Establishment of integrative medicine with patient first model in the clinical practice of hemodialysis access / 中华肾脏病杂志

Vascular accesses are the lifelines for hemodialysis patients. This paper proposes to establish an integrative medicine with patient first model in the clinical practice of vascular access based on characters of hemodialysis patients and combined with the domestic and global innovation of management of vascular access. This model emphasizes the integration of vascular access plan with the whole life plan of renal replacement therapy, the combination of characters of vessel and entire condition of the patient, as well as balanced with patient's psychosocial characters. To implement this model in clinical practice, a multidisciplinary team with different professional background should be built, suitable job position should be set up and workflows should be formulated and optimized.

Analysis of differential expression profiles of Piwi-interacting RNA in diabetic nephropathy patients / 中华肾脏病杂志

Objective:To investigate the correlation between Piwi-interacting RNA (piRNA) and diabetic nephropathy (DN).Methods:The differential expression profiles of piRNAs in renal tissues of patients with DN (experimental group) and renal tissues adjacent to tumors of patients with renal tumors (control group) were detected by high-throughput sequencing. The biological function of differentially expressed piRNAs was described by gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis. Real-time fluorescence quantitative PCR was used to detect the serum expression level of target piRNAs in patients with DN. Spearman correlation analysis was used to analyze the correlation between serum target piRNAs and clinical indexes of patients with DN.Results:The results of high throughput sequencing showed that there were 127 differentially expressed piRNAs between DN group and control group, with screening condition of |log 2(fold changes)|≥2 and P<0.05. Among them, there were 99 up-regulated piRNAs and 28 down-regulated piRNAs. The top 5 up-regulated piRNAs were piRNA-hsa-161686, piRNA-hsa-349255, piRNA-hsa-355720, piRNA-hsa-151229 and piRNA-hsa-154959, respectively. The top 5 down-regulated piRNAs were piRNA-hsa-1929960, piRNA-hsa-174194, piRNA-hsa- 148658, piRNA-hsa-172594 and piRNA-hsa-172421, respectively. The PCR verification results of 3 up-regulated genes and 3 down-regulated genes with low P values and high expression levels showed that serum expression level of piRNA-hsa-77976 was significantly down-regulated in patients with DN ( P=0.028), which was consistent with that of sequencing, while the expression levels of other genes were inconsistent with the sequencing results or had no statistical significance. Bioinformatics analysis results predicted that significantly differentially expressed piRNAs might participate in the regulation of DN through Rap1, Ras, PI3K-Akt and axon guiding pathways. The results of correlation analysis showed that the expression level of piRNA-hsa-77976 was negatively correlated with blood urea nitrogen ( r=-0.584, P=0.028), serum creatinine ( r=-0.637, P=0.014), cystatin C ( r=-0.738, P=0.003) and β2 microglobulin ( r=-0.822, P<0.001), and positively correlated with estimated glomerular filtration rate ( r=0.661, P=0.010). Conclusion:The differential expression of piRNA is closely related to DN, and may be used as a new biomarker for the diagnosis and prognosis of DN.

Risk factors of hemodialysis catheter-related bloodstream infection and prediction model / 中华肾脏病杂志

Objective:To investigate the risk factors for catheter-related bloodstream infection (CRBSI) in hemodialysis (HD) patients with tunnel-cuffed catheter (TCC) and construct a risk prediction model for the prevention and treatment of catheter infection.Methods:It was a retrospective study. Patients who had their TCC removed in Hemodialysis Access Center of the First Affiliated Hospital of Zhengzhou University from July to December 2020 were randomly divided into a training set (for model building) and a validation set (for model validation) in the ratio of 7∶3. The training set was divided into CRBSI group and non-CRBSI group with reference to the 2019 Kidney Disease Outcomes Quality Initiative clinical practice guidelines for vascular access, and the risk factors for the occurrence of CRBSI were analyzed. The odds ratio ( OR) values of the variables in the multivariate logistic regression analysis were applied to construct a risk prediction model, and the assessment ability of the model was validated in the validation set. Results:A total of 254 HD patients were included. The training set consisted of 179 patients with male-to-female ratio of 1.36∶1, age of (55.81±15.95) years old, median dialysis age of 18(8, 27) months, median TCC retention time of 15(5, 24) months, and 40 patients with confirmed CRBSI. Logistic regression analysis showed that, combined diabetes ( OR=2.711, 95% CI 1.174-6.258, P=0.019), history of catheter-related infection within 3 months ( OR=3.674, 95% CI 1.541-8.760, P=0.003), more than 4 times nursing interventions within 1 month ( OR=3.128, 95% CI 1.343-7.283, P=0.008), and central venous disease ( OR=2.572, 95% CI 1.130-5.854, P=0.024) were the independent influencing factors for CRBSI occurrence in HD patients with TCC. The OR values of the variables in the multivariate logistic regression were rounded to the assigned scores of the risk prediction model. The corresponding scores of each factor were summed in the training set to obtain the risk score. The receiver operating characteristic (ROC) curve was plotted, with area under the curve ( AUC) of 0.761(0.683-0.839) and maximum Youden index of 0.461, at which time the corresponding cut-off value was 6, with sensitivity of 90.0% and specificity of 56.1%. The model was validated in the validation set with AUC of 0.794(0.674-0.914) and cut-off value of 6, with sensitivity of 61.6% and specificity of 82.5%. Conclusions:Combined diabetes, history of catheter-related infection within 3 months, more than 4 times nursing interventions within 1 month, and central venous disease are the independent risk factors for CRBSI, and the prediction model based on the above factors has good efficacy in predicting the risk of CRBSI and can provide guidance for the prevention and treatment of CRBSI in HD patients.

