Objective To establish the measurement of IgA1 O-glycan-specific antiglycan autoantibodies in patients with IgA nephropathy (IgAN), and evaluate their role in the development and progression of IgAN. Methods In the IgAN regular follow-up cohort of Peking University Institute of Nephrology from January 2006 to December 2015, 170 patients drawn by stratified randomization were enrolled in this study. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of plasma galactose-deficient IgA1 (Gd-IgA1) and antiglycan autoantibody (IgG and IgA1). The correlation between antiglycan autoantibodies and clinicopathological parameters was analyzed by linear correlation and multiple linear regression analysis. The receiver operating characteristic curve (ROC) was used to evaluate the value of plasma anti glycide antibodies in the diagnosis of IgAN. Results IgG and IgA1 antiglycan autoantibodies that specifically recognized Fab-hinge region (Fab-HR) antigens could be detected in both IgAN and healthy control group. Agglutinin inhibition test showed that the specific antigen epitope was N-acetylgalactosamine (GalNAc) residue exposed to galactose deficiency in IgA1 hinged region. There was no significant difference in the absolute levels of plasma IgG antiglycan autoantibodies between IgAN and healthy controls (P=0.963). After adjustment of the plasma level of IgG, the normalized antiglycan autoantibody (ln[IgG antiglycan antibody/IgG]) in patients with IgAN was significantly higher than that in healthy controls (0.58±0.31 vs 0.37±0.11, P﹤0.01). The normalized level of IgG antiglycan autoantibody in IgAN patients was positively correlated with 24 h urine protein level during renal biopsy (Spearman r=0.183, P﹤0.05), and was also significantly correlated with 24 h urinary protein level after adjusting for baseline clinical and pathological factors (β=0.713, 95%CI 0.323-1.102, P﹤0.01). The area under ROC curve (AUC) of normalized IgG antiglycan autoantibody in the diagnosis of IgAN was 0.764 (95% CI 0.682-0.845, P﹤0.05). Using the cut-off value of 0.396, the sensitivity and specificity of normalized IgG antiglycan autoantibody for IgAN were 0.729 and 0.700 respectively. There was no significant difference in the absolute or normalized levels of IgA1 antiglycan autoantibodies between IgAN patients and healthy controls. Conclusions Gd-IgA1-specific antiglycan autoantibodies can be detected both in IgAN patients and healthy controls. They are elevated in some patients with IgAN and possibly involved in the development of IgAN.

Objective To analyze the pathological characteristics and prognostic factors of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods A retrospective analysis of AAV patients with renal biopsy results admitted to Kidney Disease Center of the First Affiliated Hospital from January 2004 to February 2017 was performed. The patients were divided into 4 types according to Berden classification, and their clinical, pathological characteristics and prognosis were compared. The survival curves of each type of patients were plotted by Kaplan-Meier method, and the difference of survival curves was compared using Log-rank test. With entering the maintenance dialysis as the endpoint, Cox regression was used to analyze the prognostic factors. Results A total of 175 patients with AAV, including 59 cases (33.7%) of focal type, 39 cases (22.3%) of crescent type, 32 cases (18.3%) of sclerosis type, 45 cases (25.7%) of mixed type. The basal serum creatinine levels in crescent type group and sclerosis type group were significantly higher than those in the focal type group or mixed type group (all P＜0.05), and loop necrosis rate in sclerosis type group was significantly lower than chat in the focal type group or crescent type group (both P＜0.05). The median follow-up period was 11.8 (0.5-86.7) months. The event-free survival rates were 83.1%, 77.8%, 64.1% and 50.0% in the focal type, mixed type, crescent type and sclerotic type groups (Log-rank χ2=11.537, P=0.009). Cox regression analysis showed higher parathyroid hormone (HR=1.013, 95%CI 1.007-1.019, P＜0.001), glomerular sclerosis ≥50% (HR=10.532, 95%CI 2.903-38.203, P＜0.001) were independent risk factors for AAV patients entering maintenance dialysis, and higher estimated glomerular filtration rate (HR=0.943, 95%CI 0.896-0.993, P=0.025) was protective factor. Conclusion The prognosis of AAV renal damage is worsened according to focal, mixed, crescent and sclerosis types. Lower estimated glomerular filtration rate, higher parathyroid hormone and glomerular sclerosis ≥50% are independent risk factors for AAV patients entering maintenance dialysis.

