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    Clinical Study

  • Xia Li, Wang Junni, Xie Xishao, Xiang Shilong, Zhang Xiaohui, Chen Jianghua, Han Fei
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    Objective To observe the clinical characteristics and prognosis of patients with rapidly progressive glomerulonephritis (RPGN) caused by lupus nephritis, antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, or primary glomerulonephritis who were treated with peritoneal dialysis (PD) and then withdrew PD because of renal recovery. Methods Data of the above patients were retrospectively analyzed. The patients were diagnosed as RPGN and received PD therapy in Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University from February 2009 to August 2018. The patients were divided into early withdrawal group (PD time≤183 days, n=24) and late withdrawal group (PD time>183 day, n=24). The differences of clinical characteristics between the two groups were compared. The cumulative incidence of adverse events in both groups was analyzed using Kaplan-Meier curves. Cox proportional hazards model was used to analyze the risk factors influencing the prognosis of patients. Results Forty-eight RPGN patients were included. The median time of maintaining PD was 178(76, 378) days. Compared with the late withdrawal group, the patients in early withdrawal group had lower levels of urine volume, serum albumin and parathyroid hormone, and lower rates of gross hematuria and hypertension at the beginning of PD, and received higher rates of methylprednisolone impulse, combined immunosuppressive agents, and hemodialysis or continuous renal replacement therapy (all P<0.05). At the time of PD withdrawal, the levels of serum creatinine, serum calcium, serum albumin and parathyroid hormone in the early withdrawal group were significantly lower than those in the late withdrawal group (all P<0.05). The Kaplan-Meier curves showed that there was no significant difference in the cumulative survival of patients in both groups (log-rank test χ2=3.485, P=0.062). Cox regression analysis revealed serum creatinine≥209 μmol/L at the time of PD withdrawal was an independent risk factor for poor prognosis (HR=5.253,95%CI 1.757-15.702, P=0.003). Conclusions PD can be used for RPGN patients caused by lupus nephritis, ANCA-associated vasculitis and primary nephritis. Serum creatinine≥209 μmol/L at the time of PD withdrawal is an independent risk factor for poor prognosis.

  • Tong Yan, Fang Junyan, Deng Hai, Song Ahui, Zhu Tongying, Ge Xiaolin, Liu Yingli
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    Objective To compare the expression level of exosomal miR-503 in peritoneal dialysis effluent (PDE) from patients of different peritoneal transport characteristics, predict the target genes of miR-503 and provide bioinformatic data for researches of peritoneal transport characteristics. Methods Twenty-four stable peritoneal dialysis (PD) patients were selected and divided into high transport group (H group, n=12) and low transport group (L group, n=12) according to the results of peritoneal equilibration tests (PET). The 500 ml PDE that was left on the patient's abdomen overnight was collected and concentrated using ultrafiltration cell. Exosomes in PDE were resuspended in phosphate buffered saline (PBS) after ultracentrifugation and the characteristics of PDE exosomes were identified by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA), Western blotting and fluorescent staining. MicroRNAs were extracted from PDE exosomes. The expression levels of PDE exosomal miR-503 in the two groups were detected by quantitative real-time PCR. Then the relations between the relative quantity of PDE exosomal miR-503 and PET values or 24 h ultrafiltration volume (UF) were analyzed. Targetscan and miRDB databases were used to predict the target genes of miR-503. Gene ontology (GO) functional enrichment and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analysis were relied on DAVID (https://david.ncifcrf.gov/). Results The exosomes in PDE showed a round and cup-shaped morphology under TEM, and the diameters were approximately 100 nm measured by NTA. The specific biomarkers of exosomes, CD63, CD81 and heat shock protein -70 (HSP-70) were all detected by Western blotting. The internalization and uptake of the exosomes was observed after fluorescent staining. The relative expression level of PDE exosomal miR-503 in H group was found to be significantly higher than that in L group (P=0.002), and the relative quantity of PDE exosomal miR-503 was significantly positively correlated with PET values (r=0.547, P=0.006), but not 24 h UF (r=-0.297, P=0.159). There were 156 target genes of miR-503 in total that could be predicted by two different databases at the same time. GO analysis of these 156 target genes was mainly focused on kinase binding, regulation of protein modification and catabolic process as well as regulation of epithelial cell proliferation. KEGG enriched many tumor associated or classical signaling pathways, including transforming growth factor-β (TGF-β) signaling pathway and vascular endothelial growth factor (VEGF) signaling pathway. The prediction showed that vascular endothelial growth factor A (VEGFA) was a direct target gene of miR-503 and it was also related to many proteins involved in fibrosis mechanism. Conclusions The expression level of PDE exosomal miR-503 is significantly higher in H group, and positively correlates with PET values, which may regulate the angiogenesis of peritoneal vessels by targeting VEGFA.

