Objective To analyze the clinical and pathological characteristics in children diagnosed with primary focal segmental glomerulosclerosis (FSGS) after repeated renal biopsy. Methods The clinicopathological data of children who ever experienced renal biopsy in Jinling Hospital from January 1, 2000 to December 31, 2020 were retrospectively reviewed. Clinical manifestations, pathological characteristics and treatment responses were analyzed. Results Of the 34 enrolled patients, there were 22 males and 12 females. The median age of the first renal biopsy was 14 years old (1-18 years old), and the median interval between repeat renal biopsy and first renal biopsy was 6 months (1-151 months). Thirty-one showed nephrotic syndrome, of which 22 had microscopic hematuria, and 4 had elevated serum creatinine. Among the other 3 patients, 2 had hematuria and proteinuria, and 1 had proteinuria. In the first renal biopsy, 16 cases were diagnosed as minimal change disease, 14 cases were diagnosed as mesangial proliferative glomerulonephritis, 2 cases were diagnosed as IgA nephropathy, and 2 cases were diagnosed as IgM nephropathy. All 34 children showed poor responses to hormone and immunosuppressive therapies. The pathological features of the first renal biopsy in some patients were adhesion (2/34), decreased loop podocyte attachment (2/34), peripheral loop extension to the urinary pole (2/34), renal tubular reflux (4/34), capillary thrombosis (2/34) and IgM deposition (12/34). Conclusions The initial diagnosis of FSGS is difficult, and the lesions are atypical and easily misdiagnosed. The patients have poor responses to hormone and immunosuppressive therapies. For patients with the pathological changes of adhesion, decreased loop podocyte attachment, peripheral loop extension to the urinary pole, renal tubular reflux, capillary thrombosis and IgM deposition, follow-up is required, and if necessary, repeat renal biopsy needs be performed to determine whether it is FSGS.

Objective To investigate the clinical manifestations, pathological characteristics, treatment and prognosis of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) in 13 children. Methods The clinical and pathological data of 13 cases of AAV in children′s Hospital of Nanjing Medical University from June 2000 to December 2021 were retrospectively analyzed. Results Among the 13 cases, 12 cases were diagnosed with microscopic polyangiitis (MPA) and 1 case was granulomatosis with polyangiitis (GPA), including 10 females and 3 males. The onset age ranged from 3 years and 11 months to 13 years and 10 months. The most frequently involved organ was the kidney (12 cases, 92.3%), followed by respiratory system (7 cases, 53.8%), skin (5 cases, 38.5%), digestive system (4 cases, 30.8%), nervous system (4 cases, 30.8%) and cardiovascular system (3 cases, 23.1%). There were 10 cases with orthotic anemia, 7 cases with positive antinuclear antibody, and 3 cases with mildly decreased complement C3. Among the 12 children with renal impairment, 9 cases were accompanied by abnormal renal function at the beginning of the disease. Renal biopsy was classified according to the Berden as follows: sclerotic in 5 cases, crescentic 3 cases, focal in 2 cases and mixed in 2 cases. All children were treated with glucocorticoid combined with immunosuppressant. During the follow-up time from 8 months to 128 months, 4 cases acquired complete remission, 8 cases achieved partial remission and 1 case recurred after complete remission, and 7 cases progressed to chronic kidney disease stage 5. Three children with complete remission underwent repeated renal biopsy, including 2 cases of mixed type and 1 case of crescent type initially, and all changed to focal type. Conclusions AAV in children occurs mainly in school-age female, and most of AAV in children is MPA. The clinical manifestations are various. Most of them have renal damage and anemia, and lung damage is also common. Patients with skin purpura onset may be misdiagnosed as Henoch-Schonlein purpura, and AAV with ANA positive or complement reduction should exclude systemic lupus erythematosus. Once the renal function is abnormal in AAV, especially estimated glomerular filtration rate<60 ml·min^-1·(1.73 m²)^-1 and the pathological classification is sclerotic type or crescent type, it is difficult to reverse even after active treatment. Early diagnosis and treatment are very important for AAV.

