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Chinese Journal of Nephrology 2024 Vol.40
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Summary of the first working meeting of the 8th Editorial Committee of Chinese Journal of Nephrology
Peng Miao, Yang Kekui, Mao Haiping, Yu Xueqing
2024, 40 (1): 1-3. https://doi.org/10.3760/cma.j.cn441217-20231207-01253
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The first working meeting of the 8th Editorial Committee of Chinese Journal of Nephrology was held in Guangzhou, China on November 30, 2023. At the meeting, the list of the 8th Editorial Committee was announced, the work of the journal in the past 5 years was summarized, and the future work of the Editorial Committee was planned and discussed. Jiang Yongmao, former deputy secretary-general of the Chinese Medical Association, Jin Dong, deputy general manager of the Chinese Medical Journals Publishing House Co., Ltd, Lu Quan, editor of the Journal Management Department of Chinese Medical Association, Yu Xueqing, editor-in-chief of the 8th Editorial Committee, Cai Guangyan, Chen Jianghua, Zhao Minghui and Mao Haiping, deputy editor-in-chief of the 8th Editorial Committee, and 69 members of the 8th Editorial Committee, attended the meeting. The meeting came to a successful conclusion, and provided guidance for how to break through the difficulties, publish high-quality content and achieve high-quality development under the new situation.

Single-center retrospective analysis of efficacy and safety of daratumumab plus dexamethasone for light chain amyloidosis nephropathy
Xue Han, Wang Yaomin, Chen Liangliang, Han Quan, Ren Pingping, Lan Lan, Liu Guangjun, Chen Jianghua, Han Fei
2024, 40 (1): 4-10. https://doi.org/10.3760/cma.j.cn441217-20230526-00531
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Objective To analyze the efficacy and safety of daratumumab plus dexamethasone in the treatment of renal injury patients with light chain amyloidosis, and to provide clinical reference. Methods It was a single center retrospective observational study. The clinical data before and after daratumumab treatment of renal injury patients with light chain amyloidosis treated with daratumumab plus dexamethasone from December 2021 to August 2022 were retrospectively collected. The hematologic response, kidney response, prognosis, and adverse events were analyzed. The treatment regimen was 16 mg/kg intravenous infusion of daratumumab on day 1 + 20 mg intravenous push of dexamethasone on day 1-2, once every 2 weeks. The follow-up was up to February 28, 2023. Results The study included 18 patients, with age of (58.4±7.7) years old, and a male to female ratio of 11∶7. Eleven patients were newly diagnosed and 7 patients were retreated. There were 7, 5, 5 and 1 patients, respectively at the stage Ⅰ, Ⅱ, Ⅲ and Ⅳ of light chain amyloidosis according to 2012 Mayo stage criteria. The median course of disease before onset was 2.5 (1.0, 8.0) months and the follow-up time was (8.7±2.8) months. The patients received (10±3) times of treatment. The overall hematologic response rates were 9/13, 11/13 and 13/13 at 1 month, 3 months, and 6 months respectively after treatment, meanwhile 8/13, 10/13 and 12/13 achieved at least very good partial response at 1 month, 3 months, and 6 months respectively (the other 5 patients did not undergo detailed evaluation due to baseline difference of serum free κ and λ light chain <20 mg/L). The median duration of hematologic response was 16 (13, 40) days. At 3 months, 6 months and the end of follow-up, 10, 13 and 13 of 18 patients respectively achieved renal response, and the median duration of response was 66 (26, 182) days. During follow-up, the median difference of serum free κ and λ light chain decreased by 93% (72%, 97%). Until the last follow-up, one patient died of organ hemorrhage. Other infusion reactions, leukopenia, neutropenia and infection all improved after symptomatic treatments. Conclusion Daratumumab plus dexamethasone treatment is effective for light chain amyloidosis nephropathy in inducing hematologic remission and kidney remission, with good safety.

Correlation between serum sclerostin and sarcopenia-related indicators in chronic kidney disease patients
Xing Tingting, Li Yan, Wen Luona, Li Chunlei, Liu Yan, Zhong Xiaoshi, Tan Rongshao
2024, 40 (1): 11-17. https://doi.org/10.3760/cma.j.cn441217-20230815-00821
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Objective To investigate the correlation between serum sclerostin and sarcopenia-related indicators in chronic kidney disease (CKD) patients, and to find biomarkers and potential therapeutic targets that can take into account both osteoporosis and sarcopenia. Methods It was a single-centre cross-sectional study. The clinical data of CKD stage 5 patients undergoing maintenance hemodialysis regularly and CKD stage 1-5 non-dialysis inpatients in the Hemodialysis Centre of Guangzhou Red Cross Hospital from March 2021 to March 2023 were collected retrospectively. The enzyme-linked immunosorbent assay was used to detect the level of serum sclerostin. The anthropometric data such as height, weight, upper arm circumference, upper arm muscle circumference, skinfold thickness, pinch strength and handgrip strength were measured. Body composition analyzer was used to measure the body composition. The patients were divided into CKD stage 1-3 group, CKD stage 4-5 group, and stage 5 hemodialysis group. One-way ANOVA, Kruskal-Wallis H test, and chi-square test were used to compare the differences of demographics and clinical characteristics in different stages of CKD. Spearman correlation analysis and multiple linear stepwise regression analysis were utilized to analyze the correlation between serum sclerostin and sarcopenia-related indicators in CKD patients. Results The study included 104 patients with CKD stage 5 hemodialysis and 104 patients with CKD stage 1-5 non-dialysis patients, with age of (61.8±13.7) years old and 114 males (54.8%). There were 89 patients (42.8%) with diabetic nephropathy and 67 patients (32.2%) with sarcopenia. As renal injury progressed, serum sclerostin levels were 0.4 (0.3, 0.9) ng/L, 0.5 (0.3, 1.1) ng/L, and 1.1 (0.6, 2.3) ng/L in patients with CKD stage 1-3, stage 4-5, and stage 5 undergoing hemodialysis (χ2=8.934, P<0.001), and the prevalence of sarcopenia was 16.4% (10/61), 34.9% (15/43), and 40.4% (42/104) (χ2=10.312, P=0.006), respectively. Spearman correlation analysis showed that serum sclerostin was negatively correlated with estimated glomerular filtration rate (r=-0.314, P<0.001), pinch strength (r=-0.229, P=0.007), skinfold thickness (r=-0.254, P<0.001), appendicular skeletal muscle index (r=-0.169, P=0.010), body cell mass (r=-0.174, P=0.020), and phase angle (r=-0.264, P<0.001), and positively correlated with serum phosphorus (r=0.227, P=0.002) and intact parathyroid hormone (r=0.297, P<0.001). Multiple linear stepwise regression analysis showed that lg[appendicular skeletal muscle index] was negatively correlated with male (β=0.330, t=5.675, P<0.001) and serum sclerostin (β=-0.125, t=-2.143, P=0.033), and positively correlated with body mass index (β=0.474, t=8.090, P<0.001). Conclusion Serum sclerostin can be used as a good index and a potential therapeutic target for sarcopenia in CKD patients.

High-risk screening combined with family screening for Fabry disease in adult hemodialysis populationa family report of GLA IVS4+919G>A mutation in Fabry disease
Chen Bingrong, Tong Minqing, Lu Zhihong, Mao Jianhua
2024, 40 (1): 18-23. https://doi.org/10.3760/cma.j.cn441217-20230625-00634
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Objective To explore the combination of high risk screening and family screening for potential patients with Fabry disease in adult hemodialysis population, and to improve the diagnostic efficiency of the disease. Methods It was a cross-sectional investigation study. High-risk screening for Fabry disease was performed on adult hemodialysis patients with end-stage kidney disease who were admitted to Yongkang First People's Hospital of Zhejiang Province between November 2022 and February 2023. Dry blood paper α-galactosidase A (α-Gal A) detection assay was performed in males, or glycosphingolipids (Lyso-GL-3) detection assay was performed in females. GLA genetic assay was performed for further diagnosis after abnormal screening results. Family screening was carried out on the family members of the confirmed Fabry disease patients, and α-Gal A activity and Lyso-GL-3 of peripheral blood were measured. Additionally, urine routine, blood biochemistry, eye examination, hearing test, cranial magnetic resonance imaging, and electrocardiogram were performed to assess organ damage. Results Among 244 hemodialysis patients, 139 (56.97%) were males and 105 (43.03%) were females. The age ranged from 25 to 81 years (with median age of 61 years). One female patient with Fabry disease was identified GLA IVS4+919G>A mutation, resulting in a total prevalence of 0.41%. Pedigree screening was conducted on 41 family members of the patient, leading to the confirmation of 12 patients (including the proband), including 3 males and 9 females. Among them, 9 patients were abnormal in enzyme examination, 10 patients were abnormal in substrate, and 11 patients were abnormal in gene sequencing. None of the 12 patients exhibited limb pain, hypohidrosis, angiokeratoma, corneal opacity, and hearing impairment. Eight patients had heart abnormalities. Nine patients had abnormal urine routine (albuminuria or hematuria) and one patient had abnormal renal function. Four patients had abnormal cranial magnetic resonance imaging findings. Conclusions One GLA IVS4+919G>A mutation family is successfully identified through the combination of high-risk screening and family screening in adult hemodialysis patients, with a total of 12 cases of Fabry disease. The combination of high-risk screening and family screening proves to be effective in detecting potential patients with Fabry disease, and improve the screening efficiency of Fabry disease.

Analysis of clinical phenotype and genotype of PAX2 mutation in Chinese children
Ma Xueqing, He Yonghua, Yang Jing, Xu Rongrong, Yang Siying, Liang Wenpei, Zhou Jianhua, Yuan Huiqing, Qiu Liru
2024, 40 (1): 24-35. https://doi.org/10.3760/cma.j.cn441217-20230518-00520
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Objective To analyze and summarize the clinical, genotypic and pathological characteristics of children with PAX2 gene mutation in China, and to provide information for the monitoring, treatment and prognosis of the disease. Methods It was a case series analysis study. The clinical data of children with PAX2 gene mutation in Pediatric Nephrology Department, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from January 2014 to December 2022 were collected, and peripheral blood gene DNA was extracted and sequenced for whole exome sequencing. The clinical, pathological and genotypic characteristics of PAX2 gene variation of children in China were summarized by searching PubMed, Medline, China National Knowledge Infrastructure and Wanfang database and compared with the cases in this single center. Results Among the 13 children with PAX2 gene mutation, there were 9 males and 4 females, 12 patients with abnormal urine tests, 7 patients with small kidney volume by imaging examination, and 5 patients with renal cysts. The clinical phenotypes were congenital renal and urinary tract malformations in 8 cases, renal coloboma syndrome in 1 case, and hematuria or proteinuria in 3 cases. Five patients underwent renal biopsies, showing focal segmental glomerulosclerosis and C3 glomerulopathy in 1 case, focal segmental glomerulosclerosis in 1 case, thin basement membrane lesion in 1 case, and IgA nephropathy in 2 cases. The genetic testing in 13 children showed 9 de novo mutations and 4 new mutations of c.321G>A, c.213-8C>G, c.63C>A and c.449C>T. There were 2 cases of 76dupG (p.V26Gfs*28) mutant. A total of 51 Chinese children with PAX2 gene mutation were found in the literature search. There were 32 males and 19 females, 8 cases with small kidney volume and 12 cases with renal cysts. The clinical phenotypes were congenital anomalies of kidney and urinary tract in 28 cases, renal coloboma syndrome in 17 cases, and hematuria or proteinuria in 6 cases. Seven patients underwent renal biopsies, including 2 cases with focal segmental glomerulosclerosis, 1 case with minimal lesion, 1 case with mesangial proliferative glomerulonephritis, 1 case with IgA nephropathy, 1 case with membranous nephropathy and a case with focal proliferative sclerosing purpura nephritis combined with glomerular hypertrophy. Thirty-four cases were de novo mutations, and 12 mutations were from the father or mother. The father or mother of 5 children had no clinical manifestations, with normal renal function. There were 11 cases of 76dupG (p.V26Gfs*28) mutant. Conclusions The clinical phenotypes and genotypes of PAX2 gene variation in Chinese children are diverse. The most common clinical phenotype of PAX2 gene variation is congenital anomalies of kidney and urinary tract. c.76dupG (p.V26Gfs*28) is the most common of PAX2 gene variant.

