Objective To explore the influencing factors of arteriovenous graft (AVG) dysfunction in hemodialysis (HD) patients, and provide a basis for predicting the risk of dysfunction and prolonging the service time. Methods Retrospective analysis was performed on the clinical and follow-up data of patients who underwent AVG surgery in Department of Vascular and Interventional Surgery, Nanfang Hospital, Southern Medical University from January 2013 to September 2018. The factors of AVG dysfunction were determined by statistical methods. Results A total of 139 patients were enrolled, including 58 males (41.7%); the median age was 57; in which 83 patients (59.7%) developed AVG dysfunction within 24 months. Kaplan-Meier survival analysis showed that the primary patency rates were 76.1%, 56.8%, and 38.5% at 6, 12, and 24 months after the establishment of AVG. The results of Kaplan-Meier survival analysis showed that at 24 months after surgery, the risk of AVG dysfunction in elderly patients (>65 years old) was significantly higher than that of patients≤65 years old (Log-rank χ²=7.632, P=0.006); the risk of AVG dysfunction in patients with mean platelet volume (MPV)>10.1 fl was significantly higher than that of patients with MPV≤10.1 fl (Log-rank χ²=19.910, P<0.001); the risk of AVG dysfunction in patients with platelet distribution width (PDW)>11.4 fl was significantly higher than that of patients with PDW≤11.4 fl (Log-rank χ²=35.410, P<0.001); the risk of AVG dysfunction in patients with platelet-larger cell ratio (P-LCR)>24.8% was significantly higher than that of patients with P-LCR≤24.8% (Log-rank χ²=7.181, P=0.007). Multivariate Cox proportional risk regression analysis showed that high MPV (MPV>10.1 fl, HR=6.501, 95%CI 1.916-22.054, P=0.003), high PDW (PDW>11.4 fl, HR=3.625, 95%CI 1.957-6.714, P<0.001) and low P-LCR (P-LCR>24.8%, HR=0.145, 95%CI 0.045-0.470, P=0.001) were independent influencing factors for AVG dysfunction. The establishment of a functional prediction equation based on the above factors had a certain value in predicting the risk of AVG dysfunction in HD patients (likelihood ratio test: χ²=49.360, P<0.001). Conclusions There are multiple factors that affect AVG dysfunction in HD patients, among which MPV, PDW and P-LCR levels may be the influencing factors for AVG dysfunction. Preoperative examination or postoperative comprehensive review of these factors during the follow-up period has certain directive significance for the prevention of AVG dysfunction.

Objective To explore the relationship between aortic arch calcification (AoAC) and arteriovenous fistula (AVF) failure in maintenance hemodialysis (MHD) patients. Methods The patients who underwent initial AVF and started MHD in the General Hospital of Ningxia Medical University from September 2016 to September 2017 were retrospectively recruited and prospectively followed up until two years after AVF surgery or withdrawal from MHD or death. Calcification of the aortic arch was estimated with plain chest radiology. The patients were divided into four groups (0-3 grade) according to the aortic arch calcification score (AoACs). Spearman correlation analysis was used to analyze the relationship between AoACs and AVF failure. Multivariate logistic regression was used to analyze the influencing factors of AVF failure. Results A total of 165 MHD patients were included in this study, with age of (55.52±14.06) years old and 102 males (61.82%). Among 128 AoAC patients (77.6%), 45 patients were categorized as grade 1 (27.3%), 35 patients as grade 2 (21.2%) and 48 patients as grade 3 (29.1%). There was significant difference in the, age, pulse pressure, corrected calcium, phosphorus, diastolic blood pressure, intact parathyroid hormone and AVF failure between AoAC group and no AoAC group (grade 0 calcification) (all P<0.05). The results of Spearman correlation analysis showed that AoACs was positively correlated with AVF failure (r=0.759, P=0.010), age (r=0.407, P<0.001), pulse pressure (r=0.575, P=0.006), and diabetes history (r=0.848, P=0.049), blood calcium (r=0.591, P=0.018), and blood phosphorus (r=0.509, P=0.012), and negatively correlated with diastolic blood pressure (r=-0.614, P=0.013). Multivariate logistic regression analysis showed that diabetes history (OR=6.702, 95%CI 1.431-31.396, P=0.016), high corrected calcium (OR=10.830, 95%CI 3.479-35.300, P=0.008), high phosphorus (OR=3.792, 95%CI 1.128-12.750, P=0.031) and AoAC (OR=4.473, 95%CI 1.490-13.428, P=0.008) were the independent influencing factors of AVF failure. Conclusions AoAC is an independent risk factor for AVF failure in MHD patients. Evaluation of AoAC has predictive value for AVF failure.