  • Zhang Xiaohua, Li Jing, Wang Lihua
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    Objective To understand the current situation of vascular access selection in maintenance hemodialysis (MHD) patients in Shanxi Province, and analyze the factors affecting vascular access selection and risk factors of death in MHD patients. Methods MHD patients with clear vascular access information in Shanxi Province from January 2014 to December 2018 were enrolled in this study. The clinical data of patients were collected. The vascular access information of the selected candidates was clear. Multivariate logistic regression equation method was used to analyze the influencing factors of vascular access and the risk factors of death in MHD patients. Results Among the 10.236 patients with MHD, 9.130 patients (89.2%) selected autologous arteriovenous fistula (AVF) as vascular access, and 5.138 patients (50.2%) chose tunnel-free and non-polyester sheath central venous catheter (NCC) for the first dialysis. Multivariate logistic regression analysis showed that the primary disease of diabetic nephropathy (OR=0.517, 95%CI 0.281-0.796, P<0.001) and dialysis age<1 year (OR=0.483, 95%CI 0.219-0.811, P<0.001) were the influencing factors of patients with MHD who did not to choose AVF. Primary disease of diabetic nephropathy (OR=2.242, 95% CI 1.816-2.828, P<0.001), and using of central vein catheter (OR=1.785, 95% CI 1.237-2.579, P<0.001) were independent risk factors of death in MHD patients. Conclusions AVF is the first choice for MHD patients in Shanxi Province. There is higher proportion of the use of NCC as the first dialysis vascular access. Primary disease of diabetic nephropathy and dialysis age<1 year are the influencing factors for MHD patients not to choose AVF. Primary disease of diabetic nephropathy and use of central vein catheter may increase the risk of death in MHD patients.

  • Zhang Dihua, Liao Kang, Zhong Xiaoqing, Wang Xin, Qiu Yagui, Zheng Xunhua, Li Jianbo, Xu Yuanwen, Li Guangran, Yang Xiao, Huang Fengxian
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    Objective To assess the bacterial profiles and antimicrobial susceptibility patterns in uropathogens, and help to inform the empiric treatment decisions for urinary tract infection in outpatient settings. Methods A single institutional retrospective analysis was performed on positive urine cultures from outpatient settings between January 1998 and December 2018. To analyze changes over time, trends analysis were undertaken on bacterial profiles, antimicrobial susceptibility and resistance. Results A total of 1.172 pathogenic bacteria were isolated after exclusion of duplicate strains originated from the same patient, including 991(84.6%) Gram-negative bacterial strains and 181(15.4%) Gram-positive strains. The most common Gram-negative uropathogens were Escherichia coli (60.8%) and Klebsiella pneumonia (8.1%). Enterococcus faecalis (4.6%) was the predominant Gram-positive strain. The detection rate of Escherichia coli increased significantly, from 50.8% to 63.2% (χ2=7.978, P=0.046), and no significant difference was observed in the distribution of major uropathogenic bacteria over the 20 years (all P>0.05). The proportion of extended-spectrum β-lactamase (ESBLs) producing strains increased significantly across the 20 years (P<0.05). The resistance rates of Escherichia coli to amoxicillin and clavulanate potassium, aztreonam, ceftazidime, ciprofloxacin and sulbactam+cefoperazone increased significantly (all P<0.05). All the isolates sustained high susceptibility to tazobactam+piperacillin, amikacin, imipenem and nitrofurantoin (95.0%, 95.7%, 97.9% and 91.1%). Similar to those of Escherichia coli, Klebsiella pneumoniae remained a high and stable sensitivity to tazobactam+piperacillin, amikacin and imipenem during the 20 years (79.1%, 88.0% and 80.3%). However, the proportion of ESBLs producing strains increased significantly (P<0.05). Among Gram-positive bacteria isolates, the sensitivity rates of Enterococcus faecalis to ampicillin, nitrofurantoin and penicillin G were 100.0%. No vancomycin resistant strain was detected in Gram-positive bacteria. Conclusions From 1998 to 2018, Escherichia coli and Klebsiella pneumoniae are the most common Gram-negative bacteria uropathogens obtained in outpatient settings. Significant increases of resistance to some antimicrobial agents such as second- and third-generation cephalosporins and fluoroquinolones are observed during the 20 years and high susceptibilities to tazobactam+piperacillin, amikacin, imipenem and nitrofurantoin sustain over time. Local treatment strategies of urinary tract infections on outpatient basis should be made according to epidemiology of drug resistance and individual characteristics to control the spread and curb the prevalence of drug resistant.

