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Objective:To study the changes in long non-coding RNA C2dat1 expression in kidney tissues of rats at different stages of diabetic kidney disease (DKD) and its relationship with renal interstitial fibrosis.Methods:Forty-eight male SD rats were randomly divided into two groups with 24 rats in each group: control group and DKD group. The rats in the control group were fed with ordinary diet, while those in the DKD group were fed with high-fat diet and drank water freely. After eight weeks of feeding, the rats were fasted for 12 h with free access to water. Then, the DKD group was given a one-time intrabitoneal injection of streptozotocin and the control group was given an equal dose of sodium citrate buffer. After 72 h, the random peripheral blood glucose concentration (≥ 16.7 mmol/L for three consecutive days) and urine sugar (positive) were tested to assess the establishment of the diabetes model. Urine, blood and kidney samples were collected at 3, 6, 9 and 12 weeks. The urinary protein excretion rate within 24 h, urinary creatinine and serum total cholesterol were measured by automatic biochemical apparatus. Pathological changes in kidney tissues were observed by HE staining. The expression of calcium/calmodulin-dependent protein kinase Ⅱ delta (CaMK2D), p65, p50, α-SMA and E-cardherin was detected by immunohistochemistry. Quantitative real-time PCR (qPCR) was used to detect the expression of lncRNA C2dat1 and CaMK2D. The relationship of lncRNA C2dat1 with α-SMA, E-cardherin and CaMK2D was analyzed by correlation analysis. In in vitro experiment, renal tubular epithelial cells HK-2 were induced by high glucose. The expression of lncRNA C2dat1 and CaMK2D in HK-2 cells was detected by qPCR after 24, 48 and 72 h of intervention. Results:The rats in the DKD group showed typical symptoms such as polydipsia, polyphagia, significant weight loss and increased blood glucose as compared with the rats in the control group. Results of the biochemical tests revealed that compared with the control group, the DKD group had increased 24 h excretion rate of urinary protein, decreased urinary creatinine and up-regulated total cholesterol. HE staining showed that the rats in the control group had intact glomeruli, normal basement membrane and no mesangial hyperplasia or inflammatory cell infiltration. However, enlarged glomeruli and evenly thickened basement membrane were observed in the DKD group. Immunohistochemistry indicated that the expression of CaMK2D, p50 and α-SMA was higher in the DKD group than in the control group, while the expression of E-cardherin was lower in the DKD group. qPCR results showed that the expression of lncRNA C2dat1 and CaMK2D at mRNA level was higher in the DKD group than in the control group. In in vitro experiment, the expression of lncRNA C2dat1 and CaMK2D at mRNA level was also higher in HK-2 cells induced by high glucose than in the control group. Correlation analysis indicated that lncRNA C2dat1 was positively correlated with α-SMA and CaMK2D, but negatively correlated with E-cardherin. Conclusions:During the progression of DKD, the high expression of lncRNA C2dat1 might promote diabetic renal interstitial fibrosis by regulating the expression of CaMK2D to activate the NF-κB signaling pathway.
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The clinical data of maintenance hemodialysis (MHD) patients from twenty hemodialysis centers in Guizhou province from June to September 2020 were collected by cross-sectional study. The patients were divided into AFD group and non-AFD group according to whether AFD had occurred. LTI was measured by body composition monitor. The results showed that the incidence of AFD in 2 781 MHD patients was 30.0% (835/2 781). Median LTI level was 15.2 (13.2, 17.5) kg/m 2. The LTI level in the AFD group was higher than that in the non-AFD group ( P < 0.05). According to the tertiles of LTI, low LTI group (LTI ≤ 13.9 kg/m 2) had the highest incidence of AFD (35.5%, 334/940), and the high LTI group had the lowest incidence of AFD (26.3%, 241/916), and the difference among the three groups was statistically significant ( χ2=20.182, P < 0.001). Multivariate logistic regression analysis showed that low LTI group as the reference, the risk of AFD in moderate LTI group (13.9 kg/m 2 < LTI ≤ 16.6 kg/m 2) and high LTI group were associated with the 20.0% ( OR=0.800, 95% CI 0.650-0.986, P=0.036) and 22.8% ( OR=0.772, 95% CI 0.616-0.966, P=0.024) decrease, respectively. These results suggest that low LTI level is independently associated with an increased risk of AFD in MHD patients.
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The clinical data of maintenance hemodialysis (MHD) patients from twenty hemodialysis centers in Guizhou province from June to September 2020 were collected by cross-sectional study. The patients were divided into AFD group and non-AFD group according to whether AFD had occurred. LTI was measured by body composition monitor. The results showed that the incidence of AFD in 2 781 MHD patients was 30.0% (835/2 781). Median LTI level was 15.2 (13.2, 17.5) kg/m2. The LTI level in the AFD group was higher than that in the non-AFD group (P < 0.05). According to the tertiles of LTI, low LTI group (LTI ≤ 13.9 kg/m2) had the highest incidence of AFD (35.5%, 334/940), and the high LTI group had the lowest incidence of AFD (26.3%, 241/916), and the difference among the three groups was statistically significant (χ2=20.182,P < 0.001). Multivariate logistic regression analysis showed that low LTI group as the reference, the risk of AFD in moderate LTI group (13.9 kg/m2 < LTI ≤ 16.6 kg/m2) and high LTI group were associated with the 20.0% (OR=0.800, 95% CI 0.650-0.986, P=0.036) and 22.8% (OR=0.772, 95% CI 0.616-0.966, P=0.024) decrease, respectively. These results suggest that low LTI level is independently associated with an increased risk of AFD in MHD patients.
