Predictive Factors Upon Discontinuation of Renal Replacement Therapy for Long-Term Chronic Dialysis and Death in Acute Kidney Injury Patients.

The specific timing for discontinuing renal replacement therapy (RRT) in acute kidney injury (AKI) patients is debatable. The predictive abilities of variables at the time of discontinuation of RRT for the long-term prognoses of patients have not been explored. This study aimed to explore the prognostic factors upon discontinuation of RRT for long-term chronic dialysis and death of patients with acute RRT-requiring AKI, thus improving decision making regarding the discontinuation of RRT and the follow-up of patients thereafter. A cohort of 302 AKI patients who required acute RRT and remained alive and free of dialysis for at least 30 days after discharge from January 2009 to December 2012 were followed up. The predictive abilities of general characteristics, RRT details, and variables upon discontinuation of RRT for long-term chronic dialysis and all-cause death were evaluated using Cox proportional hazards models. Kaplan-Meier analysis with a log-rank test was used to compare the survival curves between the strata of levels of good predictors upon discontinuation of RRT. After a median follow-up time of 4.1 years, 20 (6.6%) patients initiated chronic dialysis and 56 (18.5%) patients died. A higher CysC level upon discontinuation of RRT (HR 1.520, 95% CI 1.082-2.135; P = 0.016), comorbid chronic kidney disease, and a higher non-renal Charlson comorbidity index (CCI) were independently predictive for chronic dialysis. The hemoglobin level upon discontinuation of RRT was inversely predictive of death (HR 0.986, 95% CI 0.973-0.999; P = 0.035), and comorbid malignancy, the presence of multiple organ dysfunction syndrome, and a higher non-renal CCI also predicted death. Urine output upon discontinuation of RRT was marginally inversely predictive of death (HR 0.997, 95% CI 0.994-1.000; P = 0.056). Patients who discontinued RRT with CysC levels <2.97 mg/L, hemoglobin levels >85 g/L, and urine output >1130 mL/24 h showed significantly higher non-chronic dialysis and survival rates according to a log-rank test. Our study suggested that upon discontinuation of RRT, higher serum CysC levels had the most promising predictive value for long-term chronic dialysis, and lower hemoglobin levels predicted long-term death; lower urine output also marginally predicted long-term death. Based on the remission of the comprehensive condition, lower CysC levels and higher hemoglobin levels and urine output should be considered in the decision to stop RRT. Patients showing worse levels of these indices upon discontinuation of RRT should undergo stricter follow-up and treatment to improve long-term outcomes.

Atorvastatin attenuates experimental contrast-induced acute kidney injury: a role for TLR4/MyD88 signaling pathway.

OBJECTIVES: To investigate the protective effect of different atorvastatin doses on contrast-induced acute kidney injury and the related mechanism. METHODS: Healthy male Sprague-Dawley (SD) rats were randomly divided into the blank control group, experimental control group and different-dose atorvastatin groups. A rat model of contrast-induced acute kidney injury was established. We detected changes in serum creatinine (Scr) and blood urea nitrogen (BUN) before and after model establishment, observed and scored renal tubular injury, analyzed rat renal cell apoptosis, and measure the expression of signal pathway proteins and downstream inflammatory factors. RESULTS: After contrast agent injection, the Scr and BUN levels of the experimental control group were significantly increased, the different doses applied in the atorvastatin group significantly reduced the Scr and BUN levels (p < .05) and ameliorated the contrast-induced acute kidney injury (p < .05) and significantly reduced Toll-like receptor 4 (TLR4), Myeloid differentiation factor 88 (Myd88), and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) protein expression and relative mRNA expression levels (p < .05) and significantly decreased expression levels of downstream inflammatory factors (p < .05). CONCLUSION: Different atorvastatin doses have protective effects on contrast-induced acute renal tubular injury in rats, possibly by targeting TLR4, suppressing TLR4 expression, regulating the TLR4/Myd88 signaling pathway, and inhibiting the expression of downstream inflammatory factors.