Objective To observe the clinical efficacy of angiotensin-receptor neprilysin inhibitors (ARNI) in the treatment of maintenance hemodialysis (MHD) with heart failure. Methods The clinical data of heart failure patients who accepted MHD in Central China Fuwai Hospital were retrospectively collected. All patients accepted regular treatments of heart failure, and then the treatment group was treated with ARNI, while the control group was treated with valsartan. The treatment course was 6 months. The cardiac parameters: left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), pulmonary artery pressure, right ventricular end-diastolic dimension (RVED), right atrial end-diastolic dimension (RAED), N-terminal pro-B-type natriuretic peptide (NT-pro BNP), and serum potassium were collected and compared between the two groups. Multivariate ordered logistic regression analysis was adopted to analyze the influencing factors of treatment effect. Results A total of 60 MHD patients with heart failure were enrolled with age of (53.92±11.88) years old, 37 males (61.7%), dialysis age of (27.83±12.92) months, and blood pressure of (154.22±15.27) mmHg/(85.43±12.31) mmHg. (1) There was no significant difference of the clinical data and cardiac parameters between the treatment group (n=30) and the control group (n=30) before treatment (all P>0.05); (2) After treatment of 6 months, the total effective rate [28/30(93.3%)] in the treatment group was significantly higher than that in the control group [20/30(66.7%)] and the rehospitalization rate [2/30(6.7%)] in the treatment group was significantly lower than that in the control group [10/30(33.3%)] (both P<0.05); (3) After treatment of 6 months, LVEF, LVEDD, LVESD, pulmonary artery pressure, RVED, RAED, NT-pro BNP, and blood pressure were all improved significantly compared with the baseline in both groups (all P<0.05) and there was no significant difference of serum potassium and body weight before and after treatment in the two groups (all P>0.05); (4) After treatment of 6 months, LVEF in the treatment group was higher than that in the control group and LVEDD, LVESD, pulmonary artery pressure, NT-pro BNP, and blood pressure in the treatment group were lower than those in the control group (all P<0.05). There was no significant difference of RVED, RAED, serum potassium and body weight between the two groups after treatment (all P>0.05); (5)The difference values before and after treatment of LVEF, LVEDD, LVESD, NT-pro BNP, body weight, systolic blood pressure, and diastolic blood pressure were different between the two groups (all P<0.05); (6)Therapy method (β=-1.863, 95%CI -2.948-0.777, P=0.001) and residual urine （β=-1.686, 95%CI -3.079- -0.293, P=0.018) were independent influencing factors of treatment effect (the treatment effect of ARNI was better than that of valsartan; the treatment effect of patients with normal urine volume was better than that of patients with oliguria and anuria). Conclusions ARNI can effectively improve cardiac function in MHD patients with heart failure, inhibit ventricular remodeling, and improve disease prognosis.

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.

Objective To explore the value of detecting plasma donor-derived free DNA (dd-cfDNA) fraction in distinguishing antibody mediated-rejection (ABMR) and T cell-mediated rejection (TCMR) of renal allografts. Methods Patients with acute rejection confirmed by allograft biopsy in the First Affiliated Hospital of Medical College of Zhejiang University from December 1, 2017 to July 18, 2019 were retrospectively included. Based on pathological classification of Banff renal allograft rejection in 2017, the patients were divided into ABMR group and TCMR group, and the latter was subdivided into TCMRⅠsubgroup and TCMRⅡ subgroup. The second generation sequencing and target region capture were used to detect candidates' peripheral blood dd-cfDNA. The demographic and clinicopathological data of the two groups were compared. The receiver operating characteristic curve (ROC) was used to evaluate the differential value of plasma dd-cfDNA and serum creatinine levels in two kinds of acute renal allograft rejection. Results A total of 60 patients with acute rejection of renal transplantation were enrolled in this study, including 42 patients in TCMR group and 18 patients in ABMR group. The plasma dd-cfDNA percentage (%) in the ABMR group was significantly higher than that in the TCMR group [2.33(1.19, 4.30)% vs 0.98(0.50, 1.82)%, P=0.001]. The absolute value of dd-cfDNA in ABMR group was obviously higher than that in TCMR group [0.94(0.60, 2.27) ng/ml vs 0.43(0.20, 0.96) ng/ml, P=0.003]. ROC analysis to discriminate TCMR from ABMR showed that, the area under the curve (AUC) of dd-cfDNA% was 0.76(95%CI 0.64-0.88), when the threshold was 1.11%, the sensitivity and specificity were 88.89% and 59.52%, respectively; the AUC of absolute value of dd-cfDNA was 0.74(95%CI 0.61-0.86), when the threshold was 0.53 ng/ml, the sensitivity was 88.89% and the specificity was 54.76%. TCMR subgroups were further analyzed, there was no significant difference between TCMR subgroups on the absolute value and percentage of dd-cfDNA (both P>0.05); dd-cfDNA% in ABMR group was apparently higher than that in TCMRⅠ subgroups (P=0.008) and TCMRⅡsubgroup (P=0.030). The absolute value of dd-cfDNA in ABMR group was significantly higher than that in TCMRⅠsubgroups (P=0.003). Conclusion Plasma dd-cfDNA level may help to distinguish between ABMR and TCMR rejection.

