Objective To explore the features of ambulatory blood pressure in patients with primary glomerular disease and their correlation with target organ damage (TOD)． Methods Patients with primary glomerular disease admitted to the Nephrology Department, the Third Affiliated Hospital of Sun Yat?sen University from May 2010 to May 2015 were enrolled. Ambulatory blood pressure monitoring (ABPM), clinical BP, ultrasonographic assessment and other clinical data were collected. Univariate and multivariate analyses were used to ascertain the relationship between ABPM results and clinical parameters. Results 808 patients were enrolled. Patients turned out to have a higher level of 24?hour systolic blood pressure (SBP), day?time SBP, and night?time SBP as their kidney function declined (rs=0.547, 0.538, 0.546, P＜0.01). Compared with that in CKD 1?3, The percentage of dipper blood pressure pattern decreased and that of reversed dipper blood pressure pattern increased in CKD stage 4?5 (P＜0.05). A higher level of 24 h SBP was independently associated with kidney function damage (OR=1.069, P＜0.01), and a higher level of night?time SBP was an independent factor affecting left ventricular hypertrophy (OR=1.033, P＜0.01) and reduction of diastolic function of left ventricle (OR=1.019, P＜0.01) after multivariate logistic regression analyses. Conclusion With advancing CKD stage, the level of 24 h SBP, day?time SBP, and night?time SBP was higher and the percentage of reversed dipper blood pressure pattern was higher. The parameters of ABPM were closely related to renal damage and cardiovascular injuries．

Objective To further investigate the association among clinical pathology, complement activation and renal secretory IgA (SIgA) deposition in patients with IgA nephropathy (IgAN). Methods The activation of serum complements were detected by immunoturbidimetry and ELISA. Renal deposition of SIgA and activation of complements were detected by immunofluorescence. Then the association among clinical pathology, complement activation and renal SIgA deposition were analyzed in IgAN patients. Results In all 201 patients with IgAN，59 patients had SIgA deposition with higher incidences of mucosal infection history and hematuria (P＜0.05), lower levels of serum cystatin C, β2 microglobulin and lower tubulointerstitial lesion grades and T?grade in the Oxford classification (P＜0.05), when compared with patients without SIgA deposition. Both alternative and mannose binding lectin (MBL) pathways were activated in patients with or without SIgA deposition. Patients with MBL pathway activation had lower estimate glomerular filtration rate (P＜0.01), higher serum creatinine, higher proportion of glomerulosclerosis and S?grade in the Oxford classification, more severe tubulointerstitial lesion (P＜0.05). Conclusions Compared with patients without SIgA deposition, patients with SIgA deposition have a stronger link to mucosal immune. The deposition of SIgA is associated with different clinical and pathological manifestations; however, the complement activation is similar in both groups of patients. Patients with MBL pathway activation show more severe kidney injury.

Objective To explore the clinical characteristics of IgG4?related disease (IgG4?RD) in Chinese by detailed clinicopathological and laboratory assessments. Methods The baseline features of 36 patients with biopsy?proven disease were reviewed. The diagnosis was confirmed by pathology review according to consensus diagnostic criteria and clinicopathologic correlation. Disease activity and damage were assessed by the IgG4?RD responder index (RI). Results Thirty (83.3%) of the patients were male, while six were female, and the average age of onset was 65.1 years. All of the 36 patients had active disease, in which submandibular gland, lymph nodes, retroperitoneal tissue were the most common affected organs in this group of patients. Among 36 patients, 77.7% had elevated serum IgG4 concentrations and 44.4% had hypocomplementemia. Patients with elevated serum IgG4 had a higher RI, a greater number of organs involved (P＜0.01 for all comparisons). The correlation between serum IgG4 level and RI (r=0.737, P＜0.01) was stronger than IgG, ESR, CRP and serum complement levels. The incidence of hypocomplementemia in IgG4?RD patients with renal involvement was higher than that in IgG4?RD patients with other organs involvement (P＜0.01). Twenty?eight patients received glucocorticoids therapy, and had lower RI and serum IgG4 concentration after therapy (P＜0.05). Conclusions Both IgG4?RD RI and IgG4 concentration may be regarded as assessment markers of disease activity and therapeutic effect of IgG4?RD. The diagnosis of IgG4?RD should be supported by histopathology and clinical features.

