Clinicopathological features, diagnosis, and treatment of IgA nephropathy with minimal change disease related to exposure to mercury-containing cosmetics: a case report
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AIM: Membranous nephropathy and minimal change disease (MCD) have been involved in mercury-induced nephrotic syndrome. IgA nephropathy is not known to be a common pathological type. In the present article, we report a case of IgA nephropathy with MCD following exposure to mercury-containing skin lightening cream. MATERIAL AND METHODS: The patient was a 39-year-old woman who presented with nephrotic syndrome. She had a 6-month history of using as many as 8 kinds of skin-lightening creams, and urinary mercury excretion was high. Renal biopsy revealed IgA nephropathy with MCD. The use of cosmetics was stopped and chelation therapy was given. After 4 courses (1 month) of chelation therapy, there was a complete remission of proteinuria and hematuria, and urine tests remained normal during the 5-year follow-up period. RESULTS AND CONCLUSIONS: The unique clinical and pathological features of IgA nephropathy with MCD had raised the controversial question of whether MCD and IgA deposition are separate entities or a common pathophysiology. Repeated renal biopsy and similar cases were helpful and should be carried out as far as possible.
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Corrigendum to "Irbesartan Ameliorates Diabetic Nephropathy by Suppressing the RANKL-RANK-NF-κB Pathway in Type 2 Diabetic db/db Mice".

[This corrects the article DOI: 10.1155/2016/1405924.].

Irbesartan Ameliorates Diabetic Nephropathy by Suppressing the RANKL-RANK-NF-κB Pathway in Type 2 Diabetic db/db Mice.

The receptor activator of NF-κB ligand (RANKL) and its receptor RANK are overexpressed in focal segmental glomerular sclerosis (FSGS), IgA nephropathy (IgAN), and membranous nephropathy (MN). However, the expression and the potential roles of RANKL and RANK in diabetic nephropathy (DN) remain unclear. Irbesartan (Irb) has beneficial effects against diabetes-induced renal damage, but its mechanisms are poorly understood. Our present study investigated the effects of Irb in DN and whether the renal protective effects of Irb are mediated by RANKL/RANK and the downstream NF-κB pathway in db/db mice. Our results showed that db/db mice revealed severe metabolic abnormalities, renal dysfunction, podocyte injury, and increased MCP-1; these symptoms were reversed by Irb. At the molecular level, RANKL and RANK were overexpressed in the kidneys of db/db mice and Irb downregulated RANKL and RANK and inhibited the downstream NF-κB pathway. Our study suggests that Irb can ameliorate DN by suppressing the RANKL-RANK-NF-κB pathway.

EZH2-inhibitor DZNep enhances apoptosis of renal tubular epithelial cells in presence and absence of cisplatin.

BACKGROUND: The enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase and induces the trimethylation of histone H3 lysine 27 (H3K27me3) in the promoter of many key genes; EZH2 acts as a transcriptional repressor and is an epigenetic regulator for several cancers. However, the role of EZH2 in nonneoplastic diseases, such as kidney diseases, is unknown and has been investigated. MATERIALS AND METHOD: NRK-52E cells were treated with DZNep, a potent inhibitor of EZH2, with different concentrations and for different times to evaluate the apoptosis level of NRK-52E cells by Western blot and Flow cytometry analysis. The binding of EZH2 to the Deptor promoter was determined by ChIP assay. RESULTS: The inhibition of EZH2 with 3-deazaneplanocin A (DZNep), a specific inhibitor of EZH2, led to the apoptosis of NRK-52E cells and the inhibition of mTORC1 and mTORC2 activity. A ChIP assay demonstrated that EZH2 bound the promoter region of Deptor, an endogenous inhibitor of mTORC1 and mTORC2, and regulated the transcription of Deptor by modulating H3K27me3 in its promoter region. Further experiments were performed to examine the effects of EZH2 inhibition on cisplatin-induced injured cells. Cisplatin induced the activation of mTORC1 and mTORC2 and apoptosis in NRK-52E cells, and DZNep inhibited mTORC1 and mTORC2 activity and aggravated cell apoptosis. CONCLUSIONS: These data suggested that EZH2 inhibition increased the transcription of Deptor by modifying H3K27me3 in its promoter region, subsequently inhibited mTORC1 and mTORC2 activities, downregulated the expression of apoptosis suppressor genes, and finally led to apoptosis in renal tubular cells. The inhibition of EZH2 aggravated the cisplatin-induced injury in renal tubular cells by inactivating the mTOR complexes. The present study provides new insight into renal protection and suggests that EZH2 might be a target.

