Changlin Mei - Academia.edu (original) (raw)

Papers by Changlin Mei

Nephrology Dialysis Transplantation, 2019

Background Peritoneal dialysis (PD) patients are at high risk of developing glucose metabolism di... more Background Peritoneal dialysis (PD) patients are at high risk of developing glucose metabolism disturbance (GMD). The incidence and prevalence of new-onset GMD, including diabetes mellitus (DM), impaired glucose tolerance (IGT) and impaired fast glucose (IFG), after initiation of PD, as well as their correlated influence factors, varies among studies in different areas and of different sample sizes. Also, the difference compared with hemodialysis (HD) remained unclear. Thus we designed this meta-analysis and systematic review to provide a full landscape of the occurrence of glucose disorders in PD patients. Methods We searched the MEDLINE, Embase, Web of Science and Cochrane Library databases for relevant studies through September 2018. Meta-analysis was performed on outcomes using random effects models with subgroup analysis and sensitivity analysis. Results We identified 1124 records and included 9 studies involving 13 879 PD patients. The pooled incidence of new-onset DM (NODM) w...

Computational Statistics Data Analysis, Aug 1, 2007

In this article we propose a procedure to estimate a two-components mixture model where one compo... more In this article we propose a procedure to estimate a two-components mixture model where one component is known. The unknown part is estimated with a weighted kernel function. The weights are defined in an adaptative way. We prove the convergence and unicity of our estimation procedure. Using simulations, we compared the proposed procedure with two classical approaches. We also applied our results to multiple testing procedure to estimate the posterior population probabilities and the local FDR.

BMJ open, 2015

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder... more Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder with numerous cysts developing in bilateral kidneys. Meanwhile, ADPKD can also be regarded as a systemic disease because the cystic and non-cystic abnormalities could be identified in multiple organs in patients with ADPKD. Several lines of evidence suggest the risk of post-transplant diabetes mellitus or new-onset diabetes after transplantation (NODAT) is higher in patients with ADPKD compared with non-ADPKD renal recipients, but the available results are conflicting. We describe the protocol of a systematic review and meta-analysis for investigating the risk of NODAT in patients with ADPKD. PubMed, EMBASE and The Cochrane Library will be searched. Cohort studies irrespective of language and publication status, comparing the incidence of NODAT in renal recipients with ADPKD and other kidney disease will be eligible. We will assess heterogeneity among studies. Along with 95% CIs, dichot...

Lancet (London, England), Jan 10, 2015

Acute kidney injury (AKI) has become a worldwide public health problem, but little information is... more Acute kidney injury (AKI) has become a worldwide public health problem, but little information is available about the disease burden in China. We aimed to evaluate the burden of AKI and assess the availability of diagnosis and treatment in China. We launched a nationwide, cross-sectional survey of adult patients who were admitted to hospital in 2013 in academic or local hospitals from 22 provinces in mainland China. Patients with suspected AKI were screened out on the basis of changes in serum creatinine by the Laboratory Information System, and we reviewed medical records for 2 months (January and July) to confirm diagnoses. We assessed rates of AKI according to two identification criteria: the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) AKI definition and an increase or decrease in serum creatinine by 50% during hospital stay (expanded criteria). We estimated national rates with data from the 2013 report by the Chinese National Health and Family Planning Commission and ...

International journal of biological sciences, 2015

The Hippo signaling pathway and its transcriptional co-activator Yap are known as essential regul... more The Hippo signaling pathway and its transcriptional co-activator Yap are known as essential regulators for cell proliferation and organ size. However, little is known about their roles in kidney development and ciliogenesis. We examined expression of Yap during zebrafish embryogenesis, and its transcripts were detected in pronephric duct, while Yap protein was found to be localized in the cytoplasm and apical membrane in kidney epithelium cells. By morpholino (MO) knockdown of yap expression in zebrafish, the injected larve exhibits pronephic cysts and many aspects of ciliopathy, which can be rescued by full-length yap mRNA, but not yap (S127A) mRNA. With transgenic Tg(Na(+)/K(+) ATPase:EGFP), we found that lacking Yap led to expansion and discontinuities of pronephric duct, as well as disorganization of cloaca during pronephros morphogenesis. Mis-located Na(+)/K(+) ATPase and ciliary abnormalities are also detected in pronephric duct of yap morphants. In addition, genetic analysis ...

Renal Failure, 2015

Hemodialysis catheters remain necessary for long-term vascular access in patients for whom arteri... more Hemodialysis catheters remain necessary for long-term vascular access in patients for whom arteriovenous access may be problematic or impossible. Developments in catheter design have improved long-term catheter functionality, and reduced the rate of infection and complications associated with their use. This retrospective study of 284 cases of chronic catheterization in 271 patients treated between 2009 and 2011 using Tal Palindrome™ symmetrical-tip (N = 118) or Quinton™ Permcath™ step-tip (N = 166) hemodialysis catheters evaluates the efficacy and the safety of symmetrical-tip dialysis catheters for chronic hemodialysis, compared with a step-tip catheter. Measurements of catheter performance included mean catheter dwell time, incidence of low blood flow, and rates of infection and catheter-related blood stream infection (CRBSI). The symmetrical-tip catheter had a significantly longer mean dwell time compared with the step-tip catheter; 329.4 ± 38.1 versus 273.1 ± 25.4 d (p < 0.05). In addition, the rate of occurrence of low blood flow per 1000 catheter days was lower for the symmetrical-tip compared with the step-tip catheter; 1.13 versus 6.86 (p < 0.01). The symmetrical-tip catheter was also associated with a lower incidence of complications; the rates of infection (0.28 vs. 0.78; p < 0.01) and CRBSI (0.15 vs. 0.44; p < 0.01) were lower compared with those for step-tip catheters, and catheter removal occurred less often for the symmetrical-tip catheter (8% vs. 16%; p < 0.05). The symmetrical-tip hemodialysis catheter was associated with a longer mean dwell time, lower incidence of low blood flow, and lower infection rate compared with the step-tip catheter.