Objective To explore the effect and mechanism of taxifolin (TAX) on ameliorating cisplatin-induced renal oxidative damage. Methods (1) Forty male C57BL/6 mice were divided into 4 groups: control group (n=10), TAX group (n=10), cisplatin group (n=10) and cisplatin+TAX group (n=10). The weight of mice in each group was measured. The level of serum creatinine (Scr) and blood urea nitrogen (BUN) was analyzed. Kidney histopathological change in mice was analyzed by HE staining. The pro-inflammatory cytokines levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured by enzyme linked immunosorbent assay. The levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) were measured by multifunctional microplate reader. The expression of inflammatory factors, antioxidant genes, and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1) mRNA were measured by real-time PCR. Evaluation of mitochondrial function by measuring ATP level and mtDNA content. Determination of AMP-activated protein kinase (AMPK) and phosphorylated AMPK protein expression by Western blotting. (2) Evaluate the effect of taxifolin on chemotherapy of cisplatin by establishing Lewis lung cancer transplantation tumor C57BL/6 mice model. Results Compared with the control group, the weight of the mice in the TAX group was not significantly reduced (P>0.05), and there was no obvious kidney damage (P>0.05), indicating that oral TAX had good safety. Compared with the cisplatin group, TAX could significantly delay cisplatin-induced the weight loss of mice, reduce the levels of Scr and BUN, and alleviate the pathological changes of kidney tissue (all P<0.05). TAX could reduce the levels of serum inflammatory factors IL-6 and TNF-α and the expression of renal inflammatory factors IL-6, TNF-α and IL-1β mRNA induced by cisplatin in mice (all P<0.05). TAX could significantly reduce the levels of ROS and MDA, and increase the activities of SOD, CAT and GSH in cisplatin-induced acute kidney injury mice (all P<0.01). Meanwhile, TAX could up-regulate the mRNA expression of UCP2, SOD2, CAT antioxidant genes and PGC-1α in the kidneys of mice with acute kidney injury induced by cisplatin, and increase the levels of ATP and mtDNA in cisplatin-induced acute kidney injury mice (all P<0.01). Western blotting results showed that TAX significantly promoted the expression of phosphorylated AMPK protein in cisplatin-induced acute kidney injury mice (P<0.01). In addition, through the establishment of Lewis lung cancer transplantation tumor C57BL/6 mice model, it was found that TAX had no significant effect on the anti-tumor efficacy of cisplatin. Conclusions TAX can ameliorate cisplatin-induced renal oxidative damage, and its mechanism may be related to the activation of AMPK/PGC-1α pathway.

Objective To investigate the association between cardiorespiratory fitness (CRF) and muscle strength, and the influencing factors of CRF in maintenance hemodialysis (MHD) patients. Methods It was a single-center cross-sectional study. Patients who were treated with regular MHD from September 1, 2020 to December 31, 2020 were recruited. Baseline data of MHD patients including body circumference (upper arm circumference of non-fistula, triceps skinfold thickness, and calf circumference), exercise capacity [6-min walking test (6MWT), timed up and go test (TUGT)] and upper and lower limb muscle strength (grip strength, knee extension strength) as well as clinical and biochemical data, Charlson comorbidity index were collected or measured. Cardiopulmonary exercise test (CPET) was used to test peak oxygen consumption per kg body weight (peakVO₂/kg) for reflecting CRF. Pearson correlation or Spearman correlation was used to analyze the correlation between peakVO₂/kg and clinical parameters. Multiple linear regression analysis (stepwise) was performed to analyze the influencing factors of peakVO₂/kg. Results A total of 48 patients were enrolled in the study, of whom 34 were males (70.8%). The age was (60.31±10.44) years old. The median dialysis duration was 48(15, 84) months, and the peakVO₂/kg was (12.37±2.71) ml·kg^-1·min^-1, which was well below the normal value of 30-50 ml·kg^-1·min^-1. Furthermore, peakVO₂/kg was positively correlated with lower extremity muscle strength (r=0.322, P=0.026) and 6MWT (r=0.307, P=0.034), and negatively correlated with age (r=-0.300, P=0.038). Multiple linear regression analysis demonstrated that lower extremity muscle strength (β=0.241, P=0.009) and age (β=-0.235, P=0.022) were the influencing factor of peakVO₂/kg. Conclusions CRF of MHD patients is significantly decreased. The decrease of lower extremity muscle strength is an influencing factor of CRF reduction.

