Association of vitamin D metabolites with arteriovenous fistula function in hemodialysis patients: A single center study.

INTRODUCTION: Arteriovenous fistula (AVF) is a primary dialysis vascular access commonly used for maintaining hemodialysis (MHD) patients. Vitamin D (VD) is a fat-soluble steroid hormone that is closely related to vascular endothelial function. This study aimed to investigate the association between VD metabolites and AVF failure in patients undergoing HD. METHODS: This study included 443 HD patients using AVF between January 2010 and January 2020. The AVF operations in these patients were newly created by the same physician. We analyzed the AVF patency rates using the chi-square test. Univariate and multivariate logistic regression analyses were performed to explore risk factors for AVF failure. Survival analysis was performed to explore AVF survival at different serum 25-hydroxyvitamin D (25(OH)D) concentrations. RESULTS: Logistic regression analyses showed that male sex; age; BMI; serum albumin, triglyceride, phosphorus, 25(OH)D, iPTH and hemoglobin levels, history of hypertension, CHD, diabetes, stroke, and antiplatelet drug use; and smoking habits were not risk factors for AVF failure. The failure incidence rates of AVF in subjects in the VD deficiency and non VD deficiency group were not statistically significant (25.0% vs. 30.8%, p = 0.344). The AVF failure incidence rates at 1, 3, and 5 years in the patients with 25(OH)D levels more than 20 ng/mL were 26%, 29%, and 37%, respectively, and the one-year AVF failure incidence rates were 27% in the patients with 25(OH)D levels less than 20 ng/mL. In addition, the Kaplan-Meier analysis suggested that the no significant differences were noted when calculating the cumulative survival rates of AVF between the two groups within 50 months of AVF using. CONCLUSION: Our findings suggest that 25(OH)D deficiency is not associated with AVF failure incidence rates, and that 25(OH)D deficiency has no significant impact on long-term cumulative AVF survival rate.

Machine Learning-Based Prediction of Acute Kidney Injury Following Pediatric Cardiac Surgery: Model Development and Validation Study.

BACKGROUND: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a major complication following pediatric cardiac surgery, which is associated with increased morbidity and mortality. The early prediction of CSA-AKI before and immediately after surgery could significantly improve the implementation of preventive and therapeutic strategies during the perioperative periods. However, there is limited clinical information on how to identify pediatric patients at high risk of CSA-AKI. OBJECTIVE: The study aims to develop and validate machine learning models to predict the development of CSA-AKI in the pediatric population. METHODS: This retrospective cohort study enrolled patients aged 1 month to 18 years who underwent cardiac surgery with cardiopulmonary bypass at 3 medical centers of Central South University in China. CSA-AKI was defined according to the 2012 Kidney Disease: Improving Global Outcomes criteria. Feature selection was applied separately to 2 data sets: the preoperative data set and the combined preoperative and intraoperative data set. Multiple machine learning algorithms were tested, including K-nearest neighbor, naive Bayes, support vector machines, random forest, extreme gradient boosting (XGBoost), and neural networks. The best performing model was identified in cross-validation by using the area under the receiver operating characteristic curve (AUROC). Model interpretations were generated using the Shapley additive explanations (SHAP) method. RESULTS: A total of 3278 patients from one of the centers were used for model derivation, while 585 patients from another 2 centers served as the external validation cohort. CSA-AKI occurred in 564 (17.2%) patients in the derivation cohort and 51 (8.7%) patients in the external validation cohort. Among the considered machine learning models, the XGBoost models achieved the best predictive performance in cross-validation. The AUROC of the XGBoost model using only the preoperative variables was 0.890 (95% CI 0.876-0.906) in the derivation cohort and 0.857 (95% CI 0.800-0.903) in the external validation cohort. When the intraoperative variables were included, the AUROC increased to 0.912 (95% CI 0.899-0.924) and 0.889 (95% CI 0.844-0.920) in the 2 cohorts, respectively. The SHAP method revealed that baseline serum creatinine level, perfusion time, body length, operation time, and intraoperative blood loss were the top 5 predictors of CSA-AKI. CONCLUSIONS: The interpretable XGBoost models provide practical tools for the early prediction of CSA-AKI, which are valuable for risk stratification and perioperative management of pediatric patients undergoing cardiac surgery.

Relationship between peritoneal solute transport and dialysate inflammatory markers in peritoneal dialysis patients: A cross-sectional study.

