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    Clinical Study

  • Fan Xiaoguang, Shao Zehua, You Zhenzhen, Huo Shuai, Zhang Zhu, Shao Fengmin
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    Objective To explore the risk factors of poor renal prognosis in patients with coronary artery bypass surgery (CABG)-associated acute kidney injury (AKI), and establish a preliminary clinical risk prediction model for chronic kidney disease (CKD) progression in CABG-associated AKI patients, and evaluate its predictive efficacy. Methods It was a retrospective, observational cohort study. The study subjects were patients who underwent CABG at Central China Fuwai Hospital from January 1, 2018 to December 31, 2020, with a baseline estimated glomerular filtration rate (eGFR)>60 ml·min-1·(1.73 m2)-1 and postoperative complication of AKI. The patients were followed up for 90 days after discharge from hospital. The endpoint event was defined as progression to CKD after 90 days of the occurrence of CABG-associated AKI. The patients were divided into CKD group and non-CKD group based on whether they experienced endpoint events. The baseline clinical data were compared between the two groups. The logistic regression model was used to analyze the risk factors of endpoint event. The receiver-operating characteristic curve was drawn to evaluate the performance of the clinical risk prediction model for predicting poor renal prognosis in CABG-associated AKI patients. Results A total of 124 CABG-associated AKI patients were enrolled in the study, including 95 males and 29 females, aged (62.57±9.61) years old. Thirty-eight patients (30.8%) progressed to new-onset CKD 90 days after CABG-associated AKI. Compared with non-CKD group, CKD group had lower preoperative hemoglobin (t=2.778, P=0.006) and baseline eGFR (t=3.603, P<0.001), higher proportion of women (χ2=10.714, P=0.001), and higher preoperative blood NT-proBNP (Z=-2.150, P=0.030) and discharged serum creatinine (Z=-5.290, P<0.001). The multivariate logistic regression analysis results revealed that female (OR=5.179, 95% CI 1.535-17.477, P=0.008), high preoperative blood NT-proBNP (OR=1.049, 95% CI 1.004-1.095, P=0.032), low baseline eGFR (OR=0.928, 95% CI 0.889-0.968, P=0.001), and high serum creatinine at discharge (OR=1.019, 95% CI 1.009-1.029, P<0.001) were independent influencing factors of CABG-associated AKI to CKD. The clinical risk prediction model including female, preoperative blood NT-proBNP, preoperative baseline eGFR, and serum creatinine at discharge produced a moderate performance for predicting CABG-associated AKI to CKD (AUC=0.872, 95% CI 0.806-0.939, P<0.001). Conclusion Patients with CABG-associated AKI are at high risks for new-onset CKD. Female, preoperative high NT-proBNP, preoperative low baseline eGFR and high serum creatinine at discharge can help identify patients with a high risk of CABG-associated AKI to CKD.