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Humans , Cross-Sectional Studies , Renal Dialysis/adverse effects , Body CompositionABSTRACT
Objective:To explore the association between platelet/lymphocyte ratio (PLR) and frequent peritoneal dialysis (PD) - associated peritonitis (PDAP) in PD patients.Methods:The data of PD patients with PDAP from Guizhou Provincial People's Hospital between January 2015 and June 2019 were analyzed retrospectively. The patients were divided into mono group (only once PDAP occurred in one year) and frequent group (2 or more PDAP occurred in one year) according to the frequency of PDAP. The demographic data including gender, age, height and weight, the clinical data including blood pressure, duration of PD, causes of peritonitis, the laboratory data at the first time of PDAP and the prognosis of PDAP were compared between two groups. Logistic regression analysis method was applied to analyze the relationship between PLR and frequent PDAP. The predictive power of PLR was evaluated by receiver operating characteristic curve (ROC).Results:A total of 78 PD patients with PDAP were enrolled, including 53 males and 25 females, with average age of 45.2 years. The total person-year was 765.1 person-years and the incidence of peritonitis was 0.10 case/person-year during the median follow-up of 16 months. All patients were divided into two groups: 53 patients in mono group and 25 patients in frequent group. Compared with mono group, the patients in frequent group had lower body mass index, longer dialysis duration, higher systolic blood pressure level, higher PLR level, lower uric acid level, and higher rate of drug-resistant bacteria in peritoneal effusion (all P<0.05). The extubation rate of the frequent group was 44.0%(11/25), which was significantly higher than that [15.1%(8/53)] of mono group ( P<0.05). Multivariate logistic regression analysis showed that higher PLR level was an independent related factor for frequent PDAP( OR=1.006, 95% CI 1.002-1.010, P=0.003), and the area under the ROC curve of PLR was 0.783(95% CI 0.663-0.904, P<0.001). Conclusions:High PLR level is an independent related factor of frequent PDAP for PD patients, and PLR can be a potential predictor of frequent PDAP.
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Objective:To investigate the effect of acteoside on the expressions of high mobility group box 1 (HMGB1) and nuclear factor-κB (NF-κB) in the renal tissue of diabetic nephropathy mice.Methods:Among 20 healthy 8-week old C57BL/6J mice, 5 mice were randomly selected as normal control group, the rest were established as type 1 diabetes mellitus (T1DM) models by a single intraperitoneal injection of streptozocin (STZ, 150 mg/kg). T1DM mice were randomly divided into three groups: 5 mice without treatment, 5 mice treated with acteoside and 5 mice treated with irbesartan. After continuous administration for 8 weeks, serum, urine, and kidney tissue were collected for biochemical, pathological, and related mRNA and protein detection. The renal tubular epithelial cells (NRK-52E cells) were divided into control group (1 g/L glucose), high glucose group (4.5 g/L glucose) and high glucose+acteoside group (4.5 g/L glucose+32 μmol/L acteoside). Real-time PCR and Western blotting were used to assess the expressions of HMGB1 and NF-κB after 48 hours and 72 hours culturing.Results:Compared with normal control group, blood glucose, 24-hour quantitative urinary protein, blood urea nitrogen (BUN), serum creatinine (Scr) and blood and urine HMGB1 were significantly increased in model group (all P<0.05), along with interstitial inflammatory cell infiltration and messangial matrix expantion, and the expressions of HMGB1 and NF-κB were significantly enhanced (all P<0.05). Compared with model group, histopathologic changes were alleviated and the mRNA and protein expression levels of HMGB1 and NF-κB were lower in the acteoside group (all P<0.05), while the blood glucose level was maintained at high level ( P>0.05), excluding reduced quantitative 24-hour urinary protein, BUN, Scr, and serum and urine HMGB1 (all P<0.05). Compared with control group, the mRNA and protein expressions of HMGB1 and NF-κB were increased in high glucose group of NRK-52E cells (all P<0.05). Compared with high glucose group, the mRNA and protein expressions of HMGB1 and NF-κB in high glucose+acteoside group were down-regulated (all P<0.05). Conclusion:Acteoside may alleviate the nephropathy in STZ-induced diabetic nephropathy mice by down-regulating the expressions of HMGB1 and NF-κB.
