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Objective:To investigate the incidence of acute kidney injury (AKI) following cardiac surgery and related risk factors in 4 878 patients.Methods:The information from patients who underwent cardiac surgery through March 2015 to October 2015 was collected retrospectively from the electronic database of Beijing Anzhen Hospital. A total of 4 878 patients were divided into AKI group and non-AKI group according to whether AKI occurred within 7 days after cardiac surgery. The incidence of AKI was calculated, and the AKI incidence in different types of cardiac surgeries were compared. Clinical data such as baseline clinical information, operation information, comorbidity, hospital stay time, life ability score in discharge from the hospital, and so on, were compared between AKI group and the non-AKI group using univariate analysis. Risk factors for AKI following cardiac surgery were analyzed using the binary multivariate logistic regression.Results:A total of 933 patients suffered from AKI (19.1%) following cardiac surgery. The time of stay in the hospital was longer in AKI group than that in the non-AKI group [(14.4±8.9) vs (13.7±7.7) d, P<0.05)]. The incidence of AKI in different types of cardiac surgeries varied significantly ( P<0.001). The logistic regression analysis showed that male, diabetes, hypertension, the elevated basic serum creatinine, cardiac dysfunction (NYHA grade≥Ⅲ), cardiopulmonary bypass, a combination of operations≥3, the rethoracotomy exploration and hemostasia, and using an invasive ventilator for over 96 hours were the independent risk factors for the AKI following cardiac surgery (all P<0.05), and the odds ratio (95% confidence interval) were 1.81(1.46-2.24), 1.29(1.03-1.62), 5.85(4.73-7.22), 1.81(1.36-2.40), 4.49(3.60-5.60), 1.84(1.49-2.27), 23.24(18.25-29.59), 2.34(1.45-3.77) and 1.94(1.09-3.43) respectively. Conclusions:The incidence of AKI after cardiac surgery in Beijing Anzhen Hospital is 19.1%. AKI following cardiac surgery prolongs the time of stay in the hospital. Independent risk factors for AKI following cardiac surgery are multiple, and one of the most critical factors is a combination of operations≥3.
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Objective To investigate the influence of earlier renal fibrosis on ischemia and reperfusion induced acute kidney injury. Methods Male C57BL/6 mice at eight to twelve weeks old age were divided into 4 groups randomly: (1)Sham (n=3); (2)Unilateral ureter obstruction (UUO, n=6):UUO for 3 days (UUO3d, n=3) and UUO for 5 days (UUO5d, n=3);(3)Ischemia and reperfusion (IR, n=7): bilateral kidney ischemia for 40 minutes followed by 24 hours of reperfusion; (4)UUO for 3 days plus IR (UUO3d+IR, n=6): bilateral kidney ischemia after UUO 2 days for 40 minutes followed by 24 hours of reperfusion, and the real time for UUO was 3 days. Pathologic analysis for acute or chronic injury was performed on paraffin embedded kidney sections with hematoxylin and eosin (HE) or Masson staining. Apoptosis was detected by immunohistochemistry(IHC) and Western blotting with anti-caspase-3 antibody, and proliferation was observed by IHC with anti-ki67 antibody. Results On kidney sections with HE or Masson staining, it showed that the chronic kidney lesions and fibrosis got more severe as time of UUO prolonged from 3 days to 5 days; the area of matrix deposition increased in UUO5d and UUO3d mice significantly compared to Sham mice (P<0.05) and was smaller in UUO3d mice compared with UUO5d mice obviously (P<0.05). Acute kidney injury could be observed in UUO3d+IR mice, such as massive inflammatory cells infiltration, tubules dilation, brush border disappearance, tubular epithelial cells vacuolar degeneration, necrosis, casting formation, coexisting with chronic lesions: thinner cortex, broadened interstitial space, and increased blue stained matrix. Acute kidney injury score in UUO3d+IR mice was higher than that in IR mice significantly (P<0.05), and serum creatinine level increased significantly in UUO3d+IR mice compared to Sham mice (P<0.05). Caspase-3 expression increased and ki67 positive tubular cells decreased in UUO3d+IR mice than those in IR mice obviously (P<0.05). Conclusion Earlier renal fibrosis aggravates acute kidney injury induced by ischemia reperfusion in mice through increasing apoptosis and decreasing proliferation of tubular epithelial cells.
