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    Clinical Study

  • Fan Xiaohong, Ye Wenling, Ma Jie, Sun Ying, Cui Rui, Zhang Wei, Wang Baobao, Li Xuemei
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    Objective To determine the epidemiology of hyperkalemia and influencing factors in a general population in Pinggu district of Beijing city. Methods This study was a cross-sectional survey. The subjects were from the epidemiological survey population of chronic diseases in Pinggu district of Beijing city from March to May 2014. All participants completed a questionnaire, anthropological measurement, and venous blood samples collection to detect serum creatinine and potassium and so on. First void morning urine was collected to detect the albumin-creatinine ratio. Hyperkalemia and hypokalemia were defined as serum potassium level>5.0 mmol/L and≤3.5 mmol/L, respectively. Logistic regression analysis method was used to analyze the influencing factors of hyperkalemia. Results Of the 10 252 people in this study, the prevalence of hyperkalemia was 6.17%(95%CI 5.70%-6.67%), the prevalence of hypokalemia was 0.61%(95%CI 0.47%-0.79%), and the prevalence of participants with serum potassium>5.5 mmol/L was 0.53%(95%CI 0.40%-0.69%). Multivariate logistic regression analysis results showed that males (OR=1.269, 95%CI 1.074-1.498, P=0.005), diabetes (OR=1.226, 95%CI 1.008-1.490, P=0.041), increased total cholesterol (OR=1.219, 95%CI 1.119-1.329, P<0.001), and decreased estimated glomerular filtration rate (OR=0.971, 95%CI 0.965-0.977, P<0.001) were significantly correlated with the increased risk of hyperkalemia. Usage of renin-angiotensin-aldosterone system inhibitors and diuretics were not found to be significantly associated with the risk of hyperkalemia (OR=1.018, 95%CI 0.751-1.380,P=0.908; OR=0.638, 95%CI 0.229-1.781, P=0.391). Conclusions The prevalence of HK in the general population is 6.17%. The male, decreased estimated glomerular filtration rate, diabetes, and increased total cholesterol are influencing factors of hyperkalemia.

  • Pang Jiaoyang, Zhang Weichen, Huang Bihong, Cao Yanpei, Zhang Jiaying, Yu Chen, Ye Zhibin, Chen Jing, Wang Mengjing
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    Objective To explore the effects of dietary phosphate restriction education on serum phosphorus level, dietary phosphate intake and the knowledge of hyperphosphatemia in maintenance hemodialysis (MHD) patients. Methods This study was a retrospective cohort study. A total of 116 hemodialysis patients in Huashan Hospital, Huadong Hospital and Tongji Hospital from October 2019 to December 2020 were enrolled in this study. They were divided into short-term group (84 cases) and long-term group (32 cases). The short-term group did not receive education or received education≤60 minutes. Meanwhile, the long-term group received education>60 minutes. Serum phosphorus level, dietary phosphate intake and knowledge of hyperphosphatemia were compared between the two groups after 4 weeks. Results At baseline, age [64(56, 69) years old vs 65(60, 73) years old, Z=-1.493, P=0.136], the proportion of males [58.3%(49/84) vs 56.3%(18/32), χ2=0.041, P=0.839], dialysis age [55(26, 130) months vs 53(20, 132) months, Z=-0.062, P=0.951], body mass index, diabetes history, single-pool Kt/V, proportion of calctriol used, blood calcium, blood phosphorus, intact parathyroid hormone and dietary protein, dietary phosphorus and dietary phosphorus protein ratio had no statistical significance between short-term group and long-term group (all P>0.05). Adequate dietary phosphate restriction education reduced dietary phosphate intake [777.98(653.81, 943.16) mg/d vs 896.56(801.51, 1 015.51) mg/d, Z=-2.903, P=0.004], phosphate/protein ratio [13.16(11.52, 14.21) mg/g vs 15.27(13.31, 17.48) mg/g, Z=-3.929, P<0.001] and serum phosphorus level [(1.42±0.37) mmol/L vs (1.85±0.44) mmol/L, t=4.984, P<0.001]. Meanwhile, such education significantly improved achievement rate of serum phosphorus (62.5% vs 41.7%, χ2=4.034, P=0.045). In addition, patients in long-term group answered more questions correctly (completely correct plus partially correct) about the causes (93.8% vs 72.6%, χ2=6.120, P=0.013), poor prognosis (78.1% vs 52.4%, χ2=6.372, P=0.012) of hyperphosphatemia as well as the types of food with high phosphate (65.6% vs 52.4%, χ2=1.650, P=0.199). Conclusion Adequate dietary phosphate restriction education reduces serum phosphorus level and dietary phosphate intake, and improves the knowledge of hyperphosphatemia in MHD patients.