Analysis on clinicopathology and prognosis of primary IgA nephropathy in children with massive proteinuria
Xia Hua, Wen Yubing, Chen Chaoying, Tu Juan, Li Huarong, Geng Haiyun, Wang Nannan, Huang Yongli
2024, 40 (1): 36-41. https://doi.org/10.3760/cma.j.cn441217-20230726-00715
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Objective To investigate the clinicopathological features and the prognosis of IgA nephropathy (IgAN) in children with massive proteinuria. Methods It was a retrospective cohort study. Clinical data of IgAN children with massive proteinuria admitted to the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2008 to December 2021 were retrospectively analyzed. Patients were divided into effective group and ineffective group according to whether urine protein turned negative after 6 months of initial treatment. The follow-up endpoint event was defined as a reduction in proteinuria of less than 50% or end-stage renal disease (ESRD) achievement. MedCalc software was used to perform Kaplan-Meier survival analysis, and Log-rank test was used to compare the difference of renal survival between the two groups. Results A total of 127 patients were diagnosed as primary IgAN by renal biopsy, of whom 57 patients with IgAN showed massive proteinuria. These 57 IgAN patients with macroproteinuria accounted for 44.9% of the total IgAN patients and were enrolled in the study. Among the 57 cases, 33 cases (57.9%) were Lee's grade Ⅲ, 11 cases (19.3%) were below Lee's grade Ⅲ, and 13 cases (22.8%) were above Lee's grade Ⅲ. The follow-up time was 4.0 (3.0,5.8) years. In the initial treatment, among 57 patients, 46 (80.7%) were effective (effective group) and 11 (19.3%) were ineffective (ineffective group). Compared with the effective group, the ineffective group had a higher proportion of concurrent AKI at the onset of disease and longer recovery time of renal function, with significant difference (7/11 vs. 13/46, χ2=4.878, P=0.027). Compared with the effective group, the proportion of Lee grade Ⅲ or above was higher in the ineffective group, and the difference was statistically significant (5/11 vs. 8/46, χ2=3.971, P=0.046). There were significant differences in endocapillary hypercellularity (E1), segmental glomerulosclerosis or adhesion (S1) and cellular/fibrocellular crescents (C2) of Oxford classification between IgAN children with Lee grade Ⅲ or below and those over Lee grade Ⅲ (11/13 vs. 20/44, χ2=6.204, P=0.013; 12/13 vs. 17/44, χ2=11.566, P=0.001; 9/13 vs. 7/44, χ2=14.131, P=0.001). Among 57 patients, endpoint events occurred in 2 patients who both were urinary protein unmitigated, and none of the children progressed to ESRD. There was no significant difference in cumulative renal survival between the two groups by Kaplan-Meier survival analysis and Log-rank test (χ2=0.537, P=0.460) after addition of calcineurin inhibitors (CNIs) to the initial treatment ineffective group. Conclusions Macroproteinuria is the prominent manifestation of IgAN in children. The pathological type is mainly Lee grade Ⅲ. Children with macroproteinuria have a good prognosis in the short and medium term after active treatment. For IgAN with macroproteinuria that does not respond well to initial treatment, AKI is more common at onset, and renal function recovery time is longer. The application of CNIs may have a certain effect on improving the renal outcome of IgAN with massive proteinuria.

Canagliflozin attenuates human podocyte injury through inhibiting reactive oxygen species/NOD-like receptor thermal protein domain associated protein 3 signaling pathway
Cheng Yanlu, Chen Ying, Wang Yanan, Li Siyu, Wang Li, Wang Hao, Zhu Bingbing
2024, 40 (1): 42-48. https://doi.org/10.3760/cma.j.cn441217-20230602-00605
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Objective To investigate the efficacy and mechanism of canagliflozin (Cana) in the treatment of high glucose-induced human podocyte (HPC) injury. Methods The HPCs were divided into 5 groups: normal glucose group (NG group), mannitol group (MA group), high glucose group (HG group), Cana low dose (0.3 μmol/L) group and Cana high dose (1.0 μmol/L) group. Western blotting was used to examine the protein expressions of membrane-associated guanylate kinase inverted-2 (MAGI2), podocyte-associated protein nephrin, sodium-glucose transporter 2 (SGLT2), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis- associated speck-like protein containing a CARD (ASC), and cleaved-caspase1 in podocytes. Phalloidin staining of F-actin in podocytes was used to observe cytoskeletal injury. Intracellular reactive oxygen species (ROS) level of HPC was detected by the 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) probe. Levels of interleukin (IL)-18 and IL-1β in culture medium of podocytes were detected by enzyme-linked immunosorbent assay (ELISA). Results (1) Compared with the NG group, the protein expressions of MAGI2 and nephrin decreased (both P<0.01), the protein expression of SGLT2 increased ( P<0.01), the changes of cell morphology and cytoskeleton remodeling were obvious, intracellular ROS level increased ( P<0.01), while NLRP3, ASC and cleaved-caspase1 protein expressions decreased in the HG group (all P<0.01). The results of ELISA showed that IL-18 and IL-1β concentrations were higher in the HG group (both P<0.05). (2) Compared with the HG group, in the Cana groups, MAGI2 and nephrin expressions up-regulated (both P<0.01), the changes of cell morphology and cytoskeleton remodeling were alleviated. Meanwhile the Cana groups showed decreased SGLT2 expression ( P<0.05), lower ROS level, down- regulated NLRP3, ASC, cleaved-caspase1 expressions (all P<0.01), and decreased concentrations of IL-18 and IL-1β in culture medium of podocytes (both P<0.05). Conclusion Cana can improve high glucose-induced injury and inflammation in human podocyte, possibly due to the repression of the ROS/NLRP3 signaling pathway.

Accuracy of portable hemoglobinometer in maintenance hemodialysis patients
Zhang Xiaohao, Tang Fanglin, Rao Jialing, Li Yuanqing, Li Wei, Cheng Cailian, Peng Hui
2024, 40 (1): 49-52. https://doi.org/10.3760/cma.j.cn441217-20230711-00705
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This study aims to evaluate the accuracy of portable hemoglobinometer (Hemocue Hb 201+ hemoglobin analyzer) in patients with maintenance hemodialysis (MHD) and its diagnostic value for anemia. The data of venous hemoglobulin (Hb) and fingertip capillary hemoglobulin (DHb) in MHD patients from Lingnan Hospital, the Third Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed, and the correlation and difference between DHb and Hb and the accuracy of DHb in the diagnosis of anemia were evaluated. A total of 105 patients were included in the study. There was no significant difference between the paired DHb and Hb [(109±21) g/L vs. (108±20) g/L, t=-1.284, P=0.202]. Pearson correlation analysis showed that DHb was positively correlated with Hb (r=0.929, P<0.001). Linear regression analysis showed that DHb and Hb met the regression equation Hb=0.88×DHb+12.23, and P<0.001. Bland-Altman analysis showed that the differences between the paired DHb and Hb was (1.0±7.8) g/L with the limit of agreement as (-14.2, 16.2) g/L. The mean percentage of the differences in Hb was 1% with limit of agreement as (-13.7%, 15.7%). A DHb of >110 g/L was 0.90 sensitive and 0.83 specific to identify patients with an Hb >110 g/L and its positive and negative predictive values were 0.84 and 0.90, respectively. It suggests that, in MHD patients, Hemocue Hb 201+ analyzer shows good accuracy, and can be used to monitor the Hb trend and serve as a screen method for those reaching target Hb.

A patient with brachial artery pseudoaneurysm treated with ultrasound-guided and balloon- assisted injection of human fibrin sealant
Qian Senlin, Li Hui, Wan Ziming
2024, 40 (1): 53-55. https://doi.org/10.3760/cma.j.cn441217-20230613-00625
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The paper reports the treatment of a maintenance hemodialysis patient with pseudoaneurysm (PSA) caused by accidental injury of brachial artery during the puncture of internal fistula. The main treatment methods of PSA include surgical incision and repair, local pressure therapy, ultrasound-guided intraluminal thrombin injection, implantation of covered stent, coil embolization and so on, but they all have some defects. The patient was admitted to hospital due to poor fistula function, and the formation of brachial artery PSA was confirmed by color ultrasound. PSA was successfully treated with ultrasound-guided and balloon-assisted injection of human fibrin sealant. The fistula had good function 3 months after the operation.

A case of tubulointerstitial nephritis and uveitis syndrome complicated with Fanconi syndrome and literature review
Xu Ying, Zhang Xinyu, Wang Qinglian, Zhen Junhui, Liu Xiang
2024, 40 (1): 56-60. https://doi.org/10.3760/cma.j.cn441217-20230518-00521
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The clinical diagnosis of tubulointerstitial nephritis and uveitis (TINU) syndrome combined with Fanconi syndrome is relatively rare. The paper reports a 47-year-old female patient of TINU syndrome with hypokalemia, hypophosphatemia, hypouricemia and renal impairment as initial symptoms followed by uveitis. Serological tests showed that the patient also met the diagnostic criteria of Fanconi syndrome. Renal tissue pathology confirmed tubular interstitial injury, manifested as interstitial nephritis with acute tubular injury. Ophthalmic examination confirmed iritis in the right eye. After excluding other primary diseases, the patient was diagnosed as TINU syndrome with Fanconi syndrome. After glucocorticoid therapy, ocular symptoms, renal impairment and electrolyte disturbance were significantly improved.

Advances in pathogenesis and drug therapy in hemodialysis patients with pruritus
Tang Xiaojing, Mei Changlin
2024, 40 (1): 61-66. https://doi.org/10.3760/cma.j.cn441217-20230413-00420
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Chronic kidney disease-associated pruritus (CKD-aP), one of the most common and intolerable complications in hemodialysis patients, not only seriously affects patients' quality of life and physical and mental health, but also increases the risk of long-term mortality. The pathogenesis of CKD-aP remains unclear, and immune-inflammatory dysregulation, imbalance of endogenous opioid system, abnormal accumulation of metabolites, xerosis, abnormal histamine level as well as hyperparathyroidism, have all been shown to be associated with pruritus. There is a lack of satisfactory and effective treatment strategies for CKD-aP, which mainly include pharmacological treatment, non-pharmacological treatment and dialysis modality modification. This article mainly reviews recent advances in the pathogenesis and pharmacological treatment of pruritus among hemodialysis patients.

Application of sacubitril/valsartan in patients with chronic kidney disease
He Yi, Zhong Hui, Xue Hen, Yang Youqin, Zhao Min, Chang Xiaodong, Chen Maoli, Fu Ping
2024, 40 (1): 67-73. https://doi.org/10.3760/cma.j.cn441217-20230330-00343
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As a new strategy for the application of sacubitril/valsartan (LCZ696) in patients with CKD, much evidence showed that it improved the prognosis of patients with CKD. This review summarizes the efficacy and safety of sacubitril/valsartan in physiology, pathology, pharmacology and clinical application by searching Wanfang, CNKI, PubMed and other databases for related articles on the application of sacubitril/valsartan in CKD patients. Although LBQ657, the active product of sacubitril, has a high drug accumulation in patients with moderate, severe renal injury, and ESRD, it is not cleared in hemodialysis, and has very little eliminated in peritoneal dialysis, which does not affect its safety. Compared with angiotensin converting enzyme inhibitor and angiotensin receptor blocker drugs, LCZ696 could increase the blood pressure control rate, improve cardiac function, slow down the decline of glomerular filtration rate, and significantly improve cardiovascular outcomes without more adverse events. Sacubitril/valsartan can be used in all levels of CKD patients complicated with hypertension and/or heart failure, with reliable safety and tolerance.