Influence of hypercholesterolemia on the risk of chronic kidney disease in the middle-aged and elderly population and gender differences / 中华肾脏病杂志

Objective:To explore the influence of hypercholesterolemia on the risk of chronic kidney disease (CKD) in the middle-aged and elderly population and the gender differences.Methods:The data came from the "Epidemiological Survey of Chronic Kidney Disease among Adults in Urban Communities in Henan Province". The subjects came from 20 communities in Henan Province, aged ≥45 years old. Groups were based on the quartile of total blood cholesterol level and gender. Multivariate logistic regression and Cochran-Armitage trend test were used to analyze the effect of hypercholesterolemia on the risk of CKD and its gender differences.Results:A total of 4 779 subjects were enrolled into the study, with 1 934 males (40.5%) and 2 845 females (59.5%). The age was (61.3±7.7) years old and the blood cholesterol was (5.0±1.0) mmol/L. The prevalence rates of hypercholesterolemia, albuminuria, and reduced estimated glomerular filtration rate (eGFR) were 10.7%(305/2 845), 6.4%(182/2 845) and 2.8%(79/2 845) in females and 12.7%(245/1 934), 6.9%(133/1 934) and 2.3%(45/1 934) in males respectively. Compared with Q1 group, the prevalence of reduced eGFR in females were higher in Q2 and Q4 groups (both P<0.05). Among males, the prevalence of albuminuria and reduced eGFR increased with increasing blood cholesterol quartile (Cochran-Armitage trend test Z=12.231, 8.862, both P<0.001). Multivariate logistic regression analysis showed that hypercholesterolemia was an independent influencing factor for albuminuria and reduced eGFR ( OR=1.49, 95% CI 1.08-2.07, P=0.016 and OR=1.65, 95% CI 1.03-2.65, P=0.037, respectively). In subgroup analysis of different genders, female hypercholesterolemia was an independent influencing factor for albuminuria and reduced eGFR, while male hypercholesterolemia was not an independent influencing factor ( OR=1.54, 95% CI 0.96~2.46, P=0.075; OR=1.89, 95% CI 0.93-3.89, P=0.082, respectively). Further subgroup analysis based on the interquartile range of serum cholesterol levels found that female hypercholesterolemia was an independent influencing factor for reduced eGFR in the Q2 and Q4 groups ( OR=2.35, 95% CI 1.29-7.61, P=0.003; OR=2.51, 95% CI 1.38-8.39, P=0.001). In males, hypercholesterolemia was an independent influencing factor for albuminuria in the Q2, Q3 and Q4 groups ( OR=1.80, 95% CI 1.01-3.41, P=0.047; OR=1.85, 95% CI 1.02-3.35, P=0.044; OR=2.33, 95% CI 1.33-4.33, P=0.002). Conclusions:Hypercholesterolemia is an independent risk factor for CKD in middle-aged and elderly population, and there are gender differences, which provides a new idea for clinical prevention and control of CKD.

Risk factors for death and their predictive value on diabetic kidney disease patients in intensive care unit based on MIMIC-Ⅲ database / 中华危重病急救医学

