Objective To analyze prognosis of pregnancy and kidney disease, and evaluate effects of renal pathology on pregnant outcomes and clinical risk factors of adverse outcomes of pregnancy in IgA nephropathy (IgAN) patients. Methods IgAN patients with more than 20 weeks of pregnancy were included, by retrieving the medical database in Peking Union Medical College Hospital from January 1996 to December 2015. Their detailed information during hospitalization and follow-up was recorded, and outcomes of pregnancy and kidney diseases in IgAN patients were assessed. According to Lee's renal pathological grade system, patients were divided into gradeⅣ&Ⅴ group and below grade Ⅳ group to compare their pregnant prognosis. IgAN patients were divied into fetus survival group and fetus death group according to their pregnancy outcomes. The fetal survival factors were analyzed by single factor and multivariate regression. Results A total of 64 pregnancies in 62 patients were included with a mean age of (30.31±4.05) years. The fetus survival rate was 87.5% and the average gestational periods was (35.41±5.10) weeks (ranging from 20-40 weeks). The incidence of pregnancy-induced hypertension syndrome is 17.2% (11 cases). The preterm birth rate was 24.1% (14 cases) among the live births. Serum creatinine increased in 18 cases (28.1%) during pregnancy with median increment of 38.5 μmol/L, and 72.2% patients completely recovered to the level before pregnancy in the postpartum period of 6 months. The incidence of fetus death (38.1% vs 0.0%, P＜0.01), low birth weight infant (46.2% vs 11.1%, P＜0.05) and pregnancy-induced hypertension syndrome (33.3% vs 11.1%, P＜0.05) in Lee's grade Ⅳ&Ⅴ group was higher than those in below grade Ⅳ group. The serum creatinine, urine protein excretion, renal hypertension before pregnancy and renal segmental glomerular sclerosis were significantly increased in fetus death group as compared with those in fetus survival group (all P＜0.05). Logistic regression showed that in all patients an estimated glomerular filtration rate (eGFR)＜60 ml?min-1?(1.73 m2)-1 (OR=76.978, 95%CI 3.327-1780.939, P=0.007) and renal hypertension (OR=14.464，95%CI 1.245-168.053, P=0.033) before pregnancy were the independent risk factors for fetus death, while multipara was a protective factor (OR=0.063, 95%CI 0.005-0.876, P=0.040). Conclusions The fetus survival and kidney prognosis in IgAN patients are closely related to the severity of clinical and pathological changes before pregnancy. Reduced eGFR and complication of renal hypertension are the independent risk factors for adverse prognosis of pregnancy.

Objective To conduct a single-center retrospective analysis on the distribution characteristics and prevalence of idiopathic membranous nephropathy (IMN) patients diagnosed with pathology for the past 16 years, to investigate diagnostic and differential diagnostic value of serum anti-phospholipase A2 receptor antibodies (PLA2R-Ab), and to evaluate the correlation between PLA2R-Ab and clinical disease activity. Methods (1) 6996 biopsy-proven primary glomerular nephropathy (PGN) patients, including 1567 IMN cases, admitted to the First Affiliated Hospital of Xi'an Jiaotong University from January 2000 to December 2015 were involved. Demographics and pathological type were gathered from all patients. (2) 433 cases receiving renal biopsy and testing PLA2R-Ab from June 2015 to December 2015 were involved, with their clinical and laboratorial data being collected. During the period patients' follow-up time, therapeutic schedule and laboratory results were recorded. Results (1) IMN accounted for 22.4% of primary glomerular disease, and patients above 40 years old accounted for more than 60% of the IMN. (2) The sensitivity and specificity of serological PLA2R-Ab were 58.1%(95%CI 47.0%-68.5%) and 98.6%(95%CI 95.6%-99.6%) respectively. PLA2R-Ab positive rate was affected by immunosuppression therapy. (3) The PLA2R-Ab titers wasn't correlated with 24-hour urinary protein (r=-0.017, P=0.887), serum albumin (r=-0.072, P=0.549) and urinary red blood cell count (r=-0.030, P=0.802). There was no difference between PLA2R-Ab positive positive and PLA2R-Ab negative on proportion of IMN pathological stage I-II (P＞0.05). Thirteen cases of patients with PLA2R-Ab positive were all prescribed glucocorticoid combined with immunosuppressant. After (2.21±1.09) months, the decrease of PLA2R-Ab titers was in accordance with 24-hour urinary protein quantity descending and serum albumin ascending (P＜0.05). Conclusions The incidence of IMN increase year by year, especially in the mid-aged and the elderly. Serum PLA2R-Ab correlates not with IMN pathological stage, but with the development of IMN. Monitoring PLA2R-Ab titers individually may access the efficiency of treatment.

