A Retrospective Study from a Single Center in China to Develop a Nomogram to Predict One-Year Mortality in Patients with End-Stage Renal Disease Who Are Receiving Hemodialysis.

BACKGROUND The prognosis of end-stage renal disease (ESRD) patients receiving hemodialysis (HD) remains Poor. This retrospective study from a single center in China aimed to develop a nomogram to predict one-year mortality in patients with ESRD on HD. MATERIAL AND METHODS We enrolled 299 ethnic Han Chinese ESRD patients undergoing HD at the Second Affiliated Hospital of Nantong University from April 29, 2011 to January 30, 2021. Univariate and multivariate Cox regression analyses were used to select the predictors incorporated in the prediction model to assess the one-year mortality for ESRD patients receiving HD. We used receiver operating characteristic curves, C-index, and calibration curves to evaluate the performance of the nomogram. The predictive performance of the nomogram was also verified in different subgroup populations. RESULTS The median follow-up time was 23.30 months. The 299 ESRD patients receiving HD were divided into a death group (n=96) and a survival group (n=203), and the incidence of death was 32.11%. The main causes of death were cardiovascular disease, inflammation and cancer. A nomogram containing age, alkaline phosphatase, albumin, cystatin C, total bilirubin, and hypersensitive c-reactive protein was established. The performance of this nomogram was reflected by its moderate predictive ability, especially for patients who were male, had a primary disease of chronic glomerulonephritis, and had no history of comorbidities. CONCLUSIONS We developed and validated an easy-to-use nomogram for predicting the one-year mortality of ESRD patients undergoing HD.

Predictive value of serum ß2-microglobulin in cardiac valve calcification in maintenance hemodialysis patients.

Background: Cardiac valve calcification (CVC) is associated with adverse cardiovascular events. We studied the risk factors of CVC in maintenance hemodialysis (MHD) patients and the value of serum ß2-microglobulin (ß2-MG) levels in predicting the incidence of CVC. ß2-MG is a middle molecular weight toxin. In recent years, researchers found that elevated blood ß2-MG was associated with coronary, thoracic, and abdominal aortic calcifications with significant correlations. ß2-MG has been emerging as a strong biomarker for cardiovascular mortality in uremic patients but its role in CVC is not well studied. This study looked specifically at CVC occurrence in relation to ß2-MG for MHD patients. Methods: Patients who underwent MHD for more than 3 months in the First People's Hospital of Nantong City from November 2012 to November 2019 with complete available data were included in the study. The patients were divided into the CVC group and the non-CVC group. The general information and clinical laboratory indicators of the patients were collected in a retrospective manner. We analyzed the risk factors for developing CVC in MHD patients using binary logistic regression method. Receiver operating characteristic (ROC) curves were used to calculate the cut-off value of ß2-MG for predicting CVC. The decision tree (DT) method was used to classify and explore the probability of CVC in patients with MHD. Results: The ß2-MG in the CVC group was significantly higher than that in the non-CVC group (t=6.750, P<0.001). Multivariate binary logistic regression analysis showed that gender, age, serum ß2-MG, and hemodialysis (HD) adequacy (Kt/V urea) were independent risk factors for CVC in MHD patients. ROC analysis showed that a ß2-MG value of 25 µg/L was the best cut-off point for predicting CVC in MHD patients. According to binary logistic regression analysis, the ß2-MG ≥25 µg/L group was 3.39 times more likely to develop CVC than the ß2-MG <25 µg/L group [odds ratio (OR), 3.39; 95% confidence interval (CI), 1.63-7.06; P=0.001]. The DT model determined that serum ß2-MG ≥25 µg/L and age >69 years were important determinants for predicting CVC in MHD patients. Conclusions: Serum ß2-MG in MHD patients has a positive correlation with the severity and occurrence of CVC.

MiR-153-3p reduces extracellular matrix accumulation in high glucose-stimulated human glomerular mesangial cells via targeting PAQR3 in diabetic nephropathy.