Objective:To analyze the influencing factors of prognosis of patients with diabetic kidney disease (DKD) in intensive care unit (ICU), and analyze their predictive value.Methods:Based on the inpatient information of more than 50 000 patients from June 2001 to October 2012 in the latest version of American Intensive Care Medical Information Database (MIMIC-Ⅲ v1.4), the data of DKD patients were screened out, including gender, age, body weight, comorbidities [hypertension, coronary heart disease, chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD)], sequential organ failure assessment (SOFA) score, the length of ICU stay, the incidence of mechanical ventilation, vasoactive drugs and renal replacement therapy during the ICU hospitalization, complications of other diseases [ventilator-associated pneumonia (VAP), urinary tract infection (UTI), diabetic ketoacidosis (DKA), acute myocardial infarction (AKI)] and prognosis of ICU. At the same time, the blood routine and biochemical data of the first 24 hours in ICU and the extremum values during the ICU hospitalization were collected. Multivariate Logistic regression analysis was used to screen the prognostic factors of DKD patients in ICU, and receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of death risk factors.Results:416 DKD patients were screened out, 20 patients were excluded due to data missing, and finally 396 patients were enrolled, including 220 survival patients and 176 dead patients. Compared with the survival group, the patients in the death group were older (years old: 57.13±13.04 vs. 52.61±14.15), with lower rates of hypertension and CKD (11.4% vs. 23.6%, 26.7% vs. 41.4%), higher SOFA scores and baseline values of blood urea nitrogen (BUN), serum creatinine (SCr) and blood K + [SOFA score: 5.86±2.79 vs. 4.49±2.56, BUN (mmol/L): 18.4±10.0 vs. 14.8±9.0, SCr (μmol/L): 387.2±382.8 vs. 284.6±244.9, K + (mmol/L): 4.64±0.99 vs. 4.33±0.86], and longer ICU stay [days: 2.65 (1.48, 5.21) vs. 2.00 (1.00, 4.00)], and the differences were statistically significant (all P < 0.01). Further analysis of laboratory tests extremum values during ICU hospitalization showed that the maximum (max) and minimum (min) values of white blood cell (WBC), BUN and SCr, and K +max in the death group were significantly higher than those in the survival group [WBC max (×10 9/L): 17.3±10.3 vs. 14.5±7.3, WBC min (×10 9/L): 7.9±4.1 vs. 6.7±2.7, BUN max (mmol/L): 23.8±10.4 vs. 18.8±10.2, BUN min (mmol/L): 11.0±6.6 vs. 9.3±6.6, SCr max (μmol/L): 459.7±392.5 vs. 350.1±294.4, SCr min (μmol/L): 246.6±180.3 vs. 206.9±195.4, K +max (mmol/L): 5.35±0.93 vs. 5.09±0.99], and the minimum values of hemoglobin (Hb min) and glucose (Glu min) were significantly lower than those in the survival group [Hb min (g/L): 87.4±14.5 vs. 90.6±16.5, Glu min (mmol/L): 4.0±1.7 vs. 4.6±2.0], and the differences were statistically significant (all P < 0.05). The incidences of mechanical ventilation and vasoactive drugs during ICU hospitalization in the death group were significantly higher than those in the survival group (37.5% vs. 24.1%, 32.4% vs. 20.0%, both P < 0.01), and the incidences of UTI and AMI in the death group were significantly higher than those in the survival group (29.5% vs. 19.1%, 8.5% vs. 3.6%, both P < 0.05). Multivariate Logistic regression analysis showed that age [odds ratio ( OR) = 1.019, 95% confidence interval (95% CI) was 1.003-1.036, P = 0.023], SOFA score ( OR = 1.142, 95% CI was 1.105-1.246, P = 0.003), WBC min ( OR = 1.134, 95% CI was 1.054-1.221, P = 0.001) and BUN max ( OR = 1.010, 95% CI was 1.002-1.018, P = 0.018) were risk factors of death of DKD patients in ICU. ROC curve analysis showed that the area under ROC curve (AUC) of combination of risks factors of death was 0.706, the sensitivity was 61.6%, and the specificity was 73.2%. Conclusions:In order to prevent DKD patients from getting worse in ICU, we should pay close attention to the blood biochemical indexes, especially the renal function indexes, and give timely treatment. At the same time, we should actively prevent the occurrence of complications such as infection and cardiovascular disease.

Advances of mass spectrometry research in the diagnosis and therapy for diabetics nephropathy / 中华检验医学杂志

Diabetes kidney disease (DKD) is a serious renal complication of diabetes mellitus, also the main cause of end-stage renal disease (ESRD). Early diagnosis and treatment are very important. Mass spectrometry (MS) can detect biomarkers in blood, urine, tissue and other samples of DKD patients, which has become a research hotspot, and its great significance in early diagnosis, pathogenic research, treatment effect and prognostic evaluation.

Role of vitamin D receptor in podocyte injury and proteinuria of diabetic kidney disease / 中华肾脏病杂志

Objective:To investigate the expression level of vitamin D receptor (VDR) in podocytes of diabetic kidney disease (DKD) and its role in podocyte injury and proteinuria.Methods:(1) Sixty-five patients who had been diagnosed with type 2 diabetes mellitus (with or without albuminuria) were enrolled in this study and 25 age-and sex-matched healthy control subjects were enrolled. According to the ratio of urinary excretion of albumin/creatinine (ACR), the type 2 diabetes mellitus patients were classified into without proteinuria group (ACR<30 mg/g, n=24), microalbuminuria group (ACR 30-300 mg/g, n=18) and clinical proteinuria group (ACR>300 mg/g, n=23). Another 25 patients with DKD confirmed by renal biopsy were selected as the DKD group. Normal kidney tissue samples were taken from the same period of urinary surgical department for 10 cases of renal tumors in patients with renal resection. The test indicators in each group were compared. The VDR expression in blood, urine samples and kidney tissues of patients was detected by real-time quantitative PCR, ELISA and immunohistochemistry, and then were compared among different groups. The correlation between VDR and ACR was analyzed by Pearson correlation analysis. (2) Male db/db mice with genetic background of C57BLKs/J and db/m mice born in littermates were randomly divided into normal control group (group A), DKD control group (group B), DKD treated with dimethyl sulfoxide group (group C), DKD treated with paricalcitol (VDR agonist) group (group D). The C and D groups were treated by continuous intraperitoneal injection for 8 weeks, and the group A and B were not treated. The mice were started to intervene continuously for 8 weeks at the age of 10 weeks. At 22 weeks of age (12 weeks after starting intervention), the biochemical indexes of the mice's body weight, blood and urine were compared. The changes of β-catenin and VDR were detected by Western blotting. The expressions of podocyte marker protein podocin and podocyte injury protein α-SMA were observed by immunofluorescence. Results:(1) Compared with the normal healthy control group, the plasma levels of VDR mRNA and protein in diabetic patients without proteinuria, microalbuminuria and clinical proteinuria were lower (all P<0.05). Compared with the diabetic patients without proteinuria, the plasma levels of VDR mRNA and protein in diabetic patients with microalbuminuria and clinical proteinuria were lower (all P<0.05). (2) Compared with the normal healthy control group, the plasma levels of VDR mRNA and protein in diabetic patients without proteinuria and DKD patients were lower (all P<0.05). Compared with diabetic patients without proteinuria, the plasma levels of VDR mRNA and protein in the DKD group were also lower (both P<0.05). (3) Immunohistochemical results showed that the expression of VDR in kidney tissue of DKD group was significantly lower than that of normal control group. (4) The relative level of VDR mRNA in plasma of patients with DKD was negatively correlated with ACR ( r=-0.342, P<0.05). (5) The levels of VDR in urine supernatant of each group showed opposite trends with the plasma levels. (6) Western blotting results showed that the expression of β-catenin protein in groups B and C was higher than that in group D (both P<0.05), and the expression of VDR protein was lower than that in group D (both P<0.05). Immunofluorescence results showed that the expression of podocin in groups B and C was lower than that in group D (both P<0.05), and the expression of α-SMA was higher than that in group D (both P<0.05). Conclusion:VDR overexpression relieves podocyte injury and proteinuria in DKD.