Objective To evaluate the effectiveness and safety of coronavirus disease 2019 (COVID-19) vaccines for dialysis patients with chronic kidney disease. Methods PubMed, Medline, Embase databases and CNKI, VIP, Wanfang databases were searched systematically. The deadline was April 25, 2022. The search terms included haemodialysis, peritoneal dialysis, vaccine, seroresponse, COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The main outcome included the positive rate after vaccination, antibody titer, antibody changes during follow-up, infection rate of SARS-CoV-2, hospitalization rate and mortality. Results A total of 154 195 patients were analyzed in 26 studies. The results of meta-analysis showed that the positive rate of serum IgG antibody in patients with chronic kidney disease was 48% after the first dose of vaccine, 89% and 96% after the second dose and third dose, respectively. After vaccination with COVID-19 vaccines, there was no significant difference in serum antibody and titer between hemodialysis patients and peritoneal dialysis patients. However, compared with the healthy control group, the antibody positive rate and antibody titer of dialysis patients after vaccination were lower (both P<0.05). In the follow-up, the antibody positive rate at the third month decreased by 12% compared with at the first month, at the sixth month decreased by 15% compared with at the third month, and at the sixth month decreased by 20% compared with at the first month. The serum antibody positive rate after the third dose of vaccine increased by 38% (RR=1.38, 95%CI 1.12-1.70, P<0.001), and the antibody titer increased significantly (SMD=1.46, 95%CI 0.31-2.61, P<0.001). Although the vaccines could not reduce the infection rate of SARS-CoV-2 in dialysis patients, it could significantly reduce the hospitalization rate and mortality after infection. Conclusions After vaccination with COVID-19 vaccines, dialysis patients can produce strong serum antibodies, which can reduce the hospitalization rate and mortality after SARS-CoV-2 infection. However, the duration of antibody is short and the titer level is low, so it is necessary to timely vaccinate booster vaccine dose to obtain stronger immunogenicity.

Objective To investigate the patency rates and risk factors of arteriovenous graft (AVG), and provide a clinical guidance for further optimization of vascular access selection and improvement of dialysis quality. Methods This was a retrospective study. The clinical and follow-up data of patients who received AVG in the Blood Purification Center, First Affiliated Hospital of Zhengzhou University from January 1, 2017 to December 31, 2021 were selected. Kaplan-Meier curve and Cox regression model were used to analyze the patency rates and risk factors of AVG. Results A total of 381 cases with AVG were included, with 154 cases (40.4%) of males, age of (55.5±11.8) years old, and 140 cases (36.7%) of diabetes. The median time of primary patency was 377.00(95%CI 314.26-439.74) days, and the primary patency rates at 1, 2, and 3 years were 51.0%, 30.7%, and 15.4%, respectively. The median time of primary assisted patency was 839.00(95%CI 668.89-1 009.11) days, and the primary assisted patency rates at 1, 2, and 3 years were 78.3%, 56.4%, and 39.1%, respectively. The secondary patency rates at 1, 2, and 3 years were 96.7%, 90.1%, and 78.5%, respectively. Multivariate Cox regression analysis results showed that anastomotic vein types of basilic vein and cephalic vein (median cubital vein as a reference, HR=1.869, 95%CI 1.124-3.107, P=0.016; HR=2.110, 95%CI 1.176-3.786, P=0.012) and the diameter of anastomotic vein<3.5 mm (HR=1.411, 95%CI 1.020-1.952, P=0.037) were the independent influencing factors for abnormal primary patency of AVG. Males (HR=1.680, 95%CI 1.127-2.503, P=0.011), mean arterial pressure<70 mmHg (HR=3.228, 95%CI 1.109-9.394, P=0.032), Acuseal graft type (Intering as a reference, HR=1.884, 95%CI 1.185-2.994, P=0.007), anastomotic vein type of cephalic vein (median cubital vein as a reference, HR=2.817, 95%CI 1.328-5.977, P=0.007), the diameter of anastomotic vein<3.5 mm (HR=1.555, 95%CI 1.048-2.306, P=0.028), serum phosphorus ≤1.78 mmol/L (1.13-1.78 mmol/L />1.78 mmol/L, HR=1.737, 95%CI 1.111-2.716, P=0.015;<1.13 mmol/L />1.78 mmol/L, HR=2.162, 95%CI 1.072- 4.362, P=0.031), and ferritin<200 μg/L (HR=1.850, 95%CI 1.231-2.780, P=0.003) were the independent influencing factors for abnormal primary assisted patency of AVG. Serum albumin<40 g/L (HR=2.165, 95%CI 1.096-4.275, P=0.026) was an independent influencing factor for abnormal secondary patency of AVG. Conclusions The primary patency rates of AVG at 1, 2, and 3 years were 51.0%, 30.7%, and 15.4%, respectively. The secondary patency rates of AVG at 1, 2, and 3 years were 96.7%, 90.1%, and 78.5%, respectively. Anastomotic vein types of cephalic vein and basilic vein, and internal diameter<3.5 mm are the independent risk factors for abnormal primary patency of AVG. Anastomotic vein type of cephalic vein and internal diameter<3.5 mm are the independent risk factors for abnormal assisted primary patency of AVG. Serum albumin<40 g/L is an independent risk factor for abnormal secondary patency of AVG. It is suggested that systematic preoperative evaluation and good nutritional status of patients are important to maintain long-term patency of the AVG.