Journal of the American Society of Nephrology : JASN, Jan 13, 2015

Ischemia-reperfusion injury contributes to tissue damage and organ failure in clinical settings, ... more Ischemia-reperfusion injury contributes to tissue damage and organ failure in clinical settings, but the underlying mechanism remains elusive and effective therapies are still lacking. Here, we identified microRNA 687 (miR-687) as a key regulator and therapeutic target in renal ischemia-reperfusion injury. We show that miR-687 is markedly upregulated in the kidney during renal ischemia-reperfusion in mice and in cultured kidney cells during hypoxia. MiR-687 induction under these conditions was mediated by hypoxia-inducible factor-1 (HIF-1). Upon induction in vitro, miR-687 repressed the expression of phosphatase and tensin homolog (PTEN) and facilitated cell cycle progression and apoptosis. Blockade of miR-687 preserved PTEN expression and attenuated cell cycle activation and renal apoptosis, resulting in protection against kidney injury in mice. Collectively, these results unveil a novel HIF-1/miR-687/PTEN signaling pathway in ischemia-reperfusion injury that may be targeted for th...

Seminars in Nephrology, 2009

Chronic inflammation, characterized by increased serum levels of tumor necrosis factor-␣, interle... more Chronic inflammation, characterized by increased serum levels of tumor necrosis factor-␣, interleukin-6, C-reactive protein, and plasminogen activator inhibitor-1, and the presence of inflammatory-related diseases, are seen commonly in aging. Both the dysregulation of immune cells and phenotypic changes in parenchymal cells may contribute to chronic inflammation in aging. Moreover, senescent cells are an important source of inflammatory factors. Oxidative stress, via activation of p38 and c-Jun N-terminal kinase and induction of cell senescence, is likely to play a critical role in inflammation. Endoplasmic reticulum stress also may be present in aging and be involved in inflammation. Advanced glycation end products also are important contributors to inflammation in aging. Because the kidney is a major site for the excretion, and perhaps the degradation, of advanced glycation end products and small inflammatory molecules, reduced renal function in aging may promote oxidative stress and inflammation. Chronic inflammation in turn may potentiate the initiation and progression of lesions in the aging kidney. Semin Nephrol 29:555-568

Sleep medicine reviews, Jan 10, 2014

We conducted a meta-analysis to summarise and quantify the effects of non-pharmacological interve... more We conducted a meta-analysis to summarise and quantify the effects of non-pharmacological interventions on sleep quality improvement in uraemic patients on dialysis. We defined the primary outcome as the change of sleep quality before and after interventions (evaluated by polysomonography or subjective questionnaires such as Pittsburgh sleep quality index, PSQI). The change of fatigue scales, inflammatory cytokines and adverse events were analysed as secondary outcomes. Twelve eligible randomised controlled trials and one prospective cohort study were identified. All three identified non-pharmacological interventions could result in a greater PSQI score reduction compared to controls: 1) cognitive-behavioural therapy (CBT) versus sleep hygiene education (standardised mean difference (SMD) 0.85, 95% CI 0.37-1.34); 2) physical training versus no training (SMD 3.36, 95% CI 2.16-4.57) and 3) Acupressure (including other acupoints massages) versus control (SMD 1.77, 95% CI 0.80-2.73). In...

International journal of molecular medicine, 2014

Experimental studies have demonstrated the protective effect of heme oxygenase (HO)-1 and cyclin‑... more Experimental studies have demonstrated the protective effect of heme oxygenase (HO)-1 and cyclin‑dependent kinase inhibitors (CDKIs) in acute kidney injury (AKI), and it has been documented that some of the protective effect of HO-1 is mediated by CDKIs. However, the role of p18INK4c (p18), an inhibitor of CDK4 (INK4), which is a family member of CDKIs, has not been well characterized in kidney diseases. The aim of the present study was to demonstrate p18 protection from the relationship between p18 and HO-1 in cisplatin-induced AKI. Upregulation of p18 and HO-1 was demonstrated by quantitative polymerase chain reaction (qPCR) and western blotting in cisplatin-induced AKI in vitro and in vivo. The effect of HO-1 on p18 was determined by western blotting using the inducer and inhibitor of HO-1 in vitro. The potential effect of p18 on HO-1 in cisplatin‑induced AKI was examined by p18 gene knockout mice in vivo. The results showed that p18 and HO-1 were upregulated in cisplatin‑induced...

Medical science monitor : international medical journal of experimental and clinical research, 2015

With a prevalence of about 1:500 to 1:1,000, autosomal dominant polycystic kidney disease (ADPKD)... more With a prevalence of about 1:500 to 1:1,000, autosomal dominant polycystic kidney disease (ADPKD) often causes renal failure, with many serious complications. However, there is no Food and Drug Administration (FDA) approved therapy available. MiR-199a-5p level in ADPKD patient samples, rat model, and cell lines were determined with Realtime PCR assay. After miR-199a-5p inhibitor was transfected, we detected the cell proliferation and apoptosis using an MTT assay and an Annexin V-FITC staining kit, respectively. Finally, TargetScan version 5.1 was used to predict the miRNA target and the target gene of miR-199a-5p was proved by a Luciferase assay. We identified a dramatically up-regulated microRNA, miR-199a-5p, in ADPKD tissues and cell lines. Our data show that inhibition of miR-199a-5p suppressed cyst cells proliferation and induced cell apoptosis. We found that miR-199a-5p might exert this effect through targeting CDKN1C/p57. Up-regulation of miR-199a-5p in ADPKD tissues might pro...

Experimental and therapeutic medicine, 2014

Cyclosporine A (CsA) is an immunosuppressant agent and is utilized as a second-line drug therapy ... more Cyclosporine A (CsA) is an immunosuppressant agent and is utilized as a second-line drug therapy for refractory nephrotic syndrome (RNS). In general, the use of CsA is strictly controlled in patients with an estimated glomerular filtration rate (eGFR) <30-40 ml/min/1.73 m(2), and little is known about the safety and efficacy of CsA treatment in patients with RNS complicated by renal dysfunction. In the present study, the clinical data of 10 patients with RNS and renal dysfunction, who received CsA treatment between 2000 and 2009 in the Kidney Institute of PLA, were reviewed retrospectively. Pathologically, these patients included six cases with minimal change, two cases of diffuse mesangial proliferation and two cases of focal segmental glomerulosclerosis. Six months subsequent to the initiation of the CsA treatment, six patients achieved complete remission, two patients achieved remarkable remission and two patients achieved partial remission. Renal function was improved in all ...

