Search

This study tested the hypothesis that exendin-4 (Ex4) protects kidneys against ischemia-reperfusion (IR) injury mainly through upregulation of nuclear-factor erythroid 2-related factor 2 (Nrf2) signaling and downregulation of oxidative stress. Male-adult Sprague-Dawley rats (n=24) were equally divided into group 1 (sham-operated control), group 2 [IR only, ischemia (1 h)/reperfusion (72 h)] and group 3 (IR-Ex4, 10 μg/kg at 30 min, 24 h, 48 h after IR procedure). The in vitro study demonstrated that the protein expressions of phosphorylated (p)-Akt and Nrf2 were significantly progressively increased at time points of 0/0.5/1/3 h and 0/0.5/1/3/6/12/24 h, respectively in NRK-52E cells co-cultured with Ex4 (20 nM) (all P<0.0001). Additionally, the protein expressions of NOX-1/NOX2 were significantly increased, whereas p-Akt was significantly decreased in NRK-52E cells co-cultured with P-cresol (200 μM) that were significantly reversed after Ex4 treatment (all P<0.0001). As compared with baseline, the creatinine level, left/right kidney weight and MCP-1-positively stained area in the kidney parenchyma were significantly increased at 24 h after the IR procedure and significantly progressively decreased after that (all P<0.0001). By 27 h after IR, creatinine level/MCP-1 + area was significantly higher in group 2 than in groups 1 and 3, and significantly higher in group 3 than in group 1 (all P<0.0001). The numbers of Nrf2 +/NQO-1 + cells/SOD activity in kidney parenchyma were significantly lower in group 2 than in groups 1 and 3, and significantly lower in group 1 than in group 3 (all P<0.0001). In conclusion, Ex4 protected kidney from IR injury through upregulating antioxidants and downregulating inflammation/oxidative stress., Competing Interests: None.

Greater variability in renal function is associated with mortality in patients with chronic kidney disease (CKD). However, few studies have demonstrated the predictive value of renal function variability in relation to renal outcomes. This study investigates the predictive ability of different methods of determining estimated glomerular filtration rate (eGFR) variability for progression to renal replacement therapy (RRT) in CKD patients. This was a prospective observational study, which enrolled 1,862 CKD patients. The renal end point was defined as commencement of RRT. The variability in eGFR was measured by the area under the eGFR curve (AUC)%. A significant improvement in model prediction was based on the -2 log likelihood ratio statistic. During a median 28.7-month follow-up, there were 564 (30.3%) patients receiving RRT. In an adjusted Cox model, a smaller initial eGFR AUC%&#95;12M (P < 0.001), a smaller peak eGFR AUC%&#95;12M (P < 0.001), and a larger negative eGFR slope&#95;12M (P < 0.001) were associated with a higher risk of renal end point. Two calculated formulas: initial eGFR AUC%&#95;12M and eGFR slope&#95;12M were the best predictors. Our results demonstrate that the greater eGFR variability by AUC% is associated with the higher risk of progression to RRT.

Chronic hypoxia has been recognized as a common mechanism driving the progression of many glomerular diseases. Glomerular cells, although susceptible to hypoxic injuries, are less studied to unravel the hypoxia-related influences. In the present study, we showed that both lipopolysaccharide (LPS) and hypoxia induced B7-1 and hypoxia-inducible factor (HIF)-1α expression in podocytes. B7-1, an essential player in the regulation of podocyte stress fibers, interacted directly with the NH(2)-terminal oxygenation domain of HIF-1α protein and, therefore, might interfere with the HIF-related oxidative events. The suggestion was supported by the changes in the expression of inducible nitric oxide synthase and nitric oxide. The orderly arranged stress fibers in differentiated podocytes were disrupted by either LPS or hypoxic stimulation, and the disruption could be rescued if they were brought back to normal oxygen tension. Cell motility increased with the stimulation by LPS and hypoxia, most probably mediated by the induction of B7-1 and HIF-1α, respectively. We generated a B7-1 knockdown podocyte cell line using the lentiviral small interfering RNA system. The LPS- and hypoxia-induced stress fiber disruption was largely prevented in the B7-1 knockdown podocytes. The increased cell motility by LPS and hypoxia stimulations was also ameliorated in the B7-knockdown podocytes. In summary, we found that both B7-1 and HIF were upregulated by LPS and hypoxic stimulations in podocytes and they interacted with each other. Hypoxia disrupted the abundant stress fibers and increased cell motility. These hypoxia-induced changes were prevented in B7-knockdown podocytes, and they highlighted the importance of B7-1 expression in the hypoxia-related podocyte injuries.

Objective: False elevation of blood glucose levels measured by glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ)-based glucose self-monitoring systems; glucometer) in peritoneal dialysis (PD) patients using icodextrin solution has been well documented. However, adverse hypoglycemic events caused by misreadings for blood glucose are still being reported. We aimed to study blood glucose levels measured simultaneously using different methods in PD patients with switching of icodextrin, and throughout daily exchanges either using icodextrin or not., Design: We recruited 100 PD patients, including 40 using icodextrin; 128 hemodialysis patients served as a reference. Fasting serum glucose was measured using our laboratory reference method (LAB) and 2 glucose self-monitoring systems based on glucose dehydrogenase nicotinamide adenine dinucleotide (GDH-NAD) and GDH-PQQ respectively. 80 PD patients had a second follow-up study. A time course study was performed in 16 PD patients through measuring fingertip glucose using the 2 glucose self-monitoring systems during daily exchanges., Result: The differences in measured serum glucose levels in (PQQ minus LAB) versus (NAD minus LAB) were markedly increased in PD patients using icodextrin compared to other patient groups, and was further confirmed by the follow-up study in patients that switched to icodextrin. The high serum glucose levels measured by the GDH-PQQ-based glucose self-monitoring system were present throughout all exchanges during the day in patients using icodextrin solution., Conclusion: False elevation of blood glucose measured by GDH-PQQ-based glucose self-monitoring systems exists in patients using icodextrin. To avoid misinterpretation of hyperglycemia and subsequent over-injection of insulin, GDH-PQQ-based glucose self-monitoring systems should not be used in PD patients.