regression showed that high uric acid was a risk factor for the prognosis of IgAN patients with stage 3-4 CKD. Further multivariate Cox analysis showed that, compared with the normal uric acid group, the hyperuricemia group had a higher risk of incurring composite outcomes (hazard ratio [HR]=1.61, 95% confidence interval [CI]: 1.10-2.34). When uric acid was used as a continuous variable, the increase of 1 mg/dL in uric acid concentration was associated with an increased HR of 1.18 (95% CI: 1.08-1.29) for the composite outcome. Conclusion: High uric acid is a risk factor for poor renal prognosis in IgAN patients with stage 3-4 CKD and reducing uric acid levels may effectively improve the prognosis of high-risk IgAN patients.

[Role of Histone Modifications in Acute Kidney Injury Progressing to Chronic Kidney Disease]. / ç»„è›‹ç™½ä¿®é¥°åœ¨æ€¥æ€§è‚¾æŸä¼¤å‘æ ¢æ€§è‚¾è„ç— è½¬åŒ–ä¸­çš„ä½œç”¨.

Acute kidney injury (AKI), a clinical syndrome caused by various factors, is characterized by a rapid decline in kidney function in a short period of time. AKI affects the short-term prognosis of patients and may also induce chronic kidney disease (CKD). However, the current treatment options for AKI mainly focus on symptom management. Specific therapeutic measures available for the prevention of transition from AKI to CKD are very limited in number. Histones are basic proteins that intricately bind the DNA in chromosomes. After translation, histones undergo various modifications on their amino-terminal tails, such as methylation, acetylation, phosphorylation, ubiquitination, and lactylation, collectively forming the "histone code", which affects the expression of genes mainly by regulating the elastic structure of chromatin or recruiting specific proteins. Extensive research conducted in recent years on histone post-translational modifications (PTMs) has also sparked continuous interest in their association with the AKI-to-CKD transition. Therefore, this paper highlights the significant role of PTMs in the process of AKI developing and progressing to CKD, with a view to finding new approaches to preventing the progression of AKI to CKD.

[Vegetation change of Yamzho Yumco Basin in southern Tibet based on SPOT-VGT NDVI].

The area we studied is Lake Yamzho Yumco Basin (28 degrees 27'-29 degrees 12'N, 90 degrees 08'-91 degrees 45'E), the largest inland lake basin in southern Tibetan Plateau, China. Using the SPOT-VGT NDVI vegetation index from 1998 to 2007 in the basin, the temporal and spatial variation characteristics of NDVI and its correlation with the major climatic factors (air temperature, precipitation) were analyzed. The results show that the average NDVI of the lake basin ranges from 0.12 to 0.31 and its seasonal change is obvious; the NDVI begins to rise rapidly in May and reaches the maximum value in early September. The average NDVI of the basin shows the slow increasing trend during 1998 to 2007, and it indicates that the eco-environment of the basin is recovering. The high value of NDVI has close relationships with water supply, altitude and vegetation types, so NDVI is relatively high near water sources and is the highest in meadow grassland. The summer air temperature and precipitation are the important climate elements that influence the vegetation in the basin, and the linear correlation coefficients between NDVI and air temperature and precipitation are 0.7 and 0.71, respectively. In recent years, warm and humid trend of the local climate is prevailing to improve the ecological environment in Yamzho Yumco Basin.

[Atmospheric correction of hyperion hyperspectral image based on FLAASH].

Atmospheric correction of remote sensing image is the premise of quantitative remote sensing. The present paper evaluated the capability of FLAASH (fast line-of-sight atmospheric analysis of spectral hypercubes)in ENVI software to make atmospheric correction for EO-1 Hyperion hyperspectral image. Hyperion hyperspecreal image of Zhangye city in Heihe River valley of Gansu province, China was acquired on September 10, 2007. Canopy spectra, biochemical component and GPS data of 41 plots were measured in near real-time during the satellite overpass. Hyperion hyperspectral image was geometrically corrected using Lansat-7 ETM+ image, then DN values were transformed to radiance and apparent reflectance, and atmospheric correction of Hyperion image was made using FLAASH. The resulting radiance, apparent reflectance and reflectance after FLAASH of four typical objects, including corn, water body, desert and building, were compared. ASD spectra of corn were resampled to Hyperion corresponding bands using Gaussian filter function. The comparison between ASD resampled spectra and Hyperion spectra after FLAASH demonstrated that the atmospheric correction using FLAASH is very effective and these two spectra are consistent with each other and the correlation coefficient reached 0.987.