Expert consensus on fluid volume assessment and management in continuous renal replacement therapy
Expert group of Chinese Society of Nephrology
2024, 40 (1): 74-81. https://doi.org/10.3760/cma.j.cn441217-20230911-00911
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Recent studies have revealed that fluid overload is an independent risk factor for increasing renal function impairment, decreasing renal recovery rate and increasing mortality in severe patients with acute kidney injury (AKI), acute respiratory distress syndrome,or sepsis. The damage of fluid overload on renal function may be related to renal venous hypertension and renal interstitial edema, and eventually lead to the decrease of renal blood flow and glomerular filtration rate. However, fluid clearance with diuretics or continuous renal replacement therapy (CRRT) may increase the risk of hypovolemia, hemodynamic instability, and tissue and organ hypoperfusion. Therefore, accurate fluid volume status assessment and management in AKI patients during CRRT is critical. The expert group of Chinese Society of Nephrology formulated this expert consensus on fluid volume assessment and management in CRRT based on evidence-based medical evidence and clinical experience. Through systematic and comprehensive literature search, data analysis and professional discussion in this field, the expert group constructed five special topics on fluid volume management in CRRT: the pathophysiological basis and harm of fluid volume imbalance in AKI patients, the management strategies on fluid volume in AKI patients, the assessment on fluid volume status and reactivity in AKI patients, the grading and application of fluid volume management in CRRT, and the management target and prescription on fluid volume in CRRT. This consensus aims to standardize clinical operations, reduce the incidence of fluid volume imbalances in AKI patients, and improve the patients' prognosis.

Relationship between early dialysis anemia status and prognosis in maintenance hemodialysis patients
Fang Hui, Pan Bin, Chen Siyu, He Yongchun, Qu Lihui, Guo Qi, Chen Jianghua, Zhang Ping
2024, 40 (2): 85-93. https://doi.org/10.3760/cma.j.cn441217-20230814-00818
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Objective To analyze the status of anemia at the beginning of dialysis in maintenance hemodialysis (MHD) adult patients, and to explore the relationship between early dialysis anemia and early survival and long-term survival. Methods It was a retrospective cohort study. The baseline demographic and clinical data of newly admitted MHD patients from January 1, 2013 to December 31, 2020 were retrospectively analyzed. According to the hemoglobin (Hb) level at the beginning of dialysis, the patients were divided into high Hb group (Hb≥110 g/L), middle Hb group (80 g/L≤Hb<110 g/L) and low Hb group (Hb<80 g/L). The baseline data among the three groups were compared, and the changing trend of Hb level in MHD patients during the 8 years was analyzed. The follow-up ended at peritoneal dialysis, kidney transplantation, death or on December 31, 2021. All-cause death event within 6 months after the initiation of dialysis was defined as early death, while all-cause death event more than 6 months after the initiation of dialysis was defined as long-term death. Kaplan-Meier survival curve was used to analyze the survival rate, and log-rank test was used to compare the survival rates among the three groups. Multivariate Cox regression analysis model was used to analyze the association between anemia (Hb<110 g/L) at the beginning of dialysis and both early and long-term mortality. Results A total of 36 216 MHD patients were included in this study, with age of (61.3±15.5) years old and 22 163 males (61.20%). The Hb at the beginning of dialysis was (89.33±20.89) g/L. The compliance rate of Hb (≥110 g/L) was 16.43% (5 952/36 216). There were 12 232 patients (33.78%), 18 032 patients (49.79%), and 5 952 patients (16.43%) in low Hb group, middle Hb group, and high Hb group, respectively. There were statistically significant differences in gender distribution, age, serum creatinine, blood phosphorus, blood calcium, C-reactive protein, intact parathyroid hormone, blood leukocytes, platelets, serum albumin, triglyceride, total cholesterol, and proportions of chronic glomerulonephritis, diabetic nephropathy, diabetes mellitus, cardiovascular and cerebrovascular diseases, tumors, emporary catheter, long-term catheter and autologous arteriovenous fistula among the three groups (all P<0.05). During the 8-year period, the Hb level had an increased trend steadily each year, and Hb was (88.48±22.07) g/L, (88.52±21.43) g/L, (87.86±21.29) g/L, (88.93±20.69) g/L, (88.87±20.69) g/L, (90.03±20.47) g/L, (90.74±20.31) g/L and (90.31±20.54) g/L year by year. There were 2 176 early deaths (6.01%), and 6 557 long-term deaths (18.10%) by the end of follow-up. Kaplan-Meier survival curve showed that early survival rate of low Hb group was significantly lower than those of high Hb group (log-rank test, χ2=57.115, P<0.001) and middle Hb group (log-rank test, χ2=49.918, P<0.001), and long-term survival rates of low Hb group (log-rank test, χ2=107.097, P<0.001) and middle Hb group (log-rank test, χ2=47.430, P<0.001) were significantly lower than that of high Hb group. Multivariate Cox regression analysis showed that Hb<80 g/L at the beginning of dialysis was an independent influencing factor of early death (Hb ≥110 g/L as a reference, HR=1.307, 95% CI 1.096-1.559), and 80 g/L≤Hb<110 g/L and Hb<80 g/L at the beginning of dialysis were the independent influencing factors of long-term death (Hb≥110 g/L as a reference, HR=1.108, 95% CI 1.021-1.203; HR=1.228, 95% CI 1.127-1.339, respectively) in MHD patients. Conclusions The compliance rate of Hb at the beginning of dialysis in MHD patients is low. Hb <80 g/L at the beginning of dialysis is an independent risk factor of early death, and Hb <110 g/L at the beginning of dialysis is an independent risk factor of long-term death in MHD patients.

Influencing factors of cardiac autonomic dysfunction in hemodialysis patients
Chen Yafei, Li Xu, Zhu Li, Wang Yan, Gan Liangying, Zuo Li
2024, 40 (2): 94-100. https://doi.org/10.3760/cma.j.cn441217-20230817-00826
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Objective To investigate the influencing factors of cardiac autonomic dysfunction in maintenance hemodialysis (MHD) patients by recording 48 h heart rate variability. Methods It was a single-center cross-sectional study. MHD patients at the Hemodialysis Center of Peking University People's Hospital between October 1, 2021 and December 31, 2022 were enrolled in the study. These patients initiated hemodialysis for more than three months and were older than 18 years old, and patients with tachyarrhythmia, implanted cardiac pacemaker and the recording time less than 48 h were excluded. Demographic data, comorbidity, laboratory data, hemodialysis session data and heart rate variability were collected. Multivariate linear regression model was used to analyze the influencing factors for cardiac autonomic dysfunction in MHD patients. Results A total of 110 patients were enrolled in the study, including 37 females (33.6%) and 36 diabetic patients (32.7%). The age of the patients was (57.8±14.8) years old, and the median dialysis vintage was 73.00(27.75±130.25) months. At baseline, the serum phosphate level was (1.6±0.4) mmol/L, and the N-terminal pro B-type natriuretic peptide (NT-proBNP) after ln transformed {ln[NT?proBNP(ng/L)]} was 8.4±1.2. The standard deviation of all normal R-R interval (SDNN) was (90.6±27.9) ms, ln[root mean square of successive differences in R-R interval (RMSSD, ms)] 3.2±0.8, ln[low frequency (ms2)] 3.4±1.3, ln[high frequency (ms2)] 3.1±1.4, and ln[low frequency/high frequency ratio] 0.28±0.64. After adjusting the age, coronary heart disease, diabetes, hemoglobin, serum phosphate and 25-hydroxy-vitamin D, serum natrium (β=2.042, 95% CI 0.021–4.064, P=0.048) and ln[NT-proBNP (ng/L)] (β=-7.027, 95% CI -12.247–-1.808, P=0.009) were independently correlated with SDNN (adjusted R2=0.218). Univariate linear regression model showed that diabetes was correlated with ln[low frequency(ms2)] of MHD patients (β=-0.659, 95% CI -1.171–-0.146, P=0.012), but in the multivariate linear regression model, significant correlation between diabetes and low frequency was not found. After adjusting the diabetes, coronary heart disease, dialysis vintage, hemoglobin, serum phosphate, serum albumin, pre-dialysis systolic blood pressure, post-dialysis systolic blood pressure, pre-dialysis diastolic blood pressure, increasing age (β=-0.011, 95% CI -0.019–-0.003, P=0.007) and ln[NT-proBNP(ng/L)] (β=-0.151, 95% CI -0.253–-0.048, P=0.004) were independently correlated with a decrease in the ln[low frequency/high frequency ratio]. In the multivariate linear regression model with ln[high frequency(ms2)] or ln[RMSSD(ms)] as dependent variable, after adjusting the relevant factors, serum phosphate level was independently correlated with ln[RMSSD(ms)] (β=-0.421, 95% CI -0.777–-0.065, P=0.021) or ln[high frequency(ms2)] (β=-0.752, 95% CI -1.325–-0.180, P=0.010). Conclusions Hyperphosphatemia is an independent influencing factor of parasympathetic nervous system in MHD patients. Higher NT-proBNP is associated with lower SDNN and lower ratio of low frequency/high frequency, so serum phosphate control and volume control should be highlighted. Age is associated with autonomic dysfunction in MHD patients, so more attention should be paid to elder patients.

Low intramuscular adipose tissue index is a protective factor of all-cause mortality in maintenance dialysis patients
Zheng Jing, Hou Shimei, Lu Keqi, Yan Yu, Zhang Shuyan, Yuan Li, Li Min, Cao Jingyuan, Wang Yao, Yang Min, Liu Hong, Zhang Xiaoliang, Liu Bicheng, Wang Bin
2024, 40 (2): 101-110. https://doi.org/10.3760/cma.j.cn441217-20230301-00302
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Objective To investigate the relationship between intramuscular adipose tissue index (IATI) calculated from computed tomography images at transverse process of the first lumbar and all-cause mortality in maintenance dialysis patients, and to provide a reference for improving the prognosis in these patients. Methods It was a multicenter retrospective cohort study. The clinical data of patients who received maintenance hemodialysis or peritoneal dialysis treatment from January 1, 2017 to December 31, 2019 in 4 grade Ⅲ hospitals including Zhongda Hospital Affiliated to Southeast University, Taizhou People's Hospital Affiliated to Nanjing Medical University, Affiliated Hospital of Yangzhou University, and the Third Affiliated Hospital of Soochow University were retrospectively collected. IATI was calculated by low attenuation muscle (LAM) density/skeletal muscle density. The receiver-operating characteristic curve was used to determine the optimal cut-off value of IATI, and the patients were divided into high IATI group and low IATI group according to the optimal cut-off value. The differences of baseline clinical data and measurement parameters of the first lumbar level between the two groups were compared. The follow-up ended on December 23, 2022. The endpoint event was defined as all-cause mortality within 3 years. Kaplan-Meier survival curve and log-rank test were used to analyze the survival rates and the differences between the two groups. Multivariate Cox regression analysis models were used to analyze the association between IATI and the risk of all-cause mortality in maintenance dialysis patients. Multivariate logistic regression analysis model was used to analyze the influencing factors of high IATI. Results A total of 478 patients were eligibly recruited in this study, with age of (53.55±13.19) years old and 319 (66.7%) males, including 365 (76.4%) hemodialysis patients and 113 (23.6%) peritoneal dialysis patients. There were 376 (78.7%) patients in low IATI (<0.42) group and 102 (21.3%) patients in high IATI (≥0.42) group. The proportion of age ≥ 60 years old (χ2=24.746, P<0.001), proportion of diabetes mellitus (χ2=5.570, P=0.018), fasting blood glucose (t=-2.145, P=0.032), LAM density (t=-3.735, P<0.001), LAM index (t=-7.072, P<0.001), and LAM area/skeletal muscle area ratio (Z=-9.630, P<0.001) in high IATI group were all higher than those in low IATI group, while proportion of males (χ2=11.116, P<0.001), serum albumin (Z=2.708, P=0.007) and skeletal muscle density (t=12.380, P<0.001) were lower than those in low IATI group. Kaplan-Meier survival analysis showed that the 3-years overall survival rate of low IATI group was significantly higher than that in high IATI group (Log-rank χ2=19.188, P<0.001). Multivariate Cox regression analysis showed that IATI<0.42 [<0.42/≥0.42, HR(95% CI): 0.50 (0.31-0.83), P=0.007] was an independent protective factor of all-cause mortality, and age ≥60 years old [HR (95% CI): 2.61 (1.60-4.23), P<0.001], diabetes mellitus [HR (95% CI): 1.71 (1.06-2.78), P=0.029] and high blood neutrophil/lymphocyte ratio [HR (95% CI): 1.04 (1.00-1.07), P=0.049] were the independent risk factors of all-cause mortality in maintenance dialysis patients. Stepwise Cox regression analysis showed that IATI<0.42 was still an independent protective factor of all-cause mortality in maintenance dialysis patients [<0.42/≥0.42, HR (95% CI): 0.45 (0.27-0.76), P=0.003]. Multivariate logistic regression analysis showed that low skeletal muscle density [OR (95% CI): 0.84 (0.81-0.88), P<0.001] and high serum triglyceride [OR (95% CI): 1.39 (1.07-1.82), P=0.015] were the independent influencing factors of IATI≥0.42. Conclusion IATI<0.42 of the first lumbar level is an independent protective factor of all-cause mortality in maintenance dialysis patients. Localized myosteatosis within high-quality skeletal muscle may reduce the risk of all-cause mortality in these patients.