Study on the methods of antigen retrieval in paraffin section of kidney biopsy / 中华肾脏病杂志

Objective:To compare the effect of various antigen retrieval methods in paraffin sections of renal biopsy tissue, and explore the best antigen retrieval method.Methods:Forty-five renal biopsy specimens were collected from the First Affiliated Hospital of Zhengzhou University, including lupus nephritis ( n=10), membranous nephropathy ( n=10), IgA nephropathy ( n=10) and amyloidosis glomerulopathy ( n=15). Five retrieval methods (including high pressure thermal retrieval combined with trypsin retrieval, microwave thermal retrieval combined with trypsin retrieval, high pressure thermal retrieval, microwave thermal retrieval and gastroprotease retrieval) were used for immunofluorescence staining of paraffin sections. Renal tissue specimens were divided into six groups according to different antigen retrieval methods, frozen section specimens used as a control group. The immunofluorescence semi-quantitative scores of paraffin sections of the five heat-repairing antigen methods and frozen sections were compared. Results:Immunofluorescence staining of hyperbaric thermal retrieval combined with trypsin retrieval group and microwave thermal retrieval combined with trypsin retrieval group were similar with those of frozen sections. Compared with the control group, there were no significant difference in the semi-quantitative immunofluorescence scores between the two groups (all P>0.05). However, Immunofluorescence staining of hyperbaric thermal retrieval, microwave thermal retrieval, pepsin digestion had significantly higher false negative rate than those of frozen sections. Compared with the control group, the difference in semi-quantitative immunofluorescence score was statistically significant (all P<0.05). Conclusion:High pressure heat retrieval combined with trypsin retrieval or microwave heat retrieval combined with trypsin retrieval is the first choice of antigen retrieval methods.

Value of the baseline Geriatric Nutritional Risk Index in evaluating the prognosis of maintenance peritoneal dialysis patients / 中华肾脏病杂志

Objective@#To explore the value of baseline geriatric nutritional risk index (GNRI) in evaluating the prognosis of patients with end-stage renal disease (ESRD) who underwent peritoneal dialysis (PD).@*Methods@#The clinical data of patients who underwent PD catheterization and started PD therapy at the First Affiliated Hospital of Zhengzhou University from January 1, 2013 to December 30, 2018 were collected retrospectively. The follow-up endpoint was death or hemodialysis. The follow-up deadline was March 1, 2019. The GNRI cut-off value was determined according to the ROC curve, and the patients were divided into GNRI≤90.5 group and GNRI>90.5 group. The differences of clinical data and laboratory tests were compared between the two groups. Kaplan-Meier survival curves were used to compare the difference in PD rate between the two groups during follow-up, and the factors that affecting patients PD withdrawal were analyzed by Cox regression.@*Results@#The GNRI cut-off value was determined to be 90.5 based on the ROC curve. Until the deadline for follow-up, the drop-out rate of GNRI≤90.5 group was significantly higher than the GNRI>90.5 group (35.88% vs 21.58%, P=0.003). Kaplan-Meier survival curves showed a higher rate of maintaining PD in the GNRI>90.5 group than that in GNRI≤90.5 group during follow-up (P=0.021). Cox univariate regression showed that male, GNRI and serum Alb were protective factors for PD patients, and Scr was a risk factor. After multiple factors correction, male and GNRI were also the protective factors for PD patients.@*Conclusion@#As an objective indicator of nutritional evaluation, baseline GNRI can be used as a prognostic indicator for PD patients.