Objective To explore the role of phospholipase A2 receptor 1 (PLA2R1) in the diagnosis, differential diagnosis and evaluation of idiopathic membranous nephropathy (IMN) in adult patients. Methods A total of 242 renal disease patients diagnosed by renal biopsy from March 2015 to January 2016 were enrolled, consisting of 90 IMN, 20 secondary membranous nephropathy (SMN), 82 IgA nephropathy (IgAN), 30 minimal changed disease (MCD), 16 focal segmental glomerulosclerosis (FSGS) and 4 membranoproliferative glomerulonephritis (MPGN). Their clinical data including age, sex, serum creatinine (Scr), serum albumin and 24 h urinary protein were collected. Serum PLA2R1 was measured by enzyme linked immunosorbent assay. PLA2R and IgG subclasses in glomeruli were detected by indirect immunofluorescence assay. The positive rate of serum PLA2R1 among those groups and its correlation with clinical-pathological parameters were analyzed. Results Compared with IMN patients, SMN, MCD and FSGS patients were younger (all P＜0.01); IgAN patients were younger and had higher serum albumin and lower 24 h proteinuria (all P＜0.001); MPGN patients had higher Scr (all P＜0.01). The positive rate of serum PLA2R1 was 75.6% in IMN patients, while it was 0.0% in non-IMN patients. The distribution between serum PLA2R1 and pathological diagnosis had difference (P＜0.001), their positive coincidence rate was 100%, negative coincidence rate was 87.4%, total coincidence rate was 90.9% and their consistency was well (Kappa=0.795, P＜0.001). Among IgG subtype comparisons between IMN patients and SMN patients in the glomeruli, only moderate or more positive IgG4 had statistical differences (82.2% vs 5.0%, P＜0.001); the positive rate of glomerular PLA2R1 was 41.1% in IMN patients, higher than 10.0% in SMN patients (P=0.009); positive PLA2R1 with moderate or more positive IgG4 in glomeruli in IMN patients was more than that in SMN patients (40.0% vs 0.0%, P＜0.001), which could improve the diagnostic specificity of IMN. In IMN patients serum PLA2R1 and glomerular PLA2R1 had statistical differences (P＜0.001). Spearman rank correlation analysis showed that serum PLA2R1 of IMN patients positively correlated with 24 h proteinuria (r=0.315, P=0.002), negatively correlated with serum albumin (r=-0.228, P=0.030) and didn't correlate with Scr (r=0.199, P=0.059). Conclusions Serum PLA2R can be used as the specific indicator for diagnosis, differential diagnosis of IMN and to reflect the severity of IMN in patients.

Objective To explore how neutrophil-lymphocyte ratio (NLR) is related with inflammation and atherosclerosis, and the role of NLR in hospitalization in maintenance hemodialysis (MHD) patients. Methods MHD patients treated in hemodialysis center of Sichuan Provincial People's Hospital from June till November 2013 were enrolled. Patients with severe infection, cardiovascular events and malignant carcinoma were excluded. NLR was determined from complete blood count differential. Clinical parameters such as serum albumin, lipids, intact parathormone, ferritin, C-reactive protein (CRP), 25-(OH) vitamin D, interleukin-6 (IL-6) and alkaline phosphatase (ALP) were collected. Pulse wave velocity (PWV) and ankle-brachial index (ABI) were used to evaluate the arterial stiffness. Spearman analysis was used to evaluate the relationship between NLR and these parameters. All patients were divided into low NLR group (NLR≤3.25) and high NLR group (NLR＞3.25) on the median NLR, and their differences in these indexes were analyzed. During the one-year follow-up, the reasons and rates of hospitalization and survival were analyzed. Results One hundred and thirteen MHD patients including 58 males and 55 females were enrolled with (69±49) dialysis age and (54±15) average age. (1) The NLR was significantly correlated with whole blood count (WBC, r=0.538, P＜0.001), ABIL (r=0.201, P=0.033), ABIR (r=0.235, P=0.012) and total cholesterol (TC, r=-0.414, P＜0.001) and low-density lipoprotein cholesterol (LDL-C, r=-0.378, P＜0.001). (2) Low NLR patients had increased TC, LDL-C and IL-6 as compare with high NLR patients, however decreased ABIL and ABIR (all P＜0.05). (3) Forty one patients were hospitalized 63 times during the follow-up period. Annual hospitalization rate was 558/1000 and the mortality rate was 17.7/1000. (4) NLR in patients at least hospitalized once a year was significantly lower than in patients without hospitalization, while ALP was higher (all P＜0.05). Compared with those in other patients, NLR and hemoglobin (Hb) were significantly lower in patients with hospitalization due to infection, while ALP was higher (all P＜0.05). Conclusions NLR is related with WBC, ABI, TC and LDL-C in MHD patients. Lower NLR may indicate high risk for cardiovascular, atherosclerosis and hospitalization, probably different form non-MHD patients, which needs more studies to verify.

