Objective    To investigate the risk factors of acute kidney injury (AKI) in patients after acute myocardial infarction (AMI).    Methods    A total of 1 371 adult patients diagnosed AMI in the First People's Hospital of Changzhou from January 2008 to December 2012 were analyzed retrospectively. AKI was defined according to the 2012 KDIGO AKI criteria. Based on the occurrence of AKI, the patients were divided into AKI group and non-AKI group. According to the AKI timing, the patients were divided into subgroups including conservative treatment groups, coronary angiography(CAG) groups and coronary artery bypass grafting (CABG) groups, respectively. Related risk factors of AKI were analyzed by univariate and multivariate logistic regression.    Results    Of the 1 371 patients，410(29.9%) developed AKI. Compared to the non-AKI group, in-hospital mortality increased significantly in the AKI group (17.1% vs 3.9%, χ2=68.0, P＜0.001). Multifactor retrospective analysis showed that decreased baseline eGFR (OR=2.049, 95%CI: 1.246-3.370), increased fasting plasma glucose(FPG) (OR=1.070, 95%CI: 1.018-1.124), diuretics (OR=1.867, 95%CI: 1.220-2.856) and Killip class 4 status (OR=1.362, 95%CI: 1.059-3.170) were all independent risk factors of AKI, while increased DBP on admission was a protective factor (OR=0.986, 95%CI: 0.974-0.998) for the conservative management group. Decreased baseline eGFR (OR=2.371, 95%CI: 1.500-3.747), increased FPG(OR=1.009, 95%CI: 1.005-1.012), diuretics (OR=1.674, 95%CI: 1.042-2.690), intraoperative hypotension (OR=2.276, 95%CI: 1.324-3.575) and acute infection (OR=1.678, 95%CI: 1.023-2.754) were independent risk factors of AKI for the CAG group. Decreased baseline eGFR (OR=2.246, 95%CI:1.340-3.981), increased FPG (OR=1.059, 95%CI: 1.018-1.124), diuretics (OR=1.723, 95%CI: 1.122-2.650),  and low cardiac output syndrome after operation (OR=2.331, 95%CI: 1.277-3.286) were independent risk factors of AKI for CABG group.    Conclusions    AKI is a common complication and associated with increased mortality after AMI. Decreased baseline renal function, increased FPG and diuretics were common independent risk factors of AKI after AMI.

Objective    To evaluate the value of serum bicarbonate concentration as a prognostic indicator of renal function by following up the renal function in the acute kidney injury (AKI) patients.    Methods    169 cases of AKI patients were enrolled in the study. Clinical data were collected prospectively. Risk factors of the renal outcome were evaluated. The patients were followed up for average 19 months.    Results    The serum bicarbonate concentration on AKI (r=-0.302, P＜0.001), 3 months after AKI (r=-0.363, P＜0.363), and 6 months after AKI (r=-0.591, P＜0.001) were all negatively correlated with serum creatinine. Compared with renal function recovered group, the serum bicarbonate concentration of renal function unrecovered group on AKI (21.92 mol/L vs 24.58 mol/L), 3 months after AKI (22.58 mol/L vs 25.54 mol/L), 6 months after AKI (21.89 mol/L vs 25.42 mol/L), 12 months after AKI (19.85 mol/L vs 24.07 mol/L) were all significantly decreased (all P＜0.05). When AKI occurred, the Scr, serum bicarbonate concentration, the combined value of Scr and serum bicarbonate concentration to predict prognosis of kidney, area under the receiver-operating characteristic (ROC) curves were 0.840, 0.667, 0.837, sensitivity were 68.6%, 51%, 80.4%, specificity were 88.9%, 80.9% and 73.6%, respectively. 3 months AKI after, the Scr, serum bicarbonate concentration, the combined value of Scr and serum bicarbonate concentration to predict prognosis of kidney, area under the ROC curves were 0.838, 0.732, 0.848, sensitivity was 83.3%、 69.2%、91.7%, specificity were 79.5%, 70.8% and 74.4%, respectively. 6 months the after AKI, Scr, serum bicarbonate concentration, the combined value of Scr and serum bicarbonate concentration to predict prognosis of kidney, area under the ROC curves were 0.948, 0.798, 0.952, sensitivity were 100%, 80%, 100%, specificity were 84%, 80% and 88%, respectively. Combined 3 time points of serum bicarbonate concentration when AKI occurred, 3 month and 6 months after AKI, the area under the ROC curve was 0.850, sensitivity was 85.7%, specificity was 84.2%. When combined 3 time points of the Scr levels of AKI occurred, 3 months and 6 months after AKI, area under the ROC curve was 0.940, sensitivity was 100%, specificity was 84.2%. When combined 3 time points of combined value of Scr levels and serum bicarbonate concentrations of AKI occurred, 3 months and 6 months after AKI, the area under the ROC curve was 0.962, sensitivity was 100% and specificity was 94.7%. The Kaplan-Meier survival curve analysis showed that the serum bicarbonate concentration on AKI＜21.65 mmol/L, serum bicarbonate concentration 3 months after AKI＜24.3 mmol/L or serum bicarbonate concentration 6 months after AKI＜23.5 mmol/L were all significantly correlated with poor renal prognosis. Conclusion    Serum bicarbonate concentration is helpful to predict the renal ont come after AKI.    Combination of serum bicarbonate concentrations and serum creatinine levels increased the accuracy of prediction.

