Association of Bowman's capsule rupture with prognosis in patients with lupus nephritis.

BACKGROUND AND OBJECTIVE: Lupus nephritis is one of the most severe manifestations of systemic lupus erythematosus. The clinical and prognostic significance of Bowman's capsule rupture in patients with lupus nephritis is unknown. METHODS: One hundred eighty patients with lupus nephritis were enrolled in the study and the integrity of Bowman's capsule was assessed. Both inflammatory and proliferative cells were detected by immunochemistry staining. The primary events of interest were end-stage renal disease and death. RESULTS: After retrospective analysis of the data, 52 (28.9%) patients were found to have Bowman's capsule rupture, which was accompanied by high levels of serum creatinine, 24 h urine protein, and Activity/Chronicity Index. Bowman's capsule rupture was correlated with the level of crescents, tubular atrophy, and interstitial fibrosis. The number of CD20+ cells was higher in the Bowman's capsule rupture ( +) group compared with the Bowman's capsule rupture (-) group, while no differences in other inflammatory cells were observed. In addition, the end stage renal disease-free survival in the Bowman's capsule rupture ( +) group was lower than in the Bowman's capsule rupture (-) group. Moreover, serum creatinine (HR 39.56, P < 0.001), Activity Index (HR 1.50, P < 0.05) as well as Bowman's capsule rupture (HR 1.09, P < 0.05) predicted end-stage renal disease progression. Notably, for patients with existing crescents, Bowman's capsule rupture increased the cumulative risk of end-stage renal disease. CONCLUSIONS: Bowman's capsule rupture is an important renal pathological lesion, which correlates with severe clinical manifestations, pathological changes, and poor prognosis in patients with lupus nephritis.

Blocking ribosomal protein S6 phosphorylation inhibits podocyte hypertrophy and focal segmental glomerulosclerosis.

Ribosomal protein S6 (rpS6) phosphorylation mediates the hypertrophic growth of kidney proximal tubule cells. However, the role of rpS6 phosphorylation in podocyte hypertrophy and podocyte loss during the pathogenesis of focal segmental glomerulosclerosis (FSGS) remains undefined. Here, we examined rpS6 phosphorylation levels in kidney biopsy specimens from patients with FSGS and in podocytes from mouse kidneys with Adriamycin-induced FSGS. Using genetic and pharmacologic approaches in the mouse model of FSGS, we investigated the role of rpS6 phosphorylation in podocyte hypertrophy and loss during development and progression of FSGS. Phosphorylated rpS6 was found to be markedly increased in the podocytes of patients with FSGS and Adriamycin-induced FSGS mice. Genetic deletion of the Tuberous sclerosis 1 gene in kidney glomerular podocytes activated mammalian target of rapamycin complex 1 signaling to rpS6 phosphorylation, resulting in podocyte hypertrophy and pathologic features similar to those of patients with FSGS including podocyte loss, leading to segmental glomerulosclerosis. Since protein phosphatase 1 is known to negatively regulate rpS6 phosphorylation, treatment with an inhibitor increased phospho-rpS6 levels, promoted podocyte hypertrophy and exacerbated formation of FSGS lesions. Importantly, blocking rpS6 phosphorylation (either by generating congenic rpS6 knock-in mice expressing non-phosphorylatable rpS6 or by inhibiting ribosomal protein S6 kinase 1-mediated rpS6 phosphorylation with an inhibitor) significantly blunted podocyte hypertrophy, inhibited podocyte loss, and attenuated formation of FSGS lesions. Thus, our study provides genetic and pharmacologic evidence indicating that specifically targeting rpS6 phosphorylation can attenuate the development of FSGS lesions by inhibiting podocyte hypertrophy and associated podocyte depletion.

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Exosomes are in a size of 30-100 nm vesicles released by various cells, with a double-layered lipid membrane containing DNA, RNA, and protein. In the past, exosomes were considered to be molecular waste, and recently exosomes have been shown to be involved in many pathophysiological processes, including intercellular communication, immune response, nerve repair, and tumorigenesis. Exosomes are present in numerous body fluids, and urinary exosomes have been shown to be biomarkers of a variety of kidney diseases.

Acute major gastrointestinal bleeding caused by hookworm infection in a patient on warfarin therapy: A case report.

