Objective    To raise the awareness of acute kidney injury (AKI) and improve the level of diagnosis.    Methods    All the hospitalized adult patients in the Affiliated People's Hospital  of Shanxi Medical University from January 2012 to July 2013 were screened. Those patients diagnosed as AKI were retrospectively analyzed in terms of incidence, the rate of missed diagnosis, etiology, distribution and prognosis of AKI.    Results    (1) The incidence of AKI in the patients was 0.67% (381/56 835), the ratio of male to female was 1.91∶1, and the average age was (63.45±16.95) years. (2)There were 321 cases diagnosed as pre-renal AKI (84.25%), 42 cases diagnosed as renal AKI (11.02%) and 18 cases diagnosed as post-renal AKI (4.72%). (3)There were 189 cases(49.61%) missed diagnosed among all the screened cases. The rates of missed diagnosis in neurosurgery, general surgery and cardiac surgery department was 62.96%, 59.09% and 50.00%, in cardiology, respiratory and neurology department was 50.00%, 50.00% and 45.45% respectively. (4) Multivariate Logistic regression analysis showed that hypertension [odds ratio(OR)=1.631], renal replacement therapy(RRT)(OR=23.256) and oliguria history (OR=1.936) were independent risk factors of missed AKI diagnosis． Conclusion    The missed diagnosis rate of AKI is high and has certain characteristics in different departments. Hypertension, RRT and oliguria history are independent impact factors of missed AKI diagnosis．

Objective    To analyze the relationship between renal pathological characteristics and clinical prognosis in type 2 diabetic kidney disease patients, and discuss predictive value of pathological type and indexes for renal function declining rate and related outcome events.    Methods    Ninety-two type 2 diabetes patients from PUMC Hospital (with macroalbuminuria and followed up no less than 6 months, excluding patients with non-diabetic renal disease) were divided into typical diabetic glomerulopathy group (DG, n=51) and atypical diabetes-related renal disease group(ADRD, n=41) according to renal pathological findings. A retrospective cohort study was performed to investigate renal pathological features and prognosis.    Results    Total of 29 renal outcome events and 12 death events occurred in DG group and none in ADRD group; the survival rate and kidney survival rate are different between two groups (P＜0.05); DG group, thick GBM, severe vascular and tubular lesion are predicative indicators for renal outcome event; mesangial volume fraction is predicative indicator for renal outcome events independent of age and serum creatinine.    Conclusions    DG and ADRD patients have different prognosis and might undergo different pathophysiological mechanisms; renal pathological type and mesangial volume fraction could help predicting outcomes of type 2 diabetic nephropathy patients.

Objective    To evaluate the effect and safety of the combination of lanthanum carbonate and calcium carbonate in controlling the phosphate level of hemodialysis patients with hyperphosphatemia.    Methods    Seventy-three patients who developed hyperphosphatemia after hemodialysis were involved, and of which twelve patients complicated with hypercalcemia were put in the group without calcium. The other patients were divided into 3 groups: 21 patients in calcium carbonate group, 32 patients in lanthanum carbonate group and 20 patients in combination group. All the subjects took blood test every month.    Results    The level of phosphorus decreased in all the subjects participated in the trial (P＜0.01). The level of phosphatemia in combination group decreased dramatically (P＜0.01) and had little effect on calcium and parathyroid hormone. Osteoporosis and valvular calcification were the same as the begin of the trial.    Conclusions    The combination of lanthanum carbonate and calcium carbonate is more effective than alone. The incidences of adverse effects such as gastrointestinal, hypercalcemia, nausea, vomiting and constipation are low.