Hereditary features, treatment, and prognosis of the lipoprotein glomerulopathy in patients with the APOE Kyoto mutation.

Lipoprotein glomerulopathy is a rare inherited renal disease, caused by mutation of the APOE gene, characterized by proteinuria and nephrotic syndrome with elevated serum apoE. Since its treatment and outcome are unknown, we retrospectively studied 35 patients within 31 unrelated Han families with biopsy-proven lipoprotein glomerulopathy residing in the same county in southwest China. DNA sequencing detected the APOE Kyoto mutation (p. Arg25Cys) in all patients and 28 asymptomatic relatives. All shared the same ɛ3 allele. The patients presented with proteinuria, higher total triglyceride, and serum apoE levels relative to non-carriers. The serum apoE and triglyceride levels of asymptomatic carriers were between those of the patients and non-carriers. Sixteen patients received fenofibrate treatment for over 12 months. Six reached complete remission (proteinuria under 0.3 g/day with stable serum creatinine) with intensive control of their lipid profile (normalized serum apoE and triglycerides under 100 mg/dl). Eight reached partial remission. At 3 years of follow-up, patients treated with fenofibrate had superior survival and stable renal function. Thus, fenofibrate can induce lipoprotein glomerulopathy remission and the fibrate effects depend on the degree of lipid control and baseline proteinuria. Moreover, normalization of serum apoE and triglycerides can be used to judge the efficacy of lipid-lowering treatment.

A case of focal segmental glomerulosclerosis syndrome secondary to high-altitude polycythemia.

In recent years, focal segmental glomerulosclerosis has become the commonest cause of the nephrotic syndrome seen in adults. Secondary focal segmental glomerulosclerosis is observed when glomerular workload is increased. We report a case of focal segmental glomerulosclerosis with nephrotic syndrome secondary to high-altitude polycythemia (HAPC). Our case points out that for patients with focal segmental glomerulosclerosis, who presented with nephrotic syndrome secondary to HAPC, treatments for HAPC are crucial for the reduction of proteinuria and renal protection instead of glucocorticoid and immunosuppressive drugs.

Evaluation of the Chronic Kidney Disease Epidemiology Collaboration equation for estimating glomerular filtration rate in the Chinese population.

BACKGROUND: Previous studies have indicated that the performance of glomerular filtration rate (GFR) estimation equations vary according to the races of the target population. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation has not been validated in the Chinese population including patients with chronic kidney disease (CKD) and healthy controls. METHODS: A total of 977 adult persons (682 patients with CKD and 295 healthy volunteers) from nine renal institutes of university hospitals located in nine geographic regions of China were enrolled in the study. A diagnostic test study comparing the CKD-EPI two-level and four-level race equation, the Modification of Diet in Renal Disease (MDRD) Study equation and the modified MDRD equation for Chinese (the Chinese equation). The (99m)Tc- diethylenetriamine pentaacetic acid dual plasma clearance was used as a reference method for measuring GFR. RESULTS: The mean age of participants was 48.3 ± 16.0 years and 479 (49.0%) were male. The CKD-EPI two-level race equation and the Chinese equation performed better than the MDRD Study equation and CKD-EPI four-level race equation, with less bias (median difference between estimated GFR and reference GFR, 0.2 and 0.3 versus -2.4 and 3.0 mL/min/1.73 m(2)), improved precision (interquartile range of the difference, 20.5 and 20.8 versus 23.4 and 20.5 mL/min/1.73 m(2)) and greater accuracy (percentage of estimated GFR within 30% of reference GFR, 73.4 and 73.0% versus 69.8 and 70.1%). CONCLUSIONS: The CKD-EPI two-level race equation and the Chinese equation performed similarly in the Chinese population, and both performed better than the MDRD Study equation and the CKD-EPI four-level race equation.

Hyponatraemia in patients with crush syndrome during the Wenchuan earthquake.