  • Wang Shuang, Li Danyang, Wang Chen, Yu Zhuanzhuan, Xu Jin, Yu Xiaojuan, Zhou Fude, Liu Gang, Wang Suxia
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    Objective To investigate the clinicopathological characteristics of renal leukocyte chemotactic factor 2 amyloidosis (ALECT2). Methods The patients with renal ALECT2 diagnosed by renal biopsy in Peking University First Hospital, Shanxi Medical University Second Hospital and Shanxi Bethune Hospital from January 2001 to October 2021 were retrospectively enrolled. According to whether the patients had concurrent glomerular diseases, they were classified into two groups: isolated ALECT2 group and ALECT2 with concurrent renal diseases group. Clinicopathological data of the two groups were compared. Light microscopy, immunofluorescence and immunoelectron microscopy were applied to investigate pathological characteristics of renal tissues. Mass spectrometry was used to analyze the composition of renal amyloid deposits. Gene sequencing was employed to detect the leukocyte chemotactic factor 2 (LECT2) gene sequence in peripheral blood of the patients. Results Sixteen patients with ALECT2 were enrolled in this study and nine of them had concurrent renal diseases. The age of 16 patients was (65.00±8.45) years old. The sex ratio of males to females was 7 to 9. Most of patients were Han ethnicity (15/16). Eight patients came from Shanxi province. Fifteen patients presented with varying degree of proteinuria [2.16(1.07, 4.72) g/24 h]; 5 patients had nephrotic syndrome; 11 patients had renal insufficiency; 12 patients had microscopic hematuria. Part of patients also had hypertension (12/16) and diabetics (6/16). Compared with isolated ALECT2, the ALECT2 group with concurrent renal diseases had a higher proportion of nephrotic syndrome (5/9 vs 0/7, P=0.034). Renal biopsy results showed that all patients (16/16) had amyloid deposits in the interstitium of renal cortex with varying degree of inflammatory cell infiltration and fibrosis, and glomeruli (12/16) and arterioles (14/16) were involved by amyloid deposits. The amyloid deposits were strongly congophilic and immunohistochemistry for LECT2 was positive. By semi-quantitative analysis, the proportions of glomerular and overall amyloid loads in ALECT2 with concurrent renal diseases group were lower than those in isolated ALECT2 group (both P<0.05). Electron microscopy revealed randomly oriented and non-branching fibrils with a diameter of 8-12 nm. The LECT2 peptides were detected by mass spectrometry in renal amyloid deposits of 8 patients, and homozygous G allele of LECT2 was found in 7 patients by gene sequencing. Complete follow-up data of 13 patients showed that 2 patients died, 1 patient developed end-stage renal disease at the time of renal biopsy, and most of the rest patients had stable renal function (8/10). Conclusions Patients with renal ALECT2 mainly present with proteinuria, along with a high incidence of renal insufficiency, microscopic hematuria, and concurrent renal diseases. The pathologic feature is the preferential deposition of amyloid in renal cortical interstitium.