Influencing factors for hemodialysis initiation in non-diabetic kidney disease patients with predialysis fistula after arteriovenous fistula creation
Dang Xiangyun, Li Huixian, Zhang Xiaotian, Liu Chao, Yang Shifeng, Lu Wanhong
2024, 40 (2): 111-117. https://doi.org/10.3760/cma.j.cn441217-20230830-00845
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Objective To explore the influencing factors of hemodialysis (HD) initiation in non-diabetic kidney disease (NDKD) patients with predialysis arteriovenous fistula (AVF) creation. Methods This was a single-center prospective cohort study. The NDKD patients undergoing predialysis AVF creation were enrolled at the First Affiliated Hospital of Xi'an Jiaotong University from 2015 to 2018. According to the estimated glomerular filtration rate (eGFR, the Chronic Kidney Disease Epidemiology Collaboration equation) and age, patients were divided into different subgroups, eGFR: group 1 [eGFR<10 ml·min-1·(1.73 m2)-1], group 2 [ eGFR between 10 to 15 ml·min-1·(1.73 m2)-1], and group 3 [eGFR > 15 ml·min-1·(1.73 m2)-1]; age: age ≥65 years group and age <65 years group. The primary outcome was defined as the initiation of HD within 1 year after AVF surgery. The second outcome was the use of AVF access at the time of HD initiation. Cox proportional hazard regression was performed to identify which demographic and clinical factors were associated with the initiation of HD after AVF surgery. Logistic regression analysis was performed to investigate factors associated with AVF use at the initiation of HD. Results A total of 220 patients were enrolled, with age of (48.1±16.2) years, of which 143(65.0%) were males. Overall, the clinical parameters of eGFR, cystatin C, serum albumin, 24h-Urine protein, serum phosphorus were as follows respectively, 7.7 (6.6,9.2) ml·min-1·(1.73 m2)-1, (3.93±1.12) mg/L, (36.0±4.0) g/L, (2.22±1.36) g, (1.71±0.53) mmol/L. The proportion of patients initiating HD within 6 months (Fisher=6.832, P=0.020) and the level of hemoglobin (F=3.112, P=0.047) were higher in group 3 compared to the other two eGFR groups. While the median time interval between AVF creation and HD initiation (H=6.295, P=0.043) was shorter in group 1. In age <65 years group, the level of serum albumin (t=2.076, P=0.039), triglyceride (t=1.995, P=0.048) were higher compared with age ≥65 years group; interestingly, the proportion of patients initiated HD within 3 months (χ2=4.033, P=0.045) and 6 months (χ2=5.012, P=0.025) were lower in age <65 years group. The median time interval between AVF creation and HD initiation among these patients was 84 (49,174) days. The patients initiating HD within 3 months, 6 months, and 1 year after AVF creation were 112 (50.9%), 152 (69.1%), and 202 (91.8%), respectively. Multivariate Cox regression analysis indicated that higher cystatin C level (HR=1.283, 95% CI 1.121-1.469, P<0.001) was associated with earlier HD initiation within 1 year of AVF surgery in NDKD patients. AVF usage was accomplished in 64.3% of patients who initiated HD within 90 days, the ratio was 100.0% in those initiated HD between 91 to 180 days, and 88.0% in those ≥181 days after AVF surgery. No factor was independently associated with AVF use at HD initiation identified by multivariate logistic regression analyses in patients with NDKD. Conclusion Serum cystatin C level is associated with HD initiation within 1 year of the predialysis AVF creation in NDKD patients.

Effect of endovascular treatment on thrombosis of autogenous arteriovenous fistula
Li Wen, Wang Fanli, Yang Yanli, Ren Fengqin, Meng Fulei, Zhang Kaidi, Zhao Haiyan, Zhang Lihong, Ruan Lin
2024, 40 (2): 118-123. https://doi.org/10.3760/cma.j.cn441217-20230227-00231
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Objective To investigate the effectiveness and safety of ultrasound-guided endovascular therapy for autogenous arteriovenous fistula (AVF) thrombosis. Methods It was a single-center retrospective cohort study. Data of patients undergoing ultrasound-guided intravascular therapy due to AVF thrombosis in the First Hospital of Hebei Medical University from August 2018 to June 2021 were analyzed. According to different surgical procedures, the patients were divided into two groups. Patients treated with percutaneous transluminal angioplasty (PTA) + drilling thrombectomy were in group A, and patients treated with PTA only were in group B. After 1 year of follow-up, the surgical technique success rate, primary patency rate, secondary patency rate and complications were compared between the two groups. Results A total of 152 patients were enrolled, including 74 in group A and 78 in group B. There were no significant differences in gender, age, proportion of patients with diabetes and hypertension, and thrombosis time of AVF between the two groups (all P>0.05). Compared with group B, the diameter and length of thrombus in group A were larger [13.0(9.0, 16.0) mm vs. 6.0(5.0, 6.5) mm, Z=-9.362, P<0.001; 12(8, 15) cm vs. 3(3, 4) cm, Z=-10.061, P<0.001], and the establishment time of AVF was longer [5(2, 7) years vs. 2(1, 5) years, Z=-2.698, P=0.007]. Among the overall patients, the success rate of surgery was 96.7% (147/152), and the success rate of surgery was 95.9% (71/74) in group A and 97.4% (76/78) in group B respectively, with no statistical difference (χ2=0.004, P=0.952). Kaplan?Meier survival analysis showed that, overall, the primary patency rate at 3rd, 6th and 12th month after operation was 87.1%, 71.4% and 56.6%, and the secondary patency rate was 97.1%, 96.4% and 94.1%, respectively. The primary patency rate of group A at 3rd, 6th and 12th month was 82.4%, 66.7% and 53.6%, and the secondary patency rate was 95.7%, 94.2% and 89.7%, respectively. The primary patency rate of group B at 3rd, 6th and 12th month was 91.5%, 73.2% and 59.7%, and the secondary patency rate was 98.6%, 98.6% and 98.5%, respectively. There was no significant difference in the primary and secondary patency rate between group A and group B at 3rd, 6th and 12th month (all P>0.05). The duration of operation in group A was longer than that in group B [2.0(1.9, 2.0) h vs. 2.0(1.0, 2.0) h, Z=-5.181, P<0.001], but no serious complications occurred in both groups. Conclusion The two surgical methods are effective, safe and reliable in the treatment of AVF thrombosis, and have high clinical application value.

Clinical features and risk factors of the mortality in hemodialysis patients infected with SARS-CoV-2
Lan Jie, Guo Hongping, Zhen Guohua, Liu Hongting, Li Jing, Wang Lihua
2024, 40 (2): 124-130. https://doi.org/10.3760/cma.j.cn441217-20230915-00918
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Objective To investigate the clinical features of patients with maintenance hemodialysis (MHD) infected with SARS-CoV-2 and analyze the risk factors of death after SARS-CoV-2 infection, and to provide clinical data for early detection of critically ill patients and timely intervention. Methods It was a cross-sectional investigation study. MHD patients in the hemodialysis centers of four tertiary hospitals with geographical representation in Shanxi province from December 1, 2022 to January 31, 2023 were enrolled, and the demographic data, dialysis-related indicators, laboratory test results and clinical features of SARS-CoV-2 infection were collected by distributing the questionnaires on SARS-CoV-2 infection, and consulting the hospital medical record system and the outpatient hemodialysis information system. SARS-CoV-2-infected patients were divided into survival group and death group according to whether all-cause death occurred and the differences of baseline data between the two groups were compared. Multivariate logistic regression analysis method was used to analyze the risk factors of mortality in MHD patients infected with SARS-CoV-2. Results A total of 519 MHD patients were included in this study, with 508 patients (97.88%) infected with SARS-CoV-2, 474 patients in the survival group and 34 patients in the death group. The clinical symptoms of MHD patients infected with SARS-CoV-2 were diverse, and the most common initial symptom was fever (314/508, 61.81%). Other initial symptoms included cough and phlegm in 66 patients (12.99%), fatigue in 66 patients (12.99%), poor appetite in 20 patients (3.94%), dyspnea in 20 patients (3.94%), muscle pain in 14 patients (2.76%) and diarrhea in 8 patients (1.57%). Compared with the survival group, the death group had older age (t=5.229, P<0.001), high proportions of males (χ2=12.319, P<0.001) and diabetic nephropathy (χ2=49.423, P<0.001), and lower levels of red blood cells (t=-5.060, P<0.001), lymphocyte (t=-2.614, P=0.011), neutrophil (t=-5.117, P<0.001), serum albumin (t=-2.940, P=0.012), serum prealbumin (t=-3.519, P=0.001), blood phosphorus (t=-3.309, P=0.002), serum creatinine (Z=-3.607, P<0.001), total triglyceride (Z=-2.486, P=0.013), total cholesterol (Z=-3.291, P=0.001) and low-density lipoprotein cholesterol (Z=-3.292, P=0.001). Among 508 SARS-CoV-2-infected patients, 194 patients (38.19%) were treated with nonsteroidal anti-inflammatory agents, 154 patients (30.31%) were treated with antibiotics, and 98 patients (19.29%) were treated with antiviral drugs. There were 225 (43.29%) vaccinated patients against SARS-CoV-2. Multivariate logistic regression analysis showed that low red blood cells (OR=0.256, 95% CI 0.014-0.429), low lymphocytes (OR=0.487, 95% CI 0.193-0.826), low serum albumin (OR=0.613, 95% CI 0.329-0.917), older age (OR=1.227, 95% CI 1.066-1.412) and diabetes mellitus (OR=1.126, 95% CI 1.025-1.235) were the independent influencing factors of all-cause mortality in MHD patients infected with SARS-CoV-2. Conclusions The clinical manifestations of SARS-CoV-2 infection in MHD patients are varied. Low red blood cells, low lymphocytes, low serum albumin, elder age and diabetes mellitus are the independent risk factors of death after SARS-CoV-2 infection in MHD patients. Strengthening management of MHD patients especially in the elderly, and improving and correcting anemia and malnutrition in time, may reduce the death risk of SARS-CoV-2 infection in MHD patients.