Advanced oxidation protein products promote inflammation in diabetic kidney through activation of renal nicotinamide adenine dinucleotide phosphate oxidase.

The involvement of inflammatory processes has been recognized in development and/or progression of diabetic nephropathy. However, the mechanisms involved in the pathogenesis of renal inflammation have not been completely understood. In this study, we tested the hypothesis that accumulation of advanced oxidation protein products (AOPPs), which occurs in diabetes, may promote inflammatory responses in diabetic kidney. Streptozotocin-induced diabetic rats were randomized to iv injection of vehicle, native rat serum albumin (RSA), and AOPPs-modified RSA (AOPPs-RSA) in the presence or absence of oral administration of apocynin. A control group was followed concurrently. Compared with RSA- or vehicle-treated diabetic rats, AOPPs-RSA-treated animals displayed significant increase in renal macrophage infiltration and overexpression of monocyte chemoattractant protein-1 and TGF-beta1. This was associated with deteriorated structural and functional abnormalities of diabetic kidney, such as glomerular hypertrophy, fibronectin accumulation, and albuminuria. AOPP challenge significantly increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent superoxide generation in renal homogenates and up-regulated membrane expression of renal NADPH oxidase subunits p47(phox) and gp91(phox). All these AOPPs-induced perturbations in diabetic kidney could be prevented by the NADPH oxidase inhibitor apocynin. These data suggest that chronic accumulation of AOPPs may promote renal inflammation in diabetes probably through activation of renal NADPH oxidase.

Hypochlorite modified albumins promote cell death in the tubule interstitium in rats via mitochondrial damage in obstructive nephropathy and the protective effects of antioxidant peptides.

A major feature of the injury sustained by the kidney during obstructive nephropathy is a profound induction of apoptosis in the tubular epithelium. In this study, we explored the central roles of mitochondria and the mechanism of the protective effect of the mitochondrial targeted peptides in tubular cell apoptosis and interstitial fibrosis during obstructive nephropathy. Unilateral ureter obstruction (UUO) was performed on rats, and the animals were randomly assigned to intravenous treatment with normal saline, rat serum albumin (RSA), or HOCl-rat serum albumin (HOCl-RSA) in the presence or absence of SS-31. A sham-operation control group was set up by left ureteral dissociation but not ligation. Compared with the control group, UUO animals displayed fibrotic abnormalities, accompanied by increased expression of collagen-I, fibronectin, α-SMA protein and mRNA in the renal interstitium. They also displayed oxidative stress, as evidenced by increased levels of HOCl-alb, TBARS, and mitochondrial reactive oxygen species (ROS) and a decrease in MnSOD activity in the renal homogenate. Damage to mitochondrial structure and functions was observed, as evidenced by a decrease in the mitochondrial membrane potential (MMP), ATP production, mtDNA copy number alterations and release of cytochrome C (cyto C) from the mitochondria to the cytoplasm. These changes were accompanied by activation of caspase-3, caspase-7, caspase-9, and PARP-1 and increased apoptotic cells in the proximal tubules. HOCl-RSA challenge further exacerbated the above biological effects in UUO animals, but these effects were prevented by administration of SS-31. These data suggested that accumulation of HOCl-alb may promote tubular cell apoptosis and interstitial fibrosis, probably related to mitochondrial oxidative stress and damage, and that SS-31 might contribute to apoptotic pathway suppression via scavenging of ROS in the mitochondria.

Role of mitochondrial dysfunction in renal fibrosis promoted by hypochlorite-modified albumin in a remnant kidney model and protective effects of antioxidant peptide SS-31.