Toxicology and Applied Pharmacology, 2013

The kidney is a primary target for numerous toxic compounds. Cytochrome P450 enzymes (P450) are r... more The kidney is a primary target for numerous toxic compounds. Cytochrome P450 enzymes (P450) are responsible for the metabolic activation of various chemical compounds, and in the kidney are predominantly expressed in proximal tubules. The aim of this study was to test the hypothesis that renal proximal tubular P450s are critical for nephrotoxicity caused by chemicals such as chloroform. We developed two new mouse models, one having proximal tubule-specific deletion of the cytochrome P450 reductase (Cpr) gene (the enzyme required for all microsomal P450 activities), designated proximal tubule-Cpr-null (PTCN), and the other having proximal tubule-specific rescue of CPR activity with the global suppression of CPR activity in all extra-proximal tubular tissues, designated extra-proximal tubule-Cpr-low (XPT-CL). The PTCN, XPT-CL, Cpr-low (CL), and wild-type (WT) mice were treated with a single oral dose of chloroform at 200mg/kg. Blood, liver and kidney samples were obtained at 24h after the treatment. Renal toxicity was assessed by measuring BUN and creatinine levels, and by pathological examination. The blood and tissue levels of chloroform were determined. The severity of toxicity was less in PTCN and CL mice, compared with that of WT and XPT-CL mice. There were no significant differences in chloroform levels in the blood, liver, or kidney, between PTCN and WT mice, or between XPT-CL and CL mice. These findings indicate that local P450-dependent activities play an important role in the nephrotoxicity induced by chloroform. Our results also demonstrate the usefulness of these novel mouse models for studies of chemical-induced kidney toxicity.

International Journal of Molecular Medicine, 2014

Unlike native high-density lipoprotein (HDL), oxidized HDL exerts adverse effects in a number of ... more Unlike native high-density lipoprotein (HDL), oxidized HDL exerts adverse effects in a number of diseases, including chronic kidney disease (CKD); however, the mechanisms involved in this process remain unclear. In the present study, we investigated the effects of oxidized HDL on renal tubular cells, which play an important role in the progression of CKD. Human renal proximal tubule epithelial cells (HK-2) were cultured and stimulated with various concentrations of oxidized HDL in the absence or presence of CD36 siRNA. The results revealed that oxidized HDL enhanced the production of reactive oxygen species (ROS) and upregulated the expression of pro-inflammatory factors in the HK-2 cells in a dose-dependent manner. Incubation with oxidized HDL also increased the apoptosis of the HK-2 cells and reduced their migration ability in a dose‑dependent manner. Src family kinase, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) were activated following stimulation with oxidized HDL. All these effects mediated by oxidized HDL on HK-2 cells were markedly attenuated by transfection with with CD36 siRNA pior to stimulation with oxidized HDL. These findings suggest that oxidized HDL enhances the pro-inflammatory properties and impairs the function of HK-2 cells, mainly through the scavenger receptor, CD36, as well as through the Src, MAPK and NF-κB pathways.

International journal of molecular medicine, 2014

Protection of cyclin-dependent kinase inhibitors (CDKIs) has been demonstrated in acute kidney in... more Protection of cyclin-dependent kinase inhibitors (CDKIs) has been demonstrated in acute kidney injury (AKI). However, previous studies on CDKIs have mainly focused on CIP/KIP family members, with INK4 family members rarely being investigated. This study investigated the behaviors of p18(INK4c) (p18) in cisplatin-induced AKI using p18 gene knockout mice (p18-/-). AKI was induced in p18-/- and wild-type (p18+/+) mice after a single cisplatin (12.5 mg/kg) intraperitoneal injection. Protection by p18 was identified by a comparison of survival, renal function and morphological injuries between p18-/- and p18+/+ mice. Further investigation of endoplasmic reticulum stress (ERS) was performed by western blot analysis in p18-/- and p18+/+ kidneys at day 3 after cisplatin injection. The results revealed that after cisplatin injection, the survival of p18-/- mice was significantly shorter than that of p18+/+ mice, accompanied by aggravated renal function and more severe morphological injuries....

Molecular Medicine Reports, 2014

Mesangial proliferative glomerulonephritis (MsPGN) is characterized by widespread mesangial cell ... more Mesangial proliferative glomerulonephritis (MsPGN) is characterized by widespread mesangial cell proliferation and an accumulation of extracellular matrix (ECM) in the mesangial area. In a previous study we developed a polycystin‑1 N‑terminal fragment (PC‑1 NF) fusion protein that inhibits the proliferation of cyst‑lining epithelial cells in autosomal dominant polycystic kidney disease. In addition, the PC‑1 NF fusion protein arrests the cell cycle of cancer cells at the G0/G1 phase, inhibiting their proliferation. In the present study, the effect of the PC‑1 NF fusion protein on MsPGN was investigated. It was found that the PC‑1 NF fusion protein inhibited the proliferation of rat mesangial cells and induced G0/G1 phase arrest and apoptosis in vitro. PC‑1 NF fusion protein treatment also resulted in a decrease in mRNA expression levels of proliferating cell nuclear antigen, cyclin D1 and B‑cell lymphoma‑2 (Bcl‑2) and an increase in mRNA expression levels of Bcl‑2‑associated X protein (Bax) and p21Waf1. Furthermore, a decrease in Bcl‑2, c‑fos, c‑jun and protein kinase C‑α protein levels was observed, whereas Bax protein levels increased. Additionally, PC‑1 NF fusion protein induced ECM degradation and inhibited ECM expansion. The results also demonstrated that PC‑1 NF fusion protein treatment resulted in a decrease in type IV collagen and tissue inhibitor of metalloproteinase mRNA levels but an increase in matrix metalloproteinase 2 mRNA levels. In combination, these results suggest that the PC‑1 NF fusion protein inhibits proliferation, promotes apoptosis and induces ECM degradation in MsPGN rats. This study offers novel perspectives for the treatment of MsPGN.