Objective To investigate the impact of preoperative hyperuricemia on acute kidney injury (AKI) after cardiac surgery with cardiopulmonary bypass (CPB). Methods A total of 567 adult patients undergoing cardiac surgery with CPB were enrolled to conduct a retrospective cohort database analysis. The patients were divided into hyperuricemia group and non-hyperuricemia group according to preoperative serum uric acid, and the incidence of AKI in two groups were compared. Binary logistic regression analysis was used to evaluate the relationship between preoperative hyperuricemia and AKI. Results Among 567 patients after cardiac surgery with CPB, hyperuricemia occurred in 303 cases (53.4%), and AKI occurred in 217 cases (38.3%). There was significant difference in the incidence of AKI between hyperuricemia group and non-hyperuricemia group (44.6% vs 31.1%, χ2=10.874, P=0.001). The duration of intensive care unit (ICU) stay and the length of stay were longer in hyperuricemia group than those in non-hyperuricemia group (both P＜0.05). After adjusting for age, gender, comorbidities (hypertension, diabetes mellitus, cerebrovascular disease), preoperative renal function, preoperative heart function, CPB time, intraoperative aortic block time, type of cardiac surgery and postoperative hypotension, binary logistic regression analysis showed that preoperative hyperuricemia was an independent risk factor of AKI after cardiac surgery with CPB (OR=1.912, 95%CI 1.270-2.879, P=0.002). Conclusion AKI is a common complication following cardiac surgery with CPB, and hyperuricemia is independently associated with CPB-associated AKI. Hyperuricemia may be involved in the pathogenesis of AKI, and intervention before cardiac surgery may be beneficial to prevent postoperative AKI.

Objective To investigate the relationship between serum uric acid level and renal function decline by retrospective cohort study. Methods Through the physical examination system of the First People's Hospital of Foshan, the physical examination data from 2015 to 2018 of a public institution in Foshan city were obtained. The gender, age, blood cell analysis, liver function, serum creatinine, uric acid, fasting blood glucose were obtained. The change of eGFR (ΔeGFR=eGFR2018-eGFR2015) was analyzed. Results A total of 2505 subjects were followed up for four years. The subjects were divided into ΔeGFR ≥0 group and ΔeGFR＜0 group. There were 845 subjects in ΔeGFR ≥0 group, and 1660 subjects in ΔeGFR＜0 group. Compared with that in ΔeGFR＜0 group, the base-level of uric acid in ΔeGFR ≥ 0 group was higher [(349.48±87.62) μmol/L vs (325.72±82.58) μmol/L, t=6.669, P＜0.001], but the rate of uric acid decline was greater [-15.00(-53.50, 17.00) μmol/L vs 15.50(-18.00, 49.00) μmol/L, Z=-13.470, P＜0.001]. According to the levels of uric acid in 2015 and 2018, then the subjects were divided into four groups, normal to normal group (N-N, 1551 cases), normal change into high uric acid group (N-H, 299 cases), high uric acid drop to normal group (H-N, 238 cases), and high to high uric acid group (H-H, 417 cases). The ΔeGFR was -1.58(-4.17, 1.01) ml?min-1?(1.73 m2)-1 in N-N group, and -3.60(-7.24, -0.98）ml?min-1?(1.73 m2)-1 in N-H group, -0.20(-3.14, 3.27) ml?min-1?(1.73 m2)-1 in H-N group, -0.96(-4.07, 1.93) ml?min-1?(1.73 m2)-1 in H-H group, respectively. The ΔeGFR decreased most significantly in N-H group than the other three groups (χ2=103.130, P＜0.001). Multivariate logistic regression analysis showed that elevated uric acid was an independent risk factor for eGFR decline (OR=1.739, 95%CI 1.587-1.906, P＜0.001), while elevated indirect bilirubin (OR=0.968, 95%CI 0.943-0.993, P=0.013), elevated red blood cells (OR=0.815, 95%CI 0.680-0.976, P=0.026) were independent protective factors for eGFR decline. Conclusion Elevated uric acid is an independent risk factor for the decline of renal function. Good control of hyperuricemia is beneficial to the protection of renal function.