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Objective To investigate the effects of insulin-like growth factor 1 receptor (IGF-1R) inhibitor on tubulopathy in diabetic kidney disease (DKD) mice.Methods C57BL/6J male mice were randomly divided into normal control group (n=10) and DKD model group (n=30),by giving a single intraperitoneal injection of STZ 150 mg/kg to establish a DKD model.After established successfully,the mice in DKD model group were randomly divided into DKD group (n=10),benazepril group (n=10) and IGF-1R inhibitor group (n=10).IGF-1R inhibitor group was given intraperitoneal injection of IGF-1R inhibitor (30 mg· kg-1· d-1) and benazepril group was given intraperitoneal injection of benazepril (30 mg· kg-1· d-1).Normal control group and DKD group were given an equal amount of normal saline.After 8 weeks of feeding,mice were euthanatized.Body weight and kidney weight were recorded.Blood,urine and kidney samples were collected.Biochemical tests such as blood glucose and urine albumin were measured by automatic biochemical instruments and albumin excretion rate was calculated.Pathological changes of mice were observed by hematoxylin-eosin staining (HE) and periodic acid-schiff staining (PAS).Phosph (p) IGF-1R expression level was determined by immunohistochemistry and Western blotting.Results Compared with the normal control group,blood glucose,kidney weight/body weight and urinary albumin excretion rate were significantly higher in DKD group (all P ＜ 0.01).In DKD mice,glomerular expansion,tubular stenosis,tubular swelling and tubular atrophy were significantly detected.Meanwhile,the number of proximal tubular epithelial (PTE) cells was decreased,and the renal tubular injury scores,the average glomerular volume,and plGF-1R protein expression were increased (all P ＜ 0.05).Compared with the DKD group,albumin excretion rate was significantly reduced (P ＜ 0.01),the above pathological changes were alleviated and the effect of IGF-1R inhibitor was more significant.Compared with the DKD group,the pIGF-1R protein expression was reduced in IGF-1R inhibitor group (P ＜ 0.05).Compared with the benazepril group,the pIGF-1R protein expression was reduced in IGF-1R inhibitor group (P ＜ 0.05).Conclusion IGF-1R inhibitor has better effect than benazepril on alleviating the tubulopathy of DKD mice.
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Objective@#To investigate the effects of insulin-like growth factor 1 receptor (IGF-1R) inhibitor on tubulopathy in diabetic kidney disease (DKD) mice.@*Methods@#C57BL/6J male mice were randomly divided into normal control group (n=10) and DKD model group (n=30), by giving a single intraperitoneal injection of STZ 150 mg/kg to establish a DKD model. After established successfully, the mice in DKD model group were randomly divided into DKD group (n=10), benazepril group (n=10) and IGF-1R inhibitor group (n=10). IGF-1R inhibitor group was given intraperitoneal injection of IGF-1R inhibitor (30 mg·kg-1·d-1) and benazepril group was given intraperitoneal injection of benazepril (30 mg·kg-1·d-1). Normal control group and DKD group were given an equal amount of normal saline. After 8 weeks of feeding, mice were euthanatized. Body weight and kidney weight were recorded. Blood, urine and kidney samples were collected. Biochemical tests such as blood glucose and urine albumin were measured by automatic biochemical instruments and albumin excretion rate was calculated. Pathological changes of mice were observed by hematoxylin-eosin staining (HE) and periodic acid-schiff staining (PAS). Phosph (p) IGF-1R expression level was determined by immunohistochemistry and Western blotting.@*Results@#Compared with the normal control group, blood glucose, kidney weight/body weight and urinary albumin excretion rate were significantly higher in DKD group (all P<0.01). In DKD mice, glomerular expansion, tubular stenosis, tubular swelling and tubular atrophy were significantly detected. Meanwhile, the number of proximal tubular epithelial (PTE) cells was decreased, and the renal tubular injury scores, the average glomerular volume, and pIGF-1R protein expression were increased (all P<0.05). Compared with the DKD group, albumin excretion rate was significantly reduced (P<0.01), the above pathological changes were alleviated and the effect of IGF-1R inhibitor was more significant. Compared with the DKD group, the pIGF-1R protein expression was reduced in IGF-1R inhibitor group (P<0.05). Compared with the benazepril group, the pIGF-1R protein expression was reduced in IGF-1R inhibitor group (P<0.05).@*Conclusion@#IGF-1R inhibitor has better effect than benazepril on alleviating the tubulopathy of DKD mice.