Establishment of abdominal aortocaval fistula in adenine-induced renal failure rats
Zhang Yifei, Liang Liming, Kong Xianglei, Xu Shuqi, Wang Qun, Wang Zunsong, Xu Dongmei
2024, 40 (2): 131-136. https://doi.org/10.3760/cma.j.cn441217-20230612-00619
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Objective To explore the construction of abdominal aortocaval fistula (ACF) model in adenine-induced renal failure rats, and to provide a suitable animal model for subsequent mechanism and intervention researches. Methods Adult female Sprague-Dawley rats (250-300 g) were fed with 0.75% adenine diet (renal failure group, n=60) and the same diet without adenine (control group, n=10) for 4 weeks, and the rats were randomly grouped by block randomization method with a ratio of 6∶1. Thirty rats in the renal failure group were randomly selected by block randomization method at a ratio of 1∶1 to undergo laparotomies to establish ACF models (renal failure+ACF group). The serum creatinine, blood urea nitrogen detection and Masson staining were used to evaluate the establishment of renal failure model. Small animal ultrasound imaging system was applied to verify the successful construction of the ACF model. After 6 weeks of ACF observation, blood samples were collected from the heart of rats, and ACF-vascular tissues were collected for pathological study (HE staining). Results At 4 weeks of feeding, compared with the control group, serum creatinine [(63.8±23.5) μmol/L vs. (33.0±3.8) μmol/L, Z=3.651, P<0.001] and blood urea nitrogen [(13.1±6.9) mmol/L vs. (5.3±0.6) mmol/L, Z=3.254, P=0.001] in the renal failure group were both higher. Masson staining showed renal tubulointerstitial inflammatory cell infiltration, renal tubular epithelial cell atrophy, interstitial fibrosis and vascular injury. Five rats sacrificed after ACF surgeries, and the survival rate was 83.3%. Doppler ultrasound showed turbulent blood flow of arterial to venous shunt at the anastomosis of open ACF (23/25) in the renal failure+ACF group. HE staining showed typical eccentric neointimal hyperplasia in the outflow tract of ACF vein in the renal failure+ACF group. Conclusions The adenine-induced ACF rat model is successfully constructed, and ACF shows typical eccentric neointimal hyperplasia. The ACF construction would provide a reliable animal model to study the mechanism and intervention of neointimal hyperplasia for autologous arteriovenous fistula.

Chronic active EB virus infection in a child with the onset of IgA nephropathy
Fan Shuying, Wang Xin, Wei Ning, Zhou Qiumei, Wang Wenhong
2024, 40 (2): 137-140. https://doi.org/10.3760/cma.j.cn441217-20230621-00631
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Chronic active Epstein-Barr virus (CAEBV) infection with renal involvement is not common. The paper reported a child of multisystem-compromised CAEBV infection with the onset of IgA nephropathy (IgAN). The child presented with intermittent gross hematuria, and renal biopsy showed focal proliferative IgAN, administered methylprednisolone pulse followed by oral prednisolone treatment. Intermittent increase of blood Epstein-Barr virus (EBV) load and abnormal EBV antibody, pneumonia caused by EBV and Staphylococcus aureus-mixed infection, periappendiceal abscess, and pancytopenia occurred during treatment follow-up. The CAEBV infection was considered. Echocardiography suggested pulmonary hypertension. Head CT presented multiple calcifications in the bilateral basal ganglia. Bone marrow biopsy showed bone marrow EBV-DNA 6.5×103 copies per liter. Immunohistochemistry of renal biopsy showed about 50 CD8+ (scattered +) cells per high power field (HPF), about 40 CD4+ (focal +) cells per HPF (local), CD68+ (-), latent membrane protein 1 (-), EBV-encoded small RNA (scattered +) approximately 25 cells per HPF. The lymphocyte subsets infected with EBV showed CD4+ T cells EBV-DNA 3.4×104 copies per 1 million cells, CD8+ T cells EBV-DNA 3.3×105 copies per 1 million cells, B cells EBV-DNA 1.25×104 copies per 1 million cells, NK cells/NK T cells EBV-DNA 2.3×104 copies per 1 million cells. The clinical diagnosis was CAEBV infection and EBV-associated IgAN. The patient currently receives oral prednisone treatment, and it is recommended to undergo hematopoietic stem cell transplantation and treatment is under follow up.

Research progress of D-dimer and kidney diseases
Zhao Xiaoyu, Zhou Yun
2024, 40 (2): 141-145. https://doi.org/10.3760/cma.j.cn441217-20230511-00514
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D-dimer is a fibrin degradation product. The increased D-dimer indicates hypercoagulability and secondary hyperfibrinolysis, which can be used as a biomarker for activation of coagulation and fibrinolysis system. D-dimer is routinely used in the diagnosis of thrombotic diseases. D-dimer level is affected by age, pregnancy, blood glucose, infection, liver failure, cancer and stroke. The increased D-dimer is closely related to kidney diseases. The paper reviews the formation mechanism and influencing factors of D-dimer, the relationship between D-dimer and kidney diseases, and the prognostic value of D-dimer in kidney diseases, to provide references for clinical diagnosis and treatment.

Chinese expert consensus on long-acting erythropoiesis-stimulating agents in the treatment of renal anemia (2024)
Expert Committee of Nephrology & Dialysis Branch of China Non-Government Medical Institutions Association
2024, 40 (2): 146-157. https://doi.org/10.3760/cma.j.cn441217-20231025-01037
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Erythropoiesis-stimulating agents (ESAs) are commonly used drugs in the treatment of renal anemia. There are currently two types of ESAs available to clinicians, including short-acting ESAs and long-acting ESAs. Short-acting ESAs have been used for decades in China, which are being widely accepted nowadays. Several professional societies have published consensus guidelines for the use and interpretation of short-acting ESAs worldwide in recent years. The advantages of long-acting ESAs include long half-life, low infusion frequency, good patient compliance, etc. There is still a lack of guidance on the clinical use of long-acting ESAs although important progress of long-acting ESAs has been made in clinical trials in recent years. Thus, the Society of Nephrology & Dialysis of China Non-Government Medical Institutions Association organized relevant experts to jointly formulate the "Chinese Expert Consensus on Long-acting ESAs in the Treatment of Renal Anemia". This consensus mainly introduces the classification, mechanism of action and pharmacological characteristics of long-acting ESAs, their indications, timing, administration protocols, application in special populations, adverse reactions and management in renal anemia. It is the hope of this concensus will guide the clinical use of long-acting ESAs in the treatment of renal anemia.

Expert consensus on antimicrobial dosing optimization during continuous renal replacement therapy (2024)
Expert group of antimicrobial dosing optimization during continuous renal replacement therapy, Chinese Pharmaceutical Association Hospital Pharmacy Professional Committee, Infectious Diseases Society of China
2024, 40 (2): 158-174. https://doi.org/10.3760/cma.j.cn441217-20230906-00906
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Continuous renal replacement therapy (CRRT) is an important treatment for critically ill patients. Critically ill patients often need to receive antimicrobials and CRRT treatments at the same time. CRRT affects the pharmacokinetics and pharmacodynamics of antimicrobials, and there is a lack of recommendations and suggestions for the antimicrobial dosing during CRRT. The clinical medicine, pharmacy, intensive care and infectious diseases specialists in China set up an expert group on antimicrobial dosing optimization during CRRT, conducted evidence search around CRRT factors, drug characteristics, patient factors and antimicrobial dosing optimization during CRRT, and fully discussed and formulated the consensus, to provide guiding advices on the rational use of antimicrobials during CRRT.

Establishment of machine learning-based risk prediction model for acute kidney injury in acute myocardial infarction patients and compared with traditional model
Ye Nan, Zhu Chuang, Xu Fengbo, Cheng Hong
2024, 40 (3): 175-182. https://doi.org/10.3760/cma.j.cn441217-20231120-01122
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Objective To establish a predictive risk model for acute kidney injury (AKI) in acute myocardial infarction (AMI) patients based on machine learning algorithm and compare with a traditional logistic regression model. Methods It was a retrospective study. The demographic data, laboratory examination, treatment regimen and medication of AMI patients from July 2011 to December 2016 in Beijing Anzhen Hospital, Capital Medical University were collected. The diagnostic criteria of AKI were based on the AKI diagnosis and treatment guidelines published by Kidney Diseases: Improving Global Outcomes in 2012. The selected AMI patients were randomly divided into training set (70%) and internal test set (30%) by simple random sampling. SelectFromModel and Lasso regression models were used to extract clinical parameters as predictors of AKI in AMI patients. Logistic regression model (model A) and machine learning algorithm (model B) were used to establish the risk prediction model of AKI in AMI patients. DeLong method was used to compare the area under the receiver-operating characteristic (ROC) curve (AUC) between model A and model B for selecting the best model. Results A total of 6 014 AMI patients were included in the study, with age of (58.4±11.7) years old and 3 414 males (80.5%). There were 674 patients (11.2%) with AKI. There were 4 252 patients (70.7%) in the training set and 1 762 patients (29.3%) in the test set. The selected twelve clinical parameters by the SelectFromModel and Lasso regression models included the number of myocardial infarctions, ST-segment elevation myocardial infarction, ventricular tachycardia, third degree atrioventricular block, decompensated heart failure at admission, admission serum creatinine, admission blood urea nitrogen, admission peak creatine kinase isoenzyme, diuretics, maximum daily dose of diuretics, days of diuretic use and statins. Logistic regression prediction model showed that AUC for the test set was 0.80 (95% CI 0.76-0.84). The machine learning algorithm model obtained AUC in the test set with 0.82 (95% CI 0.78-0.85).There was no significant difference in AUC between the two models (Z=0.858, P=0.363), and AUC of the machine learning algorithm predictive model was slightly higher than that of the traditional logistic regression model. Conclusions The prediction effect of AKI risk in AMI patients based on machine learning algorithm is similar to that of traditional logistic regression model, and the prediction accuracy of machine learning algorithm is better. The introduction of machine learning algorithm model may improve the ability to predict AKI risk.

Establishment of nomogram model of acute kidney injury risk prediction based on clinical database
Tang Tian, Dong Ningxin, Wu Lehao, Zhao Dan, Yu Chen, Zhang Yingying
2024, 40 (3): 183-192. https://doi.org/10.3760/cma.j.cn441217-20230814-00819
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Objective To construct the risk prediction nomogram model of acute kidney injury (AKI) with R language and traditional statistical methods based on the large sample clinical database, and verify the accuracy of the model. Methods It was a a retrospective case control study. The patients who met the diagnostic criteria of AKI in Tongji Hospital of Tongji University from January 1 to December 31, 2021 were screened in the clinical database, and the patients with monitored serum creatinine within 48 hours but without AKI were included as the control group. The demographic data, disease history, surgical history, medication history and laboratory test data were collected to screen the risk factors of AKI in clinic.Firstly, based on multivariate logistic regression analysis and forward stepwise logistic regression analysis, the selected risk factors were included to construct the nomogram model. At the same time, cross validation, bootstrap validation and randomly split sample validation were used for internal verification, and clinical data of patients in the sane hospital after one year (January to December, 2022) were collected for external verification. The receiver-operating characteristic curve was used to determine the discrimination of the model, and calibration curve and decision curve analysis were carried out to evaluate the accuracy and clinical net benefit, respectively. Results A total of 5 671 patients were enrolled in the study, with 1 884 AKI patients (33.2%) and 3 787 non-AKI patients (66.7%). Compared with non-AKI group, age, and proportions of surgical history, renal replacement therapy, hypertension, diabetes, cerebrovascular accident,chronic kidney disease, drug use histories and mortality in AKI group were all higher (all P<0.05). Multivariate logistic regression analysis showed that the independent influencing factors of AKI were surgical history, hypertension, cerebrovascular accident, diabetes, chronic kidney disease, diuretics, nitroglycerin, antidiuretic hormones, body temperature, serum creatinine, C-reactive protein, red blood cells, white blood cells, D-dimer, myoglobin, hemoglobin, blood urea nitrogen, brain natriuretic peptide, aspartate aminotransferase, alanine aminotransferase, triacylglycerol, lactate dehydrogenase, total bilirubin, activated partial thromboplastin time, blood uric acid and potassium ion (all P<0.05). Finally, the predictive factors in the nomogram were determined by forward stepwise logistic regression analysis, including chronic kidney disease, hypertension, myoglobin, serum creatinine and blood urea nitrogen, and the area under the curve of the prediction nomogram model was 0.926 [95% CI 0.918-0.933, P<0.001]. The calibration curve showed that the calibration effect of nomogram was good (P>0.05). The decision curve showed that when the risk threshold of nomogram model was more than 0.04, the model construction was useful in clinic. In addition, the area under the curve of receiver-operating characteristic curve predicted by nomograph model in external validation set was 0.876 (95% CI 0.865-0.886), which indicated that nomograph model had a high discrimination degree. Conclusion A nomogram model for predicting the occurrence of AKI is established successfully, which is helpful for clinicians to find high-risk AKI patients early, intervene in time and improve the prognosis.