BACKGROUND: The associated factors of peritoneal small solute transport was not fully understood. This research aimed to investigate the connection between dialysate inflammatory markers (e.g. macrophage migration inhibitory factor, MIF) in peritoneal dialysis (PD) effluent and peritoneal solute transport rate (PSTR) properties. SUBJECTS AND DESIGN: A total of 80 stable PD patients in the First ShaoYang Hospital were enrolled in present study. Overnight PD effluent and serum inflammatory markers including MIF, MCP-1, VEGF, IL-6, TNFα and TGFß were detected. Pearson correlation analysis and Logistic regression was performed to determine the risk factors for the increased PSTR. RESULTS: A trend toward increased values of MIF, MCP-1 and IL-6 in PD effluent was observed in subjects with high PSTR when compared with those with low PSTR. The Pearson correlation test showed that D/P Cr exhibited positive correlations with dialysis effluent MIF (r=0.32, p=0.01), MCP-1 (r=0.47, p=0.01), IL-6 (r=0.48, p=0.01). Conversely, no significant correlation was found between D/P Cr and TGF-ß (r=0.04, p=0.70), TNF-ɑ (r=0.22, p=0.05), VEGF (r=0.02, p=0.86) and serum inflammatory markers. In the unadjusted regression analysis, dialysis effluent MIF (OR 2.41), MCP-1 (OR 1.72), IL-6 (OR 1.55) were associated with high PSTR condition. Multivariate logistic regression analysis showed that the adjusted odds ratios (OR) of dialysis effluent MIF for high PSTR were 2.47 in all subjects (p=0.03). CONCLUSION: Elevated MIF, MCP-1 and IL-6 levels in PD effluent were associated with increased PSTR. Elevated dialysis effluent MIF levels was an independent risk factor for high PSTR in subjects with PD treatment.

The impact of angiotensin converting enzyme insertion/deletion gene polymorphism on diabetic kidney disease: A debatable issue.

OBJECTIVE: The objective of this study was to evaluate the influence of ACE I/D gene polymorphisms on diabetic kidney disease (DKD) risk. METHODS: All eligible investigations were identified, the number of various genotype in the case and control group were reviewed. The pooled analysis was performed using Stata software. RESULTS: In overall subjects, 24,321 participants with 12,961 cases and 11,360 controls were included. the pooled analysis showed a significant link between D allele, DD or II genotype and DKD risk (D versus I: OR=1.316, 95% CI: 1.213-1.427, P=0.000; DD versus ID+II: OR=1.414, 95% CI: 1.253-1.595, P=0.000; II versus DD+ID: OR=0.750, 95% CI: 0.647-0.869, P=0.000). The subgroup pooled analysis showed that ACE I/D gene polymorphism was correlated with DKD both in Asian and in Chinese population. In addition, ACE I/D gene polymorphism was correlated with type 2 DKD (D versus I: OR=1.361, 95% CI: 1.243-1.490, P=0.000; DD versus ID+II: OR=1.503, 95% CI: 1.310-1.726, P=0.000; II versus DD+ID: OR=0.738, 95% CI: 0.626 -0.870, P=0.000). However, there was no obvious correlation in Caucasian subjects and type 1 diabetic patients. CONCLUSION: ACE I/D polymorphisms were correlated with DKD in Asian and type 2 diabetic populations. ACE D allele/DD genotype might be a risk factor, while ACE II genotype might be a protective factor for DKD.

Impact of Macrophage Migration Inhibitory Factor Gene Polymorphisms and Serum Macrophage Migration Inhibitory Factor Levels on Pulmonary and Spinal Tuberculosis Susceptibility: A Pooled Analysis.