World Journal of Urology, 2009

Hypertension in ESRD patients is common, and often refractory to common medical interventions. Bi... more Hypertension in ESRD patients is common, and often refractory to common medical interventions. Bilateral renal embolization (BRE) is an alternative to nephrectomy in treating severe refractory hypertension in hemodialysis patients, but has drawbacks in residual renal function preservation and post-infarction syndrome. We evaluated the efficacy and safety of unilateral renal embolization (URE) for the treatment of severe refractory hypertension in hemodialysis patients. From January 2000 to May 2007, 16 hemodialysis patients with severe refractory hypertension were randomized to URE or BRE group, and received percutaneous transcatheter unilateral or bilateral renal embolization, respectively. The efficacy and complications of these two procedures were compared. The plasma renin activity (PRA), plasma angiotensin II, aldosterone and endothelin-1 (ET-1) were measured pre- and post-renal embolization in both groups. The procedures were completed successfully without severe immediate complications. The blood pressure decreased from 211/122 to 127/81 mmHg in URE group (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), and in BRE group from 208/117 to 124/76 mmHg (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) with significantly reduced need for antihypertensive medications. The residual renal function was reasonably kept and post-infarction syndrome was milder in URE group compared with BRE group. No activation of RAS was observed in this series and no RAS activity dynamic change occurred post-procedure. Decreased circulating ET-1 was accompanied with the lowering of blood pressure after the procedure (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Unilateral renal embolization is as effective as BRE in treating severe refractory hypertension in hemodialysis patients, with advantages over BRE in residual renal function preservation and milder post-infarction syndrome.

Nephron Experimental Nephrology, 2005

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in two genes, PKD1 an... more Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in two genes, PKD1 and PKD2. The complexity of these genes, particularly PKD1, has complicated genetic screening, though recent advances have provided new opportunities for amplifying these genes. In the Han Chinese population, no complete mutational analysis has previously been conducted across the entire span of PKD1 and PKD2. Here, we used single-strand conformation polymorphism (SSCP) analysis to screen the entire coding sequence of PKD1 and PKD2 in 85 healthy controls and 72 Han Chinese from 24 ADPKD pedigrees. In addition to 11 normal variants, we identified 17 mutations (12 in PKD1 and 5 in PKD2), 15 of which were novel ones (11 for PKD1 and 4 for PKD2). We did not identify any seeming mutational hot spots in PKD1 and PKD2. Notably, we found several disease-associated C-T or G-A mutations that led to charge or hydrophobicity changes in the corresponding amino acids. This suggests that the mutations cause conformational alterations in the PKD1 and PKD2 protein products that may impact the normal protein functions. Our study is the first report of screenable mutations in the full-length PKD1 and PKD2 genes of the Han Chinese, and also offers a benchmark for comparisons between Caucasian and Han ADPKD pedigrees and patients.

British Journal of Nutrition, 2010

Dietary protein restriction is one major therapy in chronic kidney disease (CKD), and ketoacids h... more Dietary protein restriction is one major therapy in chronic kidney disease (CKD), and ketoacids have been evaluated in CKD patients during restricted-protein diets. The objective of the present study was to compare the efficacy of a low-protein diet supplemented with ketoacids (LPD þ KA) and a low-protein diet alone (LPD) in halting the development of renal lesions in CKD. 5/6 Nephrectomy Sprague -Dawley rats were randomly divided into three groups, and fed with either 22 % protein (normal-protein diet; NPD), 6 % protein (LPD) or 5 % protein plus 1 % ketoacids (LPD þ KA) for 24 weeks. Sham-operated rats were used as controls. Each 5/6 nephrectomy group included fifteen rats and the control group included twelve rats. Proteinuria, decreased renal function, glomerular sclerosis and tubulointerstitial fibrosis were found in the remnant kidneys of the NPD group. Protein restriction ameliorated these changes, and the effect was more obvious in the LPD þ KA group after 5/6 nephrectomy. Lower body weight and serum albumin levels were found in the LPD group, indicating protein malnutrition. Lipid and protein oxidative products were significantly increased in the LPD group compared with the LPD þ KA group. These findings indicate that a LPD supplemented with ketoacids is more effective than a LPD alone in protecting the function of remnant kidneys from progressive injury, which may be mediated by ketoacids ameliorating protein malnutrition and oxidative stress injury in remnant kidney tissue.

PROTEOMICS - CLINICAL APPLICATIONS, 2008

Protein phosphorylation is a very important PTM. Phosphorylation/dephosphorylation of a protein c... more Protein phosphorylation is a very important PTM. Phosphorylation/dephosphorylation of a protein can alter its behavior in almost every conceivable way. Previous studies indicate that abnormal phosphorylation is involved in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). However, large-scale proteomic analysis of altered phosphoproteins in ADPKD has not been reported. In this study, total proteins from ADPKD cystic kidney tissues (n = 5) and normal kidney tissues (n = 5) were extracted and phosphoproteins were enriched by phosphate metal affinity chromatography, then separated by 2-DE and identified by LC-MS/MS. Between the two groups, 48 protein spots showing more than a twofold difference were detected. Among them, 28 spots were up-regulated and 20 down-regulated in ADPKD kidney tissues. Of these, 38 different proteins were identified including cell signaling proteins, cytoskeleton proteins, mitochondria metabolic enzymes, antioxidant proteins, molecular chaperones, transcription factors and regulators. Two differential phosphoproteins, annexin II and tropomyosin, were further confirmed by immunoprecipitation and Western blot analysis. The results show that there are many kinds of abnormal phosphoproteins in ADPKD cystic kidney tissues. More studies on the functions of the differential phosphoproteins may provide us new clues for ADPKD pathogenesis and treatment.