Objective To investigate and analyze the clinical phenotypes and genotypes in children diagnosed with nephronophthisis (NPHP), and to provide references for clinical diagnosis.Methods Clinical data of 9 children with NPHP diagnosed by genetic testing in the Department of Nephrology, Wuhan Children′s Hospital from April 2017 to January 2022 were retrospectively collected. The clinical characteristics and genetic test results were analyzed. Results The median onset age was 11.2(3.4, 14.2) years old in 9 patients, including 5 females and 4 males. There were 8 cases of glomerular proteinuria, 8 cases of renal tubular proteinuria, and 7 cases of reduced urinary gravity in 9 patients. All the children had varying degrees of impaired renal function at the time of diagnosis. Seven cases entered chronic kidney disease (CKD) stage 5, 1 case entered CKD stage 3, and 1 case entered CKD stage 4 at the time of diagnosis. All the children had renal ultrasound abnormalities of varying degrees: size change (3/9), echo enhancement (8/9) and cysts (3/9). Extrarenal phenotypes were present in 3 children. Genetic test showed that 6 patients had mutation of NPHP1 gene, 1 patient had mutation of WDR19 gene, 1 patient had mutation of NPHP3 gene and 1 patient had mutation of NPHP5 gene. Conclusions Deletion mutation of NPHP1 gene is the most common, while NPHP3, NPHP5 and extremely rare WDR19 mutations have also been found in NPHP patients. The clinical manifestations of NPHP are not typical, so it is necessary to find a specific diagnosis method in the early.

Objective To analyze the efficacy and safety of enzyme replacement therapy (ERT) in Chinese patients with Fabry disease. Methods A retrospective analysis of the clinical manifestations, genetic variations, family screening, treatments and adverse reactions was conducted in five patients with Fabry disease admitted to the First Affiliated Hospital of Zhejiang University College of Medicine from July 2020 to May 2021. The dosage of agalsidase β was 1 mg/kg by intravenous pump once every 2 weeks. Results Five male patients with median age of 37 years old (29-51 years old) were diagnosed based on clinical features, family history, α-galactosidase A (α-Gal A) activity, genetic analysis results and kidney biopsy. The clinical manifestations varied in these five patients. All patients had abnormal electrocardiogram, abnormal cardiac ultrasonography and abnormal urinalysis results, three experienced acroparaesthesia during childhood (one patient had persistent pain until adulthood), three had cutaneous angiokeratoma, four had renal insufficiency, four had hypohidrosis, four had diarrheas, four had cornea verticillata and two had high-frequency hearing loss. Two missense mutations of the GLA gene were identified: c.272T>C(p.I91T) and c.868A>G(p.Met290Val). Two nonsense mutations were c.1024C>T(p.Arg342*) and c.838C>T(p.Gln280*). Furthermore, the frameshift mutation c.348del p.(Ile117Phefs*4) was detected, which was not included in the known database, presented with classical Fabry disease. There was no serious adverse reaction during agalsidase β infusion in 5 patients. ERT reduced the plasma globotriaosylsphingosine (lyso-GL-3) levels after treatment of 2-10 months (P<0.05), and the long-term diarrhea symptom were significantly improved. Conclusions The clinical manifestations of Fabry disease are varied. Severe adverse events rarely occur in patients treated with short-term ERT. Plasma lyso-GL-3 levels decrease significantly after treatment.