objective    To investigate the value of NT-proBNP in assessing the volume status in maintenance hemodialysis patients with non-dominant edema.    Methods    One hundred and forty-five patients were recruited. Bioimpedance measurements were performed for overhydration (OH). NT-proBNP was detected by colloidal gold method. Patients were divided into three groups by levels of OH variability (△OH, equal to OH minus weight increase) as group H (hypervolemia, n=90); group N (normovolemia, n=36) and group L (hypovolemia, n=19). Hemoglobin，albumin，blood urea nitrogen and serum creatinine were assayed, blood pressure and body mass increase were recorded. Dry weight of patients in Group H were adjusted in 3 months，the relationship between NT-proBNP and volume change were assessed.    Results    (1) At baseline, overall plasma NT-proBNP levels were higher than normal range. The median NT-proBNP levels in group H and group N were [1318.50(IQR 717.00, 3154.25) pg/ml] and [703.50 (IQR 873.00, 450.50) pg/ml], respectively. NT-proBNP was positively correlated with △OH value (r=0.801, P＜0.001). (2) After 3 months, NT-proBNP levels in group H was significantly lower than baseline. Forty-one patients reached normal volume range (group H1), 49 patients were resistant hypervolemia (group H2). The median NT-proBNP levels in group H1 and group H2 were [685.00 (IQR 422.50, 988.50) pg/ml] and [1569.00 (IQR 982.50, 2500.50) pg/ml], △OH in group H1 and group H2 were [(0.63±0.23)L] and [(1.75±0.71)L], respectively. NT-proBNP and △OH value in two groups had significant difference (P＜0.05). NT-proBNP was positively correlated with     △OH value (r=0.684, P＜0.001). (3) The area under ROC curve for NT-proBNP was 0.818，95%CI(0.733～0.904)，P＜0.001, since the absolute value of normovolemia was defined as ≤1. The cut off value of plasma NT-proBNP was set at 962.50 pg/ml in MHD patients with non-dominant edema, the diagnostic specificity and sensitivity were 79.6% and 73.2%.    Conclusion    NT-proBNP could be used to assess volume status in MHD patients with non dominant edema.

Objective    To evaluate the associated factors about cardiovascular disease and survival among maintenance hemodialysis patients.    Methods    The newly diagnosed patients with ESRD in the 44th hospital of People's Liberation Army and Changzheng hospital during the period of 2008-2012 were analyzed retrospectively. The baseline variables and laboratory results were collected. Cardiovascular disease and survival were recorded. Logistic regression and multivariate COX regression were used to detect the relative factors.    Results    A total of 158 patients were included in the study. The mean age was 54.61±16.98. Cardiovascular complications were recorded in 40 cases. Heart and coronary artery disease were recorded 24 cases, strokes were recorded in 16 cases. Cox proportional hazards regression model showed that age (HR=1.051, 95%CI:1.023-1.081), male (HR=6.025, 95%CI:2.571-14.121), increased neutrophile granulocyte(%) (HR=1.073, 95%CI:1.028-1.121), increased LDL (HR=1.562, 95%CI:1.058-2.305), high calcium concentration dialysate (HR=5.025, 95%CI:1.163-21.739) were risk factors for cardiovascular disease. Compared to conventional hemodialysis, in-center nocturnal hemodialysis was a protective factor (HR=0.288, 95%CI:0.090-0.924). In our study, 7 patients died. After adjusted to multiple variances, we found diabetes was a risk factor for survival (HR=15.385, 95%CI：1.692-145.851). Compared to conventional hemodialysis, hemodiafiltration may reduce the risk of CVD (HR=0.145, 95%CI:0.021-1.016, P=0.052).    Conclusions    To maintenance hemodialysis patients, age, male gender, the percent of neutrophile granulocyte, LDL, high calcium concentration dialysate are risk factors for CVD. In-center nocturnal hemodialysis reduces the risk of CVD. Diabetes increase the risk of death, while hemodiafiltration may reduce the risk of death.