Objective: This study was designed to evaluate the association between macrophage migration inhibitory factor (MIF) gene polymorphisms, serum MIF levels and tuberculosis (TB) susceptibility. Methods: All satisfactory studies were included; the MIF genotype number and serum MIF levels were reviewed. The Stata and Review Manager software were used for the pooled analyses. Results: The pooled analyses showed that the MIF-173G/C gene polymorphism was associated with TB (allele C vs allele G: odds ratio (OR) = 1.44, 95% confidence interval (CI): 1.28-1.62, p < 0.01; genotype CC vs genotype GG: OR = 1.69, 95% CI: 1.05-2.73, p = 0.03; genotype CC+GC vs genotype GG: OR = 1.56, 95% CI: 1.34-1.81, p < 0.01; genotype GC vs genotype GG: OR = 1.50, 95% CI: 1.28-1.75, p < 0.01). The subgroup analysis showed that the MIF-173G/C gene polymorphism was significantly associated with the risk of both pulmonary tuberculosis (PTB) and spinal tuberculosis (STB).The MIF CATT-794 gene polymorphism was associated with the PTB susceptibility in Asian subjects (genotypes 5/X+6/X vs genotypes 7/X+8/X: OR = 0.39, 95% CI: 0.24-0.64, p < 0.01; genotypes 5 + 6 vs genotypes 7 + 8: OR = 0.57, 95% CI: 0.48-0.69, p < 0.01). Both PTB and STB patients had significantly elevated serum MIF levels compared to healthy controls. Conclusion: The MIF-173G/C gene polymorphism is related to both PTB and STB susceptibility in both Asian and Caucasian populations. The C allele and CC genotype of the MIF-173G/C SNP appear to be TB risk factors. The MIF CATT-794 gene polymorphism is associated with the PTB susceptibility in Asian subjects; serum MIF levels were significantly increased in PTB and STB patients.

Impact of Vitamin D Receptor Gene Polymorphism on Systemic Lupus Erythematosus Susceptibility: A Pooled Analysis.

Background: This study was designed to evaluate the influence of vitamin D receptor (VDR) gene polymorphisms on systemic lupus erythematosus (SLE) susceptibility. Methods: All eligible investigations were identified, the number of the various genotypes in the case and control groups were reviewed. A pooled analysis was performed using the Stata software. The study was carried out according to the Ethics Review Committee of The Third Xiangya Hospital, Central South University. Results: This meta-analysis included 19 studies. In our analysis, the VDR Apal polymorphism was correlated with SLE susceptibility in the overall population (AA vs. aa: odds ratio [OR] = 1.374, 95% confidence interval [CI]: 1.115-1.692, p = 0.003; AA + Aa vs. aa: OR = 1.342, 95% CI: 1.139-1.583, p < 0.01). The VDR Bsml and Apal polymorphisms were correlated with SLE susceptibility in Caucasian subjects (BB vs. Bb + bb: OR = 0.734, 95% CI: 0.593-0.909, p = 0.005; B vs. b: OR = 0.865, 95% CI: 0.760-0.983, p = 0.026; AA vs. aa: OR = 1.329, 95% CI: 1.016-1.740, p = 0.038). The VDR BsmI and FokI polymorphisms were correlated with SLE in African subjects (B vs. b: OR = 1.898, 95% CI: 1.458-2.470, p＜0.01; BB + Bb vs. bb: OR = 2.935, 95% CI: 1.944-4.430, p < 0.01; FF vs. Ff + ff: OR = 2.424, 95% CI: 1.673-3.512, p < 0.01; F vs. f: OR = 1.720, 95% CI: 1.417-2.087, p < 0.01; FF vs. ff: OR = 3.154, 95% CI: 2.083-4.774, p < 0.01; FF + Ff vs. ff: OR = 1.803, 95% CI: 1.363-2.384, p < 0.01). In addition, the VDR Apal polymorphism was correlated with SLE in female subjects (AA vs. aa: OR = 1.392, 95% CI: 1.049-1.849, p = 0.022) when stratified by gender. But there was no association between the VDR TaqI polymorphism and SLE susceptibility in our analysis. Conclusions: The VDR Apal polymorphism was associated with SLE susceptibility in general populations; in addition, Apal polymorphism was associated with SLE in female subjects. The VDR Bsml gene polymorphism was correlated with SLE susceptibility in Caucasian and African populations, whereas the VDR FokI polymorphism was correlated with SLE in African populations. But there was no association between the VDR TaqI polymorphism and SLE susceptibility in our analysis.

The Influence of ACE Insertion/Deletion Gene Polymorphism on the Risk of IgA Nephropathy: A Debatable Topic.