  • Pan Wei, Wang Menglong, Xu Yao, Zhang Jishou, Zhao Mengmeng, Wan Jun
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    Objective To explore the changes of disease burden and risk factors of chronic kidney disease (CKD) due to type 1 and type 2 diabetes mellitus in China from 1990 to 2019, and to provide reference data for the prevention and control of diabetic kidney disease (DKD). Methods The Chinese DKD data were obtained from the 2019 Global Burden of Disease (GBD) database. The morbidity, prevalence, mortality, years lived with disability (YLD), years of life lost (YLL), and disability-adjusted life year (DALY) were used to compare the disease burden of CKD due to type 1 and type 2 diabetes mellitus from 1990 to 2019. In addition, the risk factors of DKD were analyzed. Results The numbers of CKD patients due to type 1 and type 2 diabetes mellitus in China were 574 (95% UI 495-665) and 31 076 (95% UI 28 152-33 909) thousand, and the numbers of new cases were 9 (95% UI 8-11) and 434 (95% UI 390-481) thousand in 2019, respectively. The numbers of death were 13 (95% UI 8-18) and 63 (95% UI 50-77) thousand, respectively. The age groups with the largest number of patients and new cases of CKD due to type 1 diabetes mellitus were 30-34 years old and <5 years old, respectively. The age group with the largest number of patients and new cases of CKD due to type 2 diabetes mellitus were 50-54 years old and 70-74 years old, respectively. From 1990 to 2019, the age-standardized prevalence rate of DKD patients in China was relatively stable, but the age-standardized incidence rate and YLD rate showed an upward trend, while the age-standardized mortality rate, YLL rate, and DALY rate showed a downward trend. The main risk factors associated with DKD death were high fasting plasma glucose, kidney dysfunction, high systolic blood pressure, high body mass index, high sodium diet, and lead exposure. The proportions of DKD death caused by high systolic blood pressure and high body mass index in the Chinese population were still increasing. Conclusions From 1990 to 2019, the age-standardized incidence and YLD rate of DKD in China shows an upward trend, while the age-standardized prevalence rate is relatively stable, and the age-standardized mortality rate, YLL rate, and DALY rate show a decreasing trend. High fasting glucose, renal failure, high systolic blood pressure, high body mass index, high sodium diet, and lead exposure are risk factors associated with death in DKD patients. With the progress of aging, the disease burden of DKD in China will continuously increase. Future work should be focused on population-specific interventions, taking into consideration the risk factors identified within the study.

  • Pu Jinyun, Ye Lei, He Yonghua, Xu Rongrong, Yang Siying, Yuan Huiqing, Liu Siyuan, Liang Wenpei, Qiu Liru
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    Objective To determine a relationship between ultrasound shear wave elastography (SWE) and pathological lessions of renal tissues in children with chronic kidney disease (CKD). Methods It was a cross-sectional observational study, involving children admitted to the Department of Pediatrics of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January to December 2021 with definite pathological diagnosis through kidney biopsy. The SWE was used to determine the Young's modulus (elastic modulus) of the cortex and medulla of the upper, middle, and lower poles of the kidney. The renal histopathology was classified or graded. The statistical method was used to analyze the relationship between Young's modulus of the inferior polar cortex (YMcor) and medulla (YMmed) of the right kidney and renal pathology. Results The study included 110 children with definite pathological diagnosis through renal biopsy, aged (10.1±3.4) years old (2-17 years old), with 55 males (50.0%). The body mass index was (20.6±2.4) kg/m2, and mean arterial pressure was (95±24) mmHg. There were 94 patients (85.4%) with CKD stage 1, 8 patients (7.3%) with CKD stage 2, and 8 patients (7.3%) with CKD stage 3. There was no significant difference of YMcor and YMmed in the upper and middle poles of the right kidneys, and YMmed in the lower poles of right kidneys in CKD patients with different stages (all P>0.05). Both YMcor [(15.75±3.36) kPa] and YMmed [(13.50±2.43) kPa] of CKD stage 3 patients were significantly higher than those of CKD stage 1 patients [(12.94±2.45) kPa, (11.88±2.23) kPa](both P<0.05). There was no significant difference of YMcor and YMmed in the lower poles of right kidneys between stage 1 and stage 2 CKD patients (both P>0.05). YMcor[(17.93±3.23) kPa] and YMmed [(15.50±1.48) kPa] in patients with crescentic glomerulonephritis were higher than those in patients with focal segmental glomerulosclerosis [(12.71±2.42) kPa, (11.57±2.63) kPa] and mesangial proliferative glomerulonephritis [(12.73±2.04) kPa, (11.48±2.10) kPa](all P<0.05). There was no significant difference of YMcor and YMmed between focal segmental glomerulosclerosis and mesangial proliferative glomerulonephritis (both P>0.05). YMcor [(16.30±2.63) kPa] and YMmed [(15.54±1.59) kPa] of Lee's Ⅳ grade of IgA nephropathy were higher than those of Lee's Ⅲ grade [(13.32±2.70) kPa, (12.57±2.50) kPa](both P<0.05), while the International Study of Kidney Disease in Children grade of purpura nephritis had no significant correlation with YMcor and YMmed (both P>0.05). YMcor [(15.41±2.37) kPa] and YMmed [(13.82±2.59) kPa] of interstitial fibrosis/tubular atrophy (T1/T2) group of IgA nephropathy mixed with purpura nephritis were significantly higher than those of T0 group's [(12.99±2.40) kPa, (11.79±2.05) kPa] (both P<0.05). Moreover, crescent formation (C1) group had a higher YMcor [(14.21±2.77) kPa] and YMmed [(12.80±2.47) kPa] than those in C0 group [(12.73±2.15) kPa, (11.59±1.97) kPa] (both P<0.05), while YMcor and YMmed were unrelated to the mesangial hypercellularity (M), endocapillary cellularity (E), segmental sclerosis or adhesion (S) indicators (all P>0.05). In lupus nephritis patients, YMcor (r=0.744, P=0.035) and YMmed (r=0.728, P=0.009) were favorably linked with the chronic index, but not with the activity index (both P>0.05). Conclusions Renal interstitial fibrosis/tubular atrophy and crescentic development are connected with YMcor and YMmed at the lower pole of the kidney as measured by SWE. SWE can be used to assess the chronic renal lesions in children with CKD in the early and middle stages. It may develop into a new noninvasive way to assess renal pathology.