BACKGROUND: Although sodium disturbances are common in hospitalised patients, no study has specifically investigated the epidemiology of hyponatraemia in patients with crush syndrome. OBJECTIVES: To describe the incidence of hyponatraemia and assess its effect on outcome in patients with crush syndrome during the Wenchuan earthquake. METHODS: A retrospective study was conducted in 17 reference hospitals during the Wenchuan earthquake. We excluded patients younger than 15 years and those with missing sodium values within 3 days after being rescued from the ruins. RESULTS: Hyponatraemia (serum sodium concentration <135 mmol/l) was seen in 91/180 (50.6%) patients on admission. Compared with patients with normonatraemia, those with hyponatraemia were younger, had more severe traumatic injury and renal failure, underwent more fasciotomies, received more blood transfusion and renal replacement therapy. In the multivariable-adjusted model, the number of extremity injuries (OR=1.59, 95% CI 1.08 to 2.33) and serum creatinine (OR=1.30, 95% CI 1.07 to 1.59) were independently associated with the occurrence of hyponatraemia. Covariate adjusted multiple logistic regression analysis showed an independent mortality risk rising with hyponatraemia (OR=5.74, 95% CI 1.18 to 28.00). CONCLUSIONS: Hyponatraemia was common in the patients with crush syndrome during the Wenchuan earthquake and associated with poor prognosis. Water, commercial drinks and hypotonic intravenous fluids should be supplied carefully to patients with crush syndrome.

Involvement of parathyroid hormone-related protein in vascular calcification of chronic haemodialysis patients.

AIMS: To investigate the role of parathyroid hormone-related protein (PTHrP) in vascular calcification of patients with chronic hemodialysis. METHODS: The inferior epigastric arteries were obtained from 23 patients on chronic haemodialysis and 16 patients with renal carcinoma as control. Haematoxylin-eosin staining, elastic fibre staining, Alizarin Red calcium staining and immunohistochemical staining of PTHrP, bone morphogenetic protein-2 (BMP-2), Cbfa1/Runx2 were performed. Real-time polymerase chain reaction (PCR) was used to examine mRNA expressions of PTHrP, BMP-2 and Cbfa1/Runx2. Western blot and real-time PCR were used to detect the effects of PTHrP-siRNA and rh-PTHrP-1-34 on the expressions of PTHrP, BMP-2 and Cbfa1/Runx2 in human aortic smooth muscle cells (HASMC). Alkaline phosphatase (ALP) activities and intracellular calcium content in HASMCs were assessed after treatment with 10 mmol/L ß-glycerol phosphoric acid for 48 h. RESULTS: Vascular calcification was confirmed in 78.2% of patients on chronic haemodialysis, and the expressions of PTHrP, BMP-2 and Cbfa1 in the arteries were significantly upregulated. PTHrP-siRNA could downregulate the expression of PTHrP by 60%, BMP-2 by 25% and Cbfa1 by 25% at 24 h (P < 0.05). Exogenous rh-PTHrP-1-34 could upregulate the expressions of BMP-2 and Cbfa1 by 1.37-fold and 1.46-fold, respectively, at 24 h in a time-independent manner (P < 0.05), which were attenuated by PTHrP-siRNA. Moreover, it could promote intracellular calcium deposition and increase ALP activities, which were partially blocked by PTHrP-siRNA (P < 0.05). CONCLUSIONS: Vascular calcification was common in patients with chronic haemodialysis, to which PTHrP might contribute by activating BMP-2/ Cbfa1 signalling pathway.

[Relation between bone matrix proteins and monocyte chemoattractant protein-1 in renal small artery in diabetic nephropathy rats].