RATIONALE: The use of anticoagulants is a contributor to gastrointestinal (GI) bleeding. Most bleeding patients on anticoagulant therapy such as warfarin commonly have basic lesions existing in their GI mucosa. PATIENT CONCERNS: We report a case of major GI bleeding following the use of anticoagulants in a patient with hookworm infection. DIAGNOSES: The patient was diagnosed with nephrotic syndrome with pulmonary embolism. INTERVENTIONS: He was treated with anticoagulants and suffered from acute major GI bleeding during the treatment. Capsule endoscopy revealed many hookworms in the lumen of jejunum where fresh blood was seen coming from the mucosa. OUTCOMES: The patient was successfully rescued and cured with albendazole. LESSONS: Latent hookworm infection can be a cause of massive small-bowel hemorrhage in patients on anticoagulant therapy and anthelmintic treatment is the key to stop bleeding.

Hookworm Infection Caused Acute Intestinal Bleeding Diagnosed by Capsule: A Case Report and Literature Review.

Hookworm infections are rare causes of acute gastrointestinal bleeding. We report a middle aged man with primary nephrotic syndrome and pulmonary embolism. During the treatment with steroids and anticoagulants, the patient presented acute massive hemorrhage of the gastrointestinal tract. The results of gastroscopy showed red worms in the duodenum. Colonoscopy and CT angiogram of abdomen were unremarkable. Capsule endoscopy revealed fresh blood and multiple hookworms in the jejunum and ileum. Hookworms caused the acute intestinal bleeding. The patient responded well to albendazole. Hematochezia was markedly ameliorated after eliminating the parasites. Hence, hookworm infection should be considered in the differential diagnosis of a patient with obscure gastrointestinal bleeding. Capsule endoscopy may offer a better means of diagnosis for intestinal hookworm infections.

HMGB1 Enhances the AGE-Induced Expression of CTGF and TGF-ß via RAGE-Dependent Signaling in Renal Tubular Epithelial Cells.

BACKGROUND/AIMS: Advanced glycation end products (AGEs) induce epithelial mesenchymal transition (EMT) in renal proximal tubular epithelial cells (PTECs) by promoting the two EMT regulators, transforming growth factor beta (TGF-ß) and connective tissue growth factor (CTGF). However, the exact signaling mechanism remains largely unclear. METHODS: We investigated the promotion to high mobility group box 1 (HMGB1) in renal tubular epithelial HK-2 cells by AGE-BSA with quantitative PCR and western blot assay, and then determined the regulatory role of HMGB1 in the AGE-BSA-induced CTGF and TGF-ß. In addition, the dependence of the receptor of advanced glycation end products (RAGE) was also examined in the CTGF and TGF-ß promotion by AGEs and HMGB1 in HK-2 cells using the RNAi method. RESULTS: It was demonstrated that AGEs induced translocation and release of HMGB1 from tubular epithelial HK-2 cells, and the released HMGB1 enhanced the promotion to CTGF and TGF-ß by AGEs in HK-2 cells. On the other side, the HMGB1 knockdown by siRNA attenuated the AGE-BSA-induced expression of TGF-ß. Moreover, the CTGF and TGF-ß promotion in HK-2 cells by AGEs and HMGB1 was RAGE-dependent. CONCLUSION: Our results indicated that AGEs induced HMGB-1 and promoted the CTGF and TGF-ß in renal epithelial HK-2 cells RAGE-dependently. And there was a synergism between AGEs and HMGB1 in the RAGE signaling activation. The in vitro data suggested that the AGE-RAGE and HMGB-1-RAGE signaling might play an important role in the promotion of CTGF and TGF-ß in the renal fibrosis process of diabetic nephropathy.

Risk factors for mortality in Chinese patients on continuous ambulatory peritoneal dialysis.