  • Xu Tian, Liu Hong, Xie Xiaotong, Wang Bin, Zhang Xiaoliang, Liu Bicheng
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    Objective To observe the efficacy and safety of roxadustat in the treatment of renal anemia in calciphylaxis dialysis patients who had poor response to recombinant human erythropoietin (rHuEPO). Methods This study was a prospective cohort study. The dialysis patients who were diagnosed with calciphylaxis and had previous regular use of rHuEPO≥3 months with hemoglobin (Hb) levels<110 g/L in the Department of Nephrology of Zhong Da Hospital affiliated to Southeast University from January 1, 2019 to March 28, 2021 were recruited. The effect of oral roxadustat in calciphylaxis dialysis patients with renal anemia was analyzed by self-comparison method. Results There were totally 18 calciphylaxis dialysis patients with renal anemia enrolled in the study and the age was (49.7±16.2) years old, including 11 males and 7 females, and 14 cases on hemodialysis and 4 cases on peritoneal dialysis. The high-sensitivity C-reactive protein level was 27.3(15.6, 48.5) mg/L (reference value 0-3 mg/L) at baseline. The baseline Hb level was (85.4±11.6) g/L, and after 3 months of oral roxadustat, the Hb level was (105.8±15.2) g/L (t=-9.282, P<0.001). The Hb compliance rate was 44.4%(8/18). Ferritin decreased significantly at 3 months compared with the baseline level [208.0(59.0, 306.3) μg/L vs 229.0(127.3, 385.2) μg/L, Z=-3.637, P<0.001]. The total iron binding capacity level increased significantly compared with the baseline level [127.0(65.0, 211.5) μmol/L vs 105.5(43.8, 153.7) μmol/L, Z=-2.156, P=0.031]. Transferrin saturation level at 3 months was lower than that at baseline, but there was no significant difference [20.2%(14.2%, 27.7%) vs 20.5%(18.7%, 34.9%), Z=-1.546, P=0.122]. No adverse reactions occurred during the observation period. Conclusion The application of roxadustat can effectively correct Hb level and improve iron metabolism with high safety in calciphylaxis dialysis patients with renal anemia under inflammatory status.

  • Su Kaijie, Wang Xiaoxiao, Tang Wen
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    Objective To analyze the effect of anticoagulant or antiplatelet drugs on bleeding and cardio-cerebral vascular events in perioperative period of catherization for peritoneal dialysis. Methods The clinical data of patients undergoing peritoneal dialysis catheterization in Peking University Third Hospital from July 1, 2010 to December 31, 2020 were collected and analyzed retrospectively. The patients were divided into drugs discontinuation group and drugs continuation group according to whether the anticoagulant drugs or antiplatelet drugs were discontinued or not. Baseline clinical data and bleeding and cardio-cerebral events after surgery were compared between the two groups. Multivariate logistic regression model was used to analyze the influencing factors for bleeding and cardio-cerebral events. Results A total of 57 patients were included in the study, with 34 males and 23 females. The age was (67.37±13.93) years old (range from 27 to 97 years old). There were 37 patients in drugs discontinuation group and 20 patients in drugs continuation group. The proportions of acute myocardial infarction events in drugs continuation group were higher than those in drugs discontinuation group in 3 months and 6 months before surgery (10/20 vs 3/37, χ2=10.671, P=0.001; 11/20 vs 3/37, χ2=12.980, P<0.001 respectively). The median drugs discontinuation time was 5.0(2.0, 14.0) d (range from 1 to 30 d) before surgery, and median restore medication time was 4.0(3.0, 7.0) d (range from 1 to 14 d) after surgery in drugs discontinuation group. There was no significant difference in the proportion of bleeding (10/37 vs 8/20, χ2=1.011, P=0.315) and cardio-cerebral events (4/37 vs 0/20, χ2=0.964, P=0.326) between drugs discontinuation group and drugs continuation group within 2 weeks after surgery. The results of multivariate logistic regression analysis showed that drugs discontinuation before surgery was not an independent influencing factor for bleeding events (OR=0.656, 95%CI 0.195-2.206, P=0.496), however combination of aspirin and clopidogrel before surgery was an independent influencing factor for bleeding events (OR=4.038, 95%CI 1.044-15.626, P=0.043). All cardio-cerebral events (4 cases) happened in drugs discontinuation group, and myocardial angina in 6 months before surgery (OR=9.764, 95%CI 0.928-102.682, P=0.058) and increased serum calcium concentration (OR=1.491, 95%CI 0.976-2.278, P=0.065) were related with an elevated trend for cardio-cerebral events. Conclusions Whether anticoagulant or antiplatelet drugs are discontinued before catherization surgery for peritoneal dialysis is not an independent influencing factor for bleeding events after surgery. The risk of postoperative bleeding in patients using combination of aspirin and clopidogrel should be paid attention. Myocardial angina in 6 months before surgery and higher serum calcium are related with an elevated trend for cardio-cerebral events after drugs discontinuation.