Oxidative stress aggravates renal fibrosis, a pathway involved in almost all forms of chronic kidney disease (CKD). However, the underlying mechanism involved in the pathogenesis of renal oxidative stress has not been completely elucidated. In this study, we explored the role and mechanism of hypochlorite-modified albumin (HOCl-alb) in mediating oxidative stress and fibrotic response in a remnant-kidney rat model. Five-sixths nephrectomy (5/6 NX) was performed on the rats and then the animals were randomly assigned to intravenous treatment with either vehicle alone, or HOCl-rat serum albumin (RSA) in the presence or absence of SS-31 (administered intraperitoneally). A sham-operation control group was set up concurrently. Compared with the control group, 5/6 NX animals displayed marked mitochondrial (mt) dysfunction, as evidenced by decrease of mitochondrial membrane potential (MMP), ATP production, mtDNA copy number alterations and manganese superoxide dismutase (MnSOD) activity, release of cytochrome C (Cyto C) from mitochondria to the cytoplasm, and increase of mitochondrial reactive oxygen species in renal tissues. They also displayed increased levels of HOCl-alb in both plasma and renal tissues. These changes were accompanied by accumulation of extracellular matrix, worsened proteinuria, deteriorated renal function, and a marked increase of macrophage infiltration along with up-regulation of monocyte chemoattractant protein (MCP)-1 and transforming growth factor (TGF)-ß1 expression. HOCl-alb challenge further exacerbated the above biological effects in 5/6 NX animals, but these adverse effects were prevented by administration of SS-31, a mitochondrial targeted antioxidant peptide. These data suggest that accumulation of HOCl-alb may promote renal inflammation and fibrosis, probably related to mitochondrial oxidative stress and dysfunction and that the mitochondrial targeted peptide SS-31 might be a novel therapy for renal fibrosis and chronic renal failure (CRF).

[Effects of statins on delaying progression of chronic kidney disease: a meta-analysis].

OBJECTIVE: Whether statins can slow down the progression of chronic kidney disease (CKD) remains controversial. We performed a meta-analysis to evaluate the effects of statin therapy on disease progression in adult patients with CKD who did not require dialysis therapy. METHODS: We searched the electronic databases for relevant randomized controlled trials (RCTs) published by February 2015. Random-effects meta-analysis of RCTs was used to pool the renal outcomes of the patients. RESULTS: Twenty-eight studies (30 RCTs) involving a total of 45 688 participants were included in the analysis. Compared with the control groups, statins produced no effects in preventing end-stage renal disease (ESRD) [relative risks (RR) 0.98, 95% confidence intervals (CI): 0.91-1.05] and in reducing the risk of doubling of the serum creatinine level (RR 1.43, 95% CI: 0.26-7.79). Statin therapy was associated with a lowered risk of estimated glomerular filtration rate (eGFR) reduction by 25% or more (RR 0.91, 95% CI: 0.83-0.99) and delayed the reduction of eGFR [standardized mean differences (SMD) 0.04, 95% CI: 0.02-0.07]. In subgroup analyses, the benefit of statins on changes in eGFR was statistically significant in patients with moderate CKD (SMD 0.09, 95% CI 0.04-0.13). Among different statins, atorvastatin was associated with a beneficial effect on kidney function (SMD 0.10, 95% CI 0.03-0.17). Patients who received high-intensity statin therapy showed significant changes in eGFR (SMD 0.12, 95% CI: 0.02-0.21). CONCLUSION: Statin therapies may not prevent ESRD or doubling of serum creatinine level, but can improve GFR or delay the reduction of GFR in CKD patients. The therapeutic effects are associated with the patients' baseline eGFR levels, statin types and therapy intensity.

Hypochlorite-Modified Albumin Upregulates ICAM-1 Expression via a MAPK-NF-κB Signaling Cascade: Protective Effects of Apocynin.