Analysis of risk factors for progression of acute kidney injury to acute kidney disease / 中华肾脏病杂志

Objective@#To investigate the risk factors of clinically diagnosed acute kidney injury (AKI) patients progressing to acute kidney disease (AKD).@*Methods@#The clinical data of AKI patients admitted to the First Affiliated Hospital of Zhengzhou University from January 1, 2018 to December 31, 2018 were retrospectively analyzed. According to the outcome of the patients, AKI patients were divided into non-acute kidney disease (NAKD) group and AKD group. Clinical characteristics and laboratory data of two groups were compared. The risk factors of AKD in patients with AKI were analyzed by logistic regression, and then the receiver operating characteristic curve (ROC) was drawn to evaluate the predictive value of these risk factors.@*Results@#A total of 254 patients with AKI were enrolled, and 186 patients developed AKD with an incidence of 73.2%. The incidences of AKD in stage 1, stage 2 and stage 3 of AKI were 20.0%, 46.7% and 83.5% respectively. Multivariate logistic regression analysis showed increased peak serum creatinine (within 7 days after AKI diagnosis) (OR=2.561, 95% CI 1.584-4.140, P<0.001), proteinuria (OR=2.952, 95% CI 1.162-7.500, P=0.023) and increased intact parathyroid hormone (OR=1.757, 95%CI 1.104-2.797, P=0.017) were independent risk factors for progression to AKD in patients with AKI. The ROC showed that increased peak serum creatinine (within 7 days after AKI diagnosis) was an important predictor of AKD in patients with AKI (AUC=0.798, P<0.001).@*Conclusion@#Increased peak serum creatinine (within 7 days after AKI diagnosis), proteinuria and increased intact parathyroid hormone are independent risk factors for progression to AKD in patients with AKI, providing new evidences and ideas for clinical preventions and treatments of AKD.

Analysis of risk factors for progression of acute kidney injury to acute kidney disease / 中华肾脏病杂志

Objective To investigate the risk factors of clinically diagnosed acute kidney injury (AKI) patients progressing to acute kidney disease (AKD). Methods The clinical data of AKI patients admitted to the First Affiliated Hospital of Zhengzhou University from January 1, 2018 to December 31, 2018 were retrospectively analyzed. According to the outcome of the patients, AKI patients were divided into non - acute kidney disease (NAKD) group and AKD group. Clinical characteristics and laboratory data of two groups were compared. The risk factors of AKD in patients with AKI were analyzed by logistic regression, and then the receiver operating characteristic curve (ROC) was drawn to evaluate the predictive value of these risk factors. Results A total of 254 patients with AKI were enrolled, and 186 patients developed AKD with an incidence of 73.2％. Theincidences of AKD in stage 1, stage 2 and stage 3 of AKI were 20.0％, 46.7％and 83.5％respectively. Multivariate logistic regression analysis showed increased peak serum creatinine (within 7 days after AKI diagnosis) (OR=2.561, 95％ CI 1.584-4.140, P<0.001), proteinuria (OR=2.952, 95％ CI 1.162-7.500, P=0.023) and increased intact parathyroid hormone (OR=1.757, 95％CI 1.104-2.797, P=0.017) were independent risk factors for progression to AKD in patients with AKI. The ROC showed that increased peak serum creatinine (within 7 days after AKI diagnosis) was an important predictor of AKD in patients with AKI (AUC=0.798, P<0.001). Conclusion Increased peak serum creatinine (within 7 days after AKI diagnosis), proteinuria and increased intact parathyroid hormone are independent risk factors for progression to AKD in patients with AKI, providing new evidences and ideas for clinical preventions and treatments of AKD.

Discipline construction of critical care medicine under the guideline of "excellence, high-quality and sustainability"in the First Affiliated Hospital of Zhengzhou University / 中华危重病急救医学

Critical?care?medicine?plays?an?important?role?in?public?health?emergencies,?major?disasters?and?treatments?of?critically?ill?patients?as?an?emerging?clinical?discipline.?Our?hospital?put?critical?care?medicine?in?an?important?position?and?apply?multiple?measures?under?the?guidance?of?the?spirit?of?graded?diagnosis?and?national?medical?system?reform?combined?with?our?concept?of?"more?detailed,?more?excellent,?high?quality?and?sustainable?development".?Our?hospital?promote?rapid,?high-quality?sustainable?development?of?critical?care?by?increasing?discipline?construction,?scientific?research,?professional?training,?talent?introduction,?academic?exchange,?information?construction,?and?precision?medical?treatment,?etc.

Mechanism of cellular senescence in acute kidney injury that leads to chronic kidney disease in elderly mice / 中华肾脏病杂志