Objective To investigate the prevalence of chronic constipation in maintenance hemodialysis (MHD) patients and analyze the risk factors of chronic constipation. Methods Using the cross-sectional survey method, patients who received MHD in Huadu District People′s Hospital of Guangzhou from September 1, 2021 to September 30, 2021 were enrolled as the research objects. The patient′s demographic, general data and laboratory results were collected. The anxiety level and quality of life were assessed by questionnaires. The patients were divided into constipation group and non-constipation group according to whether they had chronic constipation. The Rome Ⅳ criteria was used to diagnose chronic constipation, and the differences of clinical data between the constipation group and the non-constipation group were compared. The risk factors of chronic constipation in MHD patients were analyzed by logistic regression analysis method. Results A total of 321 MHD patients were enrolled in this study, with 168 males, 153 females and age of (59.5±13.4) years old (ranged from 29 to 87 years old). There were 160 patients (49.8%) with chronic constipation. The proportions of males, long dialysis age, taking sevelamer and lanthanum carbonate, diabetic nephropathy, and diabetes in the constipation group were higher than those in the non-constipation group, and the differences between the two groups were statistically significant (all P<0.05). The serum calcium, serum phosphorus, calcium-phosphorus product, anxiety scores, average weekly ultrafiltration volume/dry weight in the constipation group were significantly higher than those in the non-constipation group (all P<0.05), and the serum albumin, serum magnesium, urea clearance index (Kt/V) and geriatric nutritional risk index were significantly lower than those in the non-constipation group (all P<0.05). The results of logistic regression analysis showed that moderate to severe anxiety (moderate, OR=3.233, 95%CI 1.339-7.805, P=0.009; severe, OR=5.103, 95%CI 1.906-13.663, P=0.001), existed risk of nutrition (low risk, OR=3.705, 95%CI 1.440-9.533, P=0.007; moderate risk, OR=5.638, 95%CI 2.557-12.430, P<0.001; severe risk, OR=15.097, 95%CI 4.112-55.436, P<0.001), >60 years old (≤40 years old as a reference, OR=4.050, 95%CI 1.366-12.006, P=0.012), diabetes history (OR=2.224, 95%CI 1.253-3.946, P=0.006), taking sevelamer (OR=2.290, 95%CI 1.207-4.346, P=0.011), and calcium-phosphorus product (OR=1.704, 95%CI 1.329-2.186, P<0.001), intact parathyroid hormone (OR=1.013, 95%CI 1.003-1.022, P=0.007), blood urea nitrogen (OR=1.092, 95%CI 1.002-1.189, P=0.045) and serum magnesium (OR=0.042, 95%CI 0.006-0.294, P=0.001) were the independent influencing factors for chronic constipation in MHD patients. Conclusions The prevalence of chronic constipation in MHD patients is 49.8%. Adequate dialysis, improving calcium and phosphorus metabolism, improving nutritional status, relieving anxiety, and increasing serum magnesium level may help to reduce the risk of chronic constipation in MHD patients.

Objective To explore the role of prostacyclin (PGI₂) in the development of kidney and vascular system in mice. Methods The prostacyclin synthase (PGIS) knockout model was established in C57BL/6J mice. The effects of PGIS knockout on the survival rate of mice were observed by genotyping analysis. The effects of PGIS knockout on the development of kidney and vascular system in mice were observed by hematoxylin and eosin staining and periodic acid-Schiff staining. The morphological changes of kidneys in PGIS knockout mice were observed. Blood urea nitrogen was tested to evaluate the function of kidney in mice. Real-time quantitative PCR was used to analyze the effect of PGIS knockout on the mRNA expression of prostaglandin synthetase PGES and TXAS. The expression of PGIS in vascular system was observed by immunofluorescence staining. The blood pressure and heart rate of mice were measured by the tail-cuff method. Results Most of the systemic complete PGIS knockout (PGIS^-/-) fetal mice sacrificed. The kidneys of PGIS^-/- fetal mice developed abnormally, which showed sparse interstitial, abnormal tissue differentiation, lengthened renal vesicle, and significant decrease in the number of “S”-shape bodies (P<0.01). The kidneys of PGIS^-/- mice showed tissue atrophy, surface irregularities and cyst formation. Blood urea nitrogen level in the PGIS^-/- mice was significantly higher than that in the wild type (PGIS^+/+) mice [(36.89±5.39) mmol/L vs (5.07±0.69) mmol/L, n=3, P<0.01]. There was no significant difference in the mRNA expression of PGES and TXAS between PGIS^+/+ mice and PGIS^-/-mice. PGIS was widely expressed in renal vascular endothelial cells and smooth muscle cells of PGIS^+/+ mice. Vascular system developed abnormally, which showed loss of smooth muscle layer, width of subendothelial loose layer, thinning of the pipe wall, and discontinuity of the inner elastic plate in PGIS^+/- mice. There was no significant difference in the blood pressure and heart rate between PGIS systemic half-knockout (PGIS^+/-) mice and PGIS^-/- mice. Conclusion PGIS plays an important role in the development of kidney and vascular system in mice.