INTRODUCTION: This study aims to explore the effect and related molecular mechanism of miR-153-3p on high glucose-stimulated human glomerular mesangial cells. MATERIALS AND METHODS: The quantitative real-time polymerase chain reaction (qPCR) assay was employed to check miR-153-3p and PAQR3 expression levels in diabetic nephropathy patients. (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay was applied to investigate the effects of miR-153-3p transfection or PAQR3 administration on mesangial cell (MC) activity. ELISA assays were used to check the expression levels of extracellular matrix (ECM) related proteins. The bioinformatics method and dual-luciferase reporter assay were employed together to anticipate and check the targeting relationship between miR-153-3p and PAQR3. Western blot assays were applied to check the PAQR3, PI3K and AKT expression after miR-153-3p transfection or PAQR3 administration. RESULTS: The expression level of miR-153-3p was lower in diabetic nephropathy patients, while the expression of PAQR3 was concomitantly higher. Upregulation of miR-153-3p can reduce MC proliferation and ECM accumulation. Further research indicated that miR-153-3p directly regulated PAQR3 expression via coupling with the 3'-UTR of PAQR3. Finally, the fact that miR-153-3p regulates the PI3K/AKT pathway by PAQR3 was confirmed. CONCLUSION: MiR-153-3p regulates the PI3K/AKT pathway through PAQR3, thereby playing a role in regulating cell proliferation and ECM accumulation in high glucose-stimulated MCs.

Correlation between lactate dehydrogenase and QTc interval prolongation in maintenance hemodialysis patients: a cross-sectional study.

BACKGROUND: Corrected QT (QTc) interval prolongation is one of the common causes of sudden cardiac death in patients with maintenance hemodialysis (MHD) patients. However, there are few studies on QTc prolongation in MHD patients. The concentration of lactate dehydrogenase (LDH) in hemodialysis population increased, and LDH was associated with the mortality of MHD patients. This study aimed to investigate the relationship between QTc interval prolongation and LDH in MHD patients. METHODS: This is a cross-sectional observational study. Patients who underwent MHD for more than 3 months in the Second Affiliated Hospital of Nantong University from November 2012 to November 2019 with complete data were selected as the research subjects. The patients were divided into the normal QTc interval group and the QTc interval prolongation group. The general data of patients and clinical laboratory indicators were collected retrospectively from the electronic medical record system. Pearson correlation analysis and binary logistic regression were used to analyze the correlation between LDH and QTc interval prolongation; the cut-off value of LDH predicting QTc interval prolongation was calculated by receiver operating characteristic (ROC) curve. RESULTS: The LDH level in the prolonged QTc interval group was significantly higher than that in the normal group (301.96±110.91 vs. 215.39±67.65, t=-8.03, P<0.001). QTc interval and LDH (r=0.386) were positively correlated. Binary logistic regression analysis showed that LDH, serum potassium <4 mmol/L, serum phosphorus, and left ventricular end-diastolic diameter (LVDd) were independent related factors for QTc interval prolongation. The ROC curve results showed that LDH =220 U/L was the best cutoff point for predicting QTc interval prolongation in MHD patients, with a sensitivity of 81.45% and a specificity of 59.35%. Binary logistic regression analysis showed that the LDH >220 U/L group was 6.34 times more likely to have QTc interval prolongation than the LDH ≤220 U/L group (OR 6.34, 95% CI: 3.47-11.58, P<0.001). CONCLUSIONS: LDH in MHD patients is closely related to QTc interval prolongation. Serum LDH, ionic calcium, serum phosphorus and potassium may predict QTc interval prolongation. Monitoring related indicators can remind clinicians to intervene as soon as possible to reduce the potential risk of arrhythmia and sudden cardiac death (SCD).

Clinical significance of cancer stem cell markers in lung carcinoma.

The identification of side population (SP) cells in several cancer studies has been proved to be involved in the treatment failure (chemotherapy) and tumor relapse. Here we have sorted 7% of side population (SP) cells from lung adenocarcinoma by Hoechst 33342 dye expulsion method. Further, the characterization of sorted SP cells showed cancer stem like properties such as transcriptional upregulation of stemness genes (OCT-4, SOX2 and NANOG), ATP binding cassette (ABC) transporter protein (ABCG2) and enhanced level of stem cell surface markers such as CD133 and CD44. Therefore, the aforesaid properties of lung adenocarcinoma SP cells play a significant and functional role in tumor invasion, metastasis, chemotherapeutic drug resistance and tumor recurrence in lung cancer.

MiR-153-3p reduces extracellular matrix accumulation in high glucose-stimulated human glomerular mesangial cells via targeting PAQR3 in diabetic nephropathy.