Objective To investigate the mechanism of cellular senescence in ischemia reperfusion injury (IRI)-induced acute kidney injury (AKI) that leads to chronic kidney disease (CKD) in elderly mice.Methods An acute kidney injury model was established in C57B1/6 male mice at ages 8-10 weeks (young group) or 20-24 months (old group) by bilateral IRI.The animals were randomly divided into 4 groups as follows:Young-Sham (n=8),Old-Sham (n=8),Young-IRI (n=8),and Old-IRI groups (n=8).All mice were weighted,and their blood was collected from the tail vein at days 1,3,and 7 after surgery.The mice were killed on day 14 after surgery,and their kidneys were harvested for further analysis.Serum was used for the creatinine test.The changes of the renal tissue morphology and pathology were assessed using hematoxylin-eosin staining and sirius red staining.Immunofluorescence staining of collagen Ⅰ,F4/80,phosphor-histone H3 (p-HH3),and Ki67 were performed to determine the stage of the collagen deposit,macrophage filtration,and cell cycle G2/M arrest.The collagen Ⅰ expression was analyzed using western blot.The expression levels of TNF-α,IL-6,TGF-β,and collagen Ⅰ were determined using real-time PCR.Results Compared with that in the sham group,the serum creatinine levels in both Young-IRI and Old-IR1 groups were obviously increased.The Young-IRI group recovered completely on day 7.The Old-IRI group had higher creatinine levels than the Young-IRI group at each time point.Morphology and pathology analyses revealed that acute injury was repaired in the Young-IRI group,but slight inflammatory cell filtration and collagen deposition were observed in the Old-Sham and Old-IRI groups,respectively.Immunofluorescence staining revealed some F4/80-positive macrophage filtration,collagen Ⅰ deposition,and p-HH3 and Ki67 double-positive nuclear tubular epithelial cells in the Old-Sham group,but considerably more positive results were found in the Old-IRI group.Western blot analysis revealed that collagen Ⅰ expression level was higher in the Old-IRI group than in the Young-IRI group (P ＜ 0.01) and in the Old-Sham group than in the Young-Sham group (P ＜ 0.05).Real-time PCR demonstrated that the mRNA expression levels of cytokines and fibrosis markers,including of TNF-α,IL-6,TGF-β,and collagen Ⅰ,in the Old-Sham and Old-IRI groups were increased as compared with those in the Young-Sham and Young-IRI groups (P ＜ 0.05).Conclusions The levels of kidney inflammation,fibrosis,and cell-cycle arrest are lower in the old mice.After IRI injury,a sustained and ongoing inflammatory reaction is involved and more cells are arrested in the cell cycle G2/M,which inhibit renal repair and promote fibrosis progression.

Relationship between benign prostatic hyperplasia and renal function in men aged 80 years and over / 中华老年医学杂志

Objective To explore the relationship between benign prostatic hyperplasia and renal function in men aged 80 years and over.Methods Eighty-three clinical BPH patients (mean age of 85.8±4.7 years,range of 80-98 years) admitted to Geriatric Department of the First Affiliated Hospital of Zhengzhou University were recruited to this cross-sectional study from January 2017 to June 2017.They were grouped into treatment group (Gt,n=43) and non-treatment group (Gn,n=40) based on their choices for a therapy or observation.The prostate volume (PV) and post-void residual urine volume (PVR) were measured by abdominal ultrasound.A self-reported lower urinary tract symptoms (LUTS) was evaluated by International Prostate Symptoms Score (IPSS).An estimated glomerular filtration rate (eGFR) was calculated based on the serum level of creatinine and other indexes.Spearman and multiple linear regression analysis were applied to analyze correlations between BPH and renal function.Results The systolic and diastolic blood pressures were lower in Gt group than in Gn group (all P＜0.05).The PVR and IPSS were significantly lower in Gt group than in Gngroup[(28.9±16.6) ml vs.(67.3±32.8) ml;(18.2±9.1)vs.(24.7±10.3),all P＜0.05].The serum level of creatinine was lower in Gt group [(73.7±16.3) μmol/L] than in Gn group [(85.4±19.8) μmol/L] (P＜0.05).The eGFR was higher in Gt group[(77.2±11.4) ml · min 1 ·1.73 m-2] than in Gn group[(69.8±13.9) ml · min 1 · 1.73 m-2] (P＜0.05).No statistical differences were observed in PV between Gt group[(24.6 ± 11.4) ml] and Gn group[(27.0 ± 20.8) ml] (P＞0.05).Spearman relation analysis showed that creatinine level was negatively correlated with treatment for BPH (r=-0.337,P＜0.05).Multiple linear regression analysis showed that non-receiving of treatments for BPH was an independent risk factor for an increased creatinine level(r=-0.349,t=-2.802,P＜0.01).Conclusions For men aged 80 years and over,BPH is associated with decreased eGFR,and the treatment for BPH may improve renal function.

Correlation analysis between serum α-klotho level and the development of obesity-related glomerulopathy / 中华肾脏病杂志

Objective To detect the level of serum α-klotho in different obese people and to investigate the correlation between serum α-klotho and obesity-related glomerulopathy (ORG).Methods A total of 48 cases of ORG diagnosed by renal biopsy were enrolled in the study.Fortyeight gender-,age-and BMI-matched obese participants,and 48 obese chronic kidney disease (CKD) patients without ORG were included as controls.The clinical manifestations,laboratory examinations of all three groups were collected,and the level of serum α-klotho protein was measured by ELISA.Results The patients with ORG were characterized by decreased serum α-klotho concentration compared with obese patients group and obese CKD patients group [572.66(439.92,690.58) pg/ml vs 635.85(559.52,769.20) pg/ml and 690.30(516.15,828.20) pg/ml,P＜ 0.01].Multinomial multiple logistic regression analysis revealed that serum α-klotho (per 100 pg/ml increased) was independently associated with the prevalence of ORG,and the risk of ORG decreased by 35％ in the obese participants (OR=0.652,95％ CI:0.487-0.872) and 38％ in CKD patients (OR=0.617,95％ CI:0.453-0.832) respectively.Conclusions The level of serum α-klotho is significantly decreased in ORG and associated with the prevalence of ORG independently.Serum α-klotho may be a protective factor for ORG.