OBJECTIVE: The intent of this study was to evaluate the clinical outcome and risk factors affecting mortality of the continuous ambulatory peritoneal dialysis (CAPD) patients in a single peritoneal dialysis (PD) center over a period of 10 years. PATIENTS AND METHODS: We retrospectively analyzed patients on PD from June 2001 to June 2011. The clinical and biochemical data were collected from the medical records. Clinical variables included gender, age at the start of PD, smoking status, body mass index (BMI), cause of end-stage renal disease (ESRD), presence of diabetes mellitus and blood pressure. Biochemical variables included hemoglobin, urine volume, residual renal function (RRF), serum albumin, blood urea nitrogen (BUN), creatinine, total cholesterol, triglyceride, comorbidities, and outcomes. Survival curves were made by the Kaplan-Meier method. Univariate and multivariate analyses to identify mortality risk factors were performed using the Cox proportional hazard regression model. RESULTS: A total of 421 patients were enrolled, 269 of whom were male (63.9%). The mean age at the start of PD was 57.9 ± 14.8 years. Chronic glomerulonephritis was the most common cause of ESRD (39.4%). Estimation of patient survival by Kaplan-Meier was 92.5%, 80.2%, 74.4%, and 55.7% at 1, 3, 5, and 10 years, respectively. Patient survival was associated with age (hazard ratio [HR]: 1.641 [1.027 - 2.622], p = 0.038), cardiovascular disease (HR: 1.731 [1.08 - 2.774], p = 0.023), hypertriglyceridemia (HR: 1.782 [1.11 - 2.858], p = 0.017) in the Cox proportional hazards model analysis. Estimation of technique survival by Kaplan-Meier was 86.7%, 68.8%, 55.7%, and 37.4% at 1, 3, 5, and 10 years, respectively. In the Cox proportional hazards model analysis, age (HR: 1.672 [1.176 - 2.377], p = 0.004) and hypertriglyceridemia (HR: 1.511 [1.050 - 2.174], p = 0.026) predicted technique failure. CONCLUSION: The PD patients in our center exhibited comparable or even superior patient survival and technical survival rates, compared with reports from other centers in China and other countries.

Cytokine profiles in peritoneal dialysis effluent predicts the peritoneal solute transport rate in continuous ambulatory peritoneal dialysis patients.

Cytokine profiles in peritoneal dialysis effluent (PDE) vary among patients of continuous ambulatory peritoneal dialysis (CAPD), which may indicate the therapeutic efficiency of CAPD. We examined the cytokine profiles of PDE with stable CAPD and analyzed their relation with the peritoneal solute transport rate (PSTR). The peritoneal equilibration test (PET) was performed to evaluate peritoneal solute transport rate (PSTR) by calculating dialysate/plasma creatinine (D/P Cr). Patients were then divided into either low and low-average transport (L/A), or high and high average transport (H/A) groups according PET results. Overnight PDE were collected from 30 CAPD patients and various cytokines and growth factors were detected using the Luminex Flex Map 3D system. The concentrations of interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor (TNF)-α in dialysate were 66.4±59.8, 221±96.1 and 1.79±0.34 pg/mL respectively while IL-17A, IL-17F, IL-21, IL-22 or IL-23 could not be detected. Higher IL-6 levels were found in the H/A group as compared with the L/A group (P<0.05); however MCP-1, TNF-α, transforming growth factor (TGF)-ß1 and VEGF levels were not significantly different between these two groups (P>0.05). We found that IL-6, MCP-1, vascular endothelial growth factor (VEGF) and TGF-ß1 levels were closely correlated with each other and all significantly associated with D/P Cr. Multivariate analysis showed that D/P Cr was independently correlated with IL-6 and negatively correlated with serum albumin (r=-0.369, P=0.045). In conclusion, our study indicates that systemic analysis of cytokine profiles in PDE reveals the transport characteristics of CAPD patients. Long-term follow-up study should be necessary to further confirm the value of cytokine detection in evaluation of PD therapeutic efficiency.

Construction of a CTGF and RFP-coexpressed renal tubular epithelial cell and its application on evaluation of CTGF-specific siRNAs on epithelial-mesenchymal transition.