  • Huang Yang, Yu Shuangjin, Chen Haiwei, Wu Guobin, Qi Fangze, Liu Yanhan, Yang Yuying, Chen Tong, Ruan Hehuan, Zhang Tao, Chen Honghui, Chen Chuanbao, Zhao Qiang, Guo Zhiyong, Chen Guodong, Qiu Jiang, He Xiaoshun
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    Objective To explore the long-term preservation value and repair effect of normothermic machine perfusion (NMP) on clinically discarded kidneys. Methods A case of clinical discarded donor kidney was collected, and NMP was carried out in vitro for 9 hours with recovered blood. The dynamic changes of renal appearance, blood gas and biochemistry analysis of perfusate and renal pathology were recorded. Results In the second to fifth hour of NMP, the appearance of renal was pink and ex vivo normothermic perfusion assessment score (EVNP) was grade Ⅰ. While, the sixth hour and beyond of NMP, the appearance of kidney turned to dark red and EVNP was grade Ⅲ. The renal perfusion blood flow maintained above 150 ml/min in the first 6 hours and decreased significantly after that, and at the end, was only 50 ml/min. During the whole process of perfusion, urine output was maintained at about 100 ml/h. PO2 remained above 100 mmHg in the first 5 hours of perfusion and from the 6th hour, was lower than 80 mmHg and continued to decline, and was close to 0 at the end of perfusion. The results showed that although the K+ concentration changes in blood and urine in the first 5 hours of NMP had a good consistency, the lactic acid level had been rising. In addition, there was no significant change in the histopathology at the fourth hour of perfusion compared with that before zero-point puncture, and the fibrinous thrombus in glomeruli was improved compared with that before perfusion. However, at the sixth hour after perfusion and before the end of perfusion, the pathological changes of renal tissue were significantly worse. There were a large of thrombosis in glomerular blood vessels, renal tubular atrophy and acute tubular necrosis. Conclusions NMP can realize the evaluation of extended criteria donors before transplantation, and it proves the feasibility and repair potential of NMP in kidney to a certain extent. At the same time, NMP also provides a new way to expand the source of donor kidney and to pre-treat organ in vitro.

  • Basic Study

  • Zhou Yan, Zhou Haiyan, Liu Nanchi, Xu Yan, Zhang Xingjian, Ding Lin, Ma Ruixia
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    Objective To investigate the protective effect and potential mechanisms of microRNA-26a-5p (miR-26a-5p) on podocyte injury in diabetic kidney disease (DKD). Methods (1) In vivo experiment: Four-week-old db/db mice were divided into db/db group, db/db+agomir-NC group and db/db+miR-26a-5p agomir group according to random number table method, with 10 mice in each group, and 10 db/m mice of the same week-old were set as normal control group. At the age of 10 weeks, pathological changes were observed through light and electron microscopy. Kidney weight /body weight (KW/BW), urinary albumin to creatinine ratio (ACR), fasting blood glucose (FBG) and other biochemical indicators were also detected. The position and expression of miR-26a-5p in kidney tissue were determined through fluorescence in situ hybridization and quantitative real-time PCR, while the expressions of transient receptor potential cation channel-6 (TRPC6) and Nephrin in kidney tissue were determined by Western blotting and immunohistochemistry. (2) In vitro experiment: The immortalized mouse podocytes (MPC5) were divided into 5 groups: normal glucose group, high mannitol group, high glucose group, high glucose+miR-26a-5p mimic group, and high glucose+mimic-NC group. The expressions of miR-26a-5p, TRPC6 and Nephrin were detected. Luciferase reporter assay was conducted to research the relationship of miR-26a-5p and TRPC6. Results (1) In vivo experiment: Compared with db/m group, db/db mice exhibited lower KW/BW and disrupted conditions of ACR, FBG, total cholesterol, triglycerides and low density lipoprotein cholesterol (all P<0.01). Increased glomeruli volume, more extracellular matrix deposition, thicker basement membrane and more foot process fusion were observed by light and electron microscope. Increased expression of TRPC6 protein as well as decreased expression of Nephrin protein and miR-26a-5p were detected in kidney tissues of db/db mice (P<0.05). Compared with db/db+agomir-NC group, db/db mice transfected by miR-26a-5p agomir exhibited less albuminuria, with less protein expression of TRPC6 and more Nephrin in kidney tissue (all P<0.05). (2) In vitro experiment: Compared with normal glucose group, high glucose-treated podocytes exhibited increased expression of TRPC6 (P<0.05), as well as decreased expression of Nephrin (P<0.05) and miR-26a-5p (P<0.01). Compared with high glucose+mimic-NC group, lower expression of TRPC6 and higher expression of Nephrin were detected in podocytes transfected by miR-26a-5p mimic (both P<0.05). Luciferase reporter assay confirmed that miR-26a-5p could regulate the expression of TRPC6 precisely. Conclusions The expression of miR-26a-5p in podocytes is down-regulated in the context of high glucose and miR-26a-5p protects podocytes from injury via inhibiting the expression of TRPC6 in DKD.

