Background: Astragaloside IV (AS-IV) was reported to play a role in improving diabetic nephropathy (DN), however, the underlying mechanisms still remain unclear. The aim of the present study is to investigate whether AS-IV ameliorates DN via the regulation of endothelial nitric oxide synthase (eNOS).Methods: DN model was induced in Sprague-Dawley (SD) male rats by intraperitoneal injection of 65 mg/kg streptozotocin (STZ). Rats in the AS-IV treatment group were orally gavaged with 5 mg/kg/day or 10 mg/kg/day AS-IV for eight consecutive weeks. Body weight, blood glucose, blood urea nitrogen (BUN), Serum creatinine (Scr), proteinuria and Glycosylated hemoglobin (HbA1c) levels were measured. Hematoxylin-Eosin (HE) and Periodic Acid-Schiff (PAS) staining were used to detect the renal pathology. The apoptosis status of glomerular cells was measured by TUNEL assay. The phosphorylation and acetylation of eNOS were detected by western blot. The effects of AS-IV on high-glucose (HG)-induced apoptosis and eNOS activity were also investigated in human renal glomerular endothelial cells (HRGECs) in vitro.Results: Treatment with AS-IV apparently reduced DN symptoms in diabetic rats, as evidenced by reduced BUN, Scr, proteinuria, HbA1c levels and expanding mesangial matrix. AS-IV treatment also promoted the synthesis of nitric oxide (NO) in serum and renal tissues and ameliorated the phosphorylation of eNOS at Ser 1177 with decreased eNOS acetylation. Moreover, HG-induced dysfunction of HRGECs including increased cell permeability and apoptosis, impaired eNOS phosphorylation at Ser 1177, and decreased NO production, were all reversed by AS-IV treatment.Conclusions: These novel findings suggest that AS-IV ameliorates functional abnormalities of DN through inhibiting acetylation of eNOS and activating its phosphorylation at Ser 1177. AS-IV could be served as a potential therapeutic drug for DN.

Aims: About 20–40% patients with type 2 diabetes mellitus (T2DM) had an increased risk of developing diabetic nephropathy (DN). Dipeptidyl peptidase-4 inhibitors (DPP-4i) were recommended for treatment of T2DM, while the impact of DPP-4i on renal function remained unclear. This study aimed to explore the effect of DPP-4i on renal parameter of estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) in T2DM. Methods: A systematic search was performed across PubMed, Embase and Cochrane Library. A fixed or random-effects model was used for quantitative synthesis according to the heterogeneity, which was assessed with I² index. Sensitivity analysis and publication bias were performed with standard methods, respectively. Results: A total of 17 randomized controlled trials were identified. Administration of DPP-4i produced no significant effect on eGFR (WMD, -0.92 mL/min/1.73m², 95% CI, -2.04 to 0.19) in diabetic condition. DPP-4i produced a favorable effect on attenuating ACR (WMD, -2.76 mg/g, 95% CI, -5.23 to -0.29) in patients with T2DM. The pooled estimate was stable based on the sensitivity test. No publication bias was observed according to Begg’s and Egger’s tests. Conclusions: Treatment with DPP-4i preserved the renal parameter of eGFR in diabetic condition. Available evidences suggested that administration of DPP-4i produced a favorable effect on attenuating ACR in patients with T2DM. International Prospective Register for Systematic Review (PROSPERO) number: CRD.42020144642.

Background. The efficacy of clopidogrel is often attenuated in the setting of renal impairment. High on-treatment platelet reactivity (HPR) is an independent correlate of adverse event. Here we performed a quantitative evaluation of the prevalence and impact of HPR in patients with chronic kidney disease (CKD). Methods. We systematically searched PubMed, EMBASE and the Cochrane Library from their inception to 1 March 2018 for cohort studies assessing the risk ratio (RR) of prevalence of HPR in CKD versus non-CKD patients and association of cardiovascular outcome with HPR in CKD patients treated with clopidogrel. Outcome measures included major adverse cardiac event, myocardial infarction and stent thrombosis. RRs and 95% confidence intervals (CIs) were used as estimates of effect size in random-effect models. Results. Ten studies comprising a total of 3028 CKD patients and 11138 non-CKD patients were included in the evaluation. Compared to patients with normal renal function, patients with CKD had a significantly higher risk of HPR (OR: 1.34, 95% CI: 1.23-1.46). In CKD patients, HPR was associated with increased risk of MACE (RR 2.99, 95% CI 1.19 to 7.53; p < 0.00001), myocardial infarction (RR1.74, 95% CI 1.29 to 2.33; p = 0.0002), and stent thrombosis (RR 2.98, 95% CI 1.42 to 6.26; p = 0.004). Conclusions. Based on pooled analysis, CKD appeared correlated with HPR and this association had prognostic significance. Further studies with standardised laboratory methods and specifically defined protocols are required to validate the clinical relevance of such response variability to clopidogrel in CKD patients.

Objective: To investigate the association of short-term blood pressure variability (BPV) with cardiovascular mortality in hemodialysis (HD) patients, using a reliable index called average real variability (ARV), and to assess the factors associated with ARV in incident HD population. Methods: A total of 103 HD patients were recruited, with 44-h ambulatory blood pressure monitoring performed after the midweek HD session. Systolic BPV was assessed by SD, coefficient of variation (CV), and ARV, respectively. Laboratory data were obtained from blood samples before the midweek HD. All patients were followed up for 24 months. Results: According to the median of BPV indices, the comparisons between patients with the low and high values were conducted. Kaplan–Meier analysis showed the survival curves corresponding to median of SD and CV exhibit similar performance for the low and high groups (p = .647, p = .098, respectively). In contrast, patients with higher ARV had a lower survival rate than those with lower ARV (77.8% vs. 98.0%, p = .002). After adjustment for demographics and clinical factors, ARV (HR: 1.143; 95% CI: 1.022–1.279, p = .019) and high-sensitivity C-reactive protein (HR: 1.394; 95% CI: 1.025–1.363, p = .021) were associated with increased risk of cardiovascular mortality in HD patients. Age and interdialytic weight gain (IDWG) were related factors for ARV (β = 0.065, p = .005; β = 0.825, p = .003, respectively). Conclusions: Greater ARV was independently associated with increased risk of cardiovascular mortality in HD patients. Age and IDWG were independent related factors for ARV.