OBJECTIVE: To observe the expressions of bone matrix proteins and monocyte chemoattractant protein-1 ((MCP-1) in the renal arteriole of diabetic nephropathy (DN) rats and analyze their correlations and roles in diabetic nephropathy. METHODS: Adult Sprague-Dawley male rats were used to establish the animal model of diabetic nephropathy induced by peritoneal injection of 55 mg/kg of streptozocin. Calcium deposit around the renal arteriole was observed by alizarin red staining. The protein and mRNA levels of core-bind factor alpha 1 (cbfalpha1), bone morphogenetic protein 2 (BMP-2) and matrix Gla protein (MGP) in renal arteriole of DN rats were detected by immunohistochemistry, in-situ hybridization and real-time PCR. The biochemical indices were detected by routine test. RESULTS: 1. Blood glucose and Urine protein of 24 h were significantly increased in the renal arteriole of DN rats versus the control rats (P < 0.05), serum creatinine (SCr) and phosphorus were significantly increased from 12 weeks. 2. Little deposit of calcium salt was observed in the renal arteriole of DN rats at the 4th week and a large amount of deposit was observed at 24th week, but no calcium deposit was observed in control rats. 3. Cbfalpha1 and BMP-2 expressions were significantly increased in the renal arteriole of DN rats from 4 to 24 weeks vs. the control rats. MGP mRNA expression in the renal arteriole of DN rats was significantly decreased from 4 to 24 weeks. MCP-1 expression was obviously upregulated in the renal arteriole of DN rats at 24th week versus that at 4th and 12th week. No MCP-1 expression was observed in the renal arterioles of control rats. MCP-1 were positively correlated with the expression of cbfalpha1 and BMP-2. CONCLUSION: Bone matrix proteins has already expressed in renal arteriole before the formation of vascular calcification. MCP-1 can affect the expression of cbfalpha1, BMP-2; cbfalpha1, BMP-2, MGP and MCP-1 may be involved in the formation of vascular lesions of DN.

[Comparison of the effects of alpha-keto/ amino acid supplemented low protein diet and diabetes diet in patients with diabetic nephropathy].

OBJECTIVE: To investigate if a-keto/amino acid supplemented low protein diet can slow down the progression of diabetic nephrophathy in comparison with non-supplemented diabetes diet. METHODS: A prospective, randomized, controlled clinical study was conducted. Twenty three cases of type 2 diabetic nephropathy in IV stage were randomly divided into alpha-keto/amino acid supplemented diet group (trial group) and conventional diabetes diet group (control group), The treatment duration was 52 weeks. 24 h urine protein was measured at 0, 12, 20, 36 and 52 weeks. Before and after the 52 weeks treatment, all the patients received the measurement of glomerular filtration rate (GFR), blood glucose, blood lipids, inflammatory markers, as well as nutritional status. RESULTS: After the treatment for 20, 36, 52 weeks, mean 24 h urine protein decreased significantly in trial groups (P < 0.05), and 24 h urine protein in trial group were significantly decreased (P < 0.05) compared with control group in 20 weeks after treatment. Either in trial group or in control group, GFR remained relatively stable during the observation period. Nutrition status, inflammatory markers, and serum calcium, phosphorus levels between the two groups were no significantly difference. The adverse events experienced by the patients in trial group were similar and consistent with the patients underlying renal diseases. CONCLUSION: Alpha-keto/amino acid can reduce proteinuria more effectively, while improve renal function and nutritional status in diabetic nephropathy patients with well-toleration.

[Influence of high glucose and mannose binding lectin complement pathway activation to IL-6 and TNF-alpha's expression by human renal glomerular endothelial cells].