OBJECTIVE: To construct a connective tissue growth factor (CTGF) and red fluorescent protein (RFP)-coexpressed renal tubular epithelial cell that can be used to quantitatively evaluate the CTGF-induced epithelial-mesenchymal transition (EMT). METHODS: The CTGF and RFP coding sequences were linked with a "2A" peptide, cloned into an expressing vector, and the HK-C2AR cell clone, which could express CTGF and RFP, were selected from the HK-2 cells after the recombinant plasmid transfection. Then, the CTGF-induced EMT in this cell line was determined, to further determine the association of RFP fluorescence intensity with the CTGF expression or CTGF-induced EMT. CTGF-specific ribonucleic acid (RNA) interference was also used to reconfirm the association. RESULTS: The constructed HK-C2AR cells could stably express RFP and CTGF proportionally, and the CTGF expressed in the cell line could induce EMT of cells, whereas the RFP expressed in the cell could exhibit bright red fluorescence after excitation. After the silence in CTGF, the RFP expression was also decreased, and the CTGF-induced EMT was also inhibited. CONCLUSION: The CTGF and RFP-coexpressing renal tubular epithelial cell, HK-C2AR, could be used to quantitatively evaluate CTGF-specific small interfering RNAs on EMT by quantitatively detecting the RFP expression. Also, this cell line could be used to quantitatively determine the mechanism of CTGF-induced EMT in renal tubular epithelial cells.

Functional and structural alterations of peritoneum and secretion of fibrotic cytokines in rats caused by high glucose peritoneal dialysis solutions.

OBJECTIVE: To determine functional and structural alterations of peritoneum and fibrotic cytokines expression in peritoneal dialysis (PD) rats. METHODS: 28 Sprague-Dawley (S-D) rats were randomly divided into four groups and dialyzed with various solutions daily for four weeks: (1) no solution (CON group), (2) 0.9% Saline solution (NS group), (3) 1.5% Dianeal (LG group), (4) 4.25% Dianeal (HG group). Peritoneal equilibration tests, ultrafiltration function and effluent protein quantification were measured. Peritoneum morphology was studied and immunohistochemistry were performed for detection of transforming growth factor ß1 (TGF-ß1), connective tissue growth factor (CTGF), and fibronectin (FN) proteins. Reverse transcriptional-polymerase chain reaction was used to analyze the expression of TGF-ß1, CTGF mRNA. RESULTS: Administration of 4.25% Dianeal caused functional and structural changes of peritoneum, including protein loss through the transport process, decrease of peritoneal solute transport rate and ultrafiltration capacity. The collagen of peritoneum in the HG group was thicker than the other groups. The levels of CTGF, TGF-ß1, and FN proteins were significantly the highest in the HG group, followed by the LG group. The liner correlation analysis showed positive correlations between the levels of CTGF, TGF-ß1, and FN proteins and the collagen thickness. The expression of TGF-ß1 and CTGF mRNA in the HG group were significantly higher than those in the other groups and were indicated positive correlation. CONCLUSION: Using high glucose peritoneal dialysis solutions in rats may not only lead to processing of peritoneal fibrosis, which is promoted by ectopic expression of TGF-ß1, but also increase the expression of CTGF. CTGF is an important fibrotic media of peritoneal fibrosis in PD rats.

Greater omentum folding in the open surgical placement of peritoneal dialysis catheters: a randomized controlled study and systemic review.

BACKGROUND: Mechanical catheter dysfunction caused by omentum entrapment remains a major complication of peritoneal dialysis (PD) therapy. The purpose of this study was to determine the outcomes of omentum folding at the time of primary open catheter insertion. METHODS: From March 2008 to December 2012, a total of 67 PD subjects were enrolled in the study and randomly assigned to receive either regular open insertion (ROI group, n = 33) or open insertion with omentum folding (OIOF group, n = 34). The primary outcome was defined as PD catheter tip migration with dysfunction. A systematic review was performed to analyze the outcomes of omentum management in PD catheter implantation, based on published data from 1990 to 2013. RESULTS: There was no statistical difference in baseline patient characteristics between the ROI and OIOF groups. Nine (27.3%) patients in the ROI group presented with catheter malposition in the late stage (>60 days) of the study, significantly more than in the OIOF group (two; 5.9%) (P = 0.049). Significant differences in catheter survival rate between the two groups were observed in the late stage (P = 0.030) and over the entire study period (P = 0.028). A higher incidence of irreversible catheter dysfunction was shown in the ROI group (15.2%), whereas none occurred in the OIOF group (P = 0.031). No statistical difference was determined in other catheter-related complications or patient survival rate. There were no statistical differences in peritoneal transport characteristics or dialysis adequacy between the two groups upon evaluation at 3, 6 and 12 months. Systemic review of current publications suggested that PD catheter placement with omentum management could lead to less irreversible catheter dysfunction and improved outcome of catheter survival. CONCLUSIONS: Our data suggest that omentum folding at the initial time of open catheter placement can significantly reduce the risk of catheter tip migration with dysfunction and improve the outcome of the PD technique.