Nephrology Dialysis Transplantation, 2019

Background Peritoneal dialysis (PD) patients are at high risk of developing glucose metabolism di... more Background Peritoneal dialysis (PD) patients are at high risk of developing glucose metabolism disturbance (GMD). The incidence and prevalence of new-onset GMD, including diabetes mellitus (DM), impaired glucose tolerance (IGT) and impaired fast glucose (IFG), after initiation of PD, as well as their correlated influence factors, varies among studies in different areas and of different sample sizes. Also, the difference compared with hemodialysis (HD) remained unclear. Thus we designed this meta-analysis and systematic review to provide a full landscape of the occurrence of glucose disorders in PD patients. Methods We searched the MEDLINE, Embase, Web of Science and Cochrane Library databases for relevant studies through September 2018. Meta-analysis was performed on outcomes using random effects models with subgroup analysis and sensitivity analysis. Results We identified 1124 records and included 9 studies involving 13 879 PD patients. The pooled incidence of new-onset DM (NODM) w...

Computational Statistics Data Analysis, Aug 1, 2007

In this article we propose a procedure to estimate a two-components mixture model where one compo... more In this article we propose a procedure to estimate a two-components mixture model where one component is known. The unknown part is estimated with a weighted kernel function. The weights are defined in an adaptative way. We prove the convergence and unicity of our estimation procedure. Using simulations, we compared the proposed procedure with two classical approaches. We also applied our results to multiple testing procedure to estimate the posterior population probabilities and the local FDR.

BMJ open, 2015

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder... more Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder with numerous cysts developing in bilateral kidneys. Meanwhile, ADPKD can also be regarded as a systemic disease because the cystic and non-cystic abnormalities could be identified in multiple organs in patients with ADPKD. Several lines of evidence suggest the risk of post-transplant diabetes mellitus or new-onset diabetes after transplantation (NODAT) is higher in patients with ADPKD compared with non-ADPKD renal recipients, but the available results are conflicting. We describe the protocol of a systematic review and meta-analysis for investigating the risk of NODAT in patients with ADPKD. PubMed, EMBASE and The Cochrane Library will be searched. Cohort studies irrespective of language and publication status, comparing the incidence of NODAT in renal recipients with ADPKD and other kidney disease will be eligible. We will assess heterogeneity among studies. Along with 95% CIs, dichot...

Lancet (London, England), Jan 10, 2015

Acute kidney injury (AKI) has become a worldwide public health problem, but little information is... more Acute kidney injury (AKI) has become a worldwide public health problem, but little information is available about the disease burden in China. We aimed to evaluate the burden of AKI and assess the availability of diagnosis and treatment in China. We launched a nationwide, cross-sectional survey of adult patients who were admitted to hospital in 2013 in academic or local hospitals from 22 provinces in mainland China. Patients with suspected AKI were screened out on the basis of changes in serum creatinine by the Laboratory Information System, and we reviewed medical records for 2 months (January and July) to confirm diagnoses. We assessed rates of AKI according to two identification criteria: the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) AKI definition and an increase or decrease in serum creatinine by 50% during hospital stay (expanded criteria). We estimated national rates with data from the 2013 report by the Chinese National Health and Family Planning Commission and ...

International journal of biological sciences, 2015

The Hippo signaling pathway and its transcriptional co-activator Yap are known as essential regul... more The Hippo signaling pathway and its transcriptional co-activator Yap are known as essential regulators for cell proliferation and organ size. However, little is known about their roles in kidney development and ciliogenesis. We examined expression of Yap during zebrafish embryogenesis, and its transcripts were detected in pronephric duct, while Yap protein was found to be localized in the cytoplasm and apical membrane in kidney epithelium cells. By morpholino (MO) knockdown of yap expression in zebrafish, the injected larve exhibits pronephic cysts and many aspects of ciliopathy, which can be rescued by full-length yap mRNA, but not yap (S127A) mRNA. With transgenic Tg(Na(+)/K(+) ATPase:EGFP), we found that lacking Yap led to expansion and discontinuities of pronephric duct, as well as disorganization of cloaca during pronephros morphogenesis. Mis-located Na(+)/K(+) ATPase and ciliary abnormalities are also detected in pronephric duct of yap morphants. In addition, genetic analysis ...

Renal Failure, 2015

Hemodialysis catheters remain necessary for long-term vascular access in patients for whom arteri... more Hemodialysis catheters remain necessary for long-term vascular access in patients for whom arteriovenous access may be problematic or impossible. Developments in catheter design have improved long-term catheter functionality, and reduced the rate of infection and complications associated with their use. This retrospective study of 284 cases of chronic catheterization in 271 patients treated between 2009 and 2011 using Tal Palindrome™ symmetrical-tip (N = 118) or Quinton™ Permcath™ step-tip (N = 166) hemodialysis catheters evaluates the efficacy and the safety of symmetrical-tip dialysis catheters for chronic hemodialysis, compared with a step-tip catheter. Measurements of catheter performance included mean catheter dwell time, incidence of low blood flow, and rates of infection and catheter-related blood stream infection (CRBSI). The symmetrical-tip catheter had a significantly longer mean dwell time compared with the step-tip catheter; 329.4 ± 38.1 versus 273.1 ± 25.4 d (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). In addition, the rate of occurrence of low blood flow per 1000 catheter days was lower for the symmetrical-tip compared with the step-tip catheter; 1.13 versus 6.86 (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). The symmetrical-tip catheter was also associated with a lower incidence of complications; the rates of infection (0.28 vs. 0.78; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) and CRBSI (0.15 vs. 0.44; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) were lower compared with those for step-tip catheters, and catheter removal occurred less often for the symmetrical-tip catheter (8% vs. 16%; p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). The symmetrical-tip hemodialysis catheter was associated with a longer mean dwell time, lower incidence of low blood flow, and lower infection rate compared with the step-tip catheter.