  • Wang Weina, Yuan Jing, Chen Jianghua, Lou Xiaowei, Li Xiaodan, Liang Jia, Xu Jingning
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    Objective To study the effect of blood volume feedback control system on improving intradialytic-hypotension (IDH) in maintenance hemodialysis (MHD) patients. Methods It was a prospective cohort study. Thirty MHD patients with recurrent IDH in the Dialysis Center of the First Affiliated Hospital of Zhejiang University School of Medicine from March 2021 to March 2022 were selected. A self-control study was conducted in MHD patients. The patients were treated with routine hemodialysis in both baseline phase (A1) and reversal phase (A2), while with hemodialysis under the blood volume feedback control system in intervention phase (B). Each phase lasted for 4 weeks (12 hemodialysis sessions). The average occurrences of IDH and IDH-related adverse events (IDH-RAE, stopping dehydration for more than 10 minutes or getting off the hemodialysis machine 10 minutes earlier due to IDH) of each patient between phase A1, B, and A2 were calculated and compared. In a total of 1 080 dialysis records, a logistic regression analysis model was established with age, sex and intervention as independent variables and with the occurrence of IDH-RAE as the outcome. Results A total of 30 eligible patients were included in the study, including 14 males (46.7%) and 16 females (53.3%), aged 63.0 (56.5, 72.5) years old, with a median dialysis age of 84.0 (37.2, 120.0) months. The average times of IDH in 30 MHD patients decreased from 1.17 (0.83, 1.67) in stage A1 (before intervention) to 0.33 (0.25, 0.58) in stage B (after intervention) (P<0.05). The frequency of IDH-RAE decreased significantly from 0.29 (0.19, 0.47) in stage A1 to 0.17 (0,0.25) in stage B (P<0.05). Logistic regression analysis results indicated that the use of blood volume feedback control system reduced the risk of IDH-RAE by 53% (OR=0.47, 95% CI 0.34-0.64, P<0.001). Conclusions The application of blood volume feedback control system can effectively reduce the occurrences of IDH and the risk of IDH-RAE in MHD patients.