Objective To assess the risk factors of intradialytic-hypotension (IDH) and the prognosis of IDH among maintenance hemodialysis (MHD) patients for the prevention and treatment of IDH. Methods 276 MHD patients were enrolled during Jan. 2009 to Mar. 2009. Intradialytic blood pressure was monitored during a 3-month period. IDH was defined as an event characterized by a sudden drop in systolic BP more than 20 mmHg or in mean artery pressure (MAP) more than 10 mmHg associated with clinical events and need for interventions. Dialysis-related information was collected. Kaplan-Meier method, log-rank test, logistic regression and Cox regression analyses were performed to examine the association between IDH and survival, using a follow-up through 31 May 2014. Results A total of 276 patients were recruited. The incidence rate of IDH was 40.9%. 163 patients with no-IDH (＜1/10 hypotensive events/3 months) served as controls. 113 patients with IDH (≥1/10 hypotensive events/3 months) were identified among all 276 patients. Multivariate logistic regression analysis showed that age, ultrafiltration rate, gender, serum NT-proBNP, serum albumin and aortic rool inside dimension (AoRD) were associated with IDH among MHD patients. During the 5-year follow-up, 74 patients died, with a mortality rate 5.2 per 100 person-year. Kaplan-Meier survival curve showed significant difference of overall and CV mortality rates between 2 groups. The multivariate Cox regression model indicated that IDH increased the risk of death (HR=1.572, 95%CI 1.077-2.293, P=0.019). So did the rise of LVMI (HR=1.010, 95%CI 1.009-1.085, P=0.020). Conclusion Elderly, female, high ultrafiltration rate, high level of serum NT-proBNP, hypoalbuminemia and shorter AoRD are independent risk factors for IDH among MHD patients. LVMI can predict the outcome of MHD patients. Intradialytic hypotension is an independent risk factor for long-term mortality in MHD patients.

Objective By simulating a high-glucose condition of peritoneal dialysis (PD) fluid, to explore the effect of high glucose on the expression of leptin and its relationship with peritoneal angiogenesis. Methods Adipocytes differentiated from 3T3-L1 were divided into high glucose group (139 mmol/l glucose) and high mannitol group. Leptin levels in supernatant collected at 0 h, 12 h, 24 h and 48 h were measured by ELISA. Endothelial cells (ECs) were respectively cultured with normal glouse, high glucose, high mannitol condition, supernatants of adipocyte induced by normal glouse, high glucose and high mannitol, high glucose supernatants+leptin antibody, and high mannitol supernatants+leptin antibody. Tubular structure formation and migration of ECs were detected. Results Adipocytes exposed to high glucose for 48 h produced more leptin as compared with control group, high mannitol group, 12 h-high glucose group and 24 h-high glucose group (all P＜0.05). Compared with ECs in normal group, ECs in high glucose had less tubular structure formation and increased migration (all P＜0.01). Compared with those of ECs in high glucose, the tubular structure formation and the migration of ECs in adipocyte supernatants induced by high glucose had increased (all P＜0.01), and these effects were reduced by leptin antibody (all P＜0.01). Conclusion There is an up-regulation of leptin in adipocytes exposed to high glucose, which may be an alternative way to prevent peritoneal angiogenesis.

Objective To investigate the role of cyclooxygenase-2 (COX-2) in podocyte injury in diabetic rats mediated by the disruption of low-density lipoprotein receptor (LDLr) pathway. Methods Eight-week old male Sprague-Dawley (SD) rats were treated for 12 weeks by dividing into three groups: control rats, streptozotocin (STZ) induced diabetic rats (DM), and diabetic rats treated with aspirin (DM+Aspirin). The plasma lipid profile was checked by clinical biochemistry assay. The ratio of urinary microalbumin to creatinine (ACR) was detected by enzyme-linked immunosorbent assay. Intracellular lipid accumulation was evaluated by Oil Red O staining and a free cholesterol quantitative assay. The glomerular podocyte injury and the expression of molecules related with LDLr pathway were evaluated by electron microscope, immunohistochemical staining, immunofluorescent staining, and Western blotting. Results There were increased levels of urinary ACR (P＜0.01) and podocyte injury(P＜0.01) in DM rats compared with the controls. Additionally, lipid accumulation in kidneys of DM rats were significantly increased (P＜0.01), due to increased protein expressions of COX-2, LDLr, sterol regulatory element–binding protein (SREBP) cleavage activating protein (SCAP), and SREBP-2 (P＜0.01). However, these changes were significantly inhibited by an inhibitor of COX-2, Aspirin (P＜0.05). It's worth noting that, COX-2 protein expression was closely correlated with LDLr protein expression (r=0.85, P＜0.01). Conclusion Dysregulation of LDLr pathway contributes to podocyte injury in diabetic nephropathy, which may be mediated through the increased COX-2 expression.