Objective  To study the correlation of serum hepcidin with residual renal function and micro-inflammation state in continuous ambulatory peritoneal dialysis (CAPD) patients.    Methods  Thirty-four stable CADP patients were involved in this study as observers (CAPD group), who had accepted CAPD treatment more than three months; twenty non-dialysis patients with stage 5 of chronic kidney disease were selected as control group. According to the level of high sensitivity Creactive protein (hs-CRP), CAPD patients were divided into two subgroups. There were 14 patients in the hs-CRP elevated group (hs-CRP＞3.00 mg/L) and 20 patients in the hs-CRP normal group. In addition, there had been 14 patients with residual renal function in CAPD group. Serum hepcidin was measured by ELISA. Serum Ferritin (FER), hs-CRP, routine blood and biochemistry were measured by routine methods. Calculated estimated glomerular filtration rate (eGFR). Pearson correlation and linear regression were used to assess the correlation of serum hepcidin with other laboratory parameters in CAPD patients.    Results    (1) Serum hepcidin was significantly higher in CAPD patients than control group, but eGFR was significantly lower (P﹤0.01). (2) Serum hepcidin levels of no residual renal function patients increased more significantly in CAPD group (P﹤0.05). (3) Serum hepcidin levels were higher in hs-CRP elevated group than hs-CRP normal group (P﹤0.05). (4) Pearson correlation analyses revealed that serum hepcidin was positively correlated with hs-CRP (r=0.501) and FER (r=0.847, all P﹤0.01), and was negatively correlated with Hb (r=-0.919), TRF (r=-0.751), TIBC (r=-0.532, all P＜0.05). (5) Multiple linear regression analysis showed that ferritin and hs-CRP were closely associated with serum hepcidin level in CAPD.    Conclusions    Serum hepcidin level markedly elevate in CAPD patients, especially in the patients with no residual renal function and micro inflammatory state increased more significantly.

Objective    To evaluate the association between body-mass index and prognosis in peritoneal dialysis (PD) patients.    Methods    In this observational study of a single nephrology unit in Shanghai East Hospital, 81 incident continuous ambulatory peritoneal dialysis(CAPD) patients were included from Jan 2008 to Dec 2013, whom were followed-up by 36 months or until death. The patients were classified as underweight (BMI＜18.5 kg/m²); normal weight (18.5～23.9 kg/m²); overweight (24～27.9 kg/m²) and obese (BMI≥28 kg/m²). The patients and technique survival rates were estimated by Kaplan-Meier analysis. Cox proportional hazards analyses were used to elucidate relationship between BMI and all-cause mortality and technique failure in PD patients.    Results    The overall survival rate was similar between normal and overweight groups (P=0.96), but significantly lower in underweight group and obese group (P＜0.01 respectively). The overall technical survival rate of obese group was lower compare with normal group (P＜0.01). The main cause of technical failure was peritonitis (81.3%). BMI was positively correlated with albumin (r=0.24, P＜0.05), hemoglobin (r=0.56, P＜0.01), glucose(r=0.23, P＜0.05) and cholesterol (r=0.41, P＜0.01), but negatively correlated with Kt/V (r=-0.36, P＜0.01) and Ccr(r=-0.34, P＜0.01). In adjusted Cox proportional hazard mode 3, obese was independently associated with all-cause mortality (HR: 5.93, 95%CI: 1.10～31.79). Obese and peritonitis were independently associated with technical failure (HR: 10.33, 95%CI: 1.04～78.02 and HR: 2.74, 95%CI: 1.17～6.40 respectively).    Conclusions    Underweight and obese CAPD patients have poorer outcome. Obese CAPD patients also have lower technical survival rate. Obesity was an independent risk factor for all-cause mortality in CAPD patients.