Hypochlorite-modified albumin (HOCl-alb) has been linked to endothelial dysfunction, which plays an important role in the development of hypertension, diabetes, and chronic kidney disease. However, whether HOCl-alb induces endothelial dysfunction via vascular inflammation and whether a signaling pathway is involved are unknown and have not been investigated. HOCl-alb was found to upregulate ICAM-1 expression in human umbilical vein endothelial cells (HUVECs) in a time- and dose-dependent manner. HOCl-alb time-dependently phosphorylated ERK1/2 and p38(MAPK). HOCl-alb also activated NF-κB. ICAM-1 expression was dose-dependently inhibited by U0126 (a specific inhibitor of MEK1/2, a signal upstream from ERK1/2), SB203580 (a specific inhibitor of p38(MAPK)), and SN50 (a specific inhibitor of NF-κB). U0126 and SB203580 both counteracted the activation of NF-κB, whereas the phosphorylation of ERK1/2 and p38(MAPK) was not blocked by SN50. ERK1/2 phosphorylation was blocked by U0126 but not by SB203580, and p38(MAPK) activity was reduced by SB203580 but not by U0126. Apocynin, a specific NADPH oxidase (NOX) inhibitor, inhibited ICAM-1 expression and the activity of ERK1/2, p38(MAPK), and NF-κB. These results indicate that HOCl-alb-induced ICAM-1 expression is caused by the activation of a redox-sensitive intracellular signal cascade involving ERK1/2 and p38(MAPK), culminating in the activation of NF-κB and involving NOXs among the upstream signals.

Stent implantation technique through PEG-like pathway for treatment of malignant gastroduodenal obstruction.

OBJECTIVE: To investigate feasibility and safety of stent implantation technique through percutaneous endoscopic gastrostomy (PEG)-like pathway for treatment of malignant gastroduodenal obstructions. METHODS: Twelve patients with malignant gastroduodenal obstructions accepted PEG-like operations. A stent implantation pathway was established in abdominal wall under endoscopic guide. A guide wire and a stent release device were introduced through this pathway followed by an intestinal stent implantation. After operation, efficacy and safety of this technique were assessed by collecting data such as operation time, complications, postoperative medication, and hospitalization time during postoperative 2-12 months of follow-up. RESULTS: Twelve patients were successfully treated with stent implantation technique through PEG-like pathway for the first time. The average operation time was 31 minutes. No severe complications occurred during treatment. On the fourth days after operation, patents were give liquid diet and treatment of rehydration, acid suppression, hemostasis and anti-inflammation. The average hospitalization time was 5 days. The follow-up time was 2-12 months. Twelve (100%) patients achieved complete remissions. The stent related complications and obstruction did not appear within 2 months after operations. The quality of life improved significantly. CONCLUSION: The stent implantation technique through PEG-like pathway for treatment of malignant gastroduodenal obstruction is a feasible, effective, and safe choice.

A novel spherical magnetic compression device for colorectal anastomosis in a Swine model.

BACKGROUND: We designed a novel, spherical magnetic compression colorectal anastomosis device and established a swine model to assess the feasibility and safety, as well as advantages, of the device. METHODS AND MATERIALS: Fifteen animals were divided into five groups (sacrificed on Days 3, 5 7, 9, and 14) with 3 in each group. In each group, a magnetic compression device was used in 2 animals (experimental animals), and a stapled device was used in 1 animal (control animal). Feeding status, bowel movements, the discharge time of the magnetic anastomosis device, burst pressure, and magnetic field strength were recorded. Gross anatomical and histological examinations were performed. RESULTS: The average device discharge time was 7.5 days. The burst pressure increased over time for both the experimental and control animals. Both the gross anatomical and histological examinations suggested that the inflammatory reaction was milder. Healing occurred more quickly, and the incidence of complications was lower for the experimental animals than for the control animals. CONCLUSIONS: The potential benefits of the spherical magnetic compression colorectal anastomosis device, relative to the stapled device, were in terms of effectiveness and complication incidence, which encourages us to further study its application in gastrointestinal anastomosis.

Sesquiterpene lactones inhibit advanced oxidation protein product-induced MCP-1 expression in podocytes via an IKK/NF-κB-dependent mechanism.

