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    Clinical Study

  • Dai Rufeng, Shen Qian, Yin Lei, Kang Yulin, Li Yufeng, Chen Jing, Zeng Mei, Xu Hong, Nephrology Group of Pediatric Branch of Shanghai Medical Association
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    Objective To investigate the clinical characteristics and short-term follow-up outcomes of primary nephrotic syndrome (PNS) children infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the Omicron variant outbreak in Shanghai, and to provide a reliable reference for clinicians in the diagnosis and treatment. Methods It was a case-control study. The clinical data of children with PNS (PNS group) who were diagnosed and followed-up up to 1 year in the nephrology department of four children's medical centers in Shanghai, and the children (control group) who had no underlying diseases and were infected with SARS-CoV-2 in Shanghai Jinshan Public Health Center, including the data when they were infected with SARS-CoV-2, were retrospectively analyzed. Results (1) From March 30th to April 13th, 2022, 6 PNS children in Shanghai were infected with SARS-CoV-2, including 5 boys and 1 girl. The median age was 4.5 (2.0, 11.0) years old. And 30 children were matched by sex, age and disease type as control group, including 20 males and 10 females. The median age was 4.5 (2.0, 9.0) years. There were no significant differences between the PNS group and the control group in clinical symptoms (including fever duration), treatment regimens, vaccine doses and virus clearance time (all P>0.05). (2) The 6 children with PNS included 3 cases of steroid-sensitive type, 3 cases of steroid-resistant type, 2 cases of minimal change disease, 2 cases of focal segmental glomerulosclerosis and 2 cases with no renal biopsy. Before SARS-CoV-2 infection, their primary disease-PNS were stable, and urine protein was negative, four of them were under maintenance treatment with oral steroids or immunosuppressive drugs. At the time of SARS-CoV-2 infection, the symptoms of all of the 6 cases were mild, no severe, critical or fatal cases, and they were all cured and discharged from hospital through medical isolation observation or symptomatic treatment of infections. (3) Five cases of them still had discomfort symptoms such as cough, anorexia, and fatigue after being discharged from the hospital, which lasted for about 1 week. Within 1 year of follow-up, none of the children have suffered from "recurrent positive PCR results" or "secondary infection" of the SARS-CoV-2. (4) Among them, 4 cases of PNS relapsed after SARS-CoV-2 infection, timely addition of steroids was effective, their urine protein quickly turned negative, and there was no recurrence after 1 year of follow-up. (5) Before infection with SARS-CoV-2, the levels of immunoglobulin IgG were lower than the normal reference value in the 4 cases with PNS recurrence. Conclusions During the Omicron variant outbreak in Shanghai, the infection of SARS-CoV-2 in children with PNS are resulted in high transmission among household contacts. Most of them have mild symptoms and good prognosis. PNS is prone to relapse after SARS-CoV-2 infection, and steroid therapy is effective and safe for these relapse. IgG may be a potential marker for the prognosis of PNS children infected with SARS-CoV-2.