Expressions of oxidative stress related factors in idiopathic membranous nephropathy / 中华肾脏病杂志

Objective To investigate the expression of oxidative stress related factors,such as,superoxide dismutase (SOD),heme oxygenase-1 (HO-1),malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in patients with idiopathic membranous nephropathy (IMN) and explore the possible role of oxidative stress in the pathogenesis of IMN.Methods Serum,urine and renal tissue of 40 patients with IMN,20 patients with secondary membranous nephropathy (SMN),and 20 patients with minimal change nephropathy (MCD) were collected from the nephrology department of the First Affiliated Hospital of Zhengzhou University.All of them were diagnosed by renal biopsy from January 2016 to June 2016.Serum,urine and renal tissue of 20 healthy persons were collected as the normal control (NC).The expressions of SOD,HO-1,and 8-OHdG in renal tissues were detected by immunohistochemistry.The levels of SOD,HO-1,MDA and 8-OHdG in serum and urine specimens were detected by ELISA.The relationship between oxidative stress related factors and proteinuria in IMN was investigated as well.Results The expressions of SOD,HO-1 and 8-OHdG were significantly higher than those in MCD group and NC group in renal tissue;the expression of SOD in IMN group was significantly higher than that in MCD group and NC group in serum (all P ＜ 0.01).The expressions of HO-1,MDA and 8-OHdG in the serum and urine of the IMN group were significantly higher than those of the MCD group and the NC group (all P ＜ 0.05).There was a significant positive correlation between the urine expression of 8-OHdG and MDA and proteinuria in the IMN group.Conclusions Oxidative stress-related factors in IMN patients are elevated,which is closely related to clinical manifestations.In that sense,it is confirmed that oxidative stress is involved in the pathogenesis of IMN.

Risk factors for rheumatoid arthritis in middle-aged and elderly residents in Luohe City of Henan Province / 中华老年医学杂志

Objectives To investigate the risk factors for rheumatoid arthritis in middle-aged and elderly residents in Luohe City,Henan Province.Methods Survey questionnaires and measurements of biochemical parameters were conducted in individuals 45 years old or above,using the two-stage cluster sampling method.Risk factors for rheumatoid arthritis were evaluated according to the criteria for the classification of RA by the American College of Rheumatology and European League Against Rheumatism(ACR/EULAR) (2010).Results Among the 8 610 residents covered by the survey,8,274 people responded,representing a response rate of 96.1％.There were 3 361 male (40.62％)and 4 913 female(59.38％)respondents,with an average age of 61.4±7.4(45-91)years.The age group of 60-64 years had the highest rates of joint involvement,with those scoring 2,3 and 5 points at 2.90％,2.02％ and 0.26％,respectively.The rheumatoid factor (RF)and the anti-cycliccitrullinatedpeptide(anti-CCP)antibody titer showed skewed distributions.The low titer-positive rate of RF and anti-CCP antibody,the ESR and CRP in female residents were evidently higher than in male residents(each P＜0.05).Smoking was an independent factor for RA(OR:1.79,95 ％CI:1.34～ 3.41,P＜0.01).The risk for RA occurrence increased with the frequency of drinking ＞1 time/d(OR:6.71,95 ％ CI:0.88 ～ 51.23,P＜ 0.01).The prevalence of RA was significantly higher in rural areas than in urban and suburb areas(0.93％ to 0.48％ and 0.53％,each P＜0.05).Living on higher floors was a protective factor for RA (OR:0.61,95 ％ CI:0.36 ～ 0.94,P =0.036).Family history was an independent risk factor for RA (OR:3.09,95 ％ CI:1.53 ～ 6.27,P ＜ 0.01),and being first degree relatives of RA patients was a risk factor(OR=6.45,95 ％ CI:1.67～ 17.83,P＜0.01).Multiple factor analysis showed that female gender,first floor of residential buildings,smoking and genetics were key risk factors for RA.Conclusions The risk factors for rheumatoid arthritis in middle-aged and elderly residents in Luohe City of Henan Province are female gender,smoking and genetics.