Objective To observe the changes of senescence and autophagy in human glomerulus mesangial cells (HGMCs) induced by high glucose at different times, and to investigate the effects of rapamycin and 3-methyladenine (3-MA) on these changes. Methods HGMCs were cultured in vitro, exposed to high glucose (30.0 mmol/L glucose) for 12, 24, 48 and 72 h, and stimulated by high glucose with 500 nmol/L rapamycin or 2 mmol/L 3-MA for 72 h. Normal control group (5.5 mmol/L glucose) and hypertonic group (5.5 mmol/L glucose + 24.5 mmol/L mannitol) were set up. Cytomorphology changes were examined by light microscope to test whether cells were in senescent stage. The quantity of autophagosome was observed by electron microscope. The cell senescence was evaluated by β-galactosidase (SA β-gal) staining. The protein expressions of p53, p21, LC3 and p62 were determined by Western blotting. Results High glucose group gradually had larger size and more flat cytoplasm, polymorphonuclear cells and binucleate cells than control group as the stimulation times was prolonged. Compared with those in control group, SA β-gal positive cells in high glucose group after incubation for 72 h statistically were increased (P＜0.05); the protein expressions of p62, p53 and p21 in high glucose group after incubation for 48 h and 72 h were increased (all P＜0.05), while the autophagosome and the expression of LC3 decreased (P＜0.05). Compared with those in high glucose group, the expression of LC3 was increased dramatically in high glucose with rapamycin group (P＜0.05), while the protein expressions of p62, p53 and p21 decreased (all P＜0.05), and SA β-gal positive cells decreased (P＜0.05). However, there was no statistical difference between high glucose group and high glucose with 3-MA group in terms of above effects. Conclusions High glucose may induce HGMCs senescence through activating p53/p21 pathways and suppressing the activity of autophagy. Through enhanced autophagy activity with rapamycin, the expression of p53/p21 pathway was suppressed and senescence was relieved.

Objective To investigate the expression of macrophage migration inhibitory factor(MIF) and nuclear factor-κB/P65 (NF-κB/P65) in the kidneys of unilateral ureteral occlusion (UUO) model rats and the effect of 1,25-dihydroxyvitamin D3 on the expression. Method The cell model of obstructive nephropathy was established by renal tubular epithelial cells treated with TGF- beta 1. Thirty healthy adult male SD rats were randomly divided into 3 groups: sham operation group (n=10), UUO group (n=10) and 1,25-dihydroxyvitamin D3 group (n=10, UUO rats treated with 1,25-dihydroxyvitamin D3 by lavage 2 days before operation)．The rats in sham group and UUO group were treated with equal normal saline by lavage. Serum creatinine (Scr) and histopathological changes were tested at week 2. The expressions of collagen Ⅳ (ColⅣ), macrophage marker antigen ED-1, MIF and NF-κB/P65 in renal issue were measured by immunohistochemistry. The MIF mRNA was detected by real-time PCR and the protein expressions of MIF, NF-κB inhibitor α (IKBα) and p-IKBα were measured by Western blotting. In renal tubular epithelial cells (NRK52E) the expressions of MIF and NF-κB were detected by immunocytochemistry, and the the protein expression of MIF and the activation of IKBα were teasted by Western blotting. Results Compared with those in sham group, in model group rats had increaced Scr, tubulointerstitial damage area and expressions of ED-1 and ColⅣ, and up-regulated mRNA and protein expressions of MIF (all P＜0.05). Moreover, the amount of NF-κB/P65 nuclear positive cells and p-IKBα expression were significantly increased while the expression of IKBα decreased in model group (all P＜0.05). NRK52E cells had higher expressions of MIF, NF-κB and p-IKBα, and lower IKBα in model group than those in control group (all P＜0.05). After the application of 1,25-dihydroxyvitamin D3, those above effects were inhibited (all P＜0.05). The results of cell model and animal model were in agreement. Conclusions The expressions of MIF and the activation of NF-κB/P65 in UUO rats increased significantly. 1,25-dihydroxyvitamin D3 may ameliorate the progression of renal tubulointerstitial inflammation and renal fibrosis by intervening the expression of MIF, inducing phosphorylation of IKBα and decreasing the activation of NF-κB/P65.