Journal of the American Society of Nephrology : JASN, Jan 13, 2015

Ischemia-reperfusion injury contributes to tissue damage and organ failure in clinical settings, ... more Ischemia-reperfusion injury contributes to tissue damage and organ failure in clinical settings, but the underlying mechanism remains elusive and effective therapies are still lacking. Here, we identified microRNA 687 (miR-687) as a key regulator and therapeutic target in renal ischemia-reperfusion injury. We show that miR-687 is markedly upregulated in the kidney during renal ischemia-reperfusion in mice and in cultured kidney cells during hypoxia. MiR-687 induction under these conditions was mediated by hypoxia-inducible factor-1 (HIF-1). Upon induction in vitro, miR-687 repressed the expression of phosphatase and tensin homolog (PTEN) and facilitated cell cycle progression and apoptosis. Blockade of miR-687 preserved PTEN expression and attenuated cell cycle activation and renal apoptosis, resulting in protection against kidney injury in mice. Collectively, these results unveil a novel HIF-1/miR-687/PTEN signaling pathway in ischemia-reperfusion injury that may be targeted for th...

Seminars in Nephrology, 2009

Chronic inflammation, characterized by increased serum levels of tumor necrosis factor-␣, interle... more Chronic inflammation, characterized by increased serum levels of tumor necrosis factor-␣, interleukin-6, C-reactive protein, and plasminogen activator inhibitor-1, and the presence of inflammatory-related diseases, are seen commonly in aging. Both the dysregulation of immune cells and phenotypic changes in parenchymal cells may contribute to chronic inflammation in aging. Moreover, senescent cells are an important source of inflammatory factors. Oxidative stress, via activation of p38 and c-Jun N-terminal kinase and induction of cell senescence, is likely to play a critical role in inflammation. Endoplasmic reticulum stress also may be present in aging and be involved in inflammation. Advanced glycation end products also are important contributors to inflammation in aging. Because the kidney is a major site for the excretion, and perhaps the degradation, of advanced glycation end products and small inflammatory molecules, reduced renal function in aging may promote oxidative stress and inflammation. Chronic inflammation in turn may potentiate the initiation and progression of lesions in the aging kidney. Semin Nephrol 29:555-568

Sleep medicine reviews, Jan 10, 2014

We conducted a meta-analysis to summarise and quantify the effects of non-pharmacological interve... more We conducted a meta-analysis to summarise and quantify the effects of non-pharmacological interventions on sleep quality improvement in uraemic patients on dialysis. We defined the primary outcome as the change of sleep quality before and after interventions (evaluated by polysomonography or subjective questionnaires such as Pittsburgh sleep quality index, PSQI). The change of fatigue scales, inflammatory cytokines and adverse events were analysed as secondary outcomes. Twelve eligible randomised controlled trials and one prospective cohort study were identified. All three identified non-pharmacological interventions could result in a greater PSQI score reduction compared to controls: 1) cognitive-behavioural therapy (CBT) versus sleep hygiene education (standardised mean difference (SMD) 0.85, 95% CI 0.37-1.34); 2) physical training versus no training (SMD 3.36, 95% CI 2.16-4.57) and 3) Acupressure (including other acupoints massages) versus control (SMD 1.77, 95% CI 0.80-2.73). In...

International journal of molecular medicine, 2014

Experimental studies have demonstrated the protective effect of heme oxygenase (HO)-1 and cyclin‑... more Experimental studies have demonstrated the protective effect of heme oxygenase (HO)-1 and cyclin‑dependent kinase inhibitors (CDKIs) in acute kidney injury (AKI), and it has been documented that some of the protective effect of HO-1 is mediated by CDKIs. However, the role of p18INK4c (p18), an inhibitor of CDK4 (INK4), which is a family member of CDKIs, has not been well characterized in kidney diseases. The aim of the present study was to demonstrate p18 protection from the relationship between p18 and HO-1 in cisplatin-induced AKI. Upregulation of p18 and HO-1 was demonstrated by quantitative polymerase chain reaction (qPCR) and western blotting in cisplatin-induced AKI in vitro and in vivo. The effect of HO-1 on p18 was determined by western blotting using the inducer and inhibitor of HO-1 in vitro. The potential effect of p18 on HO-1 in cisplatin‑induced AKI was examined by p18 gene knockout mice in vivo. The results showed that p18 and HO-1 were upregulated in cisplatin‑induced...

Medical science monitor : international medical journal of experimental and clinical research, 2015

With a prevalence of about 1:500 to 1:1,000, autosomal dominant polycystic kidney disease (ADPKD)... more With a prevalence of about 1:500 to 1:1,000, autosomal dominant polycystic kidney disease (ADPKD) often causes renal failure, with many serious complications. However, there is no Food and Drug Administration (FDA) approved therapy available. MiR-199a-5p level in ADPKD patient samples, rat model, and cell lines were determined with Realtime PCR assay. After miR-199a-5p inhibitor was transfected, we detected the cell proliferation and apoptosis using an MTT assay and an Annexin V-FITC staining kit, respectively. Finally, TargetScan version 5.1 was used to predict the miRNA target and the target gene of miR-199a-5p was proved by a Luciferase assay. We identified a dramatically up-regulated microRNA, miR-199a-5p, in ADPKD tissues and cell lines. Our data show that inhibition of miR-199a-5p suppressed cyst cells proliferation and induced cell apoptosis. We found that miR-199a-5p might exert this effect through targeting CDKN1C/p57. Up-regulation of miR-199a-5p in ADPKD tissues might pro...

Experimental and therapeutic medicine, 2014

Cyclosporine A (CsA) is an immunosuppressant agent and is utilized as a second-line drug therapy ... more Cyclosporine A (CsA) is an immunosuppressant agent and is utilized as a second-line drug therapy for refractory nephrotic syndrome (RNS). In general, the use of CsA is strictly controlled in patients with an estimated glomerular filtration rate (eGFR) <30-40 ml/min/1.73 m(2), and little is known about the safety and efficacy of CsA treatment in patients with RNS complicated by renal dysfunction. In the present study, the clinical data of 10 patients with RNS and renal dysfunction, who received CsA treatment between 2000 and 2009 in the Kidney Institute of PLA, were reviewed retrospectively. Pathologically, these patients included six cases with minimal change, two cases of diffuse mesangial proliferation and two cases of focal segmental glomerulosclerosis. Six months subsequent to the initiation of the CsA treatment, six patients achieved complete remission, two patients achieved remarkable remission and two patients achieved partial remission. Renal function was improved in all ...