OBJECTIVE: To investigate the effect of high glucose and mannose binding lectin (MBL) complement pathway activation's effect on expression of Interleukin-6 (IL-6) and Tumor necrosis factor-alpha (TNF-alpha) from human renal glomerular endothelial cells (HRGEC), to explore unknown pathogenesy of diabetic nephropathy. METHODS: Normal HRGEC was divided randomly into normal glucose group(5 mmol/L D-glucose), manicol group (5 mmol/L D-glucose+25 mmol/L manicol) and high glucose group (30 mmol/L D-glucose). Real-time PCR was used to detect IL-6 and TNF-alpha mRNA expression in each group, Euzymelinked Immunosorbent Assay (ELISA) was performed to examine the protein expression of IL-6 and TNF-alpha in supernatant after 24 hours' culture. HRGEC was then randomly divided into two groups: single high glucose group and high glucose + MBL group. After 24 hours' culture with 30 mmol/L D-glucose, 30% MBL deficiency human serum was added into two groups, 1 microg/mL MBL was only added into high glucose + MBL group, continued the culturation for another 4 hours. Flow cytometry and immunofluorescence technique were applied to evaluate MBL, C3 and membrane attacks complex (MAC) deposition on cell surface respectively. Real-time PCR and ELISA were performed to examine mRNA and protein expression of both IL-6 and TNF-alpha in each group. RESULTS: Compared with normal glucose group and manicol group, the mRNA and protein expression of IL-6 and TNF-alpha in high glucose group were increased (P < 0.05). Flow cytometry confirmed obvious MBL and C3 co-deposition and Immunofluorescence confirmed obvious MAC deposition on cell surface in high glucose+ MBL group. Compared with single high glucose group, the mRNA and protein expression of IL-6 and TNF-alpha in high glucose+ MBL group were significantly higher (P < 0.05). CONCLUSION: High glucose can bring inflammatory factors' overexpression from cultured HRGEC; high glucose together with MBL can bring MBL complement pathway activation and inflammatory factors' overexpression, this indicates that the activation of MBL complement pathway may be a potential unknown pathogenesy of diabetic nephropathy and its proinflammatory status.

[Relationship between activation of mannan-binding lectin complement and NF-kappaB in diabetic nephropathy].

OBJECTIVE: To study the activation of mannose-binding lectin (MBL) complement in STZ-induced diabetic nephropathy (DN) rats and its relationship with NF-kappaB. METHODS: Sprague-Dawley (SD) rats were randomly divided into two groups: normal control and diabetic nephropathy. Diabetes was induced by intraperitoneal injection of STZ. Five rats were sacrificed at the end of week 1, 2, 4, 8 respectively. Blood glucose, 24 h urine, 24 h urinary albumin, serum creatinine (Scr), body mass and kidney mass were examined at the same time points respectively. Creatinine clearance and renal hypertrophy index were calculated. The renal expression of MBL, membrane attack complex (MAC) and NF-kappaB were determined by immunohistochemistry. RESULT: MBL, MAC and NF-kappaB expression were significantly increased in glomerulus of diabetic nephropathy rats compared to the controls. The expression of MBL was positively correlated with NF-kappaB expression. CONCLUSION: The activation of mannose-binding lectin complement participates in the onset and development of DN.

[Influence of mannose binding lectin to expression of TGF-beta1 and NF-kappaB in high concentration of glucose cultured human renal glomerular endothelial cells].

OBJECTIVE: To investigate the effect of mannose binding lectin (MBL) complement pathway on expression of transforming growth factor-beta1 (TGF-beta1) and NF-kappaB in cultured human renal glomerular endothelial cells (HRGECs) stimulated by high concentration of glucose. METHODS: Human glomerular endothelial cells in culture were randomly divided into 5 groups according to different managements: normal concentration of glucose as controlled group, MBL + normal concentration of glucose group, high concentration of glucose, MBL + high glucose and MBL + high glucose + MBL blocker respectively. Flow cytometry was used to detect the depositions of MBL and C3 on the surfaces of HRGECs. Real-time PCR method was used to detect the mRNA levels of TGF-beta1. Human TGF-beta1 ELISA kit was used to detect the concentration of TGF-beta1 in supernatant fluid. ESMA was used to detect the activity of NF-kappaB in HRGECs. RESULTS: Compared with the normal glucose group and high glucose group, the depositions of MBL, C3 were apparently increased in MBL + high glucose group (P < 0.05). Expression of TGF-beta1 were significantly higher (P < 0.05) in MBL + high concentration of glucose groups than the normal glucose group and the high concentration of glucose group. Compared with the high glucose group, the activity of NF-kappaB in HRGECs was apparently increased in MBL + high glucose group, which could be significantly downregulated by MBL blocking antibody. CONCLUSION: High concentration of glucose can increase the expression of TGF-beta1 of cultured human glomerular endothelial cells. At the same time, high glucose together with MBL can up regulate the expression of TGF-beta1 and the activity of NF-kappaB in HRGECs.