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Objective To investigate the inhibitory effect and associated mechanism of rapamycin on proliferation and extracellular matrix (ECM) secretion in myofibroblasts stimulated by connective tissue growth factor (CTGF). Methods Primary cultivated myofibroblasts were divided into 6 groups: control, CTGF (100 μg/L), rapamycin 20 μg/L+CTGF 100 μg/L, rapamycin 40 μg/L +CTGF 100 μg/L, rapamycin 20 μg/L, and rapamycin 40 μg/L alone. 5'-bromodeoxyuridine (BrdU) incorporation assay was used to detect the myofibroblast proliferation.Western blot was used to analysis the secretory FN protein in the supernatant medium of cultured myofibroblasts and the ERK1/2 phosphorylation in myofibroblasts. Results CTGF (100 μg/L)incubation significantly increased the number of Brdu positive myofibroblasts(P<0.01) and the level of FN protein secretory (P<0.05) in cell supernatant medium compared with control group,respectively. The number of Brdu positive myofibroblasts markedly decreased by 62% and 70% (P <0.05) in rapamycin 20 μg/L+CTGF 100 μg/L and rapamycin 40 μg/L+CTGF 100 μg/L groups, respectively. The FN protein levels in supernatant were decreased by 15% and 44% compared with CTGF 100 μg/L group, respectively; but the difference of FN protein levels was significant only in rapamycin 40 μg/L group (P<0.05). CTGF could activate ERK1/2 at 10 minutes; but as myofibroblasts were pretreated with rapamycin 40 μg/L for 30 min, it abolished CTGF-induced ERK1/2 phosphoralation. PD98059, the specific inhibitor of ERK1/2, could block the effect of CTGF-induced proliferation (7%±5% vs 85%±7%, P<0.01) and FN secretion (1.0±0.1 vs 1.6±0.3, P<0.05). Conclusions Rapamycin partially suppresses the proliferation and ECM secretion of myofibroblasts induced by CTGF. Its effect may be through inhibiting CTGF-induced activation of ERKI/2 signaling pathway.
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AIM: To investigate the anticoagulant effect of pravastatin and low molecular weight heparin (LMWH), as well as their combination, over time, in a rat model of experimental nephrotic syndrome. METHODS: Healthy SD male rats were chosen randomly to perform nephrotic syndrome models by single injection of adriamycin via tail vein, the matched normal control rats received single injection of equivalent 0.9% sodium chloride instead. After 14 days, the models were set up and randomized into model control group, pravastatin group (pravastatin 2 mg·kg-1·d-1 gavage once a day), LMWH group(LMWH 200 U·kg-1·d-1 intraperitoneal injection once a day) and combined treatment group(pravastatin 2 mg·kg-1·d-1 gavage+ LMWH 200 μ·kg-1·d-1 intraperitoneal injection), then all rats underwent measuring proteinuria every two weeks and fibrinogen, antithrombinⅢ(ATⅢ), D-dimer, platelet count, serum total protein and serum albumin after 4 weeks of treatment. RESULTS: The concentration of fibrinogen and D-dimer in model group was higher significantly than that in control group, and the level of ATⅢ was lower remarkably than that in control group, but platelet count had no obvious change; Compared with model group, pravastatin could increase the level of ATⅢ and decrease the concentration of D-dimer, but the concentration of fibrinogen and platelet count did not change obviously; LMWH and combined treatment could also decrease level of D-dimer, but had no great effects on ATⅢ, fibrinogen and platelet count; all treatment group had no obvious change of serum total protein and serum albumin. CONCLUSION: Adriamycin-induced nephrotic syndrome rat models have hypercoagulability and pravastatin can increase the level of ATⅢ.