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OBJECTIVE: To study the relationship between red blood cell volume distribution width(RDW)and protein energy wasting(PEW)in maintenance hemodialysis(MHD)patients. METHODS: A multicenter cross-sectional study was conducted in eight hemodialysis centers of Guizhou province in 2018.Clinical data,laboratory values,physical parameters and body composition data of MHD patients were collected. According to the quartile of RDW,the patients were divided into four groups. The differences in the indexes among the 4 groups were compared.Logistic regression models were used to analyze the relationships between RDW and the occurance of PEW. The receiver operating characteristic curves(ROC)was applied to evaluate the predictive power of RDW for PEW. RESULTS: Totally 594 MHD patients were enrolled and were divided into 4 groups,value according to RDW quartile(Q1,Q2,Q3 and Q4). Logistic regression analysis showed that the occurance of PEW was correlated with RDW in MHD patients. The risk of PEW in MHD Q4 group was 2.583 times higher than that of the Q1 group(95%CI 1.588-4.202, P<0.001). After adjustment for patients' age, gender, DM history,dialysis age,hemoglobin, serum phosphorus, serum alanine aminotransferase and aspartate aminotransferase,the risk of Q4 group was 2.197 fold higher than that of Q1 group(95%CI 1.306-3.698, P<0.005). Recover operating characteristic(ROC)analysis showed that the optimal threshold for predicting PEW risks in MHD patients was 15.6% with a sensitivity and specificity of 40.35% and78.72% respectively and the area under curve was 0.611(95%CI 0.570-0.650,P<0.0001). CONCLUSION:s For MHD patients,RDW is associated with the occurance of PEW and has the value for PEW.
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The brain communicates with the metabolic dependent pathway and the immune pathway of the sympathetic nervous system(SNS), and participates in the Brain-Kidney axis to a certain extent. In the course of chronic kidney disease,nervous system diseases,such as cerebrovascular disease, cognitive impairment and neuropathy,occur frequently, which indicates that there are a lot of crosstalk between kidney and brain. In this paper, the pathophysiological mechanism of BrainKidney dialogues in chronic kidney diseases is discussed from the point of nutrient metabolism in patients with chronic kidney diseases, and the two-way regulation mechanism of humral and non-humoral pathays was also studied,which is affected by microvascular and white matter lesions, homocysteinemia, disturbance of hormone and neurotransmitter regulation, immune inflammation and sympathetic nervous system,in order to provide more effective strategies for optimizing protein nutrition and improving prognosis by further understanding the causes and pathogenesis of nutritional metabolic disorders in patients with chronic kidney disease and end-stage renal disease.
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OBJECTIVE: To explore the relationship between dry weight setting and the related parameters of PEW of multicenter hemodialysis patients in Guizhou. in order to provide the basis for setting dry weight in patients. METHODS: We conducted the research in patients of 11 hemodialysis center in Guizhou province. We collected demographic data(age, gender, nationality, marital status, education level, income status and so on) by questionnaire; are collected dry weight, ECW, ICW, fat mass,lean body mass and so on by bioelectrical impedance analysis, and then we also collected physical measurement indexes, such as waist circumference, hip circumference, medium arm circumference(MAC), tricep fold thickness(TSF)and crus diameter. The data is divided into three groups according to the dry weight setings. Group 1: dry weight setting was slightly lower(dry weight setted by doctors was slightly lower than bioelectrical impedance analysis results,withen 1 kg); group 2: dry weight setting was normal; group 3: dry weight setting slightly higher group(dry weight setted by doctors was slightly higher than bioelectrical impedance analysis results,withen 1 kg). We used Chi-square analysis to analyze PEW prevalence, compared differences of the PEW indications by variance analysis, and then we used Spearman correlation analysis to analyze the correlation between PEW and the indications. Influence of various factors on the PEW was analyzed by logistic regression analysis. RESULTS: The PEW morbidity of group 3 was higher than the other two groups. PEW indicators such as upper arm midpoint diameter, tricep fold thickness, hip circumference, fat mass, BMI, Hb, Alb and prealbumin were lower than the other two groups, the difference being statistically significant(P<0.05). Correlation analysis results show that the degree of the factors associated with the PEW was as follows in turn BMI(r=-0.677, P<0.05), dry weight(r=0.636, P<0.05), upper arm midpoint diameter(r=-0.589, P<0.05), albumin(r=-0.562, P<0.05) and hip circumference(r=-0.475, P<0.05). Logistic regression showed that the factors affecting PEW were albumin(OR = 0.883, 95%CI: 0.782-0.997, P<0.05), BMI(OR = 0.671, 95%CI: 0.509-0.884, P<0.05), upper arm midpoint diameter(OR = 0.457, 95% CI: 0.318-0.655, P<0.05) and dry weight(OR = 1.191, 95%CI: 1.041-1.363, P<0.05). CONCLUSION: The dry weight setting too high, insufficient amount of ultrafiltration and inadequate dialysis can increase the occurrence of PEW.
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OBJECTIVE: To investigate the effect of probiotic on protein energy wasting and micro-inflammation in peritoneal dialysis patients. METHODS: One hundred and twelve patients who underwent peritoneal dialysis at the nephrology department of Guizhou provincial people's hospital in 2017, were randomly divided into intervention group(n=56) and control group(n=56), which were treated probiotic and placebo respectively two months, and collected biochemical, inflammatory, physical measurement and bioelectrical impedance index before and after treatment. RESULTS: The prevalence of protein-energy wasting was 64.29% and 60.71%in intervention group and control group, respectively. Compared with control group, patients in intervention group had lower urea nitrogen, triglyceride, low density lipoprotein, high-sensitivity C-reactive protein and interleukin-6 and higher serum albumin levels, and these differences were statistically significant(P<0.05). Physical measurement results showed that the upper arm muscle circumference of intervention group was increased compared to control group, and the change was statistically significant(P<0.05). Biological resistance testing results showed that the fat percentage of intervention group was significantly higher than that of control group(P<0.05).CONCLUSION: The treatment of probiotic could improve protein energy wasting and micro-inflammation in continuous peritoneal dialysis patients.