  • Zhao Sanlong, Wu Hongmei, Zhao Fei, Han Yuan, Zhu Chunhua, Cheng Xueqin, Chen Qiuxia, Huang Songming
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    Objective To analyze the clinical and pathological features of adolescent- onset primary nephrotic syndrome (PNS) in children (10 years≤age≤18 years), so as to explore the renal biopsy indications in adolescent-onset PNS. Methods It was a single-center retrospective observational study. The clinical and pathological data of adolescent-onset PNS (age≥10 years) who underwent renal biopsy in Children's Hospital Affiliated to Nanjing Medical University from December 2004 to June 2022 were analyzed retrospectively. Results A total of 110 children were included in the study, including 76 males (69.1%) and 34 females (30.9%), with the onset age ranging from 10 years to 14 years and 9 months. Forty-nine cases (44.5%) were accompanied by hematuria, including 14 cases (12.7%) of gross hematuria and 35 cases (31.8%) of microscopic hematuria. Twenty-five cases (22.7%) had hypertension, 19 cases (17.3%) had renal insufficiency, and 4 cases (3.6%) had low complement C3 at the onset. Fifty-two cases (47.3%) were steroid sensitive nephrotic syndrome and 58 cases (52.7%) were steroid resistant nephrotic syndrome. Biopsy results showed that minimal change disease(MCD) was the most common histopathological subtype (47.3%, 52 case), followed by focal segmental glomerulosclerosis (FSGS) in 22 cases (20.0%), IgA nephropathy (IgAN) in 17 cases (15.5%), membranous nephropathy (MN) in 7 cases (6.4%), mesangial proliferative glomerulonephritis in 5 cases (4.5%), IgM nephropathy in 4 cases (3.6%), membranous proliferative glomerulonephritis in 2 cases (1.8%), and C1q nephropathy in 1 case (0.9%). Among 44 children with simple type nephrotic syndrome, the pathological type was mainly MCD (77.3%), and 66 children with nephritic type nephrotic syndrome were mostly non-MCD (72.7%), such as IgAN, FSGS, MN, etc. If there are two or more clinical manifestations of persistent hematuria, hypertension, renal insufficiency or low C3 levels, the proportion of non-MCD would further increase to 92.0%(23/25). The pathological type of patient with gross hematuria or low C3-emia was non-MCD. The frequency of hematuria (69.0% vs. 17.3%, χ2=29.619, P<0.001), hypertension (31.0% vs. 13.5%, χ2=4.821, P=0.028) and renal insufficiency (24.1% vs. 9.6%, χ2=4.047, P=0.044) in non-MCD group was significantly higher than those in MCD group. Conclusions If the clinical manifestation of PNS in adolescent over 10 years old is simple type nephrotic syndrome, the histopathological lesion is mostly MCD, and most of them are steroid sensitive. It is recommended to give hormone treatment first, and then perform renal biopsy if steroid resistance occurs; If the clinical manifestation is nephritic type nephrotic syndrome, the histopathological lesion is mostly non-MCD, especially those with gross hematuria or low C3-emia, or those have two or more clinical manifestations of persistent hematuria, hypertension, renal insufficiency and hypocomplement C3-emia, a kidney biopsy should be performed at onset.

  • Zhao Bin, Wang Hui, Wang Yuzhu, Zhang Lihong, Zhan Shen
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    Objective To analyze the efficacy of balloon-assisted autologous arteriovenous fistula (AVF) maturation and its effect on patency. Methods It was a single-center prospective cohort study. The patients who underwent balloon-assisted maturation (BAM) due to poor AVF maturation in Haidian Hospital, the Third Hospital of Peking University from November 2020 to May 2021 were enrolled. The clinical data and relevant data before and after BAM were collected, and then the immediate success rate and primary patency rate at 6 and 12 months after BAM were analyzed. Cox regression analysis method was used to identify the risk factors of restenosis of AVF patency after BAM. Results A total of 96 patients treated with BAM due to poor AVF maturation were enrolled, with age of (56.98±13.20) years old, 54 males (56.25%) and 42 females (43.75%). The technical success rate of BAM was 100% (96/96), the clinical success rate of BAM was 96.88% (93/96), and there was no related serious complication. The primary patency rates were 83.33% (80/96) and 59.38% (57/96) at 6 and 12 months, respectively. The internal diameter of anastomotic vein (t=-19.257, P<0.001), internal diameter of anastomotic artery (t=-9.131, P<0.001), internal diameter of brachial artery (t=-5.445, P<0.001) and brachial artery blood flow (t=-22.739, P<0.001) after BAM were higher than those before BAM. Univariate Cox regression analysis results showed that stenosis number, stenosis length ≤2 cm, high-pressure balloons, local anaesthetic were all correlated with restenosis of AVF after BAM (all P<0.05). Multivariate Cox regression analysis results showed that stenosis length ≤2 cm was an independent related factor of restenosis of AVF after BAM at 6 months (HR=0.022, 95% CI 0.006-0.075, P<0.001) and at 12 months (HR=0.027, 95% CI 0.009-0.082, P<0.001). Conclusions BAM is safe and effective for AVF maturation, and has a high success rate and reliable patency. Preoperative stenosis length >2 cm is an independent risk factor of AVF restenosis after BAM.