  • Jin Yangguang, Huang Zena, Ye Wenhao, Yu Huaxiao, Luo Yuhang, Lin Yan, Liang Minling
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    Objective To investigate the level of endogenous hydrogen sulfide (H2S) in contrast-induced acute kidney injury (CIAKI), as well as the potential role of H2S against CIAKI by down-regulating NLRP3 inflammasome. Methods Twenty-four healthy male Sprague-Dawley rats, weighing 180-220 g, were randomly divided into three groups according to the random number table method: control group, CIAKI group (iopromide 2.9 g/kg) and CIAKI+NaHS group (NaHS 4 mg/kg for three days before 2.9 g/kg iopromide injection). Kidneys were collected for whole-genome sequencing and bioinformatic analysis. HE and PAS staining were used for kidney histological examination. TUNEL assays were applied to detect renal tubular epithelial injury. Expressions of NLRP3 inflammasome (NLRP3, ASC and caspase-1) were evaluated by immunofluorescence staining. The role of H2S in contrast (iopromide 200 mgI/kg)-induced injury on human renal tubular epithelium (HK-2 cells) was investigated, and CCK-8 assay was used to detect cellular viability. Results Compared with the control group, the expression of endogenous H2S synthetases-related genes [cystathionine β-synthase (CBS), cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST)] was lower in CIAKI group (all P<0.05). The gene expression levels of CBS, CSE and 3-MST were negatively correlated with renal function biomarkers serum creatinine, blood urea nitrogen and cystatin-C (all P<0.05). Compared with the CIAKI group, CIAKI+NaHS group showed alleviated creatinine, blood urea nitrogen and cystatin-C, improved histological changes, reduced apoptosis. Moreover, the expression levels of NLRP3, ASC and caspase-1 in CIAKI+NaHS group were lower than those in CIAKI group (all P<0.05). In HK-2 cells, compared with the contrast group, the cellular viability was higher in the contrast+NaHS group; reducing endogenous H2S by CBS inhibitor could enhance contrast-induced cell viability (P<0.05). Conclusions Injury of endogenous H2S system is pivotal to CIAKI pathogenesis. Up-regulation of H2S ameliorates renal injury of CIAKI rats, which may be related to regulation of NLRP3 inflammasome.

  • Case Report

  • Zhang Bo, Song Chundong, Ren Xianqing, Zhai Wensheng, Ding Ying, Yang Xiaoqing
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  • Lian Zhiwen, Li Wei, Liu Xiaofen, Lin Minwa, Li Huishi, Liang Zijie, Hong Hanli, Chen Dezhen, Chen Youyuan, Kong Yaozhong
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  • Review

  • Zhang Hanzhen, Hao Chuanming
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  • Jiang Zhaohui, Ma Haoyang, Gong Wei, Zhang Aihua
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