Objective To evaluate the prevalence of osteoporosis in maintenance hemodialysis (MHD) patients and analyze the risk factors. Methods Eighty-three patients on MHD and 87 healthy people were recruited, measuring and comparing their mineral density of femoral bone. Patients' age, sex, height, body weight, walking activity, medication use and laboratary tests were recorded. The relationship of bone mineral density (BMD) and other factors were analyzed using multivariate linear regression. Result The prevalence of osteoporosis was higher in MHD patients than in normal control (34.7% vs 20.7%, P＜0.05). Patients in osteoporosis group showed higher rate of menopause, lower body weight and lower walking activity. In multivariable regression model, age (β=-0.02, P=0.011), body weight (β=0.02, P=0.031) and walking activity (β=0.13, P=0.027) were independently associated with BMD in MHD patients. Conclusion The prevalence of osteoporosis is much higher in MHD patients than in healthy people. Advanced age, low body weight and inactivity are important risk factors for osteoporosis in MHD patients.

Objective To explore the prevalence of anemia, percentage of patients with hemoglobin (Hb) reaching the guideline target, and its impact factors in maintenance hemodialysis (MHD) patients in Anhui province. Methods Two thousand six hundred and one cases of MHD patients were investigated in hemodialysis centers of 26 hospitals in southern, northern and central Anhui province from January 1st, 2014 to March 31st, 2014. Age, gender and clinical information on renal disease history, duration of dialysis therapy, types of dialysis, medical history, and laboratory results, were collected. The prevalence of anemia, percentage of patients with Hb levels reaching the guideline target (Hb≥110 g/L) and the associated factors of Hb were analyzed. Results (1) Mean Hb concentration was (100.2±28.1) g/L, 82.5% of patients were diagnosed as anemia. The use rate of erythropoietin, intravenous iron and folic acid were 95.2%, 64.3% and 62.0% respectively. (2) Hb≥110 g/L rate was 32.8%. The percentage of patients with Hb≥110 g/L was higher in males than that in females (35.1% vs 29.4%, P=0.002). Patients with high flux dialysis had a higher percentage of Hb≥110 g/L than those with low flux dialysis (39.2% vs 27.9%, P＜0.001). (3) Compared with patients whose Hb≥110 g/L, patients with ＜110 g/L had shorter duration of dialysis therapy, lower albumin, creatinine, triglyceride, calcium, phosphorus, magnesium, and higher hs-CRP, higher usage rates of erythropoietin, intravenous iron and folic acid (all P＜0.05). (4) The 2.10-2.50 mmol/L calcium (OR=0.346, P=0.005), ＞2.50 mmol/L calcium (OR=0.207, P=0.001), ＞41.9 g/L albumin (OR=0.511, P=0.044), 1.11-2.01 mmol/L triglyceride (OR=0.443, P=0.008), ＞2.01 mmol/L triglyceride (OR=0.257, P＜0.001) and ≥7.63 mg/L hs-CRP (OR=1.652, P=0.049) were influence factors causing Hb to fall below. Conclusions There are high prevalence of anemia and low control rate of hemoglobin in MHD patients in Anhui province. Normal-calcium, hypercalcemia, higher albumin and triglyceride are protective factors of Hb target, but higher hs-CRP is its independent risk factors. The rational use of erythropoietin and intravenous iron, high flux dialysis, well nutrition states, correcting of the hypocalcemia and inflammatory state may contribute to improving the hemoglobin levels.