Objective To investigate whether hepatitis B virus X protein (HBx) mediates the podocyte injury through reactive oxygen species (ROS) /nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) signaling pathway. Methods HBx-overexpressing lentivirus was transfected into renal podocytes of mouse to mimic the pathogenesis of hepatitis B virus-associated glomerulonephritis. Podocytes were divided into the following five groups: blank control group (no special treatment), negative control group (transfected with control lentivirus), HBx overexpression group (transfected with HBx overexpression lentivirus), HBx overexpression+NLRP3 siRNA group (transfected with HBx overexpression lentivirus and NLRP3 siRNA), and HBx overexpression+ROS inhibitor group (transfected with HBx overexpression lentivirus and adding ROS inhibitor). The morphological changes of podocytes were observed with electron microscope. The generation of ROS was detected by dichlorodihydrofluorescein diacetate assay (DCFH-DA). Hoechst 33342 staining was used to observe the morphological and quantitative changes of podocyte nuclei. Enzyme-linked immunosorbent assay was used to detect caspase-1 activity, and the levels of lactate dehydrogenase, interleukin (IL)-1β and IL-18. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression levels of mRNA and protein of pyroptosis-related protein, such as NLRP3, apoptosis-associated speck-like protein containing card (ASC), caspase-1, IL-1β and IL-18. TUNEL staining and flow cytometer were used to detect the number of pyroptosis cells. Immunofluorescence staining was used to detect the expression levels of desmin and nephrin. Results After successful infection of podocytes with HBx-overexpressing lentivirus, pyroptosis-related morphological changes in the cells were observed under electron microscope. The level of ROS in the HBx overexpression group was significantly higher compared to the negative control group (P<0.05). Hoechst 33342 staining revealed condensed nuclei in the HBx overexpression group. TUNEL staining and flow cytometer demonstrated that podocytes underwent increased pyroptosis in the HBx overexpression group. The mRNA and protein expression levels of pyroptosis-related proteins such as NLRP3, ASC, caspase-1, IL-1β and IL-18 were up-regulated upon HBx overexpression (all P<0.05). Caspase-1 enzyme activity, lactate dehydrogenase and desmin expression levels were enhanced after HBx overexpression (all P<0.05). However, NLRP3 knockdown or addition of ROS inhibitors attenuated the pyroptosis and increased expression levels of pyroptosis-related proteins caused by HBx overexpression (all P<0.05). Conclusion ROS/NLRP3 pathway plays an important role in HBx-induced podocyte pyroptosis.

Objective To explore the characteristics and evolution trend of renal disease spectrum in Ningxia. Methods The demographic, clinical manifestations and renal pathological examination results of patients who underwent renal biopsies in the General Hospital of Ningxia Medical University from August 1, 2008 to December 31, 2019 were collected and analyzed retrospectively. According to the time period of receiving renal biopsy, the patients were divided into 2008—2013 group and 2014—2019 group. The age and sex constituent, clinical manifestation, renal disease type, pathological types of primary and secondary glomerular disease and the main clinical manifestations of patients with diabetic nephropathy were compared between the two groups. The changing trend of renal disease spectrum in Ningxia from 2008 to 2019 was analyzed. Results A total of 3 867 patients who underwent renal biopsies were enrolled in this study, with more males (53.71%, 2 077/3 867), and age of (39.59±14.05) years old. The most common clinical manifestation of patients receiving renal biopsies was nephrotic syndrome (36.33%, 1 405/3 867). Among them, primary glomerular diseases accounted for 78.79%(3047/3 867), followed by secondary glomerular diseases (18.57%, 718/3 867), renal tubulointerstitial diseases (1.45%, 56/3 867) and hereditary nephropathy (1.19%, 46/3 867). The most common primary glomerular disease was IgA nephropathy (44.60%, 1 359/3 047), followed by membranous nephropathy (30.75%, 937/3 047). The most common secondary glomerular disease was Henoch-Sch?nlein purpura nephritis (27.44%, 197/718), followed by lupus nephritis (25.07%, 180/718). Compared with the 2008—2013 group, the proportion of membranous nephropathy increased, the proportion of mesangial proliferative glomerulonephritis (non-IgA deposition) decreased (both P<0.001), the proportions of diabetic nephropathy and hypertensive renal damage increased, and the proportions of Henoch-Sch?nlein purpura nephritis and hepatitis B virus-associated glomerulonephritis decreased in 2014—2019 group (all P<0.01). Compared with the 2008—2013 group, the proportions of acute kidney injury, chronic renal failure, simple hematuria and urinary protein≤1.0 g/24 h increased in kidney biopsy patients in 2014—2019 group, while the proportion of nephrotic syndrome decreased (all P<0.05). Compared with the 2008—2013 group, the proportion of chronic renal failure in diabetic nephropathy patients increased during renal biopsy, and the proportion of albuminuria with hematuria decreased in 2014—2019 group (all P<0.05). Conclusions Primary glomerular disease is the most common kidney disease in Ningxia. IgA nephropathy is the most common cause, and the proportion of membranous nephropathy is increasing year by year. Henoch-Sch?nlein purpura nephritis is the most common secondary glomerular disease, and the proportions of diabetic nephropathy and hypertensive renal damage are increasing year by year, suggesting that the screening of renal complications of metabolic diseases in Ningxia should be strengthened and pay more attention to the patients with mild abnormal urine test.