  • Lian Qinglou, Liu Yamin, Li Yubao, Wang Yufei, Zhang Beihao, Wang Xinfang, Zhao Peixiang, Wang Ruimin, Liang Xianhui, Wang Pei
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    Objective To study the incidence and risk factors of central vein stenosis (CVS) in chronic kidney disease (CKD) patients who received arteriovenous fistula (AVF) creation for the first time, as well as effects of CVS on patency of ipsilateral AVF. Methods It was a retrospective study. The CKD patients who received AVF creation for the first time in the First Affiliated Hospital of Zhengzhou University from January 2019 to August 2020, with central vein digital subtraction angiography (DSA) results prior to angioplasty were selected as the study subjects. The differences of incidence of CVS in CKD patients with/without a history of cervical catheterization and primary patency rates of AVF between CVS and non-CVS groups were compared. Logistic regression analysis method was applied to analyze the influencing factors of CVS in CKD patients. Kaplan-Meier method was used to analyze the primary patency rate of AVF. Cox regression analysis method was used to analyze the effect of CVS on the primary patency of ipsilateral AVF. Results A total of 283 CKD patients aged (50.45±14.76) years were enrolled in the study, including 165 males (58.3%). The dialysis age was 0.5 (0, 7.0) months. There were 55 patients (19.4%) diagnosed with CVS before AVF, including 39 patients with stenosis <50% and 16 patients with stenosis ≥50%. The incidence of CVS in patients with history of right internal jugular vein central venous catheter insertion was significantly higher than that in those without this history [60.5% (26/43) vs. 9.9% (15/151), χ2=51.274, P<0.001]. Multivariate logistic regression analysis results showed that hemodialysis catheters indwelling time ≥3 months elevated the risk of CVS (OR=4.345, 95% CI 1.540-12.263, P=0.006). A subset of 268 patients who had AVF creation ipsilateral to CVS were analyzed to determine the effects of CVS on patency of AVF. The median follow-up time was 34 months. The primary patency rate of AVF in the moderate to severe CVS group was significantly lower than that in the non-CVS group (5/7 vs. 58/228, χ2=7.720, P=0.005). The primary patency rates of AVF in the subclavian vein stenosis group and superior vena cava stenosis group were significantly lower than those in the brachiocephalic vein stenosis group (4/5 vs. 8/27, χ2 =6.974, P=0.008; 6/8 vs. 8/27, χ2 =6.908, P=0.009, respectively). Moderate to severe CVS and combined diabetes were independent influencing factors of primary patency of AVF (HR=4.362, 95% CI 1.644-11.574, P=0.003; HR=2.682, 95% CI 1.624-4.431, P<0.001, respectively). Conclusions The incidence of CVS is higher in CKD patients who establish an arteriovenous fistula for the first time. Hemodialysis catheter indwelling time ≥3 months is an independent risk factor of CVS. The moderate to severe CVS is an independent risk factor of primary patency of AVF.

  • Fu Zixuan, Wang Huifang, Jiang Chunhui, Li Min, Yu Yahuan, Liu Xuemei
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    Objective To investigate the correlation between serum anti-phospholipase A2 receptor antibody (SAb) combined with glomerular complement C3 (GC3) deposition and clinicopathologic features and prognosis in patients with idiopathic membranous nephropathy (IMN). Methods It was a retrospective cohort study. The patients diagnosed with IMN in Affiliated Hospital of Qingdao University from July 1, 2019 to April 30, 2022 were enrolled, and the clinical and pathological data were collected and analyzed. The patients were divided into negative SAb and negative GC3 (SAb-/GC3-) group, negative SAb and positive GC3 (SAb-/GC3+) group, positive SAb and negative GC3 (SAb+/GC3-) group and positive SAb and positive GC3 (SAb+/GC3+) group according to the status of SAb titer and GC3 deposition. Clinical and pathological characteristics among the groups were compared. Kaplan-Meier survival curve was used to compare the cumulative renal remission rates of different groups. Cox regression analysis model was used to analyze the related factors of renal remission. Results A total of 143 IMN patients aged (53.35±12.34) years old were included in the study, including 94 males (65.7%). There were 17 patients (11.9%) in the SAb-/GC3- group, 30 patients (21.0%) in the SAb-/GC3+ group, 19 patients (13.3%) in the SAb+/GC3- group, and 77 patients (53.8%) in the SAb+/GC3+ group. Compared with SAb-/GC3- group, the level of serum albumin was lower in the SAb+/GC3+ group, and the level of 24 h urine protein, SAb titer, and the proportions of glomerular anti-phospholipase A2 receptor antigen and renal tubule atrophy were higher in the SAb+/GC3+ group (all P<0.05). After 26.0 (19.0, 36.0) months of follow-up, a total of 96 patients (67.1%) attained remission. The proportion of patients receiving immunosuppressive therapy in the SAb+/GC3+ group was higher than that in the SAb-/GC3- group [93.5% (72/77) vs. 70.6% (12/17), fisher value=8.974, P=0.016] and the proportion of renal remission rate in the SAb+/GC3+ group was lower than that in the SAb-/GC3- group [49.4% (38/77) vs. 100% (17/17), χ2=25.438, P<0.001]. Kaplan-Meier survival curve result showed that the cumulative renal remission rate in the SAb+/GC3+ group was significantly lower than that in the SAb-/GC3- group (Log-rank χ2=31.538, P<0.01). Multivariate Cox regression analysis result showed that 24 h urine protein level (HR=0.891, 95% CI 0.803-0.988, P=0.029), SAb titer (HR=0.996, 95% CI 0.992-1.000, P=0.042) and SAb+/GC3+ (with SAb-/GC3- group as reference, HR=0.414, 95% CI 0.204-0.827, P=0.013) were independent related factors for renal remission in patients with IMN. Conclusions IMN patients with positive SAb and GC3 deposition have more severe clinical and pathological changes, lower renal cumulative remission rates, and are more likely to have poor prognosis. The combined assessment of SAb and GC3 deposition may be helpful for evaluating prognosis and guiding treatment in IMN patients.