[Multi-frequency low-dose intravenous iron on oxidative stress in maintenance hemodialysis patients].

OBJECTIVE: To investigate the effect of different intravenous iron treatment regimens on anemia and oxidative stress in maintenance hemodialysis (MHD) patients. METHODS: A total of 58 MHD patients were randomly divided into a multi-frequency low-dose intravenous iron group (iron sucrose 25 mg, twice a week for 8 weeks, n=19), a less-frequency regular-dose intravenous iron group (iron sucrose 100 mg, once every two weeks for 8 weeks, n=19), and a non-iron group (n=20). Another 20 healthy people served as a control group (n=20). The changes of hemoglobin (Hb), hematocrit (HCT), serum ferritin (SF) and transferrin saturation (TSAT), as well as the oxidative stress parameters of malon-dialdehyde (MDA), superoxide dismutase (SOD) and myeloperoxidase (MPO) were detected before and after the treatment. RESULTS: After 8 weeks, compared with the non-iron group, the levels of Hb, HCT, SF and TSAT in the two iron groups were significantly elevated (P<0.01), but there was no difference between the two iron groups (P>0.05). After the single dialysis, the two iron groups had higher level of serum MDA, MPO and lower level of serum SOD than that of the non-iron supplementation group (P<0.01). The multi-frequency low-dose intravenous iron group had lower level of serum MDA [(5.37 ± 0.73) nmol/mL vs (6.37±1.67) nmol/mL], MPO [(81.41±7.60) U/L vs (96.75±16.97) U/L] and higher level of serum SOD [(84.77 ± 14.02) U/mL vs (68.23 ± 4.90) U/mL] than that of the less-frequency regular-dose intravenous iron group. After 8 weeks, there was no significant difference between the two iron groups (P>0.05). CONCLUSION: Multi-frequency low-dose intravenous iron can effectively improve anemia in MHD patients, whose acute oxidative stress is lower than that of less-frequency regular-dose intravenous iron, and is a relatively safe and effective intravenous iron treatment regimen.

Enhancing effect of ultrasound-mediated microbubble destruction on gene delivery into rat kidney via different administration routes.

OBJECTIVE: To investigate the efficiency of ß-galactosidase gene transfer into rat kidney with ultrasound-mediated microbubble destruction via different injection routes. METHODS: A total of 25 Wistar rats were randomly divided into 5 groups. Four groups received a mixture of optison microbubbles (0.2 mL) and lacz plasmids (25 µg) injection via renal artery, tail vein, anterior tibial muscle and renal parenchyma, respectively. The control group received a mixture of PBS (xx mL) and lacz plasmids (25 µg) via renal artery. Three days after the gene transfer, ultrasound with fixed frequency and power (1 MHz, xxW) was delivered to the kidneys for 3 min. The efficiency of the gene transfer and expression was evaluated on the basis of ß-galactosidase expression. The side effects of this method were evaluated by immunohistological method. RESULTS: ß-galactosidase expression could be observed only in tubules but not in glomeruli and interstitial area. The efficiency of renal artery group was higher than that of tail vein, anterior tibial muscle and renal parenchyma group (P<0.05). Immunohistochemical analysis revealed co-expression of ß-galactosidase with a roximal tubule marker, megalin, which suggested that ultrasound enhanced gene transfer into the proximal tubular epithelial cells. No ß-galactosidase expression was observed in the extrarenal organs. There were no evident pathological and biochemical changes after gene transfer. CONCLUSIONS: Ultrasound-mediated microbubble destruction can transfer gene into kidney via renal artery, tail vein, anterior tibial muscle and renal parenchyma. Compared with renal artery, administrating microbubbles via tail vein and anterior tibial muscle are more convenient and less vulnerarious.

[Placement of peritoneal catheters with the assistance of X-ray fluoroscopy].