  • Basic Study

  • Xue Rong, Ma Jingang, Huang Junyue, Li Yingping, Gao Peijuan, Huang Wenhui, Yang Xiaojun, Qian Rui, Zhao Juan
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    Objective To explore the role and mechanism of nuclear receptor subfamily 4 group A member 1 (NR4A1) in suppressing cisplatin nephrotoxicity. Methods The expression of NR4A1 gene in renal cell subpopulations was analyzed using the "Tabula-muris" single cell transcriptome sequencing database. NR4A1 gene was over-expressed by lentivirus infection in HK-2 cell line and primary renal proximal tubular epithelial cells. Cell counting kit-8 was used to detect the cytotoxicity of cisplatin. The cell death ratio was analyzed using propidium iodide (PI) staining by flow cytometry. The expression of NR4A1 and nuclear factor erythroid 2-related factor 2 (NRF2) was detected by real-time fluorescent quantitative PCR and Western blotting. Ferroptosis was analyzed by detecting the contents of malondialdehyde (MDA), oxidized glutathione (GSSG) and lipid reactive oxygen species (ROS). Results The single cell transcriptome sequencing database showed that NR4A1 gene was the lowest expression in renal proximal tubular epithelial cell subsets. Cisplatin (50 μmol/L or 100 μmol/L) could significantly induce MDA, GSSG and lipid ROS production in renal proximal tubular epithelial cells (all P<0.01), and higher cisplatin concentration accompanied with a more increase of MDA, GSSG and lipid ROS. Compared with the control HK-2 cells, the lipid ROS content and iron ion content of HK-2 cells over-expressing NR4A1 were significantly lower (all P<0.01), and the over-expression of NR4A1 inhibited cisplatin-induced cytotoxicity and ferroptosis in renal proximal tubular epithelial cells. Mechanistically, NR4A1 up-regulated the expression of anti-ferroptosis gene NRF2 in proximal renal tubular epithelial cells (P<0.01). Furthermore, single cell data analysis showed that, similar to the expression of NR4A1 in renal tissue subsets, NRF2 was also the lowest in renal proximal tubular epithelial cells. Conclusions Cisplatin can induce ferroptosis of renal proximal tubular epithelial cells in a dose-dependent manner. NR4A1 can inhibit cisplatin-induced ferroptosis by up-regulating NRF2 in renal proximal tubular epithelial cells, thereby alleviating the cytotoxicity of cisplatin.

  • Short Original Article

  • Wang Liuxi, Dong Dan, Xu Ying, Zhang Li, Xu Hongzhao, Liu Nian, Yuan Hang
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    It was a retrospective cohort study. Patients diagnosed with idiopathic membranous nephropathy (IMN) and received rituximab (RTX) alone for one course of treatment during hospitalization in the Department of Nephrology of the First Hospital of Jilin University from March 2020 to March 2022 were enrolled. The patients were divided into 1 g standard treatment group (once 1 g every 2 weeks for twice) and 375 mg/m2 experimental treatment group (375 mg/m2 once a week for 4 weeks) according to the different methods of drug administration, and the efficacy and safety of different doses of RTX in the treatment of IMN were compared between the two groups to provide a reference for optimizing the clinical treatment protocol. The patients were followed up regularly for more than 9 months after treatment and the data were complete. A total of 69 patients were included with age of (51.7±11.8) years old, and 46 males (66.7%). There were 31 patients in the 1 g standard treatment group and 38 patients in the 375 mg/m2 experimental treatment group. The proportion of first-treatment patients in the 1 g standard treatment group was higher than that in the 375 mg/m2 experimental treatment group (87.1% vs. 65.8%, χ 2=4.174, P=0.041). There were no statistically significant differences in the general data, clinical characteristics and baseline laboratory parameters between the two groups (all P>0.05). At the end of 3 months of treatment, 22 patients (31.9%) experienced remission, including 9 patients (29.0%) in the 1 g standard treatment group and 13 patients (34.2%) in the 375 mg/m2 experimental treatment group (χ 2=0.211, P=0.646). At 6 months, 30 patients (43.5%) experienced remission, including 12 patients (38.7%) in the 1 g standard treatment group and 18 patients (47.4%) in the 375 mg/m2 experimental treatment group (χ 2=0.521, P=0.470). At 9 months, 38 patients (55.1%) achieved remission, including 18 patients (58.1%) in the 1 g standard treatment group and 20 patients (52.6%) in the 375 mg/m2 experimental treatment group (χ 2=0.204, P=0.652). At 9 months, the 24 h urine protein of 1 g standard treatment group and 375 mg/m2 experimental treatment group decreased by 7.93 (6.24, 8.46) g and 7.45 (5.66, 8.67) g (both P<0.05), respectively, and serum albumin increased by 16.4 (15.5, 17.5) g/L and 15.5 (9.0, 15.8) g/L (both P<0.05), respectively, from the baseline value. Kaplan-Meier survival analysis result showed that there was no significant difference in the time of phospholipase A2 receptor titer decreasing to <5 RU/ml between the two groups (Log-rank χ 2=3.653, P=0.056). Twenty-three non-serious adverse events occurred in the 1 g standard treatment group, involving 16 patients, and 10 non-serious adverse events occurred in the 375 mg/m2 experimental treatment group, involving 10 patients. There was better safety in the 375 mg/m2 experimental treatment group than that in the 1 g standard treatment group (Fisher value=8.593, P=0.015). Both 375 mg/m2 regimen and 1 g regimen of RTX in IMN patients are effective in relieving proteinuria and elevating serum albumin. The 375 mg/m2 regimen of RTX has a lower incidence of adverse events compared with the 1 g regimen.