Objective To explore the clinical characteristics of autosomal dominant polycystic kidney disease (ADPKD). Methods Clinical data of 103 patients with ADPKD first admitted to Renmin Hospital of Wuhan University from July 2017 to April 2021 were retrospectively analyzed. The clinical characteristics of patients in different renal function stages were analyzed, and multiple linear regression analysis was used to analyze the factors reflecting the severity of the disease. Results Among the 103 patients with ADPKD, there were 49 males (47.6%), aged (51.23±10.99) years old. The extrarenal manifestation was mainly polycystic liver (64/71). The main clinical symptoms were gross hematuria (25 cases, 24.3%), lumbar distend and pain (37 cases, 35.9%) and hypertension (69 cases, 67.0%), appearing in the whole course of the disease. Early treatment was mainly drug conservative treatments (58 cases, 56.3%), followed by renal cyst aspiration (34 cases, 33.0%), and surgical treatments (11 cases, 10.7%). Patients in chronic kidney disease (CKD) stage 5 were mainly treated with conservative treatments (28/34). Laboratory examination results showed that hemoglobin, platelet, lymphocyte percentage and albumin in CKD stage 4-5 were lower than those in CKD stage 1-3 (all P<0.05）; prothrombin time (PT), PT-international standardized ratio and plasma osmotic concentration in CKD stage 4-5 were higher than those in CKD stage 1-3 (all P<0.05). Multiple linear regression analysis showed that hemoglobin (β=0.249, P=0.005), platelet (β=0.207, P=0.005), lymphocyte percentage (β=0.305, P<0.001) and plasma osmotic concentration (β=-0.362, P<0.001) were correlated with estimated glomerular filtration rate. Conclusions The clinical manifestations of ADPKD patients are hypertension, lumbar distend and pain, and gross hematuria, which can run through the whole stage of CKD. Polycystic liver is more common in extrarenal system. Hemoglobin, platelets, lymphocyte percentage and concentration osmotic concentration may be related to the disease progression of ADPKD.

Objective To evaluate the risk factors of acute kidney injury (AKI) in patients with multiple wasp stings. Methods Patients with multiple wasp stings were retrospectively enrolled in Hanzhong Central Hospital from September 2010 to November 2020. Based on whether the patients developed AKI, the patients were divided into AKI group and non-AKI group. The general characteristics and laboratory examinations between the two groups were compared. The logistic regression model was used to analyze the risk factors of AKI. Results A total of 356 patients with multiple wasp stings were recruited in this study, with 196 males (55.1%). The age was 56.0(45.0, 64.0) years old. There were 59 patients (16.6%) with hypertension and 13 patients (3.6%) with diabetes. There were 51 patients (14.3%) in the AKI group and 305 patients (85.7%) in the non-AKI group. Baseline data and biochemical examinations indicated that the two groups showed significant differences in gender, age, sting sites (systemic or local), sting needles, proportions of gross hematuria, leukocyte count, hemoglobin, creatine kinase, alanine transaminase, aspartate aminotransferase, total bilirubin, proportions of urinary protein, and proportions of urine occult blood (all P<0.05). The multivariate logistic regression analysis results showed that the increasing number of sting needles (every 10 needles increase, OR=1.866, 95%CI 1.289-2.071, P=0.001), gross hematuria (OR=9.770, 95%CI 2.586-36.910, P=0.001), decreasing hemoglobin (every 1 g/L increase, OR=0.016, 95%CI 0.001-0.355, P=0.009), increasing aspartate aminotransferase (every 100 U/L increase, OR=1.311, 95%CI 1.144-1.502, P<0.001), and increasing total bilirubin (every 10 μmol/L increase, OR=1.200, 95%CI 1.008-1.430, P=0.041) were independent influencing factors of AKI. Conclusions The increasing number of sting needles, gross hematuria, decreasing hemoglobin, increasing aspartate aminotransferase, and increasing total bilirubin are independent risk factors of AKI in patients with multiple wasp stings.