[Effect of high concentration of glucose on thickness of glycocalyx and expression of syndecan-1 and glypican-1 in cultured human renal glomerular endothelial cells].

OBJECTIVE: To investigate the influence of high concentration of glucose on the thickness of Glycocalyx and expression of core protein Sydecan-1 and Glypican-1 in cultured human renal glomerular endothelial cells (HRGECs). METHODS: HRGECs in culture were randomly divided into 3 groups, high concentration of glucose (30 mmol/L D-glucose, high glucose group), normal concentration of glucose as controlled group (5 mmol/L D-glucose+25 mmol/L mannitol, normal control group), and mannitol group (30 mmol/L mannitol) respectively. After 72 hours, confocal laser scanning microscopy (CLSM) was used to observe and characterize the fully hydrated glycoalyx of HRGECs. Real time quantitative PCR and Western blot were applied to detect the mRNA levels and protein expression of Syndecan-1 and Glypican-1, and the fluorescence microscope were used to observe the immunofluorescence change of Syndecan-1 and Glypican-1. RESULTS: Compared with normal control group, the thickness of Glycocalyx on the surface of HRGECs in high glucose group decreased to 36.8% (P < 0.05). Immunofluorescence shows the depositions of Syndecan-1 and Glypican-1 were weakened in high glucose group. The mRNA and protein expression of Syndecan-1 and Glypican-1 were significantly decreased (P < 0.05) compared with normal control group and mannitol group. CONCLUSION: High concentration of glucose can reduce thickness of Glycocalyx on the surface of human glomerular endothelial cell. At the same time, high glucose can decrease the expression of core protein Sydecan-1 and Glypican-1 of HRGECs.

[Effects of high glucose on expression of core binding factor alpha1 and osteocalcin in vascular smooth muscle cells].

OBJECTIVE: To investigate the effects of high glucose on expression of core binding factor alpha1 (cbfalpha-1) and osteocalcin (OC) in vascular smooth muscle cells (VSMCs), and discuss the mechanism of small vessels calcification induced by high glucose (GS) in vitro. METHODS: The primary cultured VSMCs from rats' aortic segments were divided into three groups, including normal control group (5 mmol/L D-glucose), high glucose group (25 mmol/L D-glucose) and mannitol group (5 mmol/L D-glucose plus 25 mmol/L mannitol). We measured quantitatively the calcium deposition in VSMCs and investigated the calcium extent of VSMCs by alizarin red stain in each group. The mRNA levels of cbfalpha-1 and OC were measured by real-time PCR, and the protein expression levels of cbfalpha-1 and OC were examined by Western blot. The activity of alkaline phosphatase was measured by alkaline phosphatase activity testing kit, and the protein level of alpha-smooth muscle actin (a-SMA) was detected by immunohistochemistry. RESULTS: When compared with the normal group and mannitol group, the high glucose group showed that the calcium deposition and calcium extent of VSMCs increased obviously, the mRNA and protein levels of cbfalpha-1 and OC also increased significantly (P < 0.05), while the protein level of alpha-SMA decreased (P < 0.05), which were in a dose-dependent manner. The level of alkaline phosphatase activity of VSMCs was approximately doubled in high glucose group. CONCLUSION: The mechanism of high glucose induced calcification in VSMCs may be due to the increased expression of cbfalpha-1 and OC. High glucose decrease the expression of alpha-SMA in VSMCs, which could induce the transdifferentiation from RVSMCs to osteoblast-like cells.