  • Guo Dandan, Wang Huifang, Liu Hang, Xu Yan, Jiang Wei, Liu Yingying, Liu Xuemei
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    Objective To explore the development and clinical application value of Nomogram model, a noninvasive early diagnosis model, in IgA nephropathy. Methods The clinical data of 712 patients with primary glomerular disease diagnosed by renal histopathological examination in Affiliated Hospital of Qingdao University during October 1, 2010 to August 31, 2019 were collected retrospectively, including 241 cases of IgA nephropathy and 471 cases of non-IgA nephropathy. According to the time of case inclusion, the patients were divided into the training set (n=426, 156 cases of IgA nephropathy and 270 cases of non-IgA nephropathy) and the validation set (n=286, 85 cases of IgA nephropathy and 201 cases of non-IgA nephropathy). Univariate and multivariate logistic regression equations were used to analyze the risk factors for diagnosing IgA nephropathy in patients of training set. Nomogram model for noninvasive diagnosis of IgA nephropathy was established according to the akichi information criteria (AIC) and applied to the validation set for validation. The discriminant degree, calibration degree and clinical practicability of the model were verified and evaluated by receiver operating characteristic curve (ROC), calibration curve and decision curve analysis (DCA), respectively. Results Multivariate logistic regression results showed that the age (OR=0.966, 95%CI 0.947-0.985, P=0.001), IgA/C3 ratio (OR=1.889, 95%CI 1.468-2.432, P<0.001), serum albumin (OR=1.091, 95%CI 1.047-1.136, P<0.001), total cholesterol (OR=0.810, 95%CI 0.694-0.946, P=0.008), and gross hematuria (OR=6.858, 95%CI 1.867-25.189, P=0.004) of patients with primary glomerular disease were independent factors for the diagnosis of IgA nephropathy. Nomogram diagnostic model was constructed based on the above indicators, and the areas under ROC curve were 0.880 and 0.887 respectively in the training set and the validation set. The calibration curve showed that the predicted probability of the model was in good agreement with the actual probability. DCA showed that the safety and clinical net benefit of the model were higher. Conclusions The Nomogram model has high accuracy and clinical practicality in diagnosing IgA nephropathy, and can be used for noninvasive and early diagnosis of IgA nephropathy to enable patients to receive early treatment.

  • Li Huarong, Chen Chaoying, Tu Juan, Geng Haiyun, Wang Nannan, Geng Yulin, Xia Hua
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    Objective To explore the related factors of poor prognostis in children with Henoch-Sch?nlein purpura nephritis (HSPN), and provide reference for predicting and improving the prognosis of children with HSPN. Methods The clinical and pathological data of children with HSPN hospitalized in the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics from May 2007 to June 2019 were retrospectively reviewed. According to the prognosis, the patients were divided into complete remission group and persistent abnormal group. Results (1) Among 108 cases, there were 73 males and 35 females, with the onset age ranging from 5 to 16 years and average age of (9.5±2.8) years. The interval time from the first clinic in our hospital to the last follow-up was 2-131 months, with average of 24.8 months. Renal involvement occurred in the course of Henoch-Sch?nlein purpura from 1 day to 51 months, and the renal biopsy time was 5 days to 60 months after renal involvement. (2) Hematuria with proteinuria type and nephrotic syndrome type were predominant, and there was no significant difference between the two groups. The proportion of gross hematuria in the persistent abnormal group were significantly higher than that in the complete remission group (52.6% vs 31.4%, χ2=4.659, P=0.031). There were significant differences in serum creatinine and urea between the two groups (both P<0.05). The proportion of hyperuricemia in the persistent abnormal group was higher than that in the complete remission group (39.5% vs 21.4%, χ2=3.998, P=0.046). After clinical treatment, though there was no significant difference in proteinuria between the two groups at the beginning of the disease, the negative transformation rate of proteinuria in the complete remission group was higher than that in the persistent abnormal group after 3 months(55.7% vs 34.2%, χ2=4.562, P=0.033). (3) According to International study of Kidney Disease in Children (ISKDC) pathology classification, 14 cases (36.8%), 21 cases (55.3%), 3 cases (7.9%) withⅡ, Ⅲ, Ⅳ level in the persistent abnormal group and 21 cases (30.0%), 49 cases (70.0%), 0 case with Ⅱ,Ⅲ, Ⅳ level (70.0%) in the complete remission group after (20.16±24.86) months of follow-up, and the difference between the two groups was not statisticcally significant (Z=-0.135, P=0.892). According to the Oxford Classification of IgA nephropathy, 36(33.3%) children had tubule-interstitial lesions (T1, 26%-50% tubular atrophy or interstitial fibrosis), and the proportion in the persistent abnormal group was significantly higher than that in the complete remission group (50.0% vs 24.3%, Z=-2.695, P=0.007). (4) Compared with T0 (0-25% tubular atrophy or interstitial fibrosis), the incidence of gross hematuria and hyperuricemia in the T1 tubule-interstitial lesion were both higher than that (respectively 63.9% vs 27.8%, χ2=13.061,P<0.001; 38.9% vs 22.2%, χ2=3.983, P=0.046). (5) Multivariate logistic regression analysis showed that renal tubule-interstitial lesion was a risk factor for poor prognosis of HSPN (OR=2.580, 95%CI 1.055-6.310, P=0.038). Conclusions Renal tubule-interstitial lesion is a risk factor for the persistent abnormal of HSPN. Gross hematuria and hyperuricemia are related to tubule-interstitial lesions.