Objective    To determine the effect of rapamycin on sublytic C5b-9-induced podocyte adhesion damage, and whether autophagy is involved in this progression.    Methods    Sublytic complement C5b-9 stimulation was used in vitro. Autophagosomes were viewed using electron microscopy. Western blotting was used to measure the change of autophagy-related markers. Attachment assay was used to assess the adhesion of podocyte. Confocal microscopy was used to explore the expression patterns of cytoskeletal protein F-actin. Flow cytometry was used to measure the level of adhesion-associated protein integrin α3.    Results    (1) For ensuring sublytic complement injury, the maximal amounts of anti-podocyte antiserum and 160×-diluted normal human serum were used without inducing cell lysis (defined as ＞5% LDH release). (2) Sublytic C5b-9 promoted autophagy in podocyte in vitro. The proautophagic effect of sublytic C5b-9 manifested in the form of accumulated autophagosomes and enhanced expression of LC3-Ⅱ. (3) Inhibition of autophagy by 3-methyadenine enhanced the effect of sublytic C5b-9-induced podocyte injury, including serious cytoskeleton damage and markedly reduced adhesion of podocyte. (4) Rapamycin treatment significantly improved the above lesions. (5) Rapamycin enhanced autophagy induced by sublytic C5b-9 in podocyte.    Conclusions    In summary, rapamycin can improve sublytic C5b-9-induced podocyte adhesion damage by appropriate autophagy activation. These findings provide important information for the development of appropriate protocols for the application of mTOR (mammalian target of rapamycin) inhibitors in podocytopathy.

Objective    To study the effect of macrophage on the repair phase of ischemic/reperfusion (IR) renal injury in mice.    Methods    A total of 24 C57BL/6 mice aged 6～8 week-old were divided into 4 groups: the Sham group, IR group, LC group and Control group. For all the groups, the bilateral renal pedicles of the mice were clipped after dorsal skin dissection, except for the Sham group, then unclipped them 25 minutes later to restore blood flow to the kidney and collected the renal specimens after 3 days. The LC group and Control group each were injected intraperitoneally with 0.15～0.20 ml/20 g per day before kidney specimens were taken. The morphology changes of renal tissues were evaluated by HE staining. Immunohistochemical testing was performed to detect the infiltration of macrophages, the expression change of Ki67, TNF-α and IL-10. In addition TNF-α, IL 10 were measured using Western blotting.    Results    Compared to the IR group and the Control group, the infiltration of macrophages was markedly decreased, the damage of renal pathology was aggravated, the cell proliferation was significantly decreased, and the expression of IL-10 was also decreased (P＜0.05), while the expression of TNF-α were increased (P＜0.05).    Conclusions    Intraperitoneal LC injection can aggravate kidney damage on the repair phase of renal ischemic/reperfusion injury in mice, which is possibly related its inhibition of proinflammatory cytokines TNF-α and the secretion of anti-inflammatory cytokine IL-10.