OBJECTIVE: To evaluate the value of X-ray fluoroscopy in preventing catheter dysfunction during catheterization of peritoneal dialysis. METHODS: A total of 168 patients with end-stage renal failure were nonrandomized into group A (the conventional catheterization group) and group B (the conventional catheterization + bedside fluoroscopy group). All patients were followed up for 1 year after the catheterization. Details of the patients' general information, catheter-related complications and incidence of catheter dysfunction were analyzed. RESULTS: Hemorrhagic complications occurred in 9 patients (5.36%), including 2 incision hematomas, 4 bloody fluid drainages, 1 bladder perforation and 1 intestinal perforation (1.20%). Dialysate leakages occurred in 4 patients (2.38%): 2 right pleural effusion and 2 scrotal edemas. Infection-related complications (2.98%) in 5 patients were observed: 1 infectious peritonitis and 4 catheter exit infections. All peritoneal dialysis-related infections were cured after the treatment. There was no significant difference in the incidence of mechanical and infectious complications between the two groups (P> 0.05). No immediate catheter dysfunction was found in all patients, but late catheter dysfunction was observed in 14 patients (8.33%), including 9 catheter migrations (5.36%), 5 of which were induced by other reasons (2.98%). Catheter dysfunction in 11 out of the 14 patients occurred within 30 days post-catheterization, whereas 2 occurred over 30 days (caused by constipation). In group A, 12 patients developed delayed catheter dysfunction (11.65%), 10 of which (83.33%) were induced by catheter migration and the other 2 by other reasons. In group B, 2 (11.65%) delayed catheter dysfunctions were observed, including 1 catheter migration and 1 constipation. The incidence of catheter dysfunction in group A was significantly higher than that in group B (P<0.05). The success rate of catheterization in group B was 91.3%. CONCLUSION: Catheter dysfunction is a common complication in peritoneal dialysis. X-ray fluoroscopy during catheter insertion helps to monitor the location of the catheter, which can effectively prevent late catheter dysfunction and increase the success of catheterization in peritoneal dialysis.

Relationship between CYP1A1 genetic polymorphisms and renal cancer in China.

AIM: To study the potential role of cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) polymorphisms in the risk of renal cell cancer in Chinese. METHODS: A total of 181 pathologically-proven renal cancers and 350 controls from the second Xiangya Hospital in Changsha were collected during the period from May 2007 to December 2010. CYP1A1 genetic polymorphisms were genotyped using PCRRFLP. Unconditional logistic regression analysis was performed to analyze their relationship with risk of RCC. RESULTS: Individuals with Val/Val genotypes had a significantly increased risk of RCC compared those with CYP1A1 IIe/IIe (OR=1.69, 95%CI=1.03-2.85). We also found CYP1A1 Wt/Vt and Vt/Vt to confer a significantly greater risk than CYP1A1 Wt/Wt (Wt/Vt: OR=2.14, 95%CI=1.24-3.45; Vt/Vt: OR=1.78, 95%CI=1.31-3.96). In smokers, a high increase risk of RCC was observed in those with CYP1A1 Val allele and Vt allele (Val allele: OR=2.13, 95%CI=1.40-2.57; Vt allele: OR=3.75, 95%CI=2.43-6.79), but no other significant interactions were found. CONCLUSION: Our study found suggestive evidence that CYP1A1 polymorphisms may play an important role in the etiology of RCC. Cigarette smoking may increase the susceptibility to RCC carcinogenesis in individuals with a high-risk genotype.

[Stages of 3,547 patients with chronic kidney disease and relevant factor analysis].

OBJECTIVE: To investigate the prevalence and distribution of chronic kidney disease(CKD) in Second Xiangya Hospital of Central South University. METHODS: We retrospectively analyzed the medical records of 3547 CKD patients (>or=14 years old) admitted to Second Xiangya Hospital for the 1st time from January 2003 to December 2008. Glomerular filtration rate (GFR) was estimated by using the MDRD equation abbreviated [eGFR=186.3*SCr-1.154*age-0.203*0.742 (for women) mL/min.1.73 m2]. Data of patients' gender, age, admission number, etiologic and functional diagnose, course of disease, blood pressure, hemoglobin, urine, renal function, blood albumin, and kidney ultra-B were collected. RESULTS: (1) The most common causes for CKD were primary glomerulonephritis(55.20%), hypertension (14.55%) and diabetes (11.78%). The composition of the causes during this 6 years was not significantly different (P>0.05). The proportion of chronic glomerulonephritis declined while that of hypertensive nephropathy and diabetic nephropathy increased as time passed. (2) Patients were respectively distributed from stage 3 to stage 5 at the following percentages: 11.59% (stage 3), 23.03% (stage 4), and 65.38% (stage 5). Middle-aged and young patients (41 years60 years) accounted for 36.88% of the CKD patients. Chronic glomerulonephritis was often seen at 21-40 and 41-60 year olds. Patients with lupus nephritis were younger, 48.35% of whom were 21-40 years old. On the contrary, patients with hypertensive nephropathy and diabetic nephropathy were much older. They were mainly seen in older than 40 year groups. (3) Obstructive nephropathy and gout nephropathy occurred mainly in men while it seemed much easier for women to suffer from lupus nephritis. (4) The majority of CKD patients was accompanied by anemia (94.28%) and hypertension (56.91%), and the incidence and degree of anemia and hypertension increased as CKD developed (P<0.005). CONCLUSION: The top 3 causes of CKD are chronic glomerulonephritis, hypertensive nephropathy, and diabetic nephropathy. The proportion of hypertensive nephropathy and diabetic nephropathy is on the rise. Elderly people are the high risk group for CKD.