Background: The connection between angiotensin-converting enzyme insertion/deletion (ACE I/D) gene polymorphisms and IgA nephropathy (IgAN) was conflicting. This pooled analysis was performed to explore this issue. Methods: All eligible investigations were identified from various electronic databases, and the pooled analysis was evaluated using Stata software. Results: 27 studies with 2538 IgAN cases and 3592 controls were included. In overall subjects, ACE D allele, DD, and II genotype were associated with IgAN susceptibility (D vs. I: OR = 1.21, 95% CI: 1.10-1.32, P < 0.001; DD vs. ID + II: OR = 1.38, 95% CI: 1.20-1.60, P < 0.001; and II vs. DD + ID: OR = 0.83, 95% CI: 0.73-0.95, P=0.007). In Asian and Chinese patients, ACE I/D gene polymorphism was also correlated with IgAN vulnerability. Moreover, ACE D allele, DD, and II genotype were correlated with the progression of IgAN (D vs. I: OR = 1.37, 95% CI: 1.09-1.73, P=0.008; DD vs. ID + II: OR = 1.57, 95% CI: 1.06-2.31, P=0.024; and II vs. DD + ID: OR = 0.69, 95% CI: 0.49-0.99, P=0.045). Conversely, in Caucasian subjects, there was no link between ACE I/D gene polymorphism and the risk of IgAN. Conclusion: ACE I/D gene polymorphism was correlated with the vulnerability and progression of IgAN in Asian and Chinese patients, and ACE D allele and DD homozygote genotype could be adverse factors for IgAN, while the II homozygote genotype could be an advantage factor. But, no significant association was found between ACE I/D gene polymorphism and IgAN in Caucasians.

The impact of angiotensin converting enzyme insertion/deletion gene polymorphism on diabetic kidney disease: A debatable issue.

OBJECTIVE: The objective of this study was to evaluate the influence of ACE I/D gene polymorphisms on diabetic kidney disease (DKD) risk. METHODS: All eligible investigations were identified, the number of various genotype in the case and control group were reviewed. The pooled analysis was performed using Stata software. RESULTS: In overall subjects, 24,321 participants with 12,961 cases and 11,360 controls were included. the pooled analysis showed a significant link between D allele, DD or II genotype and DKD risk (D versus I: OR=1.316, 95% CI: 1.213-1.427, P=0.000; DD versus ID+II: OR=1.414, 95% CI: 1.253-1.595, P=0.000; II versus DD+ID: OR=0.750, 95% CI: 0.647-0.869, P=0.000). The subgroup pooled analysis showed that ACE I/D gene polymorphism was correlated with DKD both in Asian and in Chinese population. In addition, ACE I/D gene polymorphism was correlated with type 2 DKD (D versus I: OR=1.361, 95% CI: 1.243-1.490, P=0.000; DD versus ID+II: OR=1.503, 95% CI: 1.310-1.726, P=0.000; II versus DD+ID: OR=0.738, 95% CI: 0.626 -0.870, P=0.000). However, there was no obvious correlation in Caucasian subjects and type 1 diabetic patients. CONCLUSION: ACE I/D polymorphisms were correlated with DKD in Asian and type 2 diabetic populations. ACE D allele/DD genotype might be a risk factor, while ACE II genotype might be a protective factor for DKD.

Intracellular Calcium Homeostasis and Kidney Disease.

Kidney disease is a serious health problem that burdens our healthcare system. It is crucial to find the accurate pathogenesis of various types of kidney disease to provide guidance for precise therapies for patients suffering from these diseases. However, the exact molecular mechanisms underlying these diseases have not been fully understood. Disturbance of calcium homeostasis in renal cells plays a fundamental role in the development of various types of kidney disease, such as primary glomerular disease, diabetic nephropathy, acute kidney injury and polycystic kidney disease, through promoting cell proliferation, stimulating extracellular matrix accumulation, aggravating podocyte injury, disrupting cellular energetics as well as dysregulating cell survival and death dynamics. As a result, preventing the disturbance of calcium homeostasis in specific renal cells (such as tubular cells, podocytes and mesangial cells) is becoming one of the most promising therapeutic strategies in the treatment of kidney disease. The endoplasmic reticulum and mitochondria are two vital organelles in this process. Calcium ions cycle between the endoplasmic reticulum and mitochondria at the conjugation of these two organelles known as the mitochondria-associated endoplasmic reticulum membrane, maintaining calcium homeostasis. The pharmacologic modulation of cellular calcium homeostasis can be viewed as a novel therapeutic method for renal diseases. Here, we will introduce calcium homeostasis under physiological conditions and the disturbance of calcium homeostasis in kidney diseases. We will focus on the calcium homeostasis regulation in renal cells (including tubular cells, podocytes and mesangial cells), especially in the mitochondria- associated endoplasmic reticulum membranes of these renal cells.

