Development and assessment of a predictive nomogram for the progression of IgA nephropathy.

The present study is to establish a nomogram for predicting the prognosis of IgA nephropathy (IgAN). Of the 869 IgAN patients, four-fifths were randomly assigned to the development cohort and one-fifth to the validation cohort. The primary outcome was a composite event of either a ≥ 50% reduction in estimated glomerular filtration rate (eGFR), end-stage renal disease or death. The mean follow-up time was 44 months. The Cox regression model identified urinary protein excretion (1-3.5 g/d, HR 11.639, 95% CI 3.601-37.625; ≥ 3.5 g/d, HR 32.435, 95% CI 10.079-104.380), eGFR (G2, HR 5.293, 95% CI 2.011-13.932; G3, HR 15.797, 95% CI 6.584-37.905; G4, HR 34.619, 95% CI 13.887-86.301; G5, HR 217.651, 95% CI 83.807-565.248), hyperuricaemia (HR 7.031, 95% CI 4.126-11.980), mesangial proliferation (HR 36.667, 95% CI 5.098-263.711), segmental glomerulosclerosis (HR 5.122, 95% CI 3.114-8.425), tubular atrophy/interstitial fibrosis (T1, HR 33.351, 95% CI 7.831-142.044; T2, HR 213.888, 95% CI 51.048-896.182), crescents (C1, HR 3.123, 95% CI 1.771-5.510; C2, HR 7.353, 95% CI 3.590-15.062) and glomerulosclerosis (25-49%, HR 3.123, 95% CI 1.771-5.510; ≥ 50%, HR 14.384, 95% CI 8.813-23.479) for developing the nomogram. The C-index was 0.945 (95% CI 0.914-0.976) in both the development and validation cohorts, showing good agreement between the nomogram-predicted probability and actual free-of-progression probability. Thus, our nomogram could accurately predict the progression of IgAN patients.

MicroRNA-30b Regulates High Phosphorus Level-Induced Autophagy in Vascular Smooth Muscle Cells by Targeting BECN1.

BACKGROUND/AIMS: Autophagy is an evolutionarily conserved mechanism that affects the survival and functions of vascular smooth muscle cells (VSMCs). We explored the role of microRNAs (miRNAs) in regulating autophagy in VSMCs exposed to high phosphorus (Pi) levels. METHODS: VSMCs were isolated from the thoracic aorta of rats and were cultured primarily. Real-time PCR was used to measure the mRNA expression of indicated genes. Western blotting was performed to detect the protein expression of autophagy-related markers. RESULTS: We found that treatment with high Pi levels (1 and 3 mM) activated LC3II expression and promoted autophagic flux in VSMCs. Conversely, treatment with an autophagy inhibitor decreased LC3II expression. Pi stimulation dysregulated the expression of several miRNAs such as miR-18a, miR-21, miR-23a, miR-30b, and miR-31a. However, miR-30b overexpression decreased Pi-induced expression of autophagy-related marker genes such as BECN1, ATG5, and LC3b, whereas miR-30b downregulation increased Pi-induced expression of these genes. In addition, we found that miR-30b directly targeted BECN1. CONCLUSIONS: These data suggest that miR-30b plays an important role in the regulation of high Pi level-induced autophagy in VSMCs by targeting BECN1.

High phosphorus level leads to aortic calcification via ß-catenin in chronic kidney disease.

AIMS: Vascular calcification is a risk factor for causing cardiovascular events and has a high prevalence among chronic kidney disease (CKD) patients. However, the molecular mechanism underlying this pathogenic process is still obscure. METHODS: Vascular smooth muscle cells (VSMCs) were induced by a concentration of phosphorus (Pi) of 2.5 mM, and were subjected to cell calcification analyses. The effect of high Pi on the Wnt/ß-catenin pathway was measured using a TOP/FOP-Flash reporter assay. The transcriptional regulation of ß-catenin on PIT1 (a type III sodium-dependent phosphate cotransporter) was confirmed by promoter reporter and chromatin immunoprecipitation assays. The 5/6 nephrectomized rat was used as an in vivo model and was fed a high Pi diet to induce aortic calcification. Serum levels of phosphate, calcium, creatine, and blood urea nitrogen were measured, and abdominal aortic calcification was examined. RESULTS: High Pi induced VSMC calcification, downregulated expression levels of VSMC markers, and upregulated levels of osteogenic markers. High Pi activated the Wnt/ß-catenin pathway and ß-catenin activity. ß-Catenin was involved in the process of high Pi-induced VSMC calcification. Further investigation revealed that ß-catenin transcriptionally regulated Pit1, a necessary player in VSMC osteogenic phenotype change and calcification. The in vivo study showed that ß-catenin was involved in rat abdominal aortic calcification induced by high Pi. When knockdown expression of ß-catenin in the rat model was investigated, we found that aortic calcification was reduced. CONCLUSION: These results suggest that ß-catenin is an important player in high phosphorus level-induced aortic calcification in CKD.