Inflammation is a relevant factor in the pathogenesis of diabetes nephropathy (DN). Sesquiterpene lactones (SLs), originally isolated from Tanacetum parthenium, have been reported to exhibit anti-inflammatory effects but few studies have examined their effects on DN. To determine whether advanced oxidation protein products (AOPPs) can induce the expression of chemokine monocyte chemoattractant protein- (MCP-) 1 in cultured mouse podocytes and to explore the mechanisms of the potential renoprotection of SLs, we treated podocytes with AOPPs and SLs (parthenolide and its derivatives micheliolide, compound 1, and compound 2). MCP-1 mRNA and protein expression were tested using quantitative real-time PCR and ELISA, respectively, and the protein levels of IKKß, phospho-IKKß, IκBα, NF-κB p65, phospho-NF-κB p65, and tubulin were analyzed by Western blotting. AOPPs activated the expression of MCP-1 mRNA and protein in a dose- and time-dependent manner, activated IKKß and NF-κB p65, and promoted IκBα degradation. The IKK/NF-κB inhibitor parthenolide decreased AOPP-induced MCP-1 expression. Pretreatment with SLs inhibited MCP-1 mRNA and protein expression and suppressed IKKß and NF-κB p65 phosphorylation and IκBα degradation. Taken together, these findings provide a novel explanation for the anti-inflammatory effects of SLs that will ultimately benefit DN and potentially other inflammatory and immune renal diseases.

Time-averaged serum potassium levels and its fluctuation associate with 5-year survival of peritoneal dialysis patients: two-center based study.

The time-averaged serum potassium was more comprehensive to reflect the all-time changes of serum potassium levels during peritoneal dialysis (PD). However, the association of fluctuation of time-averaged serum potassium level with long-time survival of PD patients remains unknown. In this retrospective study, we included 357 incident PD patients in 2 centers from January 1, 2007 to October 31, 2012 with follow-up through October 31, 2014. Our data demonstrated that it was the lower time-averaged serum potassium level rather than baseline of serum potassium level that was associated with high risk of death. Patients with higher standard deviation (SD) had significantly poorer all-cause (p = 0.016) and cardiovascular mortality (p = 0.041). Among the patients with time-averaged serum potassium levels below 4.0 mEq/L, a lower mean value was more important than its SD to predict death risk. In contrast, the patients with time-averaged serum potassium levels above 4.0 mEq/L, those with serum potassium SD < 0.54 mEq/L, exhibited a higher 3-year and 5-year survival rate for both all-cause and cardiovascular mortality compared to the control groups. Our data clearly suggested both time-averaged serum potassium and its fluctuation contributed disproportionately to the high death risk in PD patients.

[Effect of nitrotyrosine on renal expressions of NF-κB, MCP-1 and TGF-ß1 in rats with diabetic nephropathy].

OBJECTIVE: To observe the effect of nitrotyrosine on renal expressions of nuclear factor-κB (NF-κB), monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-ß1 (TGF-ß1) in rats with diabetic nephropathy (DN). METHODS: Rat DN models established by a single intraperitoneal injection of streptozotocin (STZ) were randomly allocated into model group, nitrotyrosine group and ebselen group, with untreated rats as the normal control group. The rats were given the corresponding drugs for 8 weeks, and after the last administration, the 24-h urinary protein level was measured and the kidneys of the rats were harvested for detecting the protein and mRNA expressions of NF-κB, MCP-1 and TGF-ß1 with immunohistochemistry and RT-PCR, respectively. The pathological changes of the kidneys were assessed microscopically. RESULTS: Compared with those in the model group, the 24-h urinary protein level and expressions of NF-κB, MCP-1 and TGF-ß1 mRNA and protein in the renal tissues were significantly increased by nitrotyrosine treatment, which also caused worsened renal pathology, while treatment with ebselen significantly ameliorated these changes. CONCLUSION: Nitrotyrosine can up-regulate the mRNA and protein expressions of NF-κB, MCP-1 and TGF-ß1 and aggravate the inflammatory reaction in the renal tissue of DN rats to promote the progression of DN.

Role of wild type p53 and double suicide genes in interventional therapy of liver cancer in rabbits.