Novel risk models to predict acute kidney disease and its outcomes in a Chinese hospitalized population with acute kidney injury.

Acute kidney disease (AKD) is a state between acute kidney injury (AKI) and chronic kidney disease (CKD), but the prognosis of AKD is unclear and there are no risk-prediction tools to identify high-risk patients. 2,556 AKI patients were selected from 277,898 inpatients of three affiliated hospitals of Central South University from January 2015 to December 2015. The primary point was whether AKI patients developed AKD. The endpoint was death or end stage renal disease (ESRD) 90 days after AKI diagnosis. Multivariable Cox regression was used for 90-day mortality and two prediction models were established by using multivariable logistic regression. Our study found that the incidence of AKD was 53.17% (1,359/2,556), while the mortality rate and incidence of ESRD in AKD cohort was 19.13% (260/1,359) and 3.02% (41/1,359), respectively. Furthermore, adjusted hazard ratio of mortality for AKD versus no AKD was 1.980 (95% CI 1.427-2.747). In scoring model 1, age, gender, hepatorenal syndromes, organic kidney diseases, oliguria or anuria, respiratory failure, blood urea nitrogen (BUN) and acute kidney injury stage were independently associated with AKI progression into AKD. In addition, oliguria or anuria, respiratory failure, shock, central nervous system failure, malignancy, RDW-CV ≥ 13.7% were independent risk factors for death or ESRD in AKD patients in scoring model 2 (goodness-of fit, P1 = 0.930, P2 = 0.105; AUROC1 = 0.879 (95% CI 0.862-0.896), AUROC2 = 0.845 (95% CI 0.813-0.877), respectively). Thus, our study demonstrated AKD was independently associated with increased 90-day mortality in hospitalized AKI patients. A new prediction model system was able to predict AKD following AKI and 90-day prognosis of AKD patients to identify high-risk patients.

Extracellular vesicles carrying miRNAs in kidney diseases: a systemic review.

MiRNAs play essential roles in processes of physiological status and disease conditions including in renal diseases, while extracellular vesicles (EVs) serve as important mediators for cell-cell communication. In body fluid or extracellular spaces, miRNAs are packaged into EVs and transferred to targeted cells to perform their bioeffects under particular conditions. In the present review, we aim to summarize and update the known and verified EV-carrying miRNAs (EV-miRNAs) and their general roles in kidney diseases. In addition to performing a systemic analysis, we try to provide some clues and perspectives for the future study of EV-miRNAs in renal diseases.

Mitochondria targeted peptide SS-31 prevent on cisplatin-induced acute kidney injury via regulating mitochondrial ROS-NLRP3 pathway.

OBJECTIVE: This study aimed to assess the effect and mechanism of SS31 on cisplatin-induced acute kidney injury (CP-AKI) both in vivo and in vitro. METHOD: Male mices and HK-2 cells were treated using cisplatin to establish models of CP-AKI. 32 C57BL/6 mices were randomly divided into four groups (control group, CP group, CP + normal saline group, CP + SS-31 group). Cisplatin was intraperitoneally injected once to the mice (25 mg/kg). SS31 was administrated for 10 days at dosages of 10 mg/kg per day. Kidney histological changes and level of reactive oxygen species(ROS) were detected. In vitro studies, HK-2 cells were incubated with cisplatin (50 u M) or combimed with SS-31(100 u M), the level of mitochondrial ROS, apoptosis rate and the the expression of NLRP3, Caspase-1 and IL-1ß were tested. RESULTS: Renal tubulointerstitial apoptosis and oxidative stress were significantly increased in CP-AKI mice. Cisplatin caused elevation of serum creatinine (Scr), blood urea nitrogen (BUN) levels and enhanced IL-1ß, caspase1 and NLRP3 expression, the electron microscopy examination showed mitochondria cristae swelling, mitochondrial spheres and partial ridge breakdown in renal tubular cell of CP-AKI mice. SS31 treatment could effectively suppress mitochondrial ROS, ameliorate these lesions and decrease the expression of NLRP3, IL-1ß and Caspase1. In vitro studies, SS31 could restored the level of mitochondrial ROS and downregulate apoptosis rate in HK-2 cells, moreover, the elevated expression of NLRP3, IL-1ß and Caspase-1were restored. CONCLUSION: SS31 could protect CP-AKI in mices, which might be due to an anti-oxidative and anti-apoptotic action via regulating mitochondrial ROS-NLRP3 pathway. NLRP3 inflammasome might be considered as a novel therapeutic target of CP-AKI.