Objective To analyze the changes in serum metabolites of patients with uremia using ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS), and provide a theoretical basis for the prevention and treatment of uremia. Methods Uremia patients from the Department of Nephrology, the Affiliated Hospital of Southwest Medical University, and the volunteers from the Health Examination Center were enrolled in this study. According to the inclusion and exclusion criteria, 20 uremia patients (experimental group) and 20 volunteers (control group) were screened out. UHPLC-MS was used to detect the metabolites in the serum of subjects from the two groups, and difference analysis was made to screen the different metabolites, followed by correlation analysis and pathway enrichment study. Results A total of 412 metabolites were identified by UHPLC-MS. Principal components analysis (PCA) proved that these metabolites could distinguish the control group and the experimental group well. The criteria [variable importance for the projection (VIP)>1, fold changes (FC)>1.25 or FC<0.8 and P value<0.05] was set to screen those significantly different metabolites. Finally, 28 significantly different metabolites were screened out, of which 18 metabolites increased significantly, the other 10 different metabolites decreased significantly. Correlation analysis results proved a certain correlation among 28 different metabolites and the experimental group and control group samples, and between the 28 differential metabolites themselves. Enrichment analysis found that 28 different metabolites might enrich the catecholamine biosynthetic pathway, and pathway analysis suggested that 28 different metabolites might affect glutamate, aspartame acid and glutamate metabolic pathways. Conclusion Based on metabonomic analysis, some metabolites in the serum of patients with uremia have changed, which can affect some metabolic pathways, thus affecting the pathophysiological process of patients with uremia.

Objective To explore the clinical and histopathologic features of lupus nephritis (LN) patients with positive antineutrophil cytoplasmic antibody (ANCA), so as to provide more theoretical basis to recognize and treat this disease. Methods Clinical data of biopsy-proven LN patients with ANCA test in the First Affiliated Hospital of Sun Yat-sen University from November 1, 2002 to September 11, 2020 were collected and analyzed retrospectively. The difference of clinical data, laboratory examination, and pathological examination of renal biopsy between ANCA-positive group and ANCA-negative group. The clinicopathological characteristics between different ANCA serotypes were compared. Results A total of 1 304 patients with LN confirmed by renal biopsy and ANCA test results were enrolled. Eighty ANCA-positive patients from 1 304 LN patients were screened. There are 55(68.8%) ANCA-positive LN patients with positive anti-myeloperoxidase antibodies (MPO). There were 14(17.5%) ANCA-positive LN patients with positive anti-proteinase 3 antibodies (PR3), and 11(13.8%) ANCA-positive patients with double positive antibodies of MPO and PR3. ANCA-positive LN patients had significantly higher serum creatinine [135.5(68.0, 361.8) μmol/L vs 88.0(64.0, 165.0) μmol/L, P=0.004] and blood urea nitrogen [12.35(6.35, 21.18) mmol/L vs 8.60(5.50, 15.70) mmol/L, P=0.026] as well as lower estimated glomerular filtration rate [45.70(13.83, 84.10) ml·min^-1·(1.73 m²)^-1 vs 66.75(38.43, 96.22) ml·min^-1·(1.73 m²)^-1, P=0.001] than ANCA-negative patients (stratified sampling of 160 patients). ANCA-positive LN patients had higher chronicity index than ANCA-negative LN patients [3(2, 7) vs 2(0, 5), P=0.006]. There were statistically significant difference in hemoglobin, serum creatinine and estimated glomerular filtration rate among ANCA-positive group, ANCA-negative group, and MPO-ANCA and PR3-ANCA double positive group. MPO-ANCA and PR3-ANCA double positive LN patients had the lowest hemoglobin and estimated glomerular filtration rate, and highest serum creatinine among the three groups (all P<0.05). Conclusions ANCA-positive LN patients have worse renal function and higher renal histological chronicity index than ANCA-negative LN patients, especially for patients with double positive MPO-ANCA and PR3-ANCA. More stringent monitoring and therapy may be needed in this subgroup of LN patients.