PURPOSE: To investigate the feasibility of interventional lipiodol embolism and multigene therapy in combination with focal chemotherapy in the treatment of VX2 liver cancer in rabbits. METHODS: Forty five rabbits with cancer larger than 2cm in diameter were randomly divided into five groups (n=9 per group). In Group 1, animals were treated with 0.9% sodium chloride. In Group 2, animals received lipiodol embolism. In Group 3, animals received lipiodol embolism and p53 gene therapy. In Group 4, animals received lipiodol embolism and TK/CD gene therapy. In Group 5, animals received lipiodol embolism and p53 and TK/CD gene therapy. Ultrasonography and CT were performed before and at ten days after interventional therapy. RESULTS: The VX2 model of liver cancer was successfully established in rabbits and interventional therapy smoothly performed. At ten days after interventional therapy, significant difference in the tumor volume was noted among five groups (p<0.05) and different treatments could inhibit the cancer growth. The inhibition of cancer growth was the most evident in the Group 5. Factorial analysis revealed gene therapy with p53 or TK/CD and lipiodol embolism independently exert significantly inhibitory effect on cancer growth. In addition, the suppression on tumor growth rate was the most obvious in the Group 5. CONCLUSIONS: Combination of gene therapy with lipiodol embolism can effectively inhibit the cancer growth and prolong the survival time. These findings demonstrate the effectiveness of multigene therapy in combination with lipiodol embolism in the treatment of liver cancer.

[Effects of Shenkangwan on renal expressions of angiotensin II and its type I receptor in rats with early diabetic nephropathy].

OBJECTIVE: To investigate the effects of Shenkangwan on the expressions of angiotensin II (AngII) and its type I receptor (AT(1)R) and the renalprotection mechanism of Shenkangwan in rats with early diabetic nephropathy (DN). METHODS: The rat models of DN established by a single injection of streptozotocin were randomly divided into 4 groups, namely the model group, Shenkangwan treatment group, irbesartan treatment group, and Shenkangwan and irbesartan treatment group, with normal rats as the control. All the rats received daily gavage for 8 weeks. The urinary protein quality in 24 h and plasma and renal contents of AngII were measured. The expressions of AT1R at the protein and mRNA levels in the kidney tissues were measured by immunohistochemistry and reverse transcription-polymerase chain reaction, respectively. The pathological changes of the kidney were observed microscopically. RESULTS: In DN rats, Shenkangwan reduced the urinary protein quantity in 24 h and the contents of AngII in the plasma and kidney tissues, decreased the renal expressions of AT(1)R protein and mRNA, and alleviated the morphological damage of the kidney. CONCLUSIONS: Shenkangwan offers renalprotection against DN probably by reducing the contents of AngII in the plasma and kidney tissues and inhibiting renal AT(1)R expressions.

[Frequent peritoneal dialysis-related peritonitis: clinical characteristics, risk factors and treatments].

OBJECTIVE: To identify the clinical characteristics and risk factors of frequent peritoneal dialysis (PD)-related peritonitis. METHODS: A retrospective analysis was conducted in the peritonitis patients undergoing continuous ambulatory peritoneal dialysis (CAPD) in our hospital. Frequent PD-related peritonitis was defined by two or more onsets in one year, and the patients with only one onset served as the control group. The clinical and laboratory data of the two groups were compared and the risk factors of PD-related peritonitis analyzed. RESULTS: Forty-four episodes of peritonitis were recorded in the 16 patients with frequent PD-related peritonitis, as compared to 53 episodes in the 45 control patients. Compared with those in the control group, the patients with frequent peritonitis had significantly higher blood pressure (P0.05). Variables identified to be associated with an increased likelihood of frequent PD-related peritonitis included hemoglobulin<70 g/L (OR=0.135, P

[A retrospective analysis of the six-year data of peritoneal dialysis in a single center].