Value of renal biopsy in the diagnosis and treatment of adult patients with acute kidney disease
Lyu Mengru, Wu Buyun, Bian Ao, Zhang Bo, Wu Lin, Zhu Jingfeng, Sun Bin, Xing Changying, Mao Huijuan
2024, 40 (3): 193-200. https://doi.org/10.3760/cma.j.cn441217-20231006-01001
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Objective To analyze the changes of diagnosis and treatment before and after renal biopsy in adult patients with acute kidney disease (AKD), and to explore the value of renal biopsy in the diagnosis and treatment of AKD. Methods It was a single-center retrospective observational study. The adult patients with AKD who underwent renal biopsy in the Department of Nephrology of the First Affiliated Hospital of Nanjing Medical University from January 1, 2017 to December 31, 2021 were enrolled. Demographic data, general clinical data, laboratory tests, and diagnosis and treatment data before and after renal biopsy were collected to analyze the concordance rate between clinical and pathological diagnoses, changes in treatment after renal biopsy, and bleeding complication. Results A total of 575 patients diagnosed with AKD by renal biopsy were included in this study, with age of 51 (36, 63) years old and 359 males (62.4%). Among them, there were 293 patients (51.0%) of acute kidney injury, 348 patients (60.5%) of hypertension and 124 patients (21.6%) of diabetes. The peak serum creatinine was 272 (190, 477) μmol/L. The hemoglobin was 106 (86, 126) g/L. The 24-hour urine protein was 2.15 (0.79, 4.82) g. There were 347 patients (60.3%) of acute glomerular diseases, 136 patients (23.7%) of acute interstitial nephritis, 47 patients (8.2%) of thrombotic microangiopathy, and 45 patients (7.8%) of acute tubular necrosis. The most common types of acute glomerular diseases were IgA nephropathy and anti-neutrophil cytoplasmic antibody-associated glomerulonephritis, accounting for 22.3% (128/575) and 12.2% (70/575), respectively. The clinical diagnoses before renal biopsy were consistent with the renal histopathological diagnoses in 454 patients, with an accuracy rate of 79.0%. Following the renal biopsy, the treatment plan involving glucocorticoids or immunosuppressants was adjusted in 394 patients (68.5%). Significant post-biopsy bleeding occurred in 15 patients (2.6%), with 12 patients requiring blood transfusion and 1 patient requiring surgical intervention. Conclusions Twenty-one clinical diagnoses do not match the pathological diagnoses in adult AKD patients, 68.5% of patients have changes in their treatment plans, and 2.6% of patients have significant hemorrhagic complications after renal biopsy. Clinicians need to carefully consider the benefits and risks and make individualized decisions about renal biopsy.

Predictive value of serum uric acid/albumin ratio for acute kidney injury after cardiac valve surgery
Zhao Xiaoru, Shao Zehua, Zhang Wenwen, Deng Xiaoyu, Li Han, Yan Lei, Gu Yue, Shao Fengmin
2024, 40 (3): 201-208. https://doi.org/10.3760/cma.j.cn441217-20230928-00938
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Objective To investigate the predictive value of serum uric acid/albumin ratio (sUAR) for acute kidney injury (AKI) after cardiac valve surgery. Methods The clinical data of adult patients undergoing cardiac valve surgery under cardiopulmonary bypass from January 2021 to December 2021 from the Heart Center of Henan Provincial People's Hospital were collected retrospectively, and the sUAR was calculated. All patients were divided into AKI group and non-AKI group according to whether AKI occurred within 7 days after cardiac valve surgery, and the differences of clinical data between the two groups were compared. Multivariate logistic regression model was used to analyze the independent correlation factors of AKI after cardiac valve surgery. The receiver operating characteristic (ROC) curve was used to evaluate the performance of relevant indicators. Results A total of 422 patients were enrolled, including 194 females (46.0%), 141 hypertension patients (33.4%) and 172 atrial fibrillation patients (40.8%). They were 57 (50, 65) years old. Their sUAR was 8.13 (6.57, 9.54) μmol/g, and hemoglobin was 135 (125, 145) g/L. There were 142 cases in AKI group and 280 cases in non-AKI group, and the incidence of AKI after cardiac valve surgery was 33.6%. Age, atrial fibrillation rate, baseline serum creatinine, N terminal pro B type natriuretic peptide, serum urea,serum uric acid, blood glucose and sUAR were higher in the AKI group than those in the non-AKI group (all P<0.05), and estimated glomerular filtration rate, lymphocyte count,hemoglobin and serum albumin were lower in the AKI group than those in the non-AKI group (all P<0.05). The median cardiopulmonary bypass time of patients in the AKI group was slightly longer than that in the non-AKI group, but the difference was not statistically significant [159 (125, 192) min vs. 151 (122, 193) min, Z=-0.797, P=0.426], and there were no statistically significant differences in other indicators between the two groups. The results of multivariate logistic regression analysis showed that sUAR (OR=1.467, 95% CI 1.308-1.645, P<0.001), age (OR=1.045, 95% CI 1.020-1.072, P<0.001), atrial fibrillation (OR=2.520, 95% CI 1.580-4.020, P<0.001), hemoglobin (OR=0.984, 95% CI 0.971-0.997, P=0.015) were the independent correlation factors. ROC curve analysis showed that the area under the curve (AUC) of sUAR predicting AKI after cardiac valve surgery was 0.710 (95% CI 0.659-0.760, P<0.001) with a sensitivity of 85.2% and specificity of 45.0% for the sUAR cut-off point of 7.28 μmol/g. The AUC for the diagnosis of AKI after cardiac valve surgery was 0.780 (95% CI 0.734-0.825,P<0.001) with a sensitivity of 72.5% and specificity of 71.8% for the combination of sUAR with age, hemoglobin and atrial fibrillation. Conclusions For patients undergoing cardiac valve surgery under cardiopulmonary bypass, preoperative high sUAR is an independent risk factor for postoperative AKI, and sUAR has a certain predictive value for postoperative AKI.

Expression of interleukin-37 in patients with diabetic kidney disease and its regulatory activity to the cytotoxic function of CD8+T lymphocytes
Bu Haixia, Xu Ke, Han Xiaojing, Wang Huan, Zhou Yanhong
2024, 40 (3): 209-220. https://doi.org/10.3760/cma.j.cn441217-20230911-00913
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Objective To investigate interleukin-37 (IL?37) expression in patients with diabetic kidney disease (DKD), and to assess the regulation of exogenous IL?37 on CD8+ T cell function in DKD patients. Methods A cross-section study was carried out. Twenty healthy controls, thirty-six patients with diabetes mellitus type 2 (T2DM), and forty-seven DKD patients were enrolled in the study. Peripheral blood was collected. Plasma and peripheral blood mononuclear cells were isolated. IL?37 and soluble IL-1 receptor 8 (IL-1R8) levels in the plasma were measured by enzyme-linked immunosorbent assay (ELISA). IL-18 receptor α chain (IL-18Rα), IL-1R8 and immune checkpoint molecules levels in CD8+ T cells were measured by flow cytometry. CD8+ T cells were purified, and were stimulated with recombinant IL?37. CD8+ T cells were co-cultured with HEK293 cells in either direct contact or indirect contact manner. Levels of perforin, granzyme B, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were measured by ELISA. The proportion of target cell death was assessed by measuring lactate dehydrogenase level. Results Plasma IL?37 levels in DKD patients [(63.42±23.30) ng/L] were significant lower than those in healthy controls [(143.02±50.67) ng/L] and T2DM patients [(87.88±40.62) ng/L] (t=8.848, P<0.001; t=3.456, P<0.001). Plasma IL?37 level had good predictive values for T2DM in health individuals and for DKD in T2DM patients [the area under the curve was 0.797 (95% CI 0.676-0.917, P<0.001) and 0.691 (95% CI 0.576-0.807, P=0.003), respectively]. Plasma IL?37 level was negatively correlated with urea nitrogen (r=-0.313, P=0.032) and creatinine (r=-0.477, P<0.001), and positively correlated with estimated glomerular filtration rate (eGFR) (rs =0.478, P<0.001) in DKD patients. IL-1R8+ CD8+ cell proportion in DKD patients (33.60%±9.47%) was significantly higher compared to healthy controls (16.29%±5.97%) and T2DM patients (17.13%±4.85%) (t=7.545, 9.516, both P<0.001), but did not correlate with fast blood glucose, urea nitrogen, creatinine, or eGFR (all P>0.05). There were no statistical differences of IL-18Rα+ CD8+ cell proportion, soluble IL-1R8 level, or immune checkpoint molecule proportion in CD8+ T cells among healthy controls, T2DM patients, and DKD patients (all P>0.05). Perforin and granzyme B secretions by CD8+ T cells were significantly elevated in DKD patients compared with healthy controls [(108.78±12.42) ng/L vs. (94.60±10.07) ng/L, t=3.096, P=0.005; (261.34±48.79) ng/L vs. (166.28±30.80) ng/L, t=3.387, P=0.002] and T2DM patients [(108.78±12.42) ng/L vs. (92.58±14.71) ng/L, t=3.263, P=0.003; (261.34±48.79) ng/L vs. (170.66±39.24) ng/L, t=2.627, P=0.014]. There were no significant differences of either IFN-γ or TNF-α secretions by CD8+ T cells among healthy controls, T2DM patients, and DKD patients (all P>0.05). In direct contact co-culture manner, CD8+ T cell-induced HEK293 cell death was down- regulated (13.03%±4.97% vs. 17.88%±5.19%, t=2.235, P=0.037). The levels of perforin [(222.02±25.79) ng/L vs. (294.30±25.58) ng/L, t=6.603, P<0.001], granzyme B [(416.27±90.24) ng/L vs. (524.71±115.53) ng/L, t=2.454, P=0.023], IFN-γ [(23.66±4.20) ng/L vs. (35.18±8.51) ng/L, t=4.026, P<0.001] and TNF-α [(1.62±0.29) μg/L vs. (2.09±0.57) μg/L, t=2.302, P=0.034] were also reduced as well. In indirect contact co-culture manner, there were no significant differences of CD8+ T cell-induced HEK293 cell death, perforin, or granzyme B levels between no stimulation and IL?37 stimulation (all P>0.05). IFN-γ and TNF-α levels in the supernatants were reduced in response to IL?37 stimulation [(23.56±6.24) ng/L vs. (32.56±9.90) ng/L, t=2.550, P=0.019; (1.41±0.31) μg/L vs. (2.10±0.44) μg/L, t=4.011, P<0.001]. Conclusion IL?37 level is reduced in DKD patients.Exogenous IL?37 suppresses the cytotoxicity of CD8+ T cells in DKD patients.