Correlation between endothelin-1 and atherosclerosis in chronic hemodialysis patients.

INTRODUCTION: Recent observations suggest that the atherosclerotic process may involve overexpression of ET-1, which could contribute to the formation of atherosclerosis. The aim of the present report was to examine the possible association between carotid IMT and serum ET-1 level and ET-1 expression in the internal iliac artery (IIA) wall in chronic hemodialysis (HD) patients. METHODS: Sixty-eight nondiabetic HD patients and 50 age- and sex-matched healthy normotensive controls participated in the study. Atherosclerotic disease in both groups was assessed by measuring intima-media thickness (IMT) and plaque score of the common carotid arteries using an ultrasound scanner. Levels of serum ET-1, C-reactive protein (CRP), interleukin-6 and lipids profile were measured. Internal iliac artery samples were obtained at the time of renal transplantation. Quantitative expression of ET-1 in internal iliac artery walls was assessed by positive unit (pu) value using an immunohistochemical method. In addition, the IMT and carotid plaque score were analyzed in relation to circulating levels of ET-1 and expression of ET-1 in internal iliac artery walls. RESULTS: Compared with control subjects, HD patients had significantly increased common carotid artery (CCA)-IMT (p=0.002). Atherosclerotic plaques were detected in 42 (61.76%) of HD patients and in 2 (4%) of controls. In HD patients, a close correlation was found between serum ET-1 level and CRP, IL-6 (p<0.01 and p<0.05, respectively). Also we found a close correlation between ET-1 pu value and CRP, IL-6 (p<0.01 and p<0.05 respectively). In HD patients, CCA-IMT and plaque score were correlated significantly with circulating levels of ET-1 (p<0.001 and p<0.05, respectively) and expression of ET-1 in internal iliac artery walls (p<0.01 and p<0.05, respectively). Multivariate analysis showed that serum ET-1 concentrations and expression of ET-1 in internal iliac artery walls were strong independent correlates of CCA-IMT (p=0.004 and p=0.005, respectively). CONCLUSIONS: In HD patients, the circulating levels of ET-1 and expression of ET-1 in internal iliac artery walls were statistically associated with CRP and IL- 6. Moreover, the circulating levels of ET-1 and expression of ET-1 in internal iliac artery walls were independent predictors of carotid atherosclerosis. The correlations may suggest that increased circulating ET-1 level and upregulated expression of ET-1 in the vasculature could contribute to the formation of atherosclerosis in HD patients.

Role of mast cells, stem cell factor and protease-activated receptor-2 in tubulointerstitial lesions in IgA nephropathy.