Objective    To investigate the effect of parathyroid hormone (PTH) on the epithelial to mesenchymal transition (EMT) in human renal proximal tubular epithelial cells (HK-2 cells), and determine the role of β-catenin signaling pathway.    Method    The expression of α-smooth muscle actin (α-SMA), E-cadherin and β-catenin in HK-2 cells was measured by real-time PCR, Western blotting and immunofluorescence technique. The signaling pathway by which PTH activated EMT in HK-2 cells was identified by using synthetic β-catenin siRNA.    Results    Parathyroid hormone (10^-10 mol/L) increased α-SMA expression and decreased E-cadherin expression in HK-2 cells (P＜0.01, respectively). Untreated cells showed the expression of E-cadherin, whereas α-SMA staining was noticeably increased in cells treated with PTH. β-catenin activity was significantly increased after exposed to PTH. Theα-SMA expression was decreased strongly and E-cadherin expression was increased after β-catenin siRNA transfection (all P＜0.05).    Conclusion    PTH significantly induces epithelial to mesenchymal transition in HK-2 cells throughβ-catenin signaling pathway.

Objective    To investigate the effect of astragaloside IV (AS-IV) on renal tubulointerstitial fibrosis and its regulation on p38 MAPK signaling. Methods  In vivo, UUO model with renal tubulointerstitial injury was constructed. Mice in AS-IV group were orally administrated AS-IV 20 mg•kg^-1•d^-1 for 7 days after operation, and mice in other groups were administrated the equal volume vehicle. Bilateral kidneys were collected in 7 and 14 days after operation. Transverse kidney slices were stained with Masson trichrome to evaluate the severity of renal tubule injury. In vitro, normal human renal tubular epithelial cells (HK-2) were stimulated with recombinant TGF-β1 (10 ng/ml) and simultaneously treated with different concentrations of AS-IV (0, 50, 100, 200 μg/ml) for 24 h. SB203580 (10 μmol/L) was also ultilized to pre-treat HK-2 cells for 1 h to inhibit phosphorylation of p38 MAPK signaling. The expression of FN, Col IV, and α-SMA were investigated by western blotting and real-time PCR. The expression of p-p38 MAPKs were also observed by Western Blotting.    Results  Astragaloside IV morphologically ameliorated renal tubulointerstitial fibrosis. The proteins and mRNA expression of FN, Col IV, α-SMA, and TGF-β1 were also increased significantly in UUO kidney tissues (all P＜0.05), which could be reversed by AS-IV administration (all P＜0.05). In vitro, the expression of FN, Col IV, and α-SMA were up-regulated by TGF-β1 after stimulating for 24 h (all P＜0.05), which were decreased by AS-IV. The inhibition effect on FN and α-SMA were similar between AS-IV and MAPK inhibitor SB203580. AS-IV inhibited p-p38 MAPK signals both in vivo and in vitro.    Conclusions    AS-IV could attenuate renal tubulointerstitial fibrosis induced by UUO and TGF-β1 through reducing FN、Col IV、α-SMA expression in renal tubular cells. The mechanism of AS-IV protective effect might be associated with inhibition of p38 MAPK phosphorylation.

Objective    To investigate the effects and underlying mechanism of calcitriol on ameliorating podocytes impairment in DN rats.    Methods    SD rats were randomly divided into four groups: normal control (NC) group, calcitriol treatment (VD) group: calcitriol 0.1μg•kg^-1•d^-1, diabetic nephropathy (DN) group: streptozocin (STZ) 58 mg/kg, DN treated with calcitriol (DN+VD) group：calcitriol 0.1 μg•kg^-1•d^-1 + STZ 58 mg/kg. Rats were sacrificed at the end of 18 weeks.    Results    Compared with the DN group, the DN+VD group exhibited significantly lower proteinuria by 36%,  improved renal histology at the end of the experiment (P＜0.05), and similar levels of blood glucose，serum urea nitrogen as well as body weight (P＞0.05). There were no significant differences in the serum concentrations of creatinine, calcium and phosphorus among the four groups (P＞0.05). In DN group, the expressions of nephrin, podocin, VDR, PI3K-p85 and p-Akt were significantly decreased and the expression of desmin was increased compared to NC group. Calcitriol treatment could attenuate the above changes. Additionally, a positive correlation was observed between the expressions of nephrin and VDR (r=0.776, P＜0.05). Likewise, the expression of nephrin was positively correlated with either PI3K-p85 or p-Akt (r=0.736, r=0.855, all P＜0.05).    Conclusion    Calcitriol can ameliorate podocytes injury in DN rats, which might be related with the further up-regulation of PI3K/p-Akt signaling pathway.