[Effects of valsartan on the renal vascular endothelial growth factor and its receptor flk-1 of diabetic rats].

OBJECTIVE: To explore effects of valsartan on expression changes of vascular endothelial growth factor (VEGF) and its receptor Flk-1 in diabetic rat kidney. METHODS: To establish the diabetic nephropathy (DN) rat models and divide the experiment rats into three groups--the DN group, the valsartan group and the control group, and use the reverse transcriptase polymerase chain reaction (RT-PCR), Western Blotting and immunohistochemical techniques to detect the expression of VEGF and Flk-1, and detect the urine protein and glomerular area and volume, then analyze the relationship of the data. RESULTS: The mRNA and protein expression of VEGF and Flk-1, the urine protein and glomerular area and volume in the DN were higher than those in the control group and valsartan group (P < 0.05). VEGF and Flk-1 were positively correlated with the urine protein and glomerular area and volume (P < 0.05). CONCLUSION: VEGF and Flk-1 play an important role in the pathogenesis of DN, of which over-expression may lead to the damage of kidney. The angiotensin II receptor antagonist--valsartan can protect kidney through the non-hemodynamic mechanism of inhibiting the abnormal expression of VEGF and Flk-1.

[Effects of shear stress on expression of plasminogen activator (tPA and uPA) in cultured kidney proximal tubular epithelial cells and its significance].

In this study, we assessed the effects of shear stress on the expression of plasminogen activator(tPA and uPA) mRNA in cultured NRK-52E cells (a kidney proximal tubular epithelial cell line of normal rat origin) and investigated the mechanism of tubulointerstitial extracellular matrix (ECM) remodeling in the early stage of diabetic nephropathy (DN). The cultured NRK-52E cells were exposed to shear stress of 5 and 10 dyn/cm2 for 1, 3 and 6 hours respectively. Semi-quantity RT-PCR was used to detect the expression of tPA and uPA mRNA. Shear stress down-regulated the expression of tPA and uPA mRNA in cultured NRK-52E cells in a magnitude and time-dependent way. The results suggested that the increased tubular shear stress in the early-stage of DN could decrease the expression of tPA and uPA in renal proximal tubular cells, lead to the reduction of tubulointerstitial fibrinolytic activity and involve in the remodeling of ECM.

Biomarkers upon discontinuation of renal replacement therapy predict 60-day survival and renal recovery in critically ill patients with acute kidney injury.

INTRODUCTION: There is no consensus on the specific indications for weaning critically ill patients with acute kidney injury (AKI) off renal replacement therapy (RRT). This study aimed to explore the prognostic value of several biomarkers measured upon discontinuation of RRT for their value in predicting 60-day survival and renal recovery in an effort to add knowledge to the decision-making process regarding RRT withdrawal. METHODS: We prospectively enrolled 102 patients with AKI who required RRT from the intensive care unit. Serum osteopontin (sOPN), serum interleukin 6 (sIL-6), serum cystatin C (sCysC), sIL-18, serum neutrophil gelatinase-associated lipocalin and urinary IL-18 and urinary neutrophil gelatinase-associated lipocalin were measured upon discontinuation of RRT. Patients were followed up at 60 days for survival and renal recovery. FINDINGS: Patients who survived showed lower levels of all serum and urinary biomarkers. Serum OPN (OR 1.029, 95% CI 1.013-1.047, P = 0.001), diabetes (OR 23.157, 95% CI 4.507-118.981, P < 0.001) and APACHE II score (OR 1.308, 95% CI 1.121-1.527, P = 0.001) were independent predictors of 60-day mortality. Patients whose sOPN values fell within the highest and middle tertiles showed 5.25- and 2.31-fold increased risks of mortality, respectively, compared with that of patients in the lowest tertile. The addition of sOPN to the clinical model resulted in significant net reclassification improvement of 0.453 (P = 0.026) and an integrated discriminative index of 0.155 (P = 0.032). Lower levels of sOPN and sIL-6 were associated with greater odds of 60-day survival (AUC 0.812 and 0.741). The AUC value for predicting survival reached its highest level when all biomarkers were combined with urine output (UO) and urinary and serum creatinine upon discontinuation of RRT (0.882). Lower sCysC performed as well as higher UO in predicting 60-day renal recovery with the greatest AUC of 0.743. DISCUSSION: Upon discontinuation of RRT, serum and urinary biomarkers, particularly sOPN, may predict 60-day survival and renal recovery in critically ill patients with AKI. The serum levels of OPN, IL-6 and CysC may be useful when considering withdrawal of RRT on the basis of conventional indicators.