BACKGROUND: To elucidate the role of mast cells (MCs) in the pathogenesis of tubulointerstitial lesions in IgA nephropathy (IgAN), we investigated the number of MCs, serum stem cell factor (SCF), protease-activated receptor-2 (PAR-2) and alpha-smooth-muscle actin (alpha-SMA) in the kidney and the correlation between MC number, SCF, PAR-2, alpha-SMA and tubulointerstitial lesions in biopsy specimens and serum creatinine levels, urinary protein excretion in patients with IgA nephropathy. METHODS: Thirty-five patients with IgA nephropathy were enrolled in this study. Clinical parameters, such as serum creatinine and urinary protein excretion, were obtained from each patient at the time of biopsy. Paraffin-embedded sections were used for immunohistochemical staining. Monoclonal antibodies to human tryptase, alpha-SMA, and SCF and polyclonal antibody to PAR-2 were used as primary antibodies. Ten cortical interstitial fields were randomly selected and assessed using a computer-assisted color image analyzer. Tubulointerstitial fibrosis was assessed as the percentage of the area stained with Masson trichrome in ten cortical interstitial fields. RESULTS: In all of the control subjects, few tryptase-positive MCs were observed in the glomeruli and interstitium. In contrast, sparse MCs were observed in the interstitium, but not in the glomeruli of diseased kidneys. The number of interstitial MCs in the tubulointerstitial lesions, the expression of SCF, PAR-2 and alpha-SMA were positively correlated with the degree of interstitial fibrosis. A close correlation between MCs, alpha-SMA, PAR-2 and SCF was found (r = 0.887 for alpha-SMA, r = 0.844 for PAR-2, r = 0.853 for SCF, P < 0.01). Also a close correlation between alpha-SMA, PAR-2 and SCF was found (r = 0.874 for PAR-2, r = 0.862 for SCF, P < 0.01). PAR-2 was correlated with SCF (r = 0.893, P < 0.01). Moreover, a significant positive correlation was observed between the number of interstitial MCs, the expression of SCF, PAR-2 and alpha-SMA and the serum creatinine level (r = 0.738 for MCs, r = 0.658 for alpha-SMA, r = 0.692 for PAR-2, r = 0.754 for SCF, P < 0.05). CONCLUSIONS: Our findings suggest that MC infiltration possibly induced by SCF in renal interstitial tissues seems to be associated with tubulointerstitial fibrosis through PAR-2 in IgA nephropathy.

Ultrasound-mediated microbubble destruction enhances beta-galactosidase gene transfection and expression in HKCs.

OBJECTIVE: To investigate the efficiency and safety of ultrasound-mediated microbubble destruction in enhancing beta-galactosidase gene (beta-gal gene) transfer into human proximal tubular cells(HKCs). METHODS: beta-gal gene was transfected to HKCs as a mark gene with ultrasound-mediated microbubble destruction. Cultured HKCs were grouped to receive the following 7 treatments respectively: ultrasound alone; microbubble alone; naked plasmid; ultrasound and plasmid; microbubble and plasmid; ultrasound, microbubble, and plasmid; and VigoFect and plasmid. In Group 6, HKCs were exposed to ultrasound under different sound intensities and time. X-gal staining, trypan blue staining, and Hochest staining were used to detect the transfection efficiency, cell survival rate, and cell apoptosis rate, respectively. RESULTS: Beta-galactosidase expression could be observed in the ultrasound-mediated microbubble destruction groups. Along with the increasing of sound intensity and exposure time, the cell survival rate of HKCs decreased, and the cell apoptosis rate increased gradually. The transduction efficiency and survival rate in middle intensity (0.3 W/cm(2)*60 s) of ultrasound exposure were higher than those of other groups, similar to those of Group 7. CONCLUSION: Under optimum sound intensity and exposure time, ultrasound-mediated microbubble destruction can increase gene transfer into HKCs. This non-invasive gene transfer method may be a useful tool for clinical gene therapy.

[Basic experimental and clinical research on peritoneal dialysis in the past 16 years].

To summarized the experiences from our basic experimental and clinical research on peritoneal dialysis. In the past 16 years, peritoneal fibrosis rat models and rabbit models of peritonitis were first established successfully in our laboratory in China. Peritoneal mesothelial cells were also separated and identificated. Besides, we assessed the biocompatibility of peritoneal dialysis fluid and analyzed the molecular mechanism of peritoneal mesothelial cell injury. We demonstrated the key role of transforming growth factor-beta1 (TGF-beta1), connective tissue growth factor (CTGF) and peroxisome proliferative activated receptor-gamma (PPAR-gamma) in the pathogenesis of peritoneal fibrosis, as well as their regulation of molecular mechanism. Furthermore, we transfected the plasmids encoding TGF-beta1-shRNA or pCTGF-shRNA into peritoneal cells and tissues by nanocarrier technologies. In clinical research, the positioning of peritoneal dialysis catheters, peritoneal dialysis treatment modalities and the prevention and treatment of its complications were studied. The characteristics and mechanism of solute transport in peritoneal dialysis was also explored.