VEGF genetic polymorphisms may contribute to the risk of diabetic nephropathy in patients with diabetes mellitus: a meta-analysis.

OBJECTIVE: This meta-analysis aimed to investigate a comprehensive and reliable conclusion on the correlations of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor (VEGF) gene with the risk of diabetic nephropathy (DN) in patients with diabetes mellitus (DM). METHODS: We screened PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CBM, and CNKI databases for those relevant studies that investigated the association of 14,945 subjects with clinicopathological parameters in gastric cancer. RESULTS: Eleven case-control studies that met all inclusion criteria were included in this meta-analysis. A total of 14,945 subjects were involved, including 3,049 DN patients and 11,896 DM patients. Our meta-analysis results revealed that VEGF rs2010963 and rs3025039 polymorphisms might contribute to the risk of DN in DM patients. Ethnicity-stratified analysis suggested that VEGF genetic polymorphisms were associated with an increased risk of DN among Asians. However, we found no correlations of VEGF genetic polymorphisms with susceptibility to DN among Caucasians. CONCLUSION: Our findings suggest that VEGF rs2010963 and rs3025039 polymorphisms may contribute to the risk of DN in DM patients, especially among Asians. Thus, VEGF genetic polymorphisms could be useful biomarkers for early diagnosis of DN in DM patients.

Protective effect of metformin on renal injury of C57BL/6J mouse treated with high fat diet.

This study aimed to investigate the protective effect of metformin on renal injury of C57BL/6J mice treated with a high fat diet. High-fat diet for 12 weeks was used to establish the mice model of metabolism syndrome and the intervention of metformin (75 mg x kg(-1) x d(-1)) for 4 weeks, and plasma biochemical indicator and body weight were used to evaluate the model. Sterol regulatory element-binding protein (SERBP)-1c, TNF-α, NADPH Oxidase (NOX)4 mRNA was determined by real time-PCR. Phospho-AMP-activated protein kinase (P-AMPK)α protein was detected by western blotting. Oil Red O staining, Masson staining and HE staining were for observing renal pathological changes. At the end of 12th week, compared with mice on low fat diet (LFD), body weight (BW), the levels of fasting insulin (FINS), plasma and renal triglyceride (TG) were higher and plasma high density lipoprotein (HDL) and insulin sensitivity index (ISI) were significantly lower, but the levels of fasting blood glycemia (FBG), plasma total cholesterol (TC) and renal TC had no changes; Oil Red O staining revealed renal lipids deposition, Masson staining and HE staining revealed glomerular hypertrophy, matrix increasing, and inflammatory cells infiltration in glomerular; the expression of p-AMPKα protein decreased and the expression of SREBP-1c, TNF-α, NOX4 mRNA increased significantly in mouse treated with high fat diet (HFD). Compared with the HFD group, through metformin interventing, metabolic disorders were significantly improved, renal lipids deposition and other pathological changes were ameliorated, the expression of p-AMPKα protein increased and the expression of SREBP-1c, TNF-α, NOX4 mRNA decreased significantly. Metformin improved metabolic disorders, upregulated activity of renal AMPK, diminished the expression of renal SREBP-1c, TNF-α, NOX4 mRNA, decreased accumulation of renal lipids, and prevened renal injury.

Effect of losartan on the glomerular protein expression profile of type 2 diabetic KKAy mice.