  • Case Report

  • Huang Ju, Ye Wei, Wen Yubing, Zheng Ke
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    The article reported one case of renal damage caused by lenvatinib in the treatment of advanced primary liver cancer. The patient was a 63-year-old male who was admitted to the hospital due to "liver cancer for 4 years, blood pressure elevation for nearly 2 years, and edema for 7 months". During the treatment of liver tumors with atezolizumab combined with lenvatinib, blood pressure increased and renal insufficiency aggravated progressively. Pathological light microscopy of renal biopsy showed endothelial cell lesion and tubulointerstitial damage, and electron microscopy showed moderate proliferation of mesangial cells and deposition of mesangial matrix. There were many agglomerated low-electron density deposits in the mesangial area, and a small amount of electron dense deposits in the subendothelium. The pathological diagnosis was endothelial cell disease (thrombotic microangiopathy) and secondary focal segmental glomerulosclerosis. Renal injury was considered as secondary to lenvatinib. After discontinuing lenvatinib and giving angiotensin receptor antagonist treatment, blood pressure was normal, urine protein turned negative, and renal function improved significantly after 8 months of outpatient follow-up.

  • Fang Xiaoyan, Tang Zifei, Hua Haimei, Zhou Qing, Chen Jing, Zhai Yihui, Miao Qianfan, Tang Xiaoshan, Xu Hong, Shen Qian
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    The paper summarizes the clinical and follow-up data of percutaneous endoscopic gastrostomy (PEG) in three infants with chronic kidney disease to explore the safety and reliability of using PEG to improve the growth and development, and nutritional status. During follow-up, the weight and height of case 1 and 3 were obviously improved. Case 2 was followed up for 3 months, due to dying of cardiac arrest, and the infant's height and weight were not significantly improved. Serum albumin and prealbumin improved in 3 cases after PEG. No PEG-related infection occurred in 3 infants.

  • Ruan Yingxin, Yan Tiekun, Jiang Jianqing, Jia Junya
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    The paper reports a rare case of alkaptonuria (AKU) with IgA nephropathy, and analyzes its clinical manifestations, imaging findings, pathological features, gene diagnosis and treatment process, so as to provide reference for the diagnosis and treatment of the disease. The clinical symptoms of the patient were mainly black urine, microscopic hematuria and proteinuria. Renal pathology showed mild mesangial hyperplasia IgA nephropathy, and renal tubular epithelial cytochrome deposition. Genetic analysis indicated that a pathogenic mutation was detected on the AKU-related homogentisate 1, 2-dioxygenase gene possibly associated with the phenotype of the patient. Genetic testing and renal pathology were effective methods to make a definite diagnosis for the case.

