Search

Diabetic nephropathy (DN), one of the more prevalent microvascular complications in patients diagnosed with diabetes mellitus, is attributed as the main cause of end-stage renal disease (ESRD). Lipotoxicity in podocytes caused by hyperglycemia has been recognised as a significant pathology change, resulting in the deterioration of the glomerular filtration barrier. Research has demonstrated how dapagliflozin, a kind of SGLT2i, exhibits a multifaceted and powerful protective effect in DN, entirely independent of the hypoglycemic effect, with the specific mechanism verified. In this present study, we found that dapagliflozin has the potential to alleviate apoptosis and restore cytoskeleton triggered by high glucose (HG) in vivo and in vitro. We also discovered that dapagliflozin could mitigate podocyte cholesterol accumulation by restoring the expression of ABCA1, which is the key pathway for cholesterol outflows. This research also mechanistically demonstrates that the protective effect of dapagliflozin can be mediated by KLF-5, which is the upstream transcription factor of ABCA1. Taken together, our data suggest that dapagliflozin offers significant potential in alleviating podocyte injury and cholesterol accumulation triggered by high glucose. In terms of the mechanism, we herein reveal that dapagliflozin could accelerate cholesterol efflux by restoring the expression of ABCA1, which is directly regulated by KLF-5. [ABSTRACT FROM AUTHOR]

Background: Radiocephalic arteriovenous fistula (RCAVF) is the best access modality to be considered initially when planning arteriovenous fistula (AVF) for maintenance hemodialysis. Considering the higher incidence of RCAVF failed maturation (M), it is important to perform proper preoperative evaluation and identification of high-risk patients. There has been no study on the influence of preoperative cardiac function on the M and patency of AVFs. The purpose of this investigation is to determine whether preoperative cardiac index (CI) is a predictor of M and primary patency of RCAVF. Method: A total of 365 end-stage renal disease patients undergoing RCAVF surgery were consecutively enrolled with a median follow-up time of 20 months in this prospective cohort study. Demographics, vascular diameters measured by duplex ultrasound examination, and CI measured by echocardiography, were analyzed for effect on RCAVF primary functional M and primary patency. Result: Patients in the group achieving primary RCAVF functional M had a significantly larger mean CI than the group with early RCAVF failure (2.93 ± 0.77 vs. 3.57 ± 0.76 L/min/m2, p < 0.001). The receiver operating characteristic curve was plotted and demonstrated that preoperative vein diameter and CI can predict failure of RCAVF M. The AUC of CI was higher (0.745 vs. 0.666). Multivariate regression analysis, adjusted for age, sex, diabetes, preoperative dialysis status and vessel diameters, showed that decreased CI remained associated with increased risk of failure of M (FM) and worse primary unassisted patency. The Kaplan-Meier survival analysis suggested that patients with CI <3 L/min/m2 had a worse primary unassisted patency rate at all time points compared with patients with CI ≥3 L/min/m2. Conclusion: This study demonstrated that preoperative CI was associated with RCAVF M and long-term patency. A decreased CI may be a possible predictor of an increased risk of FM and a shorter primary patency time. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN), an important complication of diabetic microvascular disease, is one of the leading causes of end-stage renal disease (ESRD), which brings heavy burdens to the whole society. Podocytes are terminally differentiated glomerular cells, which act as a pivotal component of glomerular filtration barrier. When podocytes are injured, glomerular filtration barrier is damaged, and proteinuria would occur. Dysfunction of podocytes contributes to DN. And degrees of podocyte injury influence prognosis of DN. Growing evidences have shown that epigenetics does a lot in the evolvement of podocyte injury. Epigenetics includes DNA methylation, histone modification, and non-coding RNA. Among them, histone modification plays an indelible role. Histone modification includes histone methylation, histone acetylation, and other modifications such as histone phosphorylation, histone ubiquitination, histone ADP-ribosylation, histone crotonylation, and histone β-hydroxybutyrylation. It can affect chromatin structure and regulate gene transcription to exert its function. This review is to summarize documents about pathogenesis of podocyte injury, most importantly, histone modification of podocyte injury in DN recently to provide new ideas for further molecular research, diagnosis, and treatment. [ABSTRACT FROM AUTHOR]