  • Basic Study

  • Liu Lichang, Suo Dongyang, Ding Yu, Wan Xiang, Zhang Yang, Yang Xiangdong
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    Objective To investigate the expression and role of the tumor necrosis factor-α (TNF-α) induced protein 8 like-1 (TIPE1) in acute kidney injury (AKI) induced by cisplatin in animal model and cells. Methods Twelve male C57BL/6 mice aged 6-8 weeks were randomly divided into the control group and the model group. Mice in the model group received a single intraperitoneal injection of 20 mg/kg of cisplatin (20 mg/kg saline in the control group). All mice were euthanized after 5 days. Meanwhile, serum and kidney samples were collected. The levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were detected by biochemical kits. Renal histopathological changes in mice were observed by HE staining. The expression of TIPE1 in kidney was examined using immunohistochemistry. qRT-PCR was used for testing the relative expression of TIPE1 mRNA in mice kidney. Western blotting was used for testing TIPE1 and NGAL protein relative expression in mice kidney. Human kidney proximal tubular cells (HK-2) were stimulated with 20 μmol/L cisplatin for 0, 6, 12 and 24 h to establish cisplatin-induced AKI cell model. The expressions of TIPE1 mRNA and protein were detected by qRT-PCR and Western blotting in HK-2 cells. The expression of TIPE1 gene in HK-2 cells was silenced by lentivirus containing TIPE1 siRNA sequence. Then, TIPE1 stable knockout HK-2 cell strains were treated with 20 μmol/L of cisplatin for 24 hours. The protein expression of tubular damage marker neutrophil gelatinase-associated lipocalin (NGAL), microtubule-associated protein 1 light chain 3 (LC3) and Beclin1 in HK-2 cells were detected by Western blotting. Results Compared with the control group, the expressions of TIPE1 mRNA and protein were up-regulated and NGAL protein expression was increased significantly in renal tissue of the model group (all P<0.05). The expressions of TIPE1 mRNA and protein were remarkably increased with the prolongation of cisplatin treatment in HK-2 cells (both P<0.05). Compared with the scramble siRNA group, the protein expressions of NGAL, LC3-Ⅱ and Beclin1 were increased significantly in the TIPE1 siRNA group after lentivirus interfered with the expression of TIPE1 gene in HK-2 cells (all P<0.05). Conclusions The mRNA and protein expressions of TIPE1 are increased in acute kidney injury models. Gene silencing of TIPE1 can promote the expressions of early renal tubular damage marker and autophagy-related proteins, which indicates the excessive autophagy aggravates renal tubular injury. It is suggested that TIPE1 may be involved in the pathogenesis of acute kidney injury.

  • Short Original Article

  • Zhang Pei, Wu Heyan, Gao Chunlin, He Xu, Shi Zhuo, Kuang Qianhuining, Yao Jun, Xia Zhengkun
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  • Case Report

  • Zhu Jiaomei, Tan Huibing, Xing Lingling, Jiao Sumin, Tian Li, Liu Like, Fu Shuxia
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  • Li Mengke, Xu Jiayun
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  • Expert Forum

  • Yin Yanqi, Jin Qizhuang
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  • Review

  • Huang Ying, Li Ruizhao, Liang Xinling
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