A case report and literature review of brachial artery ligation for treatment of infected arteriovenous graft complicated with rupture and bleeding
Liu Qian, Liao Zhennan, Yu Zongchao, Hu Bo, Huang Dexu
2024, 40 (3): 221-224. https://doi.org/10.3760/cma.j.cn441217-20230829-00843
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The paper reported a case of brachial artery ligation treatment of arteriovenous graft infection with arteriovenous graft exposure and bleeding. Based on the experience of vascular access center and the review of relevant literature, the causes and treatment options of this complication were analyzed, and the feasibility and safety of brachial artery ligation were elaborated for the treatment of this complication, to provide references for clinical diagnosis and treatment.

Researches progress on pathogenesis of IgA nephropathy
Wang Gangan, Zheng Ke, Li Xuemei
2024, 40 (3): 225-230. https://doi.org/10.3760/cma.j.cn441217-20230411-00418
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IgA nephropathy (IgAN) is currently the most common primary glomerulonephritis worldwide, with 20%-40% of patients progressing to end-stage renal disease within 20 years of diagnosis. At present, the pathogenesis of IgAN is not clear, and clinical treatment is mainly to control the progression, without specific treatment plan. A series of studies on galactose-deficient IgA1 (Gd-IgA1) suggest that the pathogenesis of IgAN involves multiple links. This review summarizes the research progress on the pathogenesis of IgAN, covering the structure characteristics of IgA1, Gd-IgA1 antibodies and Gd-IgA1 immune complexes in IgAN patients, the deposition of Gd-IgA1 immune complexes in the kidneys, kidney damage following the deposition of Gd-IgA1 immune complexes, the role of complement in IgAN, the genomics of IgAN, and mucosal immunity in IgAN, providing clues and insights for further research and clinical treatment.

Progress of interventional researches on peritoneal function protection
Zhang Mengqin, Yang Zhikai, Dong Jie
2024, 40 (3): 231-236. https://doi.org/10.3760/cma.j.cn441217-20230529-00534
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With the prolongation of peritoneal dialysis time, the peritoneum probably confronts structural and functional deterioration due to multiple factors, which will affect the efficiency of peritoneal dialysis. Clinically effective measures to protect peritoneal function are still lacking. This article reviewed studies in the last decade on protection of peritoneal function, which included strategies on dialysis prescription, medicine treatments for protection of peritoneal function, and non-medicine treatments such as far-infrared therapy and stem cell transplantation, to provide guidances for subsequent researches.

Interpretation for "sepsis associated acute kidney injury: consensus report of the 28th Acute Disease Quality Initiative Workgroup"
Liu Caihong, Koyner Jay, Zhao Yuliang, Fu Ping
2024, 40 (3): 237-244. https://doi.org/10.3760/cma.j.cn441217-20231102-01101
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Sepsis-associated acute kidney injury (SA-AKI) is defined as the presence of acute kidney injury (AKI) in the context of sepsis. In the setting of genetic susceptibility, sepsis can lead to SA-AKI through various mechanisms. Based on differences in pathophysiological mechanisms, SA-AKI is categorized into different "endotypes" and manifests as distinct "subtypes". The combination of biomarkers and predictive models has the potential to early identify high-risk AKI patients and elucidate SA-AKI "endotypes". Volume resuscitation and blood purification are optimized strategies for SA-AKI treatment. Furthermore, clinical research on SA-AKI in children is promising.

Standard for the management of hyperkalemiawhole-process management mode of multi- department cooperation
Ye Zhiming, Cai Jianfang, Chen Wei, Cheng Hong, He Qiang, Li Rongshan, Li Xiangmin, Liao Xinxue, Mao Zhiguo, Mao Huijuan, Tan Ning, Xu Gang, Zhan Hong, Zhang Hao, Zhang Jian, Yu Xueqing
2024, 40 (3): 245-254. https://doi.org/10.3760/cma.j.cn441217-20231110-01109
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Hyperkalemia is one of the common ion metabolism disorders in clinical practice. Hyperkalemia is defined as serum potassium higher than 5.0 mmol/L according to the guidelines at home and abroad. Acute severe hyperkalemia can cause serious consequences, such as flaccid paralysis, fatal arrhythmia, and even cardiac arrest. The use of renin-angiotensin- aldosterone system inhibitors, β-blockers and diuretics, low-sodium and high-potassium diets, and the presence of related comorbidities increase the occurrence of hyperkalemia. Hyperkalemia risk exist in all clinical departments, but there is a lack of a standardization in the management of multi- department cooperation in hospital. Therefore, a number of domestic nephrology and cardiology department experts have discussed a management model for multi-department cooperation in hyperkalemia, formulating the management standard on hospital evaluation, early warning, diagnosis and treatment, and process. This can promote each department to more effectively participate in nosocomial hyperkalemia diagnosis and treatment, as well as the long-term management of chronic hyperkalemia, improving the quality of hyperkalemia management in hospital.

Efficacy and safety of sacubitril⁃valsartan in lowering blood pressure in non-dialysis-dependent patients with stage 3-5 chronic kidney disease
Yan Yu, Liu Yuqiu, Li Xiaomin, Zheng Jing, Cao Jingyuan, Yin Qing, Zhang Xiaoliang, Liu Bicheng, Wang Bin
2024, 40 (4): 255-260. https://doi.org/10.3760/cma.j.cn441217-20230822-00830
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Objective To evaluate the efficacy and safety of sacubitril?valsartan (SV) in reducing blood pressure in patients with non-dialysis-dependent chronic kidney disease(NDD-CKD) stage 3-5 and concomitant hypertension. Methods It was a retrospective study. Adult NDD-CKD stage 3-5 patients with hypertension treated with SV alone or in combination with SV on the basis of 2 to 4 antihypertensive drugs having unsatisfactory effects from March 1, 2022 to June 30, 2023 in Zhongda Hospital Affiliated to Southeast University were included. SV doses ranged from 25 mg once daily to 200 mg twice daily. The primary outcome was blood pressure control. The changes of blood pressure and laboratory examination indexes between baseline and 1 to 2 months after SV treatment were compared, and adverse events were also recorded. Results A total of 37 NDD-CKD stages 3-5 patients with hypertension were included in the study, with age ranging from 29 to 85 years old, and 15 males (40.5%). The SV duration of medication was 1 (1, 1) month. At the study endpoint, there was a significant decrease in mean systolic blood pressure, diastolic blood pressure, and pulse pressure from baseline, with reduction of 20.4 (9.6, 28.8) mmHg (1 mmHg=0.133 kPa, Z=-5.243, P<0.001), (6.9±7.6) mmHg (t=5.532, P<0.001), and 13.0 (8.0, 18.8) mmHg (Z=-4.941, P<0.001), respectively. During the study period, 8 patients (21.6%) experienced worsening of renal function, and there were no statistically significant differences in the changes of serum creatinine and estimated glomerular filtration rate before and after treatment (Z=-0.487, P=0.626; Z=-0.110, P=0.912, respectively). No adverse drug reactions such as hyperkalemia, symptomatic hypotension, angioedema, hepatic impairment, and decreased hemoglobin level were observed during the study period. Conclusion SV effectively lowers blood pressure in NDD-CKD stage 3-5 patients with hypertension and exhibits good safety.

Epidemiological status and prognostic analysis of hyperphosphatemia in non-dialysis chronic kidney disease patients in China
Su Licong, Gao Qi, Zhou Shiyu, Pang Mingzhen, Nie Sheng
2024, 40 (4): 261-269. https://doi.org/10.3760/cma.j.cn441217-20230926-00934
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Objective To elucidate the prevalence of hyperphosphatemia and utilization rate of phosphorus-lowering drugs in adult non-dialysis chronic kidney disease (CKD) patients in China, and explore the relationship between hyperphosphatemia, phosphate-lowering therapy, and clinical outcomes. Methods It was a large retrospective and multicenter cohort study. The study subjects were sourced from the China Renal Data System. The first-time hospitalized patients aged 18 years old and above and diagnosed with CKD who did not enter dialysis and having serum phosphorus test results from 2013 to 2020 were included. Hyperphosphatemia was defined as an initial serum phosphorus level exceeding 1.45 mmol/L during hospitalization, and normal serum phosphorus was defined as 0.97 mmol/L ≤ serum phosphorus ≤ 1.45 mmol/L. Cox regression model was employed to assess the association of hyperphosphatemia with all-cause mortality, cardiovascular mortality, and CKD progression as well as the association of phosphorus-lowering therapy with all-cause mortality and cardiovascular mortality. Results A total of 157 987 adult non-dialysis CKD patients with serum phosphorus test results were included in the study, with age of 60 (47, 72) years old and 91 453 males (57.89%). The estimated glomerular filtration rate was 63.49 (39.12, 92.90) ml·min-1·(1.73 m2)-1. The common comorbidities included hyperlipidemia (53.48%, 84 497/157 987), hypertension (37.23%, 58 818/157 987) and heart failure (27.02%, 42 686/157 987). The prevalence of hyperphosphatemia was 14.83% (23 431/157 987). Among CKD stage 3-5 patients with hyperphosphatemia, the utilization rate of phosphate-lowering medications was 13.34% (3 962/29 705). Multivariate Cox regression analysis showed that among 64 662 patients with ≥ 90 days of follow-up [3.3 (1.5, 5.4) years], hyperphosphatemia was significantly correlated with an increased risk of all-cause mortality and cardiovascular mortality (hyperphosphatemia/normal serum phosphorus, HR=1.13, 95% CI 1.06-1.22, P=0.001; HR=1.28, 95% CI 1.04-1.56, P=0.018, respectively). Among 47 581 patients with ≥ 90 days of follow-up [1.8 (0.9, 3.2) years] and baseline estimated glomerular filtration rate > 30 ml · min-1 ·(1.73 m2)-1, hyperphosphatemia was significantly correlated with an increased risk of CKD progression (hyperphosphatemia/normal serum phosphorus, HR=1.08, 95% CI 1.00-1.17, P=0.038). Among 8 856 patients with follow-up data of death [3.3 (1.5, 5.4) years] and hyperphosphatemia,phosphate-lowering medication use was significantly correlated with a reduced risk of all-cause mortality (HR=0.88, 95% CI 0.82-0.95, P<0.001) and cardiovascular mortality (HR=0.84, 95% CI 0.72-0.97, P=0.022). Conclusions The prevalence of hyperphosphatemia is high among Chinese adult non-dialysis CKD patients, but the utilization rate of phosphate-lowering medications remains low. Hyperphosphatemia is an independent risk factor of all-cause mortality, cardiovascular mortality, and kidney function progression, while phosphate-lowering medications may mitigate these risks in non-dialysis CKD patients. Regular monitoring of serum phosphorus level for non-dialysis CKD patients, and initiating phosphate-lowering therapy for hyperphosphatemia patients may positively improve clinical outcomes.