OBJECTIVE: To investigate the epidemiology, peritoneal dialysis (PD) related complications and survival outcomes of 236 patients with end-stage renal disease (ESRD) undergoing continuous ambulatory peritoneal dialysis (CAPD) in our center from January, 2004 to November, 2009. METHODS: The data including patient gender, age, time of PD initiation, addresses, types of medical reimbursement, primary diseases, modes of PD catheter placement surgery, types of PD catheter, PD-related complications, and time of drop out were retrospectively analyzed. PD catheter migration rate, peritonitis rate, drop out rate (DOR), length of the time of PD therapy (TOT), and survival rate were calculated and compared with those of patients in other PD centers. RESULTS: The number of newly introduced patients increased gradually in the years from 2004 to 2009. The mean age of newly introduced patients was 47-/+16 years, and patients with age below 60 years accounted for 77.96%. Patients who paid for their own expenses accounted for 67.37% of all, and the rate of these patients decreased gradually. Similar to that in Asian-Pacific region, chronic glomerulonephritis was the most frequent cause of ESRD followed by diabetic nephropathy. The number of patients with chronic glomerulonephritis or obstructive nephropathy as the primary diseases was greater in this center than that reported in the Asian-Pacific region, accounting for 54.66% and 11.02% of all patients, respectively. In contrast, the patients with diabetic nephropathy or benign arteriolar renal sclerosis were less, accounting for 12.29% and 10.17% of all, respectively. PD catheter migration rate (8.05%) and peritonitis rate (1:44.22 patient-months) were both lower than those reported. The patient survival rates at 1, 2, 3 years were 83.65%, 51.59% and 29.81%, respectively, lower than those of other centers in the developed countries but higher than the mean levels in China. DOR decreased gradually to 11.56% in 2009, and TOT increased to 23.61 months. CONCLUSION: The above characteristics of the patients are related to many factors, including the "PD first" principle, high prevalence of urinary calculosis in the primary source regions of most patients, preventive partial omentum resection in some patients, education and follow-up for patients, and increased expense cover by medical insurance.

[Effects of irbesartan on renal advanced glycation end products and their receptor in rats with early diabetic nephropathy].

OBJECTIVE: To investigate the effect of irbesartan on the renal expressions of advanced glycation end products (AGEs) and their receptor (RAGEs) in rats with early diabetic nephropathy (DN) and the renoprotection mechanism of irbesartan. METHODS: Rat DN models established by a single injection of streptozotocin were randomly divided into the model group and irbesartan treatment group. With normal rats as the control, all the rats received daily gavage for 8 weeks. The 24-h urinary protein excretion and contents of AGEs in the serum and kidney tissues were measured. The expressions of RAGEs and RAGEs protein and mRNA in the kidney tissues were detected by immunohistochemistry and reverse transcription-polymerase chain reaction, respectively. The pathological changes of the kidney were also assessed microscopically. RESULTS: Irbesartan significantly reduced the 24-h urinary protein excretion and the contents of AGEs in the serum and kidney tissues of DN rats, resulting also in decreased expressions of RAGEs and RAGEs protein and mRNA levels in the kidney. The treatment obviously alleviated the pathological changes in the kidney of the DN rats. CONCLUSION: Irbesartan offers renoprotection against DN possibly by reducing the serum and renal contents of AGEs and inhibiting the renal mRNA expressions of RAGEs and RAGEs.

Advanced oxidation protein products activate vascular endothelial cells via a RAGE-mediated signaling pathway.

The accumulation of advanced oxidation protein products (AOPPs) has been linked to vascular lesions in diabetes, chronic renal insufficiency, and atherosclerosis. However, the signaling pathway involved in AOPPs-induced endothelial cells (ECs) perturbation is unknown and was investigated. AOPPs modified human serum albumin (AOPPs-HSA) bound to the receptor for advanced glycation end products (RAGE) in a dose-dependent and saturable manner. AOPPs-HSA competitively inhibited the binding of soluble RAGE (sRAGE) with its preferential ligands advanced glycation end products (AGEs). Incubation of AOPPs, either prepared in vitro or isolated from uremic serum, with human umbilical vein ECs induced superoxide generation, activation of NAD(P)H oxidase, ERK 1/2 and p38, and nuclear translocation of NF-kappaB. Activation of signaling pathway by AOPPs-ECs interaction resulted in overexpression of VCAM-1 and ICAM-1 at both gene and protein levels. This AOPPs-triggered biochemical cascade in ECs was prevented by blocking RAGE with either anti-RAGE IgG or excess sRAGE, but was not affected by the neutralizing anti-AGEs IgG. These data suggested that AOPPs might be new ligands of endothelial RAGE. AOPPs-HSA activates vascular ECs via RAGE-mediated signals.