The effect of Ginsenoside Rg1 in hepatic ischemia reperfusion (I/R) injury ameliorates ischemia-reperfusion-induced liver injury by inhibiting apoptosis.

Hepatic ischemia reperfusion (I/R) injury (HIRI) HIRI is a complex, multifactorial pathophysiological process and in liver surgery has been known to significantly affect disease prognosis, surgical success rates, and patient survival. Ginsenoside Rgl (Rgl) monomer is one of the main active ingredients of ginseng. Previous studies have demonstrated that Rgl exerts various pharmacological effects through several mechanisms including suppression of apoptosis-related proteins levels, downregulation of inflammatory mediators and as well as antioxidant, which effectively exerts an organ protective effect I/R-induced damage. However, the exact mechanisms of Rg1 on HIRI remain to be elucidated. In the present study, we investigated the protective effect of Rg1 on hepatic ischemia-reperfusion (I/R) injury (HIRI) and explored its underlying molecular mechanism. A rat warm I/R injury model in vivo and an oxygen-glucose deprivation/reperfusion (OGD/R)-treated BRL-3A cell model in vitro were established after pretreating with Rg1(20 mg/kg). The results showed that Rg1 reduced the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). TUNEL staining showed that pretreated with Rg1 inhibited the apoptosis rate compared with the I/R group. Moreover, pretreated with Rg1 significantly reduced the expression of Cyt-C, Caspase-9 and Caspase-3 to inhibit the cell apoptosis. Flow cytometry analysis showed the MMP in the I/R group was significantly increased, whereas pretreated with Rg1 effectively stabilized the MMP compared with the I/R group. in vitro, the proliferation of BRL-3A cells was significantly decreased by the OGD/R treatment, while Rg1 effectively reversed this phenomenon. In addition, western blotting showed that the increase of Cyt-C, Caspase-9 and Caspase-3 was inhibited by H2O2. These observations suggest that Rg1 exerts the protective effect by inhibiting the CypD protein-mediated mitochondrial apoptotic pathway.

Low dose of flurbiprofen axetil decrease the rate of acute kidney injury after operation: a retrospective clinical data analysis of 9915 cases.

BACKGROUND: Flurbiprofen axetil (FA) is a commonly prescribed agent to relieve perioperative pain, but the relationship between FA and postoperative acute kidney injury (AKI) remains unclear. This study attempted to evaluate the effects of different dose of perioperative FA on postoperative AKI. METHODS: A total of 9915 patients were enrolled for this retrospective study. The clinical characteristics and the prevalence of postoperative AKI among patients non-using, using low dose (50-100 mg), middle dose (100-250 mg) and large dose (≧250 mg) of FA were analyzed respectively. The impact of different dose of FA on postoperative AKI was analyzed using univariable and multivariate logistic regression analysis. RESULTS: The prevalence of postoperative AKI was 6.7% in the overall subjects and 5.1% in 2446 cases who used FA. The incidence of AKI in low dose group was significantly less than that of non use group (4.5% vs 7.2%, P < 0.001), but the incidence of AKI in large dose group was significantly higher than that in the non-use group (18.8% vs 7.2%, P < 0.001). However, there was no significant difference between patients without using FA and subjects using middle dose of FA (7.2% vs 5.6%, p = 0.355). Multivariate logistic regression analysis showed that low dose of FA was a protective factor for postoperative AKI (OR = 0.75, p = 0.0188), and large dose of FA was a risk factor for postoperative AKI (OR = 4.8, p < 0.0001). CONCLUSIONS: The impact of FA on postoperative AKI was dose-dependent, using of low dose FA (50-100 mg) perioperatively may effectively reduce the incidence of postoperative AKI.

Rs145204276 and rs4759314 affect the prognosis of prostate cancer by modulating the GAS5/miR-1284/HMGB1 and HOTAIR/miR-22/HMGB1 signalling pathways.