Effect and mechanism of soluble epoxide hydrolase inhibitor in renal fibrosis mice model / 中华肾脏病杂志

Objective To investigate the effect and mechanism of soluble epoxide hydrolase inhibitor (sEHI) for NF-κB pathway and cell circle arrest of tubular epithelial cell in unilateral ureteral obstruction (UUO) mice model.Methods Thirty-two healthy C57BL/6 male mice performed UUO surgery to induce renal interstitial fibrosis.Animals were randomly divided into 4 groups:sham group (n=8),sEHI (1 mg· kg-1·d-1) group (n=8),UUO group (n=8) and UUO+sEHI (1 mg· kg-1· d-1) group (n=8).Daily sEHI [1-(1-methylsulfonyl-piperidin-4-yl)-3-(4-trifluoromethoxy-phenyl)-urea,TUPS] or 2％ DMSO was applied to mice by oral gavage from day 1 to day 14 after surgery.All mice were sacrificed at day 14 and kidneys were harvested for further analysis.The changes of renal tissue morphology and pathology were observed by Hematoxylin and eosin (HE) and sirius red staining.The expressions of sEH,nuclear factor κB p65 (NF-κB p65) and IκB were measured by Western blotting.The expressions of TNF-α,IL-1β,MCP-1,IL-6,TGF-β,CTGF,collagen-Ⅳ and α-SMA were analyzed by real-time PCR.Immunofluorescence staining of phospho-histone H3 (p-HH3) and Ki67 was performed to determine the stage of cell cycle G2/M arrest.Results The expression and activity of sEH increased in UUO group (P ＜ 0.05).Administration of sEHI inhibited activity of sEH and infiltration of inflammatory cell in tubular interstitial,as well as attenuated tubular damage and tubular interstitial fibrosis.Western blotting analysis revealed administration of sEHI inhibited up-regulated NF-κB p65 and down-regulated IκB in UUO group (P ＜ 0.05).Real-time PCR demonstrated that administration of sEHI obviously decreased the mRNA expression of cytokines and fibrosis markers,including of TNF-α,IL-1 β,MCP-1,IL-6,TGF-β,CTGF,Collagen-Ⅳ,α-SMA (P ＜ 0.05).Immunofluorescence staining showed that there were much more p-HH3 and Ki67 double positive nuclear tubular epithelial cells and interstitial cells in UUO group,compared with Sham group (P ＜ 0.05).Administration of sEHI reduced the number of double positive nuclear cell only in tubular epithelial cells (P ＜ 0.05),but not in interstitial cells.Conclusions In UUO tubular interstitial fibrosis model,sEHI inhibits the activation of NF-κB pathway by down-regulating p65 and up-regulating IκB and ameliorates the infiltration of inflammatory cells.In addition,sEHI plays anti-fibrosis effect by moderating cell cycle G2/M arrest and reducing the excrete of pro-fibrosis factors of tubular epithelial cells.

Association of secretory IgA with clinical pathological characteristics and complement activation in IgA nephropathy / 中华肾脏病杂志

Objective To further investigate the association among clinical pathology,complement activation and renal secretory IgA (SIgA) deposition in patients with IgA nephropathy (IgAN).Methods The activation of serum complements were detected by immunoturbidimetry and ELISA.Renal deposition of SIgA and activation of complements were detected by immunofluorescence.Then the association among clinical pathology,complement activation and renal SIgA deposition were analyzed in IgAN patients.Results In all 201 patients with IgAN,59 patients had SIgA deposition with higher incidences of mucosal infection history and hematuria (P ＜ 0.05),lower levels of serum cystatin C,β2 microglobulin and lower tubulointerstitial lesion grades and T-grade in the Oxford classification (P ＜ 0.05),when compared with patients without SIgA deposition.Both alternative and mannose binding lectin (MBL) pathways were activated in patients with or without SIgA deposition.Patients with MBL pathway activation had lower estimate glomerular filtration rate (P ＜ 0.01),higher serum creatinine,higher proportion of glomerulosclerosis and S-grade in the Oxford classification,more severe tubulointerstitial lesion (P ＜ 0.05).Conclusions Compared with patients without SIgA deposition,patients with SIgA deposition have a stronger link to mucosal immune.The deposition of SIgA is associated with different clinical and pathological manifestations;however,the complement activation is similar in both groups of patients.Patients with MBL pathway activation show more severe kidney injury.

Association of FCGR3B gene copy number variations and lupus nephritis in Henan Han populations / 中华肾脏病杂志

Objective To evaluate the copy number variation of FCGR3B gene in Henan Han systemic lupus erythematosus (SLE) patients and healthy controls,and explore the association between FCGR3B gene copy number variants (CNVs) and lupus nephritis (LN) susceptibility in Henan Han population.Methods FCGR3B CNVs was investigated in 142 SLE patients with nephritis,187 SLE patients without nephritis and 328 healthy controls.A modified methodology based on competitive PCR named Multiplex AccuCopyTM Kit was used to detect FCGR3B copy number.Clinical and laboratory data were collected retrospectively from the medical record.Logistic regression analysis was used to determine the association of FCGR3B copy number variants with LN susceptibility.Rank correlation was used to determine the correlations between FCGE3B copy number variants and clinical phenotypes of LN.Results No significant difference was detected in the copy number variations of FCGR3B in different groups.Low copy number of FCGR3B was more commonly seen in patients with nephritis (P=0.042),and was a risk factor for LN (OR=2.059; 95％ CI:1.081-3.921; P=0.028).However,high copy number (＞ 2) had no effect on SLE patients without nephritis(OR=1.152; 95％CI:0.711-1.866; P=0.565) and LN patients (OR=0.838; 95％ CI:0.529-1.329; P=0.454).There were no associations between FCGR3B copy number variants and clinical phenotypes and immunologic characteristics of LN.Conclusion The low copy number of FCGR3B is a risk factor for LN in Henan Han population.