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Objective@#To compare the effect of insulin-like growth factor-1 receptor (IGF-1R) inhibitor and insulin on renal interstitial macrophage infiltration in mice with type 2 diabetic kidney disease (DKD) mice.@*Methods@#Twenty-four male C57BL/6 mice were selected. After 1 week of adaptive feeding, 6 rats were randomly selected as the control group. The other mice were intraperitoneally injected with streptozotocin (30 mg/kg) after 8 weeks of high-fat and high-sugar feeding. After 72 h, the type 2 diabetes mellitus (DM) models were successfully established if random blood glucose was greater than 16.7 mmol/L. After 8 weeks, if the proteinuria of DM mice increased, the DKD models were successful. DKD mice were divided into 3 groups by random number remainder method: DKD group (n=6), DKD+insulin group (insulin group, n=6, subcutaneous injection of 1-2 U/d insulin) and DKD+IGF-1R inhibitor (IGF-1R inhibitor group, n=6, administered with 30 mg·kg-1·d-1 IGF-1R inhibitor). They were continuously treated for 8 weeks. Random blood glucose was tested by glucometer. Blood and urine were collected, and biochemical indicators, such as serum creatinine, urea nitrogen and urine protein were measured by biochemical analyzer. Renal pathological changes were detected by hematoxylin-eosin staining (HE) and periodic acid-schiff staining (PAS). Suppressor of cytokine signaling 2 (SOCS2) mRNA and insulin-like growth factor-1 (IGF-1) mRNA were detected by in situ hybridization. The protein expressions of SOCS2, F4/80, Toll-like receptor 4 (TLR4) and CD68 were detected by immunohistochemistry.@*Results@#Compared with the control group, blood glucose, serum creatinine, serum urea nitrogen and urinary protein excretion rate were significantly higher in DKD mice (all P<0.05), and CD68+ cells number, F4/80+ cells number and the expression of TLR4 in the tubulointerstitial of DKD mice were significantly higher (all P<0.05). After intervention with insulin or IGF-1R inhibitor, serum creatinine, serum urea nitrogen and urinary protein excretion rate of DKD mice were significantly reduced (all P<0.05). Insulin intervention could significantly reduce blood glucose in mice (P<0.05), but had no significant effect on macrophages. Although IGF-1R inhibitor did not significantly reduce blood glucose, it could significantly reduce the number of CD68, F4/80 positive cells and the expression of TLR4 protein in renal interstitium of DKD mice (all P<0.05). Compared with the DKD group, insulin intervention significantly reduced the expression of IGF-1 protein and mRNA (both P<0.01), and increased the expression of SOCS2 mRNA and protein (both P<0.01). And the expression of SOCS2 protein was correlated with the number of F4/80+ cells in insulin group (R2=0.8461, P=0.005). However, IGF-1R inhibitors had no significant effect on SOCS2 expression, but had better inhibition of macrophage infiltration.@*Conclusion@#IGF-1R inhibitor has a better inhibitory effect on DKD renal interstitial macrophage infiltration than insulin. The mechanism may be related to the fact that IGF-1R inhibitor does not up-regulate SOCS2 expression, whereas insulin up-regulates SOCS2 expression to activate some potential pathways.
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Objective To compare the effect of insulin-like growth factor-1 receptor (IGF-1R) inhibitor and insulin on renal interstitial macrophage infiltration in mice with type 2 diabetic kidney disease (DKD) mice. Methods Twenty-four male C57BL/6 mice were selected. After 1 week of adaptive feeding, 6 rats were randomly selected as the control group. The other mice were intraperitoneally injected with streptozotocin (30 mg/kg) after 8 weeks of high-fat and high-sugar feeding. After 72 h, the type 2 diabetes mellitus (DM) models were successfully established if random blood glucose was greater than 16.7 mmol/L. After 8 weeks, if the proteinuria of DM mice increased, the DKD models were successful. DKD mice were divided into 3 groups by random number remainder method: DKD group (n=6), DKD+insulin group (insulin group, n=6, subcutaneous injection of 1-2 U/d insulin) and DKD+IGF-1R inhibitor (IGF-1R inhibitor group, n=6, administered with 30 mg·kg-1·d-1 IGF-1R inhibitor). They were continuously treated for 8 weeks. Random blood glucose was tested by glucometer. Blood and urine were collected, and biochemical indicators, such as serum creatinine, urea nitrogen and urine protein were measured by biochemical analyzer. Renal pathological changes were detected by hematoxylin-eosin staining (HE) and periodic acid-schiff staining (PAS). Suppressor of cytokine signaling 2 (SOCS2) mRNA and insulin-like growth factor-1 (IGF-1) mRNA were detected by in situ hybridization. The protein expressions of SOCS2, F4/80, Toll-like receptor 4 (TLR4) and CD68 were detected by immunohistochemistry. Results Compared with the control group, blood glucose, serum creatinine, serum urea nitrogen and urinary protein excretion rate were significantly higher in DKD mice (all P<0.05), and CD68+ cells number, F4/80+ cells number and the expression of TLR4 in the tubulointerstitial of DKD mice were significantly higher (all P<0.05). After intervention with insulin or IGF-1R inhibitor, serum creatinine, serum urea nitrogen and urinary protein excretion rate of DKD mice were significantly reduced (all P<0.05). Insulin intervention could significantly reduce blood glucose in mice (P<0.05), but had no significant effect on macrophages. Although IGF-1R inhibitor did not significantly