Non-coding RNAs play an important role in the pathogenesis of prostate cancer (PC). This study aims to characterize the role of GAS5 rs145204276 and HOTAIR rs4759314 polymorphisms in the pathogenesis of PC. Both INS allele of GAS5 rs145204276 and A allele of HOTAIR rs4759314 were identified to increase the survival of PC patients. And patients carrying DEL/DEL + AG genotypes tend to present higher levels of HMGB1, GAS5, HOTAIR and lower levels of miR-1284 and miR-22. In addition, the transcription activity of GAS5 promoter was increased by the deletion allele of rs145204276 polymorphism, while the G allele of rs4759314 polymorphism increased the transcription activity of HOTAIR promoter. GAS5 and HOTAIR could bind to miR-1284 and miR-22, respectively, while miR-1284 and miR-22 could bind to the 3'UTR of HMGB1. Compared with the control group, the expressions of miR-1284 or miR-22 were decreased with the presence of GAS5 or HOTAIR, and the expression of HMGB1 was the highest in the GAS5 + HOTAIR group. In summary, the findings of this study demonstrated that both GAS5 rs145204276 and HOTAIR rs4759314 polymorphisms could affect the prognosis of PC by modulating the expression of HMGB1 via modulating the GAS5/miR-1284/HMGB1 and HOTAIR/miR-22/HMGB1 signalling pathways.

Comparison of 99mTc-DTPA and serum creatinine, cystatin C in detection of glomerular filtration rate: a retrospective clinical data analysis of 744 Chinese subjects.

BACKGROUND: To compare the accuracy of various equations for estimating glomerular filtration rate. METHODS: Chronic kidney disease was classified by Tc-DTPA scintigraphy (reference glomerular filtration rate), estimating glomerular filtration rate was estimated using various formulas. The similarity to reference glomerular filtration rate decide the accuracy of estimating glomerular filtration rate. RESULTS: Overall, the Fengscr-cys equation had significantly higher accuracy and correct proportion in chronic kidney disease stage classification than other equations. The subgroup analysis showed that Fengscr-cys equation was slightly more precise than other equations both in the male and female patients. Moreover, in patients older than 60 years or whose reference glomerular filtration rate was above 60 ml/min, Fengscr-cys equation also showed better accuracy. CONCLUSION: Our data suggest that estimating glomerular filtration rate equations evaluated by serum cystatin C were better than serum creatinine-based equations, estimating glomerular filtration rate equations evaluated by both serum creatinine and cystatin C were better than those evaluated by serum creatinine or cystatin C alone. Among all enrolled equations, Fengscr-cys equation might be the best one to evaluate glomerular filtration rate in general Chinese paticipants.

The Role of Mitochondria in Systemic Lupus Erythematosus: A Glimpse of Various Pathogenetic Mechanisms.

BACKGROUND: Systemic Lupus Erythematosus (SLE) is a polysystem autoimmune disease that adversely affects human health. Various organs can be affected, including the kidney or brain. Traditional treatment methods for SLE primarily rely on glucocorticoids and immunosuppressors. Unfortunately, these therapeutic agents cannot prevent a high recurrence rate after SLE remission. Therefore, novel therapeutic targets are urgently required. METHODS: A systematic search of the published literature regarding the abnormal structure and function of mitochondria in SLE and therapies targeting mitochondria was performed in several databases. RESULTS: Accumulating evidence indicates that mitochondrial dysfunction plays important roles in the pathogenesis of SLE, including influencing mitochondrial DNA damage, mitochondrial dynamics change, abnormal mitochondrial biogenesis and energy metabolism, mitophagy, oxidative stress, inflammatory reactions, apoptosis and NETosis. Further investigation of mitochondrial pathophysiological roles will result in further clarification of SLE. Specific lupus-induced organ damage also exhibits characteristic mitochondrial changes. CONCLUSION: This review aimed to summarize the current research on the role of mitochondrial dysfunction in SLE, which will necessarily provide potential novel therapeutic targets for SLE.

Emerging Role of Ferroptosis in Acute Kidney Injury.

Acute kidney injury (AKI) is a heterogeneous group of critical disease conditions with high incidence and mortality. Vasoconstriction, oxidative stress, apoptosis, and inflammation are generally thought to be the main pathogenic mechanisms of AKI. Ferroptosis is a type of iron-dependent nonapoptotic cell death characterized by membrane lipid peroxide accumulation and polyunsaturated fatty acid consumption, and it plays essential roles in many diseases, including cancers and neurologic diseases. Recent studies have revealed an emerging role of ferroptosis in the pathophysiological processes of AKI. Here, in the present review, we summarized the most recent discoveries on the role of ferroptosis in the pathogenesis of AKI as well as its therapeutic potential in AKI.