Objective To analyze the incidence and risk factors of acute kidney injury (AKI) in patients undergoing neurosurgery. Methods This study was a single center and retrospective research. The patients hospitalized in the general neurosurgery ward of Xuanwu Hospital, Capital Medical University, due to intracranial tumors and intracranial vascular diseases from January 1, 2017 to December 31, 2020 were enrolled. Demographic, clinical data and laboratory examination results of the selected patients were collected. The patients were divided into AKI group and non-AKI group according to AKI diagnosis criteria, and the differences of clinical parameters and medication between the two groups were compared. Logistic regression analysis method was used to analyze the risk factors of AKI in neurosurgical patients. Results Among 4 509 patients undergoing neurosurgery with age of (51.93±16.03) years old, 2 361 males and 2 148 females, 152 patients (3.37%) had AKI. The incidence of AKI in patients undergoing intracranial tumor surgery was 3.69%(84/2 278), and the incidence of AKI in patients undergoing intracranial cerebrovascular surgery was 3.05%(68/2 231). The length of hospital stay (t=4.897, P<0.001) and operation time (t=5.496, P<0.001) in AKI group were significantly longer than those in non-AKI group. The proportions of diabetes mellitus, preoperative serum creatinine, blood urea nitrogen, glycosylated hemoglobin, lactic acid, fibrinogen, and systolic pressure levels in AKI group were significantly higher than those in non-AKI group (all P<0.05); the hemoglobin level in AKI group was significantly lower than that in non-AKI group (P<0.05). The proportions of patients using angiotensin converting enzyme inhibitors/angiotensinⅡreceptor antagonists, cephalosporins, proton pump inhibitors, mannitol, and nonsteroidal anti-inflammatory drugs in AKI group were also significantly higher than those in non-AKI group (all P<0.05). Multivariate logistic regression analysis results showed that hemoglobin<110 g/L (OR=4.252, 95%CI 1.569-11.527, P=0.004), elevated blood urea nitrogen (OR=1.304, 95%CI 1.139-1.492, P<0.001) and application of nonsteroidal anti-inflammatory drugs (OR=2.342, 95%CI 1.044-5.253, P=0.039) were independent risk factors of AKI in neurosurgical patients. Conclusions The incidence of AKI in patients in neurosurgery general ward is 3.37%. Anemia, elevated blood urea nitrogen and application of nonsteroidal anti-inflammatory drugs are independent risk factors of AKI in patients undergoing neurosurgery.

Objective To investigate the role of survival motor neuron (SMN) gene knockout in mice with cisplatin-induced acute kidney injury (AKI). Methods A mouse model (C57BL/6) of cisplatin-induced AKI was constructed. Twenty male wild type (WT) and SMN^+/- mice weighing 22-24 g were randomly divided into four groups: WT mice with saline injection group (WT vehicle, n=5), SMN^+/- mice with saline injection group (SMN^+/- vehicle, n=5), WT mice with cisplatin injection group (WT cisplatin, n=5) and SMN^+/- mice with cisplatin injection group (SMN^+/- cisplatin, n=5). Mice were injected intraperitoneally with 20 mg/kg cisplatin or 0.9% saline. 72 hours later, the mice were sacrificed, and serum and kidney tissues were collected. The real time PCR and Western blotting were used to measure the expression levels of SMN mRNA and protein. The sarcosine oxidation and urease method were used to measure serum creatinine (Scr) and blood urea nitrogen (BUN) levels. Renal pathologic changes were observed by PAS staining. TUNEL immunofluorescence assay was used to detect the level of apoptosis. Western blotting and immunohistochemistry were used to detect the protein expression levels of apoptosis index poly (ADP-ribose) polymerase (PARP) and endoplasmic reticulum stress index CHOP. Results Compared with WT mice, SMN mRNA and protein expression levels were lower in SMN^+/- mice, and the expression level of SMN mRNA and protein was further decreased after intraperitoneal cisplatin injection (all P<0.05). Compared with WT mice with saline injection group, WT mice with cisplatin injection group had higher levels of Scr, BUN, tubular damage scores, TUNEL positive cell numbers, PARP and CHOP, while the expression levels of above indexes in the SMN^+/- mice with cisplatin injection group were higher than those in the WT mice with cisplatin injection group (all P<0.05). Conclusions SMN gene knockout can aggravate renal pathological damage and apoptosis of renal tubular epithelial cell in cisplatin-induced AKI mice. SMN may be a potential therapeutic target of AKI.