Clinicopathological significance of extraglomerular complement C1q deposition in lupus nephritis patients
Yang Xiaoqing, Huang Yanjie, Yang Yueli, Bi Liangliang, Zhang Qiushuang, Ding Ying, Ren Xianqing, Zhai Wensheng
2024, 40 (4): 270-276. https://doi.org/10.3760/cma.j.cn441217-20230811-00817
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Objective To investigate the extraglomerular deposition of C1q in patients with lupus nephritis (LN) and explore its clinicopathological significance, and to provide immunological evidence for the mechanism of renal tubulointerstitial injury in LN. Methods It was a cross-sectional study. The clinical data of patients with LN confirmed by renal biopsy in the First Affiliated Hospital of Henan University of Chinese Medicine from March 1, 2019 to June 30, 2023 were collected. Extraglomerular deposition of C1q, including tubular basement membranes (TBMs), peritubular capillaries and interstitial arterioles, was detected by direct immunofluorescence method in paraffin sections, and the relationship between C1q expression and corresponding tissue lesions was analyzed in successive sections. Pearson correlation coefficient or Spearman correlation coefficient was used to analyze the correlation between C1q expression level and renal histopathologic scores (active tubular interstitial index, active glomerular index, active index, chronic tubular interstitial index, chronic glomerular index, chronic index), clinical indexes(24-hour urinary protein, urinary alpha-1 microglobulin, urinary N-acetyl-β?D?glucosidase and serum creatinine). Results A total of 71 patients with LN were included in the study, including 14 males (19.72%) and 57 females (80.28%), with age of (20.83±11.77) years old (7-48 years old). The paraffin sections analysis showed that 60 patients (84.51%) had extraglomerular deposits of C1q. C1q deposits occurred in the TBMs and/or peritubular capillaries and/or interstitial arterioles, with the highest positive rate (50 patients, 70.42%) in TBMs. Forty-four patients (61.97%) had scattered or focal C1q deposition in the TBMs. Thirty-two patients (45.07%) had scattered or focal C1q deposition in peritubular capillaries. The positive proportion of C1q in TBMs was the highest in type Ⅳ of LN (15/18). The positive proportion of C1q in peritubular capillaries was the highest in type Ⅱ of LN (5/6). The continuous sections of kidney tissues showed that C1q was mainly expressed in the acute tubulointerstitial inflammation area, and no positive expression was found in the tubule atrophy area. The correlation analysis showed that C1q deposition level in TBMs was positively correlated with active tubular interstitial index (r=0.640, P<0.001), urinary alpha-1 microglobulin (r=0.573, P<0.001), urinary N?acetyl-β?D?glucosaminidase (r=0.404, P=0.008) and serum creatinine (r=0.399, P=0.001). There was no correlation between the positive percentage of C1q in peritubular capillaries and 24 h urinary protein, urinary alpha-1 microglobulin, urinary N-acetyl-β?D?glucosidase, serum creatinine and renal histological scores. Conclusion C1q deposition in TBMs may be one of the causes of tubulointerstitium injury, it is recommended to be marked in the routine renal pathological diagnosis.

Clinical features and genotypes of 20 patients with nephronophthisisassociated with NPHP1 gene defect
Lai Jiayong, Sun Liangzhong, Liu Yaqing, Lin Hongrong, Yue Zhihui, Wang Haiyan, Li Min, Cai Yong, Ai Jun, Wei Haixia
2024, 40 (4): 277-288. https://doi.org/10.3760/cma.j.cn441217-20230516-00518
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Objective To explore the clinical features and genotypes of patients with nephronophthisis type 1 (NPH1) associated with NPHP1 gene defect. Methods It was a case series analysis. Clinical data and blood samples of patients who were suspected of NPH1 were collected retrospectively. Next generation sequencing (NGS) or microsatellite markers (MMS) were used to detect the variations and homozygous deletion of NPHP1. Results (1) In this study, a total of 20 patients from 16 families were diagnosed as NPH1 with NPHP1 variations and/or homozygous deletions. The median onset age of the patients was 9.5 years old (ranging from 3.0 to 21 years old), and the mean time from onset to diagnosis was 2.1 years (ranging from 0.1 to 6.5 years). The clinical manifestations of the first diagnosis were renal insufficiency in 7 cases (35.0%), polydipsia, polyuria or nocturia in 8 cases (40.0%), anemia in 4 cases (20.0%), and growth retardation in 7 cases (35.0%), of which 1 case was first diagnosed with growth retardation and thoracic malformation. In terms of renal manifestations, 10 patients (50.0%) exhibited negative urinary protein by urine routine test, while 10 patients (50.0%) presented with a small amount of proteinuria. Notably, none of the patients displayed hematuria. At first diagnosis, 18 patients (90.0%) exhibited varying degrees of renal impairment, and the median age of progression to stage 5 chronic kidney disease was 12 years (ranging from 9.1 to 16.5 years). Of the 17 patients who underwent urine protein composition analysis, 15 had elevated α1 microglobulin and β2 microglobulin, including 6 patients with negative urine routine test. The volume of the kidney was normal in 11 patients (55.0%) and decreased in 9 patients (45.0%), including 7 patients with both kidneys affected and 2 patients with a single kidney affected. B-ultrasonography and magnetic resonance hydrography showed that 12 patients (60.0%) presented with single or multiple renal cysts located at the cortical medullary junction and/or renal medulla, and 8 patients (40.0%) had no cyst. Renal biopsy performed on 9 patients consistently revealed tubular atrophy and lumen dilation, tubular basement membrane thickening or stratification, interstitial fibrosis and inflammatory cell infiltration. A total of 5 cases exhibited extrarenal manifestations, including Senior-Loken syndrome, amblyopia or ametropia, Cogan syndrome, liver cyst, etc. Among the 20 confirmed patients from 16 families, homozygous deletion of NPHP1 exon (exon 1-20) occurred in 10 patients from 8 families, heterozygous deletion accompanied by point mutation occurred in 7 patients from 5 families, and complex heterozygous point mutation occurred in 3 patients from 3 families. No statistically significant differences were found in clinical phenotypes (gender, kidney volume, cyst formation, urinary protein) among patients with different mutation types (all P>0.05). Of the 16 patients who underwent NGS (targeted exome sequencing and whole exome sequencing), 8 had pathogenic gene variants related to other ciliopathies. When compared to the 8 patients without other ciliopathy-related pathogenic gene variants, no significant differences were found in gender, age of onset, disease duration before treatment, kidney phenotype (including kidney size, cyst formation, urinary protein), and age of progression to stage 5 chronic kidney disease (all P>0.05). (2) In addition, 4 patients from 4 other families were found to have only a single heterozygous mutation in NPHP1, and lacked any other genetic variants that could explain cystic nephropathy and/or ciliopathy. Based on clinical findings, these patients were diagnosed as NPH. (3) Totally, 12 point mutations were found in this study, of which 8 novel point mutations (c.728+1G>A, c.1630delA, c.1122+1G>T, c.2081A>G, c.1333C>G, c.625-2A>T, c.1374G>T, c.968C>T) were identified. Conclusions The genotype of NPHP1 in this series of patients is significantly different from those reported abroad, with a higher proportion of novel mutation and greater genetic background diversity. There is no significant difference in clinical manifestation among patients with different genotypes.

Joint analysis of renal transcriptomics and proteomics in calcium oxalate crystal kidney injury mice
Sun Xiaoyi, Li Shan, Peng Yingchao, Gao Chunlin, Xia Zhengkun
2024, 40 (4): 289-299. https://doi.org/10.3760/cma.j.cn441217-20230824-00838
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Objective To understand the dynamic changes of genes and proteins in renal tissues of calcium oxalate crystal kidney injury, and to explore the possible mechanism of calcium oxalate crystal kidney injury. Methods Ten 8-week-old male C57BL/6J mice were adaptively fed for 1 week and divided into control group and calcium oxalate crystal kidney injury group (model group) according to random number table method. The calcium oxalate crystal kidney injury mice were established by intraperitoneal injection of glyoxylate (50%, 9 mmol/L, 100 mg·kg-1·d-1 for 5 days). Mice in control group were intraperitoneally injected with 0.9% sodium chloride solution of equal volume. HE staining, PAS staining, Masson staining, and Von Kossa staining were used to observe whether the model mice were successfully constructed. Transcriptome and proteome sequencing were performed on the kidneys of control mice and model mice. Genes and proteins related to calcium oxalate crystal kidney injury were screened according to the results of differential expressed genes (DEGs) and differential abundance proteins (DAPs), and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed based on the above results. Principal component analysis, heat map and volcano map were used to perform the transcriptomic and proteomic analysis of renal tissues. Venn diagram was used to analyze the overlap of differential genes and differential proteins. Results Von Kossa staining of the kidney showed a large amount of calcium salt deposition at the cuticer-pulp junction, and serum creatinine, blood urea nitrogen and other markers of kidney injury significantly increased in the model group, suggesting that calcium oxalate crystal kidney injury model was established successfully. Transcriptome and proteome sequencing showed that, compared with control group, 2 815 DEGs and 1 197 DAPs were obtained in the model group, respectively; 2 004 DEGs and 353 DAPs were significantly up-regulated; 811 DEGs and 844 DAPs were significantly down-regulated in the model group. A total of 338 DEGs corresponded with DAPs, 324 of which had the same trend with DAPs. The significantly different 10 molecules included serum amyloid A1 (SAA1), minichromosome maintenance 4 (MCM4), arginase 2 (ARG2), S100 calcium-binding protein A6 (S100A6), cluster of differentiation 14 (CD14), glucose-6-phosphatase catalytic subunit (G6PC), solute carrier family 22 member 6 (SLC22A6), solute carrier organic anion transporter family member 1A1 (SLCO1A1), phosphoenolpyruvate carboxykinase 1 (PEPCK1) and indolamine N-methyltransferase (INMT) in the up-regulated and down-regulated differential genes and proteins. GO analysis indicated that the commonly enriched pathways in the two groups of correlated differential molecules were primarily involved in mitochondrial dysfunction, energy metabolism pathways and immune disorder. KEGG enrichment analysis showed that the differentially expressed molecules were mainly enriched in transporter anomaly, mitochondrial dysfunction, neurodegenerative diseases, amino acid metabolism and abnormal energy metabolism pathways such as oxidative phosphorylation. Conclusions Abundant genes and proteins changes in kidneys of calcium oxalate crystal kidney injury mice. Mitochondrial dysfunction, multiple metabolic pathways abnormalities, and immune response may be important mechanisms involved in the pathogenesis of calcium oxalate crystal kidney injury.

Comparison of positive rate of peritoneal dialysis-associated peritonitis pathogens cultured by traditional method and modified method and analysis of drug resistance
Chen Chunmiao, Xu Zhihui, Wang Feifei, Yun Xiaoying, Li Bing
2024, 40 (4): 300-304. https://doi.org/10.3760/cma.j.cn441217-20230809-00809
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It was a retrospective cohort study. Peritoneal dialysis exudate samples from patients diagnosed with peritoneal dialysis-associated peritonitis (PDAP) in the Nephrology Department of the Second Affiliated Hospital of Hainan Medical College from January 1, 2021 to December 31, 2022 were collected. Based on different time of peritonitis, the specimens were split into two groups: the traditional method group and the modified method group. Only the traditional method was used for pathogen culture in the traditional method group. Both the traditional method and modified method were used for pathogen culture in the modified method group. The rates of positive culture of pathogenic bacteria, duration required to obtain positive culture results, spectrum of pathogenic bacteria, and drug resistance were analyzed. The results showed that a total of 223 patients (324 cases) with PDAP were included in the study, including 115 patients (168 cases) in the traditional method group and 108 patients (156 cases) in the modified method group. The modified method group displayed a significantly higher rate of pathogenic bacteria than the traditional method group [84.62% (132/156) vs. 69.23% (108/156), χ2 =18.903, P<0.001]. Additionally, the modified method group required less time to achieve a positive culture result of pathogenic bacteria than the traditional method group [69.0 (58.0, 90.9) h vs. 79.5 (65.6, 90.2) h, Z=2.061, P=0.039]. In this study, 120 culture-positive pathogens were identified in the traditional method group, of which, 69 (57.50%) were Gram-positive, 46 (38.33%) were Gram-negative, and 5 (4.17%) were fungi; The common strains of Gram-positive bacteria were staphylococcus epidermidis (17 strains, 14.17%) and streptococcus salivarius (10 strains, 8.33%). There were 134 culture-positive pathogens identified in the modified method group, of which 106 (79.10%) were Gram?positive, 24 (17.91%) were Gram?negative, and 4 (2.99%) were fungi; The common strains of Gram-positive bacteria were streptococcus salivarius (20 strains, 14.93%) and staphylococcus epidermidis (15 strains, 11.19%). Gram-positive bacteria had the highest resistance rate to oxacillin (50/85, 58.82%), Gram-negative bacteria had the highest resistance rate to ampicillin (21/35, 60.00%), and fungi was only resistant to fluconazole (1/9, 11.11%). The study suggests that the modified method can increase the positive rate of pathogen culture and shorten the culture time in peritoneal dialysate effluent. Gram?positive cocci are the main pathogenic bacteria of PDAP in this center. Oxacillin and ampicillin should not be the first choice for the treatment of PDAP in this center.