Objectives To determine the association between serum levels of high-mobility group box-1 (HMGB1), insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor 165 (VEGF165) and occurrence and development of diabetic nephropathy (DN). Methods A total of 136 patients diagnosed as diabetic nephropathy (DN group) in Huai'an First People's Hospital between January 2016 to January 2018 were randomly selected in the study, including microalbuminuria group (n=62), macroalbuminuria group (n=50) and renal insufficiency group (n=24). Meanwhile, 115 healthy examiners during the same period were collected as normal control group. Serum glucose, serum total cholesterol (TC), serum triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and urinary albumin/urine creatinine ratio (UAlb/Cr) were detected in all subjects. Enzyme-linked immunosorbent assay (ELISA) was adopted to detect the serum concentrations of HMGB1, IGF-1 and VEGF165. Pearson correlation test was used to analyze the correlation between serum HMGB1, IGF-1 and VEGF165. Logistic ordered multi-classification regression was used to analyze the risk factors of DN progression, and the receiver operating characteristic curve (ROC) was drawn to evaluate the clinical predictive value of HMGB1, IGF-1 and VEGF165 in the progression of DN. Results The concentrations of serum HMGB1, IGF-1 and VEGF165 in DN patients were significantly higher than those in the control group (all P﹤0.05). There was a positive association between HMGB1 and IGF-1, HMGB1 and VEGF165, IGF-1 and VEGF165 (all P﹤0.01). Logistic regression analysis showed that elevated levels of HMGB1, IGF-1 and VEGF165 were independent risk factors for DN progression (OR=5.50, 1.05, 1.24, all P﹤0.05). The sensitivity, specificity and area under ROC curve of combined detection of HMGB1, IGF-1 and VEGF165 were higher than HMGB1, IGF-1 and VEGF165 alone (AUC=0.989, 0.984, 0.942, 0.878, P﹤0.05). Conclusions The serum levels of HMGB1, IGF-1 and VEGF165 are related to the severity of DN. The clinical predictive value of combined detection of HMGB1, IGF-1 and VEGF165 for DN progression is superior to that of single index detection of HMGB1, IGF-1 and VEGF165.

Objective To investigate the clinical manifestations and genetic features of children with papillorenal syndrome caused by PAX2 gene mutation. Methods Clinical manifestations, imaging changes and sequencing data were collected and analyzed from a family with papillorenal syndrome who were diagnosed in Wuhan Children's Hospital in February 2018. "PAX2", "papillorenal syndrome" and "renal coloboma syndrome" were used as key words to search in China National Knowledge Infrastructure, Wangfang Data Knowledge Service Platform, PubMed and Human Gene Mutation Database up to April 2018. Results A ten years old girl was admitted due to "edema and urine output decreased for one week". Lab showed BUN 25.30 mmol/L, Scr 766.5 μmol/L, Urine protein 3.6 g/24 h. Imaging examination showed bilateral vesical and ureter reflux combined with left duplex kidney and duplication of ureter. Developmental dysplasia of the left hip was also found. The father of the patient had been diagnosed with chronic kidney disease for 10 years and on hemodialysis for 6 years. Next generation sequencing revealed that both the father and daughter carried a heterozygous nonsense mutation in the exon3 c.219C＞G(p.Y73X) of PAX2. No Chinese literature ever was reported about papillorenal syndrome. Ninety-four articles in English were retrieved and 177 patients with papillorenal syndrome were confirmed by gene analysis with a total of 92 PAX2 variants. Ten nonsense mutations had been reported. Developmental dysplasia of the hip (DDH) never be reported before. Conclusion Papillorenal syndrome caused by PAX2 mutation can mainly manifest as abnormal development of both kidney and optic nerve, which may be accompanied by other systemic abnormalities, it is rarely reported in China. DDH may be a new phenotype of papillorenal syndrome.