Toxicology and Applied Pharmacology, 2013

The kidney is a primary target for numerous toxic compounds. Cytochrome P450 enzymes (P450) are r... more The kidney is a primary target for numerous toxic compounds. Cytochrome P450 enzymes (P450) are responsible for the metabolic activation of various chemical compounds, and in the kidney are predominantly expressed in proximal tubules. The aim of this study was to test the hypothesis that renal proximal tubular P450s are critical for nephrotoxicity caused by chemicals such as chloroform. We developed two new mouse models, one having proximal tubule-specific deletion of the cytochrome P450 reductase (Cpr) gene (the enzyme required for all microsomal P450 activities), designated proximal tubule-Cpr-null (PTCN), and the other having proximal tubule-specific rescue of CPR activity with the global suppression of CPR activity in all extra-proximal tubular tissues, designated extra-proximal tubule-Cpr-low (XPT-CL). The PTCN, XPT-CL, Cpr-low (CL), and wild-type (WT) mice were treated with a single oral dose of chloroform at 200mg/kg. Blood, liver and kidney samples were obtained at 24h after the treatment. Renal toxicity was assessed by measuring BUN and creatinine levels, and by pathological examination. The blood and tissue levels of chloroform were determined. The severity of toxicity was less in PTCN and CL mice, compared with that of WT and XPT-CL mice. There were no significant differences in chloroform levels in the blood, liver, or kidney, between PTCN and WT mice, or between XPT-CL and CL mice. These findings indicate that local P450-dependent activities play an important role in the nephrotoxicity induced by chloroform. Our results also demonstrate the usefulness of these novel mouse models for studies of chemical-induced kidney toxicity.

International Journal of Molecular Medicine, 2014

Unlike native high-density lipoprotein (HDL), oxidized HDL exerts adverse effects in a number of ... more Unlike native high-density lipoprotein (HDL), oxidized HDL exerts adverse effects in a number of diseases, including chronic kidney disease (CKD); however, the mechanisms involved in this process remain unclear. In the present study, we investigated the effects of oxidized HDL on renal tubular cells, which play an important role in the progression of CKD. Human renal proximal tubule epithelial cells (HK-2) were cultured and stimulated with various concentrations of oxidized HDL in the absence or presence of CD36 siRNA. The results revealed that oxidized HDL enhanced the production of reactive oxygen species (ROS) and upregulated the expression of pro-inflammatory factors in the HK-2 cells in a dose-dependent manner. Incubation with oxidized HDL also increased the apoptosis of the HK-2 cells and reduced their migration ability in a dose‑dependent manner. Src family kinase, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) were activated following stimulation with oxidized HDL. All these effects mediated by oxidized HDL on HK-2 cells were markedly attenuated by transfection with with CD36 siRNA pior to stimulation with oxidized HDL. These findings suggest that oxidized HDL enhances the pro-inflammatory properties and impairs the function of HK-2 cells, mainly through the scavenger receptor, CD36, as well as through the Src, MAPK and NF-κB pathways.

International journal of molecular medicine, 2014

Protection of cyclin-dependent kinase inhibitors (CDKIs) has been demonstrated in acute kidney in... more Protection of cyclin-dependent kinase inhibitors (CDKIs) has been demonstrated in acute kidney injury (AKI). However, previous studies on CDKIs have mainly focused on CIP/KIP family members, with INK4 family members rarely being investigated. This study investigated the behaviors of p18(INK4c) (p18) in cisplatin-induced AKI using p18 gene knockout mice (p18-/-). AKI was induced in p18-/- and wild-type (p18+/+) mice after a single cisplatin (12.5 mg/kg) intraperitoneal injection. Protection by p18 was identified by a comparison of survival, renal function and morphological injuries between p18-/- and p18+/+ mice. Further investigation of endoplasmic reticulum stress (ERS) was performed by western blot analysis in p18-/- and p18+/+ kidneys at day 3 after cisplatin injection. The results revealed that after cisplatin injection, the survival of p18-/- mice was significantly shorter than that of p18+/+ mice, accompanied by aggravated renal function and more severe morphological injuries....

Molecular Medicine Reports, 2014

Mesangial proliferative glomerulonephritis (MsPGN) is characterized by widespread mesangial cell ... more Mesangial proliferative glomerulonephritis (MsPGN) is characterized by widespread mesangial cell proliferation and an accumulation of extracellular matrix (ECM) in the mesangial area. In a previous study we developed a polycystin‑1 N‑terminal fragment (PC‑1 NF) fusion protein that inhibits the proliferation of cyst‑lining epithelial cells in autosomal dominant polycystic kidney disease. In addition, the PC‑1 NF fusion protein arrests the cell cycle of cancer cells at the G0/G1 phase, inhibiting their proliferation. In the present study, the effect of the PC‑1 NF fusion protein on MsPGN was investigated. It was found that the PC‑1 NF fusion protein inhibited the proliferation of rat mesangial cells and induced G0/G1 phase arrest and apoptosis in vitro. PC‑1 NF fusion protein treatment also resulted in a decrease in mRNA expression levels of proliferating cell nuclear antigen, cyclin D1 and B‑cell lymphoma‑2 (Bcl‑2) and an increase in mRNA expression levels of Bcl‑2‑associated X protein (Bax) and p21Waf1. Furthermore, a decrease in Bcl‑2, c‑fos, c‑jun and protein kinase C‑α protein levels was observed, whereas Bax protein levels increased. Additionally, PC‑1 NF fusion protein induced ECM degradation and inhibited ECM expansion. The results also demonstrated that PC‑1 NF fusion protein treatment resulted in a decrease in type IV collagen and tissue inhibitor of metalloproteinase mRNA levels but an increase in matrix metalloproteinase 2 mRNA levels. In combination, these results suggest that the PC‑1 NF fusion protein inhibits proliferation, promotes apoptosis and induces ECM degradation in MsPGN rats. This study offers novel perspectives for the treatment of MsPGN.