BACKGROUND: To investigate the pathogenesis of diabetic nephropathy (DN) and to search for novel therapeutic targets, the glomerular protein expression profile of KKAy mice treated by losartan was analyzed by two-dimensional differential gel electrophoresis (2D-DIGE). METHODS: The eight-week-old KKAy mice were divided into the losartan treatment group and the non-treatment group, and C57BL/6 mice were used as the control group. After 12 weeks treatment, glomeruli were isolated by abdominal perfusion with magnetic beads, and the glomerular proteins were extracted. The glomerular protein expression profiles were investigated using 2D-DIGE and MALDI-TOF mass spectrometry. Western blot analysis was used to confirm the results of proteomics. RESULTS: Losartan treatment improved albuminuria and renal pathologic lesion of KKAy mice. A total of 62 glomerular proteins were differentially expressed between the KKAy losartan treatment mice and KKAy non-treatment mice. Among them, the expression of 28 proteins were up-regulated, including glycerokinase, sulfite oxidase, glycine amidinotransferase, and adenosylhomocysteinase. The expression of 13 proteins were down-regulated, including 3-mercaptopyruvate sulfurtransferase, ATP synthase subunit d, 60 kDa heat shock protein, and 75 kDa glucose-regulated protein(GRP75). A total of six proteins were found to be differentially expressed between the KKAy non-treatment mice and C57BL/6 mice glomeruli, and their differential expression was suppressed by losartan treatment, including mitochondrial ATP synthase subunit d, GRP75, and selenium-binding protein 1 et al. CONCLUSIONS: Treatment with losartan suppresses the differential expression of mitochondrial ATP synthase subunit d, GRP75, selenium-binding protein 1 etc. In diabetic KKAy mice glomeruli, may play a renoprotective role by reducing glomerular mitochondrial ROS genesis and inhibiting oxidative stress.

The role of CD44-hyaluronic acid interaction in exogenous mesenchymal stem cells homing to rat remnant kidney.

BACKGROUND/AIMS: The aim of our study was to reveal the role of CD44-Hyaluronic acid (HA) in the homing and improving renal function of systemically transplanted MSCs in chronic renal failure. METHODS: First, a remnant kidney model was established in rats and the expression of HA was determined using immunohistochemistry (IHC) and western blotting. Next, chemotaxis assay using flow cytometry, and cell migration assay of MSCs were performed in vitro. Then, MSCs were transplanted into rats, thus, sprague-Dawley (SD) rats were randomly divided into sham group, 5/6 nephrectomy (5/6 Nx) group, MSC group and MSC/Anti-CD44 group (n = 8 for all groups). Migration of MSCs to the kidney in these rats was assessed by using cell tracking experiments, and tissue damage was evaluated by morphological analysis using Masson's trichrome staining and periodic acid Schiff staining. RESULTS: HA was significantly observed in 5/6 Nx group, but not in sham group. Meanwhile, HA was discovered induced MSCs migration remarkably (p < 0.05) and anti-CD44 antibody inhibited the migration significantly (p < 0.05) in vitro. In vivo, the GFP-MSCs were observed in MSC group and the cells reduced in MSC/Anti-CD44 groups, especially, in the tubulointerstitium. CONCLUSION: Our findings reveal that CD44-HA has the potential to induce MSCs homing to injured tissue, while its effect on the ability of MSCs, improving tissue function, is not significant.

[Expression of IL-18, IL-6 and oxidative stress in rat peritoneal mesothelial cells stimulated by lipopolysaccharide].

AIM: To observe the expression of IL-18, IL-6 and the production of oxidative stress Malondialdehyde (MDA) in rat peritoneal mesothelial cells (RPMC) stimulated by lipopolysaccharide (LPS). METHODS: RPMC were primordially culture and stimulated with different concentrations (1, 10, 100 mg/L) LPS for 6h; RPMC were stimulated by 10 mg/L LPS for 3, 6, 12, 24 h. IL-18 mRNA was detected by real time-PCR. IL-6 and IL-18 were detected by ELISA in supernatants. MDA was measured by thiobarbiuric acid method. RESULTS: Compared with the control group, the expression of IL-18, IL-6 and MDA were gradually increased by LPS with different concentrations (P < 0.05) ; the expression of targets above were little by little increased with stimulated time prolonging. then the peak of IL-18 were appeared in 12 h. CONCLUSION: The expression of proinflammatory cytokine IL-6 and the production of oxidative stress MDA was increased in the RPMCs stimulated by LPS, then leads to the perpetuating amplificated inflammation, aggravate peritoneal impairment and hyperfiltration losed.