Role of Vitamin D Receptor Gene Polymorphisms on the Susceptibility to Periodontitis: A Meta-Analysis of a Controversial Issue.

Background: To assess whether vitamin D receptor (VDR) gene polymorphisms influence the susceptibility to periodontitis. Methods: We retrieved 34 relevant studies, comprising a total of 3848 subjects suffering from periodontitis and 3470 controls for this meta-analysis. The pooled data were analyzed using STATA software. Results: Among all ethnic groups examined, the VDR BsmI polymorphism was associated with periodontitis under the recessive model (odds ratio [OR] = 0.722, 95% confidence interval [CI]: 0.532-0.980, p = 0.037). There was also a link between the VDR FokI polymorphism and periodontitis in the overall population (dominant model: OR = 1.459, 95% CI: 1.050-2.028, p = 0.025 and allelic model: OR = 1.386, 95% CI: 1.026-1.874, p = 0.034) and in Chinese participants (dominant model: OR = 1.813, 95% CI: 1.185-2.774, p = 0.006; allelic model: OR = 1.602, 95% CI: 1.044-2.459, p = 0.031) when stratified by race. The FokI variant was also correlated with aggressive periodontitis (AP) (dominant model: OR = 2.204, 95% CI: 1.148-4.231, p = 0.018; allelic model: OR = 2.017, 95% CI: 1.365-2.980, p = 0.000; and recessive model: OR = 2.903, 95% CI: 1.520-5.542, p = 0.001). We also showed a correlation between the VDR TaqI variant and periodontitis susceptibility in Caucasian populations (dominant model: OR = 0.525, 95% CI: 0.318-0.866, p = 0.012). The results revealed that there was no relationship between the VDR ApaI gene polymorphism and periodontitis. Conclusions: There was a link between the VDR BsmI and FokI gene polymorphisms and periodontitis in the overall population. In addition, the FokI polymorphism was correlated with AP. There was a link between the TaqI polymorphism and periodontitis in the Caucasian population. The VDR Apal variant, however, was not correlated with periodontitis.

Mitochondria-Targeted Peptide SS31 Attenuates Renal Tubulointerstitial Injury via Inhibiting Mitochondrial Fission in Diabetic Mice.

OBJECTIVE: Renal tubular injury is an early characteristic of diabetic nephropathy (DN) that is related to mitochondrial dysfunction. In this study, we explore the effects and mechanisms of mitochondria-targeted peptide SS31 on renal tubulointerstitial injury in DN. METHOD: 40 C57BL/6 mice were randomly divided into control group, STZ group, STZ+SS31 group, and STZ+normal saline group. SS31 was intraperitoneally injected to the mice every other day for 24 weeks. Renal lesions and the expression of Drp1, Mfn1, Bcl-2, Bax, Caspase1, IL-1ß, and FN were detected. In in vitro studies, HK-2 cells were incubated with different concentrations of D-glucose (5, 30 mM) or combined with SS31 and Drp1 inhibitor Midivi1. Mitochondrial ROS, membrane potential, and morphology have been detected to evaluate the mitochondrial function. RESULTS: Compared with diabetic mice, the levels of serum creatinine and microalbuminuria were significantly decreased in the SS31 group. Renal tubulointerstitial fibrosis, oxidative stress, and apoptosis were observed in diabetic mice, while the pathological changes were reduced in the SS31-treatment group. SS31 could decrease the expression of Drp1, Bax, Caspase1, IL-1ß, and FN in the renal tissue of diabetic mice, while increasing the expression of Mfn1. Additionally, mitochondria exhibit focal enlargement and crista swelling in renal tubular cells of diabetic mice, while SS31 treatment could partially block these changes. An in vitro study showed that pretreatment with SS31 or Drp1 inhibitor Mdivi1 could restore the level of mitochondrial ROS, the membrane potential levels, and the expressions of Drp1, Bax, Caspase1, IL-1ß, and FN in HK-2 cells under high-glucose conditions. CONCLUSION: SS31 protected renal tubulointerstitial injury in diabetic mice through a decrease in mitochondrial fragmentation via suppressing the expression of Drp1 and increasing the expression of Mfn1.