Objective To investigate the influence mechanism of Cordyceps sinensis (CS) on β-glycerophosphate-induced vascular smooth muscle cell (VSMC) calcification. Methods The effect of CS on VSMC cell viability was detected by CCK-8. The cellular models of rat VSMC calcification were established by treating with β-glycerophosphate (β-GP, 10 mmol/L); then CS (10 mg/L), autophagy inhibitor 3-methyladenine (3-MA, 5 mmol/L), and AMPK inhibitor compound C (CC, 10 μmol/L) were added to the cell cultures. There were a total of 5 experiment groups: VSMC cultured in normal medium (Control), VSMC treated with β-GP, VSMC treated with β-GP and CS, VSMC treated with 3-MA, β-GP and CS, and VSMC treated with CC, β-GP and CS. The calcium nodules and calcium content were examined with alizarin red S staining and the O-cresolphthaleincomplexone method, respectively. The autophagosomes within the VSMC were observed using transmission electron microscope (TEM). Immunofluorescence showed the accumulation of microtubule-associated protein 1 light chain 3 (LC3) puncta. In addition, levels of osteogenic related proteins, autophagy related proteins, and AMPK/mTOR pathway related proteins were evaluated by Western blotting. Results CS increased the number of autophagosomes and the accumulation of LC3 puncta within VSMC. It also up-regulated the protein levels of LC3Ⅱ/LC3Ⅰ, beclin1, α-SMA, and p-AMPK; whereas, the protein levels of Runx2 and p-mTOR, as well as calcium nodules and calcium content were reduced (all P＜0.01). When the cells were pretreated with 3-MA before treating with β-GP and CS, the autophagosomes, accumulation of LC3 puncta, and protein levels of LC3Ⅱ/LC3Ⅰ, beclin1, and α-SMA were decreased (all P＜0.01); however, the protein level of Runx2, and the calcium nodules and calcium content were increased (all P＜0.01). Nevertheless, when the cells were pretreated with CC before giving β-GP and CS, the autophagosomes, the accumulation of LC3 puncta, and the expression levels of p-AMPK, LC3Ⅱ/LC3Ⅰ, beclin1, and α-SMA were significantly down-regulated (all P＜0.01); whereas, the expression levels of Runx2 and p-mTOR, as well as calcium nodules and calcium content were increased (all P＜0.01). Conclusions CS can effectively alleviate β-GP-induced VSMC calcification, which may be due to the activation of autophagy by AMPK/mTOR signaling pathway.

Objective To find the differentially expressed long non-coding RNA (lncRNA) between db/db mice that with nephropathy (DN) or not (DM). Methods In this study, 3 DM db/db mice and 2 DN db/db mice proven by renal biopsy were randomly selected, and 3 healthy db/m mice as normal control group. Then, differentially expressed lncRNAs, mRNAs and their fragments per kilobase million (FPKM) in kidney samples were detected by high-throughput next generation sequencing technology. Sequencing data were analyzed to filter out the differentially expressed lncRNA, and their function was preliminarily investigated by bioinformatics analysis and functional enrichment analysis to predict their target genes. Total RNAs of kidneys from these 8 mice were extracted to run real time PCR (RT-qPCR) for verifying the outcomes of the high-throughput sequencing. Results The urinary microalbumin/creatinine ratio (UACR), serum creatinine, and glomerular basement membrane thickness of DN db/db mice were higher than those of DM db/db mice (all P＜0.05), while there was not significant difference in glucose between DM and DN mice. Totally 160 lncRNAs were up-regulated and 99 lncRNAs were down-regulated in kidneys of DN mice compared with those of DM mice, in which the differentially expressed lncRNAs with FPKM value≥2 and differential expression≥1 fold between groups were screened and verified by RT-qPCR. Finally three lncRNAs whose variation trend were consistent with the outcomes of the high-throughput sequencing were obtained. Conclusion There was a significantly different expression pattern of lncRNA between the kidneys of DN and DM mice, which may be involved in the progress of DN．