reduce blood glucose, it could significantly reduce the number of CD68, F4/80 positive cells and the expression of TLR4 protein in renal interstitium of DKD mice (all P<0.05). Compared with the DKD group, insulin intervention significantly reduced the expression of IGF-1 protein and mRNA (both P<0.01), and increased the expression of SOCS2 mRNA and protein (both P<0.01). And the expression of SOCS2 protein was correlated with the number of F4/80 + cells in insulin group (R2=0.8461, P=0.005). However, IGF-1R inhibitors had no significant effect on SOCS2 expression, but had better inhibition of macrophage infiltration. Conclusion IGF-1R inhibitor has a better inhibitory effect on DKD renal interstitial macrophage infiltration than insulin. The mechanism may be related to the fact that IGF-1R inhibitor does not up-regulate SOCS2 expression, whereas insulin up-regulates SOCS2 expression to activate some potential pathways.
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Objective To investigate the association of serum magnesium (Mg) level with all-cause mortality in maintenance hemodialysis patients. Methods A multicenter retrospective cohort study was conducted in seven hemodialysis centers of Guizhou province. The adult outpatients who underwent hemodialysis for more than 3 months were included from June 2015 to June 2016. Demographics, baseline clinical and laboratory test results were collected. All patients were followed up until June 30, 2018. Patients were divided into 4 groups according to their baseline serum Mg levels (interquartile range). Kaplan-Meier method was used to compare the survival rates of the four group. Cox regression model was used to analyze the association of Mg with all-cause mortality. Logistic regression was used to analyze the influencing factors of low Mg level. Results A total of 868 hemodialysis dialysis patients with baseline Mg data were enrolled in this study, with age of (55.47± 16.17) years old, among whom 59.4% were male. There were 11 (1.3%) patients with hypomagnesemia (Mg＜0.7 mmol/L), 432(49.8% ) patients with hypermagnesemia (Mg＞1.05 mmol/L), and 16(1.8% ) patients with Mg＞2.0 mmol/L. Median Mg was 1.05 mmol/L and interquartile range was 0.95-1.24 mmol/L. The comparison between Mg quartile groups showed that the difference in age, hemoglobin, serum albumin, serum calcium, parathyroid hormone (PTH), serum creatinine, uric acid and urea nitrogen was statistically significant (all P＜0.05). After a median follow-up of 24 months, 207 patients died. Kaplan-Meier curves showed higher all-cause mortality in patients with Mg≤0.95 mmol/L (Q1 group) (Log - rank test χ2=15.11, P=0.002). However, after adjusting for age, comorbidities and biochemical indicators(especially albumin), there was no statistically significant difference in the hazard ratio for all-cause death among the four groups. Multiple logistic regression analysis results showed that low serum albumin (OR=0.946, 95%CI 0.913-0.979, P=0.002) and low serum uric acid (OR=0.994, 95% CI 0.992-0.997, P＜0.001) were the risk factors for baseline Mg≤0.95 mmol/L. Conclusions Hypomagnesemia is rare in MHD patients, while hypermagnesemia is more common. Baseline serum Mg≤0.95 mmol/L in MHD patients is correlated with increased risk of all-cause death, but it may be not an independent risk factor. Baseline serum Mg≤0.95 mmol/L that occurred is associated with low levels of albumin and serum uric acid.
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Objective This study aimed to investigate the renal expression change of high mobility of nucleosome binding protein 1 ( HMGN1) in epithelia-mesenchymal transition ( EMT) process, and to study the effect of HMGN1 on renal fibrosis in the diabetic nephropathy mice model. Methods 20 C57BL/6 mice were randomly divided into control group, model group, benazepril group, and insulin group. After 8 weeks of drug intervention, blood, urine and kidney tissue samples were taken from mice. The routine physiological and biochemical indexes were detected. Renal structure and fibrosis were detected by HE and Sirius red staining, respectively. Immunohistochemistry and in situ hybridization were used to investigate the protein and mRNA expression levels of HMGN1, CD68, F4/80,α-smooth muscle actin (α-SMA) , and E-cadherin in renal tissue. Results Blood glucose, renal index, and urinary albumin to creatinine ratio ( UACR) were significantly higher in the model group than those in the normal group. In the model group, HE staining showed glomerular hypertrophy and interstitial inflammatory cell infiltration, and Sirius red showed collagen deposition in the renal tissue. Compared with normal group, HMGN1, CD68, F4/80 positive cell counts andα-SMA protein expression were all increased, while E-cadherin protein expression was downregulated in the model group ( all P<0.05) . The above indexes were not improved significantly in the benazepril group. And after intervention of insulin, the expression levels of CD68 positive cell count andα-SMA protein were decreased and the expression levels of E-cadherin protein were increased compared with the model group ( all P<0.05) . The correlation analysis showed that the level of HMGN1 was correlated with CD68, F4/80, α-SMA, E-cadherin and collagen protein, while CD68 and f4/80 were correlated withα-SMA, collagen protein and blood glucose, respectively ( all P<0. 05 ) . Conclusion HMGN1 is involved in the progression of diabetic nephropathy fibrosis, and its underlying mechanism might be related to the macrophage-mediated EMT process.