Objectives    To study the efficacy of the two-compartment peritoneal dialysis fluid with low glucose degradation products in peritoneal dialysis (PD) patients.    Methods    Pubmed, EBMASE,Cochrane Library, Wanfang, VIP, CNKI, CBM and other databases were searched, at the same time the information form relevant literatures until December 2013 were searched by hand. To be eligible, studies had to be randomized controlled trials that allocated PD patients to two-compartment peritoneal dialysis fluid with low glucose degradation products (low-GPDs group) or to traditional dialysis fluid (control group). The qualities of included articles were assessed and then a meta-analysis was conducted by using RevMan 5.2 software.    Results    A total of 12 documents, 11 studies met the inclusion criteria, and 1 059 cases were included. Meta-analysis results were as follows: (1)the low-GPDs group had higher level of CA125 in peritoneal dialysis effluent, higher residual renal function compared with that in the control group and the weighted mean difference were 19.61 (95%CI 12.04-27.18, P＜0.01) and 0.78 (0.14-1.43, P=0.02), respectively; (2)There was no statistically significant difference between control and low-GPDs group in the ultrafiltration, peritonitis and plasma bicarbonate (all P＞0.05); (3)Four studies showed no difference in peritoneal dialysis technique survival between the two group (P＞0.05).    Conclusions    The two-compartment peritoneal dialysis fluid with low glucose degradation products is effective and safe, has no negative effects on the frequency of peritonitis, patient’s peritoneal member transport function and plasma bicarbonate, but it causes less mesothelial damage and has higher residual renal function in patients than conventional ones, and does not affect the technique survival time.

Objective    To study the relationship of angiotensin II type 1 receptor (AT1R) autoantibody (AT1-AA) and renal cell apoptosis induced by caspase-12 in diabetic nephropathy (DN) rats.    Methods    High-sucrose and high-fat diet and intraperitoneal injection of streptozotocin  (35 mg/kg) were utilized to establish DN rat model. Serum AT1-AA was detected by enzyme-linked immunosorbent assay (ELISA) and renal cell apoptosis was detected by TUNEL staining. Furthermore, the mRNA levels of the endoplasmic reticulum stress (ERS) chaperone protein glucose regulated protein 78 (GRP78) and ERS-associated apoptosis protein caspase-12 were measured by real-time quantitative PCR. Additionally, the levels of GRP78 and caspase-12 protein were measured by Western blotting.    Results    The renal cell apoptosis rate in DN group was increased significantly (P＜0.01), and the  renal cells apoptosis rate in AT1-AA positive DN group was higher than that in AT1-AA negative DN group [(20.05±1.71)% vs (13.24±4.93)%, P＜0.01]. The mRNA expressions of GRP78 and caspase-12 in DN group, in comparison to NC group, were increased significantly (P＜0.01), as well as the proteins (P＜0.01). And the expression of these mRNA and proteins had significant increment in AT1-AA positive DN rats when compared with AT1-AA negative DN rats (P＜0.05).     Conclusions    AT1-AA can induce ERS in the renal tissue of DN rats, and promote renal cell apoptosis likely via the modulation of caspase-12 signaling pathway.

Objective    To evaluate the effects of autophagy on oxidative stress induced by contrast media in podocytes.    Methods    The differentiated mouse podocytes were exposed to contrast media (Iopromide, 50 mg/L)、rapamycin (Rap, autophagy enhancer, 1 ng/L), 3-methyladenine (3-MA, autophagy inhibitor, 2 mmol/L) for 2 hours. The expression of autophagy protein LC3-Ⅱand Beclin-1 as well as oxidative stress-related proteins Catalase, MnSOD were detected by Western blot. The formations of autophagy were observed by MDC staining, and the levels of reactive oxygen species (ROS) by CM-H2DCFDA staining. Cell activity was evaluated by CCK8 assay.    Results    Both the levels of oxidative stress and autophagy in podocytes increased when stimulated by contrast media, the expression of LC3-Ⅱand Beclin-1 were enhanced, Catalase and MnSOD were inhibited (all P＜0.05). Rapamycin increased the expression of Catalase, MnSOD and cell activity of podocytes, reduced the generation of ROS (all P＜0.05), but in Rap group, cell activity showed no significant difference (P＞0.05). 3-MA decreased the expression of Catalase、 MnSOD and inhibited the cell activity of podocyte, increased the generation of ROS (all P＜0.05).    Conclusion    Autophagy protects podocyte from contrast media by the means of reducing oxidative stress.