The modifier protein of glyceraldehyde-3-phosphate dehydrogenase reduces free radical-mediated renal damage in a rat model of acute kidney injury.

BACKGROUND: The modifier protein (MP) of glyceraldehyde-3-phosphate dehydrogenase has been shown to promote growth of renal epithelial cells in vitro. The aim of this study was to show the in vivo effects of MP in a rat model of gentamicin-induced acute kidney injury (AKI). METHOD: MP was purified from monkey renal tubular epithelial cell line BSC-1 and confirmed by amino acid sequencing. Male Sprague-Dawley rats were divided into the following groups: normal control, gentamicin-treated, epidermal growth factor (EGF) plus gentamicin-treated, and MP plus gentamicin-treated, as well as control groups for EGF and MP alone. Levels of serum creatinine (SCr), serum and tissue lipid peroxide, nitric oxide and glutathione-S-hydrogenase for each group were measured on the 7th and 14th days of treatment. Tissue sections were studied with light microscopy. RESULTS: The gentamicin-treated group showed a marked increase in SCr compared to the normal control group. Co-treatment of gentamicin with MP and/or EGF produced similar significant decreases preventing the increase in SCr. There were also significant reductions in serum and tissue homogenate levels of lipid peroxide and nitric oxide, accompanied by an increase in the level of glutathione-S-hydrogenase, in the MP co-treated groups compared to the gentamicin-treated group. AKI was confirmed histologically in the gentamicin-treated group, with damage to the tubular epithelium recorded. This was attenuated by MP co-treatment. There were also reductions in the expression of intercellular adhesion molecule-1 and proliferating cell nuclear antigen in the MP co-treated groups. CONCLUSION: Using a gentamicin model of AKI, MP was able to reduce free radical production in kidney tissue and in the circulation, thus preventing oxidant injury and minimizing damage in renal epithelial cells.

[Lipopolysaccaride influenced peritoneal mesothelial cells on the growth and expression of tumor necrosis factor through nuclear factor kappaB pathway].

AIM: To investigate whether lipopolysaccharide (LPS) influence peritoneal mesothelial cells (PMCs) on their apoptosis, growth and expression of tumor necrosis factor (TNF) through IkappaBalpha, nuclear factor p65 pathway. METHODS: PMCs were isolated, cultured and passaged by enzymatic disaggregation, then identified by phase contrast inverted microscope, transmission electron microscope and scanning electron microscope, with immunocytochemistry method. The PMCs were treated under conditions, which included different concentration LPS (normal control group, 0.1 mg/L, 1.0 mg/L, 10 mg/L, 50 mg/L, 100 mg/L) and different time (0, 1, 3, 6, 12, 24 hours). Hoechst 33258 fluorescence dye method was used to detect the apoptosis of PMC. The inhibitory effect of LPS on cell growth was measured with MTT method. Immunofluorescence dye was used to observe the activity of p65. Western blot method was used to detect the expression of IkappaBalpha. L929 cell line was used to detect the activity of TNF. RT-PCR was used to measure the expression of TNFalpha mRNA. RESULTS: LPS could inhibit growth of PMC and induce apoptosis. LPS could lead IkappaBalpha to degration and p65 into nucleus. LPS could also induce the expression of TNF. The expression of TNF-alpha mRNA reached the peak at the 1st hour and highest TNF activity at the 3rd hour. CONCLUSION: LPS inhibit the growth of PMC and induced the apoptosis. LPS induced PMC to express TNF-alpha in a dose-dependent manner. In the early state, PMC expressed a great deal of TNF-alpha, then began to fall quickly. During the period that LPS influence PMC on apoptosis, growth and expression of TNF, IkappaBalpha-NF-kappaB p65 pathway played the important role.

[Influence of atorvastatin on the expression of monocyte chemoattractant protein-1 in peritoneal mesothelial cells by high glucose].

