Long-term exposure to ambient air pollutants and increased risk of end-stage renal disease in patients with type 2 diabetes mellitus and chronic kidney disease: a retrospective cohort study in Beijing, China.

Limited data have examined the association between air pollution and the risk of end-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). We aimed to investigate whether long-term exposure to air pollutants is related to the development of ESRD among patients with T2DM and CKD. A total of 1,738 patients with T2DM and CKD hospitalized in Peking University Third Hospital from January 1, 2013, to December 31, 2021 were enrolled in this study. The outcome was defined as the occurrence of ESRD. Data on six air pollutants (PM2.5, PM10, CO, NO2, SO2, and O3) from 35 monitoring stations were obtained from the Beijing Municipal Ecological and Environmental Monitoring Center. Long-term exposure to air pollutants during the follow-up period was measured using the ordinary Kriging method. During a mean follow-up of 41 months, 98 patients developed ESRD. Multivariate logistic regression analysis showed that an increase of 10 µg/m3 in PM2.5 (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.03-1.36) and PM10 (OR 1.15, 95% CI 1.02-1.30) concentration were positively associated with ESRD. An increase of 1 mg/m3 in CO (2.80, 1.05-7.48) and an increase of 1 µg/m3 in SO2 (1.06, 1.00-1.13) concentration were also positively associated with ESRD. Apart from O3 and NO2, all the above air pollutants have additional predictive value for ESRD in patients with T2DM and CKD. The results of Bayesian kernel machine regression and the weighted quantile sum regression all showed that PM2.5 was the most important air pollutant. Backward stepwise logistic regression showed that PM2.5 was the only pollutant remaining in the prediction model. In patients with T2DM and CKD, long-term exposure to ambient PM2.5, PM10, CO, and SO2 was positively associated with the development of ESRD.

Association between triglyceride-glucose index and risk of end-stage renal disease in patients with type 2 diabetes mellitus and chronic kidney disease.

Aims: It has been suggested that the triglyceride-glucose (TyG) index is a novel and reliable surrogate marker of insulin resistance (IR). However, its relationship with the risk of end-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) remains uncertain. Accordingly, we sought to examine the relationship between the TyG index and ESRD risk in patients with T2DM and CKD. Methods: From January 2013 to December 2021, 1,936 patients with T2DM and CKD hospitalized at Peking University Third Hospital (Beijing, China) were enrolled into the study. The formula for calculating the TyG index was ln[fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. ESRD was defined as an estimated glomerular filtration rate of less than 15 mL/min/1.73 m2 or the commencement of dialysis or renal transplantation. The relationship between the TyG index and ESRD risk was analyzed using Cox proportional hazard regression. Results: 105 (5.42%) participants developed ESRD over a mean follow-up of 41 months. The unadjusted analysis revealed a 1.50-fold (95% confidence interval [CI] 1.17-1.93; P = 0.001) increased risk for ESRD per one unit rise in the TyG index, and the positive association remained stable in the fully adjusted model (hazard ratio, 1.49; 95% CI, 1.12-1.99; P = 0.006). Analysis using restricted cubic spline revealed a significant positive association between the TyG index and ESRD risk. In addition, Kaplan-Meier analysis revealed significant risk stratification with a TyG index cutoff value of 9.5 (P = 0.003). Conclusion: In individuals with T2DM and CKD, a significant and positive association was shown between an elevated TyG index and the risk of ESRD. This conclusion provides evidence for the clinical importance of the TyG index for evaluating renal function decline in individuals with T2DM and CKD.

Simultaneous subacute interstitial nephritis and anticoagulant-related nephropathy related to novel oral anticoagulants use.

Introduction: Interstitial nephritis related to novel oral anticoagulants was only reported in sporadic case reports and none was accompanied by anticoagulants related nephropathy (ARN).Case Report: We presented here a case of biopsy-proven subacute interstitial nephritis (SubAIN) accompanied by ARN after oral dabigatran to alarm clinicians. This case manifested with gross hematuria, acute kidney injury, slightly prolonged thrombin time, moderate anemia, moderate proteinuria, a large quantity of intratubular hemoglobin casts confirmed by hemoglobin antibody immunohistochemical staining which presumed to occur around 1 week after dabigatran and subacute interstitial nephritis accompanied by focal proliferative glomerulonephritis. Serum creatinine level did not continue to elevate after discontinuation of the oral anticoagulant. With the subsequent supportive therapy, it decreased to some extent then reduced to normal with the help of prednisone (half of the full dose).Conclusions: When we came across a patient who manifested as hematuria or acute kidney injury with a history of anticoagulants usage, we should think of ARN and pay more attention on history collection. Secondly, subacute interstitial nephritis may coexist with ARN. Thirdly, hemoglobin immunohistochemical staining may be helpful to make it clear whether the intra-tubular protein casts came from red blood cells. In addition, for those patients who may have decreased kidney function, anticoagulants dose should be reduced to prevent the occurrence of ARN.

Effects of epidermal growth factor receptor and phosphatase and tensin homologue gene expression on the inhibition of U87MG glioblastoma cell proliferation induced by protein kinase inhibitors.

The aim of the present study was to analyse the antiproliferative effects and mechanisms of action of protein kinase inhibitors (PKIs) in human glioblastoma multiforme (GBM) cells with different epidermal growth factor receptor (EGFR) and phosphatase and tensin homologue (PTEN) status. The GBM cell models were established by transfection of plasmids carrying wild-type EGFR, mutated EGFRvIII or PTEN and clonal selection in U87MG cells. Phosphatidylinositol 3-kinase (PI3-K)/AKT pathway-focused gene profiles were examined by real-time polymerase chain reaction-based assays, protein expression was evaluated by western blotting and the antiproliferative effects of PKI treatment were determined by the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay in GBM cells. The cell model with intact PTEN and low EGFR levels was the most sensitive to treatment with the EGFR inhibitor erlotinib, whereas the model with EGFRvIII was the most resistant to treatment with the mitogen-activated protein kinase kinase inhibitor U0126. The dual PI3-K and mammalian target of rapamycin (mTOR) inhibitor PI103 had the most potent antiproliferative effects against all GBM cells tested. Following simultaneous stimulation of AKT and extracellular signal-regulated kinase, rapamycin concentrations > 0.5 nmol/L failed to exhibit a further growth inhibitory effect. Concurrent inhibition of mTOR and ribosomal protein s6 activity may underlie the inhibition of GBM proliferation by PKI. In conclusion, overexpression of EGFR or EGFRvIII, accompanied by a loss of PTEN, contributed to the activation of multiple intracellular signalling pathways in GBM cells. Rigorous examination of biomarkers in tumour tissues before and after treatment may be necessary to determine the efficacy of PKI therapy in patients with GBM.