Objective    To observe NLRP3 inflammasome expression and inflammatory cells infiltration in the BSA-overloaded rats kidney, and to investigate the potential mechanism of renal injury induced by proteinuria.    Methods    After unilateral right nephrectomy, eighteen healthy male Wistar rats were randomly divided into two groups: protein overload nephropathy model group (n=10), treated with intraperitoneal injections of bovine serum albumin (BSA); control group (n=8), treated with intraperitoneal injections of 0.9% saline for 9 weeks. Body weigh were measured every week and 24 h urine were collected in 0, 2, 5, 7, 9 week. The plasma levels of blood total protein (TP), albumin (Alb), serum creatinine (Scr) and blood urea nitrogen (BUN) were determined by automatic analyzers. Renal pathological changes were evaluated by PAS and Masson stains. Immunohistochemical staining was used to detect the expression of NLRP3, caspase-1, IL-1β, and IL-18, as well as the types of inflammatory cells. The NLRP3, caspase-1, IL-1β, and IL-18 protein and mRNA levels were also analyzed by Western blot and real-time PCR in two groups.    Results    It was found that there was a significant increase of proteinuria and BUN in model group compare to that in control group (all P＜0.05). However, there were no significant changes in body weight, TP, Alb and Scr between the two groups. Morphological study demonstrated that renal tubular epithelial cell injury, proteinaceous casts in tubular lumen, accompanying with the dominant macrophages and lymphocytes infiltration in interstitium in model group. The immunohistochemistry showed that there were more T (CD3+), B cells (CD20+) and macrophages (CD68+) in renal interstitium in model group than that in control group (P＜0.05). Tubulointerstitial injury score was higher than that of the control group (P＜0.05).  Immunohistochemistry, Western blot and real-time PCR all showed that the expression of NLRP3, caspase-1, IL-18 and IL-1 β were significantly increased compared to those in control group (P＜0.05). Furthermore, there were significant correlations between proteinuria and IL-1β/IL-18 expression (P＜0.05).    Conclusion    NLRP3 inflammasome activation is involved in tubulointerstitial inflammation caused by proteinuria. 
 

Objective    To investigate the effect of urinary proteins extracted from minimal change nephritic syndrome (MCNS) and advanced glycation end products (AGEs) on autophagy activity in renal tubular epithelial cells (TECs).    Methods    Kidney tissue specimens of patients with MCNS and DN were obtained from the kidney pathology library of the Affiliated Hospital of Guangdong Medical College. The kidney tissue from patients with hematuria and proven to be minimal change by pathology examination were used as control. The expression of LC3-Ⅱ in kidney was examined by immune histochemistry in vivo. Expression of LC3-Ⅱ was also studied after exposing HK-2 cells to 8 g/L urinary proteins and 100 mg/L AGE-BSA respectively. LC3-Ⅱ turnover was examined after exposure to urinary proteins in presence of Lysosomal inhibitors leupeptin (200 mg/L) or  chloroquine(10μmol/L) by western blot assay. In addition, the autophagosome or autolysosome formation was assessed after transfecting a tandem mRFP-GFP tagged LC3 (tfLC3) plasmid into HK-2 cells. Finally, the production of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were measured by ELISA after exposure of cells to autophagy enhancer rapamycin (10 μmol/L) and autophagy inhibitor chloroquine (10 μmol/L) in addition to urinary proteins.    Results    (1)In comparison with the control group, the expression of LC3-Ⅱ was significantly increased in TECs from patients with MCNS and DN(P＜0.01). (2)The expression of LC3-Ⅱwas enlarged after exposed to urinary proteins(P＜0.01), and further increased after leupeptin (autophagy inhibitor) addition. (3) Exposure to urinary proteins increased the autophogosomes and autolysosomes when observed by transfection of tfLC3 plasmid(P＜0.01). (4)The expression of LC3-Ⅱ was also elevated after treatment with AGE-BSA(P＜0.01), but no further increase after chloroquine (autophagy inhibitor) addition. (5) Only the autophogosome formation(P＜0.01), but not autolysosome formation, was found increased by transfection of tfLC3 plasmid after exposure to AGE-BSA.  (6) Pre-treatment of HK-2 cells with autophagy enhancer rapamycin reduced the productions of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), while blocking autophagy with autophagy inhibitor chloroquine exerted an opposite effect.    Conclusions    Autophagy was activated by urinary proteins, but inactivated by AGE-BSA. Autophagy activation may play a key role in protecting TECs in the progression of primary and secondary kidney diseases.