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Objective To investigate the expression of connective tissue growth factor (CTGF) and heat shock protein 47 (HSP47) in peritoneum fibrosis rats,and the mechanism of 1,25-dihydroxyvitamin D3 [1,25-(OH)2-VitD3] in inhibiting the peritoneum fibrosis.Methods Adult male Sprague-Dawley rats were randomly divided into 3 groups:control group (n=8),model group (n=8) and 1,25-dihydroxyvitamin D3 group (VitD3,n=8).The model of peritoneum fibrosis rats were induced by daily intraperitoneally injection of 15％ chlorhexidine gluconate (CHX) 0.2 ml/d with 0.1％ glucose for 4 weeks.Rats in VitD3 group were also treated with 1,25-(OH)2-VitD3 [i.p.6 ng· (100 g) 1 · d-1].Peritoneal transport function,renal function,peritoneum thickness and serum level of 25hydroxyvitamin D3 were detected.In vitro,primary cultured peritoneal mesothelial cells were divided into control group,high glucose group (HG,2.5％),CTGF siRNA intervention group (CTGF siRNA+HG),VitD3 intervention group (VitD3+HG) and combined intervention group (CTGF siRNA+VitD3+HG).Real-time PCR,Western blotting and immunofluorescence were applied to measure the expression of CTGF and HSP47,also ELISA was used to detect the protein level of FN in peritoneum and peritoneal mesothelial cells.Results Compared with control group,the peritoneal ultrafiltration in peritoneum fibrosis rats were significantly decreased (P ＜ 0.05),the absorbance level of peritoneal fibrosis,peritoneum thickness,the rate of dialysate urea nitrogen and blood urea nitrogen (DUN/BUN) and the expressions of CTGF and HSP47 were increased (all P＜0.05).After application of 1,25-dihydroxyvitamin D3,peritoneal fibrosis lesion was significantly improved,the peritoneum thickness,the expressions of CTGF and HSP47 were decreased (all P ＜ 0.05).In vitro,2.5％ high glucose induced-peritoneal mesothelial cells were respectively treated by CTGF siRNA,1,25-(OH)2-VitD3 and combined interventions,the expression of FN,CTGF and HSP47 was significantly lower than that in high glucose group (all P ＜ 0.05).Conclusions The expression of CTGF and HSP47 is significantly increased in peritoneal fibrosis rats.1,25-(OH)2-VitD3 may ameliorate the progression of peritoneal fibrosis via reducing the expression of CTGF,decreasing the expression of HSP47 and FN.
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Objective To investigate the efficacy of leflunomide combined with prednisone in the induction therapy of proliferative lupus nephritis (LN).Methods A prospective,multicenter,randomized controlled clinical trial was conducted in patients with biopsy-proved proliferative lupus nephritis recruited from 15 renal centers from 2013 to 2015.Patients were randomized to two groups.Oral leflunomide or intravenous cyclophosphamide was given to patients in each group.Both groups received a tapering course of oral prednisone therapy.All patients were followed up for 24 weeks.The blood biochemistry,urine index,clinical curative effect and adverse reaction were recorded and analyzed statistically.Results A total of 100 patients were enrolled in this clinical trial,including 48 patients in leflunomide group and 52 patients in cyclophosphamide group.After 24 weeks,the overall response rate was 79％ (95％ CI 67％-90％) in the leflunomide group and 69％ (95％ CI 56％-82％) in the cyclophosphamide group.23％ (95％CI 11％-35％) of patients in leflunomide group showed complete remission compared with 27％ (95％CI 24％-30％) in cyclophosphamide group (P=0.35).The levels of 24-hr urine protein excretion,SLEDAI and anti-dsDNA antibody titers were decreased in patients treated with leflunomide group after 24-weeks treatment.And the levels of serum albumin and complement 3 after treatment were significantly higher compared with these before treatment.There was also no significant difference in changes of 24-hr urine protein excretion,SLEDAI score,anti-dsDNA antibody titers,serum albumin and complement C3 levels after treatment between two groups.Incidence of adverse events did not differ between the leflunomide and cyclophosphamide group.Conclusions Leflunomide combined with prednisone showed same efficacy compared with cyclophosphamide as induction therapy for lupus nephritis.Leflunomide might be an useful medicine in the induction therapy of lupus nephritis.
