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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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Humanos , Estudios Transversales , Diálisis Renal/efectos adversos , Composición CorporalRESUMEN
Objective:To explore the relationship between prognostic nutritional index (PNI) and cognitive impairment (CI) in maintenance hemodialysis (MHD) patients.Methods:It was a multicenter cross-sectional study that included adult patients who received MHD treatment at 18 hemodialysis centers in Guizhou province from June to October 2020 as the study subjects. Cognitive function was assessed with the mini-mental state examination score. According to the scale score, the patients were divided into CI group (≤27 scores) and non-CI group (>27 scores), and the differences between the two groups were compared. The patients were divided into Q1 (PNI<38.0), Q2 (38.0≤PNI<40.4), Q3 (40.4≤PNI<43.0), and Q4 (PNI≥43.0) groups based on the PNI quartiles. The PNI was estimated based on the serum albumin and lymphocyte count. Multivariate logistic regression analysis was used to analyze the correlation between PNI and CI, and subgroup analysis was conducted.Results:A total of 1 740 MHD patients were enrolled in the study, with 1 021 males (62.9%) and 719 females (37.1%). The age was (55±15) years old. There were 411 patients (23.6%) with CI. The age, C-reactive protein, and the proportions of females, current smoking/drinking and diabetes in the CI group were significantly higher than those in the non-CI group, and the education level, blood lymphocyte count, blood prealbumin, serum albumin, serum creatinine, blood uric acid and PNI were significantly lower than those in the non-CI group (all P<0.05). The risk of CI in Q1 group was 1.88 times higher than that of Q4 group after adjusting for confounding factors such as sex, age, body mass index, education level, comorbidities, current smoking/drinking, dialysis age and C-reactive protein ( OR=1.88, 95% CI 1.17-2.30, P=0.008). Subgroup analysis showed that there was an interaction between age and PNI on CI ( P=0.040 for interaction). Q1 group in the patients aged 18 to 45 years old had a higher risk of CI compared to Q4 group ( OR=3.30, 95% CI 1.19-9.10). Conclusions:Low PNI significantly increases the risk of CI in MHD patients, in particularly in the patients aged <45 years old.
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The study explored the effect of acteoside on renal fibrosis in rats with unilateral ureteral obstruction. Twenty-four healthy adult male SD rats were randomly divided into sham (CON) group, unilateral ureteral obstruction (UUO) group, UUO+acteoside (ACT) group, UUO+benazepril (BZ) group by random number table method. The animal model of renal fibrosis was established by unilateral ureteral ligation. The pathological changes of renal tissues in each group of rats were observed by HE staining and Masson staining. Immunohistochemical method was used to detect the protein expression levels of collagenⅢ, heat shock protein (HSP)-47, connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), β-catenin, Bcl-2, and caspase-3. Western blotting was used to detect the protein expression of glucose-regulated protein 78 (GRP78) in renal tissue. Compared with CON group, UUO group had renal tubular dilation and significantly increased interstitial collagen fiber deposition; The degree of renal tubular dilation and interstitial collagen fibers in UUO+ACT group and UUO+BZ group were significantly reduced compared to UUO group, but still significantly heavier than CON group. Compared with CON group, the protein expression levels of collagenⅢ, HSP-47, CTGF, α-SMA, β-catenin and GRP78 in renal tissues of UUO group were significantly higher, while the protein expression level of Bcl-2 was significantly lower (all P<0.05). In comparison with UUO group, the expression levels of Bcl-2 in UUO+ACT group and UUO+BZ group were significantly higher, while the expression levels of other proteins were all significantly lower (all P<0.05). The study shows that acteoside may improve renal fibrosis by decreasing the expression levels of collagenⅢ, HSP-47, CTGF, α-SMA, β-catenin and GRP78, and upregulating the expression level of Bcl-2 in renal tissues.
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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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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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BACKGROUND: Peritoneal dialysis (PD) patients have a high incidence of poor clinical outcomes, which is related to the inflammatory and nutritional status of this population. Platelet-to-albumin ratio (PAR), recently identified as a useful biomarker to monitor inflammation and nutrition, can predict a poor prognosis in various diseases. The aim of this study was to investigate the association between PAR and technique failure and mortality in PD patients. METHODS: This single-center retrospective study enrolled 405 PD patients from 1 January 2011 to 31 December 2019 and collected complete demographic characteristics, clinical laboratory baseline data. The outcomes were technique failure and mortality. The associations between PAR and technique failure, death were analyzed by Cox proportional hazard models and competing risk regression models with kidney transplantation as a competing event. The areas under the curve (AUC) of receiver-operating characteristic analysis were used to determine the predictive values of PAR for technique failure and mortality. RESULTS: During a median follow-up period of 24.0 (range, 4.0-91.0) months, 139 (34.3%) PD patients experienced technique failure, 61 (15.1%) PD patients died. The patients with higher PAR levels had increased risk of technique failure and mortality. After adjustment for confounding factors, we found that high PAR levels were risk factor for both technique failure (subdistribution hazard ratio [SHR] 1.775; 95%CI, 1.157-2.720; p = 0.033] and mortality [SHR 3.710; 95%CI, 1.870-7.360; p < 0.001]. The predictive ability of PAR was superior to platelet and albumin based on AUC calculations for technique failure and mortality. CONCLUSIONS: PAR was a risk factor associated with technique failure and mortality in PD patients.
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Plaquetas/metabolismo , Diálisis Peritoneal/mortalidad , Albúmina Sérica/análisis , Adulto , Área Bajo la Curva , Biomarcadores/sangre , China , Femenino , Humanos , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BackgroundValue of radiomics features from the adrenal gland and periadrenal fat CT images for predicting disease progression in patients with COVID-19 has not been studied. MethodsA total of 1,245 patients (685 moderate and 560 severe patients) were enrolled in a retrospective study. We proposed 3D V-Net to segment adrenal glands in onset CT images automatically, and periadrenal fat was obtained using inflation operation around the adrenal gland. Next, we built a clinical model (CM), three radiomics models (adrenal gland model [AM], periadrenal fat model [PM], and fusion of adrenal gland and periadrenal fat model [FM]), and radiomics nomogram (RN) after radiomics features extracted to predict disease progression in patients with COVID-19. ResultsThe auto-segmentation framework yielded a dice value of 0.79 in the training set. CM, AM, PM, FM, and RN obtained AUCs of 0.712, 0.692, 0.763, 0.791, and 0.806, respectively in the training set. FM and RN had better predictive efficacy than CM (P < 0.0001) in the training set. RN showed that there was no significant difference in the validation set (mean absolute error [MAE] = 0.04) and test set (MAE = 0.075) between predictive and actual results. Decision curve analysis showed that if the threshold probability was more than 0.3 in the validation set or between 0.4 and 0.8 in the test set, it could gain more net benefits using RN than FM and CM. ConclusionRadiomics features extracted from the adrenal gland and periadrenal fat CT images may predict progression in patients with COVID-19. FundingThis study was funded by Science and Technology Foundation of Guizhou Province (QKHZC [2020]4Y002, QKHPTRC [2019]5803), the Guiyang Science and Technology Project (ZKXM [2020]4), Guizhou Science and Technology Department Key Lab. Project (QKF [2017]25), Beijing Medical and Health Foundation (YWJKJJHKYJJ-B20261CS) and the special fund for basic Research Operating Expenses of public welfare research institutes at the central level from Chinese Academy of Medical Sciences (2019PT320003).
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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 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 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 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 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 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: 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 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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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 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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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.