OBJECTIVE: To investigate the influence of atorvastatin (ATOR) on the expression of monocyte chemoattractant protein-1 (MCP-1) induced by high concentration glucose in peritoneal mesothelial cells (PMCs) and the possible mechanism thereof. METHODS: Rt PMCs were isolated, cultured, passaged, and divided into 3 groups: (1) treated with glucose of the concentrations of 0.1, 1.5, 2.5, 4.25% respectively, (2) treated with 1.5% glucose for 0, 0.5, 1, 3, 12, 24, and 48 h respectively, (3) pretreated with ammonium pyrrolidinedithiocarbomate (PDTC) of the concentrations of 5, 10, 25, or 50 micromol/L for 2 h, and then treated with 1.5% glucose for 3 h; and (4) pretreated with ATOR of the concentrations of 0.1, 1, or 10 mmol/L for 24 h, and then treated with 1.5% glucose for 3 h. Western blotting was used to measure the expression of MCP-1, p65, and inhibitor of nuclear factor-kappaBalpha (IkappaBalpha). RT-PCR was used to measure the expression of MCP-1 mRNA. RESULTS: PMCs expressed MCP-1 in the normal condition. Glucose dose- and time-dependently reduced the protein expression of IkappaBalpha in the PMCs and increased the p65 expression in the nucleus, and accelerated the PMCs to express MCP-1 mRNA and protein (P < 0.05 and P < 0.01). PDTC dose-dependently inhibited the acceleration of expression of MCP-1 mRNA and protein in the PMCs induced by high concentration glucose (P < 0.05 or P < 0.01). ATOR dose-dependently increased the IkappaBalpha expression, decreased the p65 expression in nucleus, and decreased the expression of MCP-1 mRNA and protein (P < 0.05 or P < 0.01). CONCLUSION: High concentration glucose induces PMCs to express MCP-1 in a time- and dose-dependent manner. Nuclear factor- kappaB (NF-kappaB) takes part in this regulation. ATOR inhibits PMCs to express MCP-1 through inhibiting NF-kappaB pathway.

[Regulation effect of d-alpha-tocopherol on the expression of hexokinase induced by high glucose in cultured human peritoneal mesothelium cells].

OBJECTIVE: To investigate the effect of d-alpha-tocopherol on the expression of hexokinase (HK) induced by high glucose in cultured human peritoneal mesothelium cell (HPMC). METHODS: Specimens of human omentum were obtained from consenting patient undergoing elective abdominal surgery. HPMC were isolated and subcultured by enzymatic disaggregation. Morphology and immunocytochemical method were used for identification. HPMC were divided into normal glucose group (0.1% glucose, equal to 5.5 mmol/L), high glucose group (0.5%, 1.0%, 1.5%, 2.5%, 4.25% glucose) and d-alpha-tocopherol group. After 24 h, standard G6PDH-coupled assay, temperature sensitive essay were used to detect the activity of total HK and its isozyme. Immunocytochemical staining was used for observation the intracellular location of HKII. Western blotting was used to analyze the protein expression of HKII and RT-PCR was used to detect the mRNA expression of HKII. The net glucose utilization was assayed by glucose disappearance from medium by hexokinase method. RESULTS: Primary cultured HPMC reacted positively for cytokeratin and vimentin and had numerous surface microvilli under electron microscope. High glucose induced HK activity in a dose-dependent manner and increased HKII isoform selectively. At concentration of 1.5%, 2.5% and 4.25% glucose for 24 h, the relative activity of total HK were 115.4%, 129.1% and 155.2%, respectively comparing with normal control (P < 0.05), and selectively increased HKII isoform expression. D-alpha-tocopherol blocked the activity of total HK and HKII induced by glucose. The relative activity of total HK inhibited by d-alpha-tocopherol was 82.1% (P = 0.001). After incubated with d-alpha-tocopherol, the net glucose utilization were decreased from (25.3 +/- 3.9) mmol/L to (17.3 +/- 2.1) mmol/L (P = 0.018). HKII stained light brown in cytoplasm of HPMC in normal group, accompanying with the increased concentration of glucose, the staining of HKII became strong and accumulated to nuclear. D-alpha-tocopherol made it thinning. The protein and mRNA expression of HKII were accorded with its activity. CONCLUSION: D-alpha-tocopherol inhibited the expression of HKII in activity, protein and mRNA induced by high glucose and decreased the net glucose utilization, which might become a method to improve ultrafiltration in peritoneal dialysis.

[Influence of hypoxia caused by impairment of peritubular capillary on the progression of chronic aristolochic acid nephropathy].