INTRODUCTION: This study aims to explore the effect and related molecular mechanism of miR-153-3p on high glucose-stimulated human glomerular mesangial cells. MATERIALS AND METHODS: The quantitative real-time polymerase chain reaction (qPCR) assay was employed to check miR-153-3p and PAQR3 expression levels in diabetic nephropathy patients. (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay was applied to investigate the effects of miR-153-3p transfection or PAQR3 administration on mesangial cell (MC) activity. ELISA assays were used to check the expression levels of extracellular matrix (ECM) related proteins. The bioinformatics method and dual-luciferase reporter assay were employed together to anticipate and check the targeting relationship between miR-153-3p and PAQR3. Western blot assays were applied to check the PAQR3, PI3K and AKT expression after miR-153-3p transfection or PAQR3 administration. RESULTS: The expression level of miR-153-3p was lower in diabetic nephropathy patients, while the expression of PAQR3 was concomitantly higher. Upregulation of miR-153-3p can reduce MC proliferation and ECM accumulation. Further research indicated that miR-153-3p directly regulated PAQR3 expression via coupling with the 3'-UTR of PAQR3. Finally, the fact that miR-153-3p regulates the PI3K/AKT pathway by PAQR3 was confirmed. CONCLUSION: MiR-153-3p regulates the PI3K/AKT pathway through PAQR3, thereby playing a role in regulating cell proliferation and ECM accumulation in high glucose-stimulated MCs.

A Clinical Study on the Association of Sodium-Glucose Cotransporter 2 Inhibitors and Acute Kidney Injury Among Diabetic Chinese Population.

PURPOSE: To investigate the association of Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors and acute kidney injury in comparison to other classes of drugs. PATIENTS AND METHODS: A total of 4966 diabetes mellitus patients were investigated for developing Acute Kidney Injury (AKI) who were under prescription with the following class of drugs viz. SGLT2 Inhibitors, Dipeptidyl peptidase-4 (DDP4) inhibitors, Nonsteroidal anti-inflammatory drugs (NSAIDs), first-line drugs and anti-biotics. The primary outcome was based on the hospital encounter and Kidney Disease Improving Global Outcome (KDIGO) threshold values were used to assess the serum creatinine concentration. The secondary outcome was assessed based on the concentration level of serum creatinine after 90 days of hospital admission and evaluation of the KDIGO threshold values. RESULTS: The study observed that the risk of causing AKI for SGLT2 inhibitors was 5.59% which was comparatively low compared to other class of the investigated drugs (DPP4 inhibitors = 6.47%, antibiotics = 6.30%, first-line drugs = 6.82% and NSAIDs = 10.65%). The multivariate analysis observed that ibuprofen, celecoxib, indomethacin, insulin, cephalexin, and alogliptin were mostly associated with an increased rate of AKI. SGLT2 inhibitors have the lowest risk for developing AKI compared to other drugs and control. CONCLUSION: AKI incidence is relatively low after initiation of SLGT2 inhibitors and concludes that regulatory warnings from certain health agencies about its risk for AKI on prescription are unwarranted.

Associations of Plasma Glucagon Levels with Estimated Glomerular Filtration Rate, Albuminuria and Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized by elevated fasting glucagon and impaired suppression of postprandial glucagon secretion, which may participate in diabetic complications. Therefore, we investigated the associations of plasma glucagon with estimated glomerular filtration rate (eGFR), albuminuria and diabetic kidney disease (DKD) in T2DM patients. METHODS: Fasting glucagon and postchallenge glucagon (assessed by area under the glucagon curve [AUCgla]) levels were determined during oral glucose tolerance tests. Patients with an eGFR <60 mL/min/1.73 m2 and/or a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g who presented with diabetic retinopathy were identified as having DKD. RESULTS: Of the 2,436 recruited patients, fasting glucagon was correlated with eGFR and UACR (r=-0.112 and r=0.157, respectively; P<0.001), and AUCgla was also correlated with eGFR and UACR (r=-0.267 and r=0.234, respectively; P<0.001). Moreover, 31.7% (n=771) presented with DKD; the prevalence of DKD was 27.3%, 27.6%, 32.5%, and 39.2% in the first (Q1), second (Q2), third (Q3), and fourth quartile (Q4) of fasting glucagon, respectively; and the corresponding prevalence for AUCgla was 25.9%, 22.7%, 33.7%, and 44.4%, respectively. Furthermore, after adjusting for other clinical covariates, the adjusted odds ratios (ORs; 95% confidence intervals) for DKD in Q2, Q3, and Q4 versus Q1 of fasting glucagon were 0.946 (0.697 to 1.284), 1.209 (0.895 to 1.634), and 1.521 (1.129 to 2.049), respectively; the corresponding ORs of AUCgla were 0.825 (0.611 to 1.114), 1.323 (0.989 to 1.769), and 2.066 (1.546 to 2.760), respectively. Additionally, when we restricted our analysis in patients with glycosylated hemoglobin <7.0% (n=471), we found fasting glucagon and AUCgla were still independently associated with DKD. CONCLUSION: Both increased fasting and postchallenge glucagon levels were independently associated with DKD in T2DM patients.