  • Basic Study

  • Wang Lulu, Tian Han, Yang Junwei, Jiang Lei
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    Objective To investigate the changes of podocyte circadian rhythm in the high-glucose environment and diabetic nephropathy (DN) mouse model and the protective effect of melatonin on podocyte injury in DN. Methods Primary podocytes were cultured in vitro and divided into 3 groups: control group, high glucose (30 mmol/L) group and high glucose (30 mmol/L) treated with melatonin (0.1 mmol/L or 0.5 mmol/L) group. The podocytes were collected every 4 hours for 24 hours, synchronized with dexamethasone (100 nmol/L) for 2 hours, which was recorded as zeitgeber time 0 point. Male C57BL/6J mice aged 6-8 weeks and weighing about 20 g were randomly (randomized block) assigned to three groups: control group, DN (high-fat diet+streptozotocin 120 mg/kg intravenously injected) group, and DN (high-fat diet+streptozotocin 120 mg/kg intravenously) treated with melatonin (20 mg/kg intragastric treatment) group (melatonin group). Real-time quantitative PCR was used to detect the mRNA levels of rhythm genes in podocytes. Western blotting was used to detect the protein expression levels of circadian clock genes (Clock and Bmal1), podocyte marker proteins (Nephrin, Synaptopodin, WT1, and Desmin) and autophagy-related proteins (Beclin1, LC3Ⅱ/Ⅰ and P62). Immunofluorescence staining was used to detect the protein expression level of WT1, and immunohistochemistry was used to analyze the protein expression levels of P62 and cleaved-caspase-3 in renal tissues of mice. The pathological changes of renal glomerulus were observed under electron microscope. Results (1) Dexamethasone reseted the expression and rhythmic oscillation of circadian clock genes in podocytes. The circadian rhythmic oscillations of Clock and Ck1e mRNA in the high glucose group were flattened compared to the control group, and the circadian rhythmic oscillations in Clock and Ck1e mRNA expression were partial recovery in high glucose treated with melatonin group (all P<0.05). (2) Compared with the control group, the protein expression levels of Nephrin, Synaptopodin and WT1 were lower while Desmin was higher in the high glucose group (all P<0.05). The protein expression levels of Nephrin, Synaptopodin and WT1 were higher and the protein expression level of Desmin was lower in the high glucose treated with melatonin (0.5 mmol/L) group compared with the high glucose group (all P<0.05). (3) The invivo experimental results showed that compared with the DN group, melatonin group had higher protein expression levels of glomerular Nephrin and WT1, and lower urinary albumin/creatinine ratio, width of foot process and thickness of glomerular basement membrane (all P<0.05). The protein expression levels of Beclin1 and LC3Ⅱ/Ⅰ in the DN group were lower than those in the control group, and the protein expression level of P62 was higher than that in the control group (all P<0.05). Compared with the DN group, the protein expression levels of Beclin1 and LC3Ⅱ/Ⅰ in the melatonin group were significantly higher, and the protein expression level of P62 was lower (all P<0.05). Conclusions Melatonin can partially restore the circadian rhythm of clock genes in high-glucose environment, improve autophagy and alleviate injury in podocytes.