Biomechanical bearing-based typing method for osteonecrosis of the femoral head: ABC typing.

Type classification of osteonecrosis of the femoral head (ONFH) is important for collapse prediction in ONFH, which depends on a complexity of factors. At present, most typing is based on single factors, including the location or size of the necrosis, or the bone repair capacity after ONFH, and is therefore limited. The present study proposes an 'ABC' method for ONFH typing based on biomechanics and the stress distribution characteristics of the femoral head's bone trabeculae. In total, 132 ONFH patients (223 hips) were enrolled at Guanganmen Hospital (Beijing, China). Each of the hip joints included was subjected to computerized tomography and/or magnetic resonance imaging. The images with the maximum necrotic area in the coronal femoral head were selected, and the femoral head's maximum transverse diameter was divided into three pillars (A, B and C, from the outside to the inside) according to a 3:4:3 diameter ratio. ONFH was typed according to the number of pillars involved in the necrosis. Differences in the collapse rate of different ONFH types, and the correlation between the theoretical collapse risk and the observed collapse rate was analysed. The ONFH types significantly differed in their collapse rate (χ2=76.93, P<0.001) in the following order: A-C (88.6%)>AB (74.1%)>BC (52.4%)>A (50%)>B (9.5%)>C (0%). The collapse risk was significantly correlated with the collapse rate (correlation coefficient R=1). The types A-C and AB had high collapse rates/risks, whereas types B and C had a satisfactory prognosis. The ABC typing proposed in the present study is thus suitable for collapse risk prediction in ONFH. Type classification using this method may provide a valuable reference for selecting regimens for ONFH treatment.

[Expression of VEGF in kidney of diabetic rats].

OBJECTIVE: To investigate the expression of vascular endothelial growth factor (VEGF) in the kidney of diabetic rats and probe its relationship with the development of diabetic nephropathy (DN). METHODS: Diabetes mellitus was induced in SD rats by Streptozotocin. The renal tissues of rats were taken out at 2, 4, 8, 12, 16, 20 and 24 weeks after operation. The expression of VEGF was assessed by immunohistochemistry methods. VEGF mRNA in kidney was detected by RT-PCR at the same time points. The levels of VEGF mRNA and immunostaining were quantified by computer image analysis. The relationships of VEGF with the indices of renal damage, including renal/body weight, urinary protein excretion, glomerular volume and glomerular area, were analyzed. RESULTS: The expression of VEGF mRNA in diabetic kidney was significantly up-regulated after operation from 2 weeks to 24 weeks with the peak level at 20 weeks, when compared with control at the same time-points. The positive results of VEGF staining in diabetic glomeruli was increasingly observed after operation from 2 weeks to 24 weeks, with the peak at 20 weeks. The positive results of VEGF staining in diabetic tubuli was increasingly seen from 2 weeks to 24 weeks, with the peak at 8 weeks. CONCLUSION: VEGF level is increased continuously in the diabetic kidney of rat. The increased expression of VEGF is mainly located in the glomeruli at the early and middle stages, and is in the tubuli at the middle and late stages. VEGF expression in the diabetic kidney of rat is related to the development of renal changes.