OBJECTIVE: To investigate the manifestation of impairment of peritubular capillary (PTC) in chronic aristolochic acid nephropathy (CAAN) and the influence of hypoxia caused by PTC impairment on the progression of CAAN. METHODS: Fifty-four Wistar rats were randomly divided into 2 groups: Group A (n = 30, perfused intragastrically with decoction of Caulis aristolochia manchuriensis for 8 weeks) and Group B (n = 24, perfused intragastrically with drinking water for 8 weeks). At weeks 8, 12, and 16 ten rats in Group A and 8 rats in Group B were killed. Specimens of blood and urine were collected before the killing of the rats to detect the blood urea nitrogen (BUN), serum creatinine (Scr), and urine protein. HE and Masson staining and microscopy were used to observe the pathology of the kidney. Immunohistochemistry and Western blotting were used to detect the expression of hypoxia-inducible factor-1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF), and CD34. Correlation analysis was conducted to study the relationships among these indices. RESULTS: Since week 8 BUN, Scr, and urine protein of Group A began to increase in comparison with Group B (all P < 0.05). Pathological changes of the kidney began to appear in Group A since week 8 with the decrease of PTC density. HIF-1alpha was not expressed in Group B, and in Group A HIF-1alpha expression began to increase since week 8 and became significantly higher than that of Group B since week 12. At week 16, the PTC density and VEGF-IOD of Group A were 8.10 +/- 2.28/0.13 mm(2) and (2.78 +/- 0.78) x 10(3) respectively, both significantly lower than those of Group B [(42.80 +/- 4.49)/0.13 mm(2) and (26.49 +/- 9.34) x 10(3) respectively, both P < 0.01], and the HIF-1alpha-IOD of Group A was (7.11 +/- 1.20) x 10(3), significantly higher than that of Group B [(0.44 +/- 0.10) x 10(3), P < 0.01]. CD34 was highly expressed in Group B, and the CD34 expression of Group A began to decrease since week 16. HIF-1alpha expression was positively correlated with Scr (r = -0.945, P < 0/01), and PTC density and VEGF expression were negatively correlated with Scr (r = -0.907, P < 0.01 and r = -0.690, P < 0.01). PTC density was negatively correlated with HIF-1alpha expression (r = -0.880, P < 0.01). CONCLUSION: Severe hypoxia exists following PTC injury in CAAN. Hypoxia is correlated with the progression of CAAN.

[Regulation of hexokinase activity by protein kinase C in peritoneal mesothelium cell].

OBJECTIVE: To investigate the effect of protein kinase C (PKC) on the activity of hexokinase (HK) in rat peritoneal mesothelium cell (PMC) and the functional consequences in glucose uptake. METHODS: omentum obtained from albino male rats of the Sprague Dawley strain, PMC were isolated and subculture by enzymatic disaggregation. The antibody to cytokeratin was used for identified by immunofluorescence technique. After treated with PKC activator--phorbol esters (PMA and PDD) and classical PKC (cPKC) inhibitor--Gö6976, total HK activity in PMC were measured by a standard G6PDH-coupled assay, glucose disappearance in the culture medium were tested as glucose net utilization by colorimetric method. RESULTS: The PMC were polygonal when confluent and reacted positively for cytokeratin. PMA induced HK activity in a time and dose-dependent manner and increased net glucose utilization. At concentration of 0.01, 0.1 and 1 micromol/L PMA for 24 h, the increase in HK activity were 30.7%, 59.9% and 99.1%, respectively above the level in the control (P < 0.05). After treated with 1 micromol/L PMA for 6 h, the HK activity of PMC began to up-regulation, the peak reached at 24 h (21.3% vs 100.4%, P < 0.05), and accompanied by increase in net glucose utilization (2 mmol/L, P < 0.05). The expression of HK induced by 0.1 micromol/L PDD were similar to 1 micromol/L PMA, 4 alpha-PDD whose structure resemble to PDD didn't have effect on HK. Gö6976 blocked the activity of HK induced by PMA. After incubated with Gö6976 at concentration of 10, 20, 30, 40 and 50 micromol/L for 30 min, PMC were cultured in 1 micromol/L PMA for 24 h, the decrease in HK activity were 14.6%, 26.8%, 34.2%, 44.2% and 54.9% (P < 0.05). CONCLUSIONS: Elevated HK activity by PKC was accompanied with corresponding increase in net glucose utilization, which might take part in the accelerated glucose uptake after long-term peritoneal dialysis. The blocking of HK activity by cPKC inhibitor might be an effective method for increasing ultrafiltration in peritoneal dialysis.