  • Short Original Article

  • Lin Xin, Xie Ying, Jiang Licheng, Dong Rong, Yu Jiali, Yuan Jing, Zha Yan
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    The study explored the effect of acteoside on renal fibrosis in rats with unilateral ureteral obstruction. Twenty-four healthy adult male SD rats were randomly divided into sham (CON) group, unilateral ureteral obstruction (UUO) group, UUO+acteoside (ACT) group, UUO+benazepril (BZ) group by random number table method. The animal model of renal fibrosis was established by unilateral ureteral ligation. The pathological changes of renal tissues in each group of rats were observed by HE staining and Masson staining. Immunohistochemical method was used to detect the protein expression levels of collagenⅢ, heat shock protein (HSP)-47, connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), β-catenin, Bcl-2, and caspase-3. Western blotting was used to detect the protein expression of glucose-regulated protein 78 (GRP78) in renal tissue. Compared with CON group, UUO group had renal tubular dilation and significantly increased interstitial collagen fiber deposition; The degree of renal tubular dilation and interstitial collagen fibers in UUO+ACT group and UUO+BZ group were significantly reduced compared to UUO group, but still significantly heavier than CON group. Compared with CON group, the protein expression levels of collagenⅢ, HSP-47, CTGF, α-SMA, β-catenin and GRP78 in renal tissues of UUO group were significantly higher, while the protein expression level of Bcl-2 was significantly lower (all P<0.05). In comparison with UUO group, the expression levels of Bcl-2 in UUO+ACT group and UUO+BZ group were significantly higher, while the expression levels of other proteins were all significantly lower (all P<0.05). The study shows that acteoside may improve renal fibrosis by decreasing the expression levels of collagenⅢ, HSP-47, CTGF, α-SMA, β-catenin and GRP78, and upregulating the expression level of Bcl-2 in renal tissues.

  • Case Report

  • Hu Rongrong, Wang Ying, Chen Zhichun, Hu Yan, Liu Bingyan, Qin Yan
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    The article reports a rare case of isolated persistent left superior vena cava (PLSVC) found during the catheterization of a dialysis catheter in an end-stage renal disease patient and the occurrence of guidewire entrapment in Chiari net. The patient was scheduled to have emergency dialysis due to end-stage renal disease and acute left heart failure. And a tunnel-cuffed catheter (TCC) for dialysis insertion was planned. Isolated PLSVC was found firstly by the imaging process. Then the guidewire was entrapped at the right atrium in the further operation. During the operation of the guidewire, the guidewire loosened and withdrawn with a fine fiber, which was considered a possibility of Chiari net. In the follow-up after one week, the TCC worked well, and the heart function improved after dialysis.

  • Review

  • Xu Xieguanxuan, Cai Guangyan
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    The risk factors of acute kidney injury caused by strenuous exercise include dehydration of the body, elevated body temperature, and intake of large amounts of sugary drinks after exercise, etc. The possible mechanism of the injury may be the inflammatory reaction of the body or the kidney itself, and the accumulation of various metabolites causing damage to the structure and function of the kidney under the induction of various risk factors. Repeated exposure to those risk factors not only increase the risk of acute kidney disease, but also may lead to chronic kidney disease. The paper reviews the definition, epidemiology, clinical manifestations, pathogenesis, and prevention measures of exercise-related kidney injury, to provide guidance for the formulation of appropriate exercise programs.

  • Yu Ling, Mao Jianhua
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    IgA-dominant infection-related glomerulonephritis (IgA-IRGN) is a unique form of infection-associated glomerulonephritis. The main causative organism is staphylococcus. Although IgA-IRGN is rare in children, the prevalence is gradually increasing, and the prognosis is poor in children with immunodeficiency and mucocutaneous barrier dysfunction. The clinical manifestations are varying degrees of hematuria, proteinuria, acute kidney injury and hypocomplementemia. The renal pathology is similar to postinfectious glomerulonephritis, therefore differential diagnosis is challenging. The paper reviews the current research progress of IgA-IRGN to improve the pediatrician's understanding of IgA-IRGN in children and avoid misdiagnosis.

  • Expert Consensus

  • Committee of Chinese expert consensus on the use of finerenone in patients with diabetes mellitus and chronic kidney disease
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    Diabetes is a major risk factor for chronic kidney disease (CKD). Finerenone, a novel nonsteroidal mineralocorticoid receptor antagonist, has been confirmed to have a definite renal and cardiovascular protective effect on diabetes mellitus with CKD. Long-term use can significantly reduce the urinary albumin to creatinine ratio in patients with diabetes mellitus and has little effect on blood potassium. In order to make the clinical application of finerenone more reasonable and standardized, based on research evidence and clinical practice experience, the expert group formed the Chinese expert consensus on the use of finerenone in patients with diabetes mellitus and CKD after many discussions. The mechanism of action and pharmacological properties of finerenone, evidence-based medical evidence, suitable population, specific usage and precautions were described, and 27 recommendations were formed to provide reference for clinical use of finerenone and benefit patients.