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Objective To explore the feasibility of bioelectrical impedance analysis in assessing resting energy metabolism(REM)and the association of REM with anthropometry in hemodialysis patients.Methods Adult hemodialysis patients from 11 hemodialysis facilities in Guizhou Province were enrolled in this study.Bioelectrical impedance analysis was used to measure the rest metabolic rate(RMR)and body composition of 765 patients undergoing regular dialysis.A standard method was used to measure their height,weight,upper arm circumference,triceps skinfold thickness,left calf circumference and grip strength.The upper arm muscle circumference was also calculated.The level of RMR and body composition in hemodialysis patients were compared by gender grouping.The patients were then divided into four groups according to the RMR quartile.Spearman correlation analysis and multiple linear regression analysis were derived to analyze the relationship between RMR and anthropometry.Results The level of RMR in male patients was significantly higher than that in female patients[1591(1444,1764)Rcal/d and 1226(1104,1354)Rcal/d,P ＜ 0.001].Compared with the first quartile of RMR group,upper arm circumference,upper arm muscle circumference,left calf circumference and grip strength in the fourth quartile group were increased significantly(all P ＜ 0.05).Multiple linear regression analysis showed that height(β=0.572),left calf circumference(β=0.273),upper ann muscle circumference(β=0.092)and suffering from protein energy wasting(PEW,β=-0.184)were independent influential factors of RMR(all P ＜ 0.05).Conclusions RMR levels in patients with maintenance hemodialysis are associated with left calf circumference and upper ann muscle circumference,which may become a new index to evaluate energy consumption and malnutrition in MHD patients.
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AIM:To observe the expression of Snail1 and insulin-like growth factor-1 (IGF-1) in NRK-52E cells induced by high glucose,and to investigate the relationship of Snail1 and IGF-1 in the mechanism of epithelial to mesenchymal transition (EMT) in diabetic kidney disease (DKD).METHODS:The NRK-52E cells were treated with Snail1 siRNA and IGF-1 siRNA after cultured with high glucose medium for 72 h,and divided into control group,high glucose group,non-targeting (NT) siRNA group,Snail1 RNAi group and IGF-1 RNAi group.The cells were harvested at 48 h and 72 h.Real-time PCR was used to detect the mRNA expression of Snail1,IGF-1,E-cadherin and fibronectin (FN),and the protein levels were determined by immunofluorescence staining.RESULTS:Compared with control group,the expression of E-cadherin at mRNA and protein levels declined after stimulation with high glucose (P ＜ 0.01),while that of FN was elevated (P ＜0.01).Meanwhile,the mRNA and protein levels of Snail1 and IGF-1 were markedly increased (P ＜0.01).The expression of E-cadherin at mRNA and protein levels was improved in Snail1 RNAi group as compared with high glucose group (P ＜ 0.01),while that of FN,IGF-l and Snail1 was significantly down-regulated (P ＜ 0.01).The same changes were observed in IGF-1 RNAi group (P ＜0.01).The protein expression of each factor in NT group had no significant change as compared with high glucose group (P ＞ 0.05).Pearson correlation analysis showed a close positive relationship between the expression of Snail1 and IGF-1 protein (r =0.852,P ＜ 0.01).CONCLUSION:Snail1 may facilitate DKD development by regulating IGF-1 in the process of EMT.
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AIM:To observe the expression of Snail1 and insulin-like growth factor-1 (IGF-1) in NRK-52E cells induced by high glucose,and to investigate the relationship of Snail1 and IGF-1 in the mechanism of epithelial to mesenchymal transition (EMT) in diabetic kidney disease (DKD).METHODS:The NRK-52E cells were treated with Snail1 siRNA and IGF-1 siRNA after cultured with high glucose medium for 72 h,and divided into control group,high glucose group,non-targeting (NT) siRNA group,Snail1 RNAi group and IGF-1 RNAi group.The cells were harvested at 48 h and 72 h.Real-time PCR was used to detect the mRNA expression of Snail1,IGF-1,E-cadherin and fibronectin (FN),and the protein levels were determined by immunofluorescence staining.RESULTS:Compared with control group,the expression of E-cadherin at mRNA and protein levels declined after stimulation with high glucose (P ＜ 0.01),while that of FN was elevated (P ＜0.01).Meanwhile,the mRNA and protein levels of Snail1 and IGF-1 were markedly increased (P ＜0.01).The expression of E-cadherin at mRNA and protein levels was improved in Snail1 RNAi group as compared with high glucose group (P ＜ 0.01),while that of FN,IGF-l and Snail1 was significantly down-regulated (P ＜ 0.01).The same changes were observed in IGF-1 RNAi group (P ＜0.01).The protein expression of each factor in NT group had no significant change as compared with high glucose group (P ＞ 0.05).Pearson correlation analysis showed a close positive relationship between the expression of Snail1 and IGF-1 protein (r =0.852,P ＜ 0.01).CONCLUSION:Snail1 may facilitate DKD development by regulating IGF-1 in the process of EMT.