World Journal of Urology, 2009

Hypertension in ESRD patients is common, and often refractory to common medical interventions. Bi... more Hypertension in ESRD patients is common, and often refractory to common medical interventions. Bilateral renal embolization (BRE) is an alternative to nephrectomy in treating severe refractory hypertension in hemodialysis patients, but has drawbacks in residual renal function preservation and post-infarction syndrome. We evaluated the efficacy and safety of unilateral renal embolization (URE) for the treatment of severe refractory hypertension in hemodialysis patients. From January 2000 to May 2007, 16 hemodialysis patients with severe refractory hypertension were randomized to URE or BRE group, and received percutaneous transcatheter unilateral or bilateral renal embolization, respectively. The efficacy and complications of these two procedures were compared. The plasma renin activity (PRA), plasma angiotensin II, aldosterone and endothelin-1 (ET-1) were measured pre- and post-renal embolization in both groups. The procedures were completed successfully without severe immediate complications. The blood pressure decreased from 211/122 to 127/81 mmHg in URE group (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), and in BRE group from 208/117 to 124/76 mmHg (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) with significantly reduced need for antihypertensive medications. The residual renal function was reasonably kept and post-infarction syndrome was milder in URE group compared with BRE group. No activation of RAS was observed in this series and no RAS activity dynamic change occurred post-procedure. Decreased circulating ET-1 was accompanied with the lowering of blood pressure after the procedure (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). Unilateral renal embolization is as effective as BRE in treating severe refractory hypertension in hemodialysis patients, with advantages over BRE in residual renal function preservation and milder post-infarction syndrome.

Nephron Experimental Nephrology, 2005

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in two genes, PKD1 an... more Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in two genes, PKD1 and PKD2. The complexity of these genes, particularly PKD1, has complicated genetic screening, though recent advances have provided new opportunities for amplifying these genes. In the Han Chinese population, no complete mutational analysis has previously been conducted across the entire span of PKD1 and PKD2. Here, we used single-strand conformation polymorphism (SSCP) analysis to screen the entire coding sequence of PKD1 and PKD2 in 85 healthy controls and 72 Han Chinese from 24 ADPKD pedigrees. In addition to 11 normal variants, we identified 17 mutations (12 in PKD1 and 5 in PKD2), 15 of which were novel ones (11 for PKD1 and 4 for PKD2). We did not identify any seeming mutational hot spots in PKD1 and PKD2. Notably, we found several disease-associated C-T or G-A mutations that led to charge or hydrophobicity changes in the corresponding amino acids. This suggests that the mutations cause conformational alterations in the PKD1 and PKD2 protein products that may impact the normal protein functions. Our study is the first report of screenable mutations in the full-length PKD1 and PKD2 genes of the Han Chinese, and also offers a benchmark for comparisons between Caucasian and Han ADPKD pedigrees and patients.

British Journal of Nutrition, 2010

Dietary protein restriction is one major therapy in chronic kidney disease (CKD), and ketoacids h... more Dietary protein restriction is one major therapy in chronic kidney disease (CKD), and ketoacids have been evaluated in CKD patients during restricted-protein diets. The objective of the present study was to compare the efficacy of a low-protein diet supplemented with ketoacids (LPD þ KA) and a low-protein diet alone (LPD) in halting the development of renal lesions in CKD. 5/6 Nephrectomy Sprague -Dawley rats were randomly divided into three groups, and fed with either 22 % protein (normal-protein diet; NPD), 6 % protein (LPD) or 5 % protein plus 1 % ketoacids (LPD þ KA) for 24 weeks. Sham-operated rats were used as controls. Each 5/6 nephrectomy group included fifteen rats and the control group included twelve rats. Proteinuria, decreased renal function, glomerular sclerosis and tubulointerstitial fibrosis were found in the remnant kidneys of the NPD group. Protein restriction ameliorated these changes, and the effect was more obvious in the LPD þ KA group after 5/6 nephrectomy. Lower body weight and serum albumin levels were found in the LPD group, indicating protein malnutrition. Lipid and protein oxidative products were significantly increased in the LPD group compared with the LPD þ KA group. These findings indicate that a LPD supplemented with ketoacids is more effective than a LPD alone in protecting the function of remnant kidneys from progressive injury, which may be mediated by ketoacids ameliorating protein malnutrition and oxidative stress injury in remnant kidney tissue.

PROTEOMICS - CLINICAL APPLICATIONS, 2008

Protein phosphorylation is a very important PTM. Phosphorylation/dephosphorylation of a protein c... more Protein phosphorylation is a very important PTM. Phosphorylation/dephosphorylation of a protein can alter its behavior in almost every conceivable way. Previous studies indicate that abnormal phosphorylation is involved in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). However, large-scale proteomic analysis of altered phosphoproteins in ADPKD has not been reported. In this study, total proteins from ADPKD cystic kidney tissues (n = 5) and normal kidney tissues (n = 5) were extracted and phosphoproteins were enriched by phosphate metal affinity chromatography, then separated by 2-DE and identified by LC-MS/MS. Between the two groups, 48 protein spots showing more than a twofold difference were detected. Among them, 28 spots were up-regulated and 20 down-regulated in ADPKD kidney tissues. Of these, 38 different proteins were identified including cell signaling proteins, cytoskeleton proteins, mitochondria metabolic enzymes, antioxidant proteins, molecular chaperones, transcription factors and regulators. Two differential phosphoproteins, annexin II and tropomyosin, were further confirmed by immunoprecipitation and Western blot analysis. The results show that there are many kinds of abnormal phosphoproteins in ADPKD cystic kidney tissues. More studies on the functions of the differential phosphoproteins may provide us new clues for ADPKD pathogenesis and treatment.