Objective To establish a mouse model of intra-jugular arteriovenous fistula (AVF) to screen differentially expressed genes in the process of intimal stenosis of AVF for investigating the abnormal expression signaling pathways and the mechanisms. Methods Forty-six male C57BL/6 mice were randomly divided into AVF group (n=23) and sham-operated group (n=23). The AVF group underwent internal jugular arteriovenous fistuloplasty, and the sham-operated group separated the right external jugular vein and common carotid artery and then sutured the incision. The whole-genome sequences of mice with AVF stenosis were determined by transcriptomic reversible chain terminator and synthetic sequencing. The microarray data set was established, and the Benjamini & Hochberg method of gene microarray data analysis was applied to screen the differentially expressed genes. The differentially expressed genes were screened by R-language enrichment analysis. Then, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) were performed. The subcellular localization of the differentially expressed genes was performed by BUSCA software. The protein network interaction of differentially expressed genes was analyzed by using STRING database and Cytoscape software. Results In the AVF group, 21 mice were successfully modeled and 2 mice failed. Therefore, there were 21 mice in the AVF group and only 21 mice in the sham-operated group. This mouse internal jugular AVF model was innovated using the continuous-interrupted suture method, which improved the success rate of modeling this model. The differential gene sequencing analysis showed that there were 2 514 differentially expressed genes in the AVF process, including 1 323 up-regulated genes and 1 191 down-regulated genes. GO functional enrichment analysis showed that the differential genes were mainly enriched in metabolic process, activation, redox, mitochondria and so on. KEGG pathway enrichment analysis showed that the differential genes were enriched in metabolism, energy substance synthesis, diabetes, oxidative stress and so on. Statistical analysis of subcellular localization showed that the differences were mainly in mitochondrial proteins (24.24%), cytoplasmic proteins (17.51%), nuclear proteins (13.13%), cell membrane proteins (11.45%), and extracellular proteins (10.77%). Conclusions Mitochondrial oxidative stress injury may be involved in the pathological damage process of endothelial proliferation stenosis in the AVF.

Objective To investigate whether astaxanthin (AST) down-regulates dynamin-related protein 1 (Drp1) through activating the silent mating type information regulation 2 homolog-1 (SIRT1) signaling pathway, thereby attenuating contrast-induced acute kidney injury. Methods Forty adult male Sprague-Dawley rats weighing 160-180 g were randomly divided into five groups: sham surgery group (Sham group), contrast medium injury group (CM group), astaxanthin- intervention group (AST+CM group), SIRT1 inhibitor Ex527 intervention group (Ex527+CM group), and astaxanthin combined with Ex527 intervention group (AST+Ex527+CM group). After 72 hours of modeling, heart blood was removed and kidney tissues were collected for follow-up testing. Serum creatinine (Scr), blood urea nitrogen (BUN), and oxidative stress-related indexes total superoxide dismutase (T-SOD) and malondialdehyde (MDA) were measured by biochemistry; hematoxylin and eosin staining was performed to observe the pathological changes in the kidney; mitochondrial morphology and number were observed by transmission electron microscopy; reactive oxygen species (ROS) levels were detected by ROS staining in frozen sections; TUNEL staining was performed to detect apoptosis level. The expression levels of SIRT1, p53, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), Drp1 and apoptosis-related proteins Bcl-2 and Bax were detected by Western blotting. Results (1) Compared with the CM group, Scr and BUN level were significantly lower, T-SOD level was higher and MDA level was lower in the AST+CM group, while T-SOD level decreased and MDA level increased after the combination of Ex527 (all P<0.05). (2) ROS expression was lower in the AST+CM group compared to the CM group and higher after the combination of Ex527 (both P<0.05). (3) The number of apoptotic cells was significantly reduced in the AST+CM group compared to the CM group and increased after the combination of Ex527 (both P<0.05). (4) The protein expression levels of SIRT1, PGC-1α and Bcl-2 were increased and the protein expression levels of p53, Drp1 and Bax were decreased (all P<0.05) in the AST+CM group compared with the CM group, and the protein expression levels of SIRT1, PGC-1α and Bcl-2 were decreased and the protein expression levels of p53, Drp1 and Bax were increased when Ex527 was combined (all P<0.05). Conclusion Astaxanthin can inhibit Drp1-mediated mitochondrial fission by activating the SIRT1 pathway, thereby reducing contrast-induced acute kidney injury in rats.