  • Li Yumin, Zhang Yunfang
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    Neisseria elongata is a normal group of bacteria in human oropharynx and a kind of gram-negative bacillus that cause disease, and its pathogenicity is rarely reported in China. In a few cases, it can cause septicemia, osteomyelitis and infective endocarditis. There are a few reports of other Neisseria causing peritonitis at home and abroad. The paper reported a case of Neisseria elongata-caused peritonitis and reviewed the literature. The patient was initially treated with ceftazidime combined with cefzolin overnight for 3 days, but the effect was not good. The subsequent peritoneal dialysis fluid culture results indicated Neisseria elongata, and the patient was cured and discharged after treatment with levofloxacin combined with drug sensitivity test, hoping to attract clinical workers' attention to the pathogenicity of Neisseria.

  • Review

  • Xin Yangyang, Yang Xiao
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    As a home treatment and economical and practical treatment mode, peritoneal dialysis (PD) is an effective renal replacement therapy for end-stage kidney disease. The number of PD patients in the world is increasing, and prognosis has been significantly improved. However, compared with the general population, the quality of life of PD patients is not satisfactory, and the disease burden is still very high. There is significant heterogeneity in the reports of clinical outcomes of PD in different countries and regions. The heterogeneity seriously affects the validity of clinical research evidence and the continuous improvement of the quality of PD centers. New progress has been made in the study of standardized clinical outcome of PD in recent years. The article reviews the heterogeneity of PD clinical outcome report, standardized clinical outcome classification and core outcome to standardize the report of PD clinical outcome, improve the clinical research quality and management level of PD, and finally improve the prognosis of patients.

  • Wang Li, Pu Lei
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    Osteoporosis is a comorbidity or complication of chronic kidney disease (CKD). Low bone mineral density, osteoporosis, and fractures are risk factors of poor prognosis in patients with CKD. Active prevention and treatment of osteoporosis is essential for patients with CKD. Denosumab is a fully human monoclonal antibody that targets receptor activator of nuclear factor-κB ligand (RANKL) and is not metabolized or excreted by the kidney. Clinical studies have shown that the use of denosumab in CKD (including dialysis and renal transplantation) patients with osteoporosis, can increase bone mineral density and reduce the incidence of fractures with acceptable safety. As hypocalcemia has been observed in patients with CKD, close monitoring and early supplementation of calcium and vitamin D are required before denosumab initiation, and serum calcium levels need to be monitored during treatment. The review summarized the published literature of denosumab in bone protection of CKD.

  • Expert Consensus

  • Expert group of Clinical Nephrology Committee of Chinese Medical Education Association
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    Coronavirus disease 2019 (COVID-19) is a systemic disease including pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 infects several organs and systems besides the respiratory system, including the urinary system, cardiovascular system, gastrointestinal system, nervous system, hematological system and immune system. The kidney, as one of the targeted organs of COVID-19, is damaged by SARS-CoV-2 in both direct and indirect ways. The clinical manifestations of kidney involvements include acute kidney injury (AKI), proteinuria, hematuria, etc. Patients with chronic kidney disease (CKD) are often combined with a variety of immunodeficiency, especially those receiving hormones/immunosuppressants for immune nephropathy, kidney transplantation, undergoing renal replacement therapy for end-stage renal disease (ESRD). Moreover, these patients are not only susceptible to SARS-CoV-2, but also prone to becoming seriously or critically ill after infection. The treatment of CKD patients with COVID-19 is different from that of non-CKD patients, and the use of antiviral drugs in patients with severe renal insufficiency remains controversial. Furthermore, CKD patients are often combined with malnutrition, hypercoagulability, chronic inflammation, and water-electrolyte disorders, which make treatment of COVID-19 difficult. Therefore, this expert consensus was developed to enhance the clinicians' awareness of CKD with COVID-19, standardize the clinical diagnosis and treatment, and further improve the prognosis of patients.