Objective To investigate the effects of CXC chemokine ligand 16 (CXCL16)/CXC chemokine receptor 6 (CXCR6) pathway on cholesterol accumulation of atherosclerosis in the radial artery of end-stage renal disease (ESRD) patients under inflammatory stress and further investigate its potential mechanisms modulated by purinergic receptor P2X ligand-gated ion channel 7 (P2X7R). Methods According to plasma C-reactive protein (CRP), forty ESRD patients were divided into control group (CRP＜3.0 mg/L, n=15) and inflammation group (CRP≥3.0 mg/L, n=25). Biochemical index and lipid spectrum of patients were measured. Tissues from the radial artery of patients receiving arteriovenostomy were removed surgically. Foam cell formation was observed by hematoxylin-eosin (HE) and cholesterol accumulation was assessed by filipin staining. CXCL16/CXCR6 pathway related protein expression, P2X7R protein expression and the expression of monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor α (TNF-α) and CD68 were detected by immunohistochemistry staining and immunofluorescence staining. Results Compared with that in control group, protein expression of MCP-1 and TNF-α in radial arteries were increased in inflammation group accompanied with macrophage infiltration (P＜0.05). Further more, there was significantly increased foam cell formation in continuous cross-sections of radial arteries in inflammation group, which was closely correlated with increased protein expression of CXCL16, CXCR6 and a disintegrin and metalloproteinase (ADAM)-10 (P＜0.05). CXCL16 expression was positively correlated with CRP level (r=0.79, P＜0.05) and P2X7R expression (r=0.65, P＜0.05). Conclusion Inflammation contributes to foam cell formation in the radial artery of ESRD patients by activating the CXCL16/CXCR6 pathway, and promotes atherosclerosis, which is possibly regulated by P2X7R activation.

Objective To investigate the role of vitamin D receptor (VDR) in the protection of bufalin on podocyte injury induced by adriamycin (ADR). Methods (1) In vitro: the toxic effect of different concentrations of bufalin (10-9, 10-8, 10-7, 10-6 mol/L) on podocyte was evaluated by lactate dehydrogenase (LDH) test；Annexin V-FITC and RT-PCR were utilized for podocyte apoptosis and VDR mRNA level respectively. Western blotting was used to analyze the protein expression of VDR and nephrin. SiRNA intervene was also applied to evaluate the role of VDR in bufalin's protective effect on podocyte injury induced by ADR. (2) In vitro: 24 SD rats were randomly divided into three groups: control group, ADR group and ADR+bufalin group. TUNEL assay was applied to detect the apoptosis of podocytes in the kidney. Immunofluorescence and transmission electron microscope (TEM) were applied to analyze the expression of VDR and the ultrastructure of the glomerulus. Results Bufalin concentration lower than 10-7 mol/L had no toxicity on normal podocyte. Bufalin reduced the urinary protein excretion (P＜0.05), alleviated the removal of podocyte foot processes and attenuated the changes in nephrin expression in the glomerulus of the adriamycin (ADR) rats (P＜0.05). Bufalin notably inhibited the down-regulation of VDR in protein levels on the glomerulus of the ADR rats. Additionally, bufalin inhibited the down-regulation of VDR in both mRNA levels and protein levels (P＜0.05）, nephrin protein expression (P＜0.05), and apoptosis induced by ADR in cultured podocytes. Additionally, VDR specific siRNA intervene abolished the protective effect of bufalin in ADR-induced podocyte injury. Conclusion Bufalin can alleviate ADR-induced podocyte injury via enhancing VDR expression.

Objective To investigate the regulatory effect of adrenomedullin (AM) on the cell-cell contact formation of podocytes and the possible mechanism. Methods Podocytes were treated with AM (10-7 mol/L), AM combined with a PKA inhibitor H89 (10-6 mol/L), and forskolin (10-5 mol/L) as positive control respectively for 12 hours. Immunofluorescent staining was applied to observe the distribution of cell adhesion molecules and actin-associated proteins. Western blotting assay was used to assess their protein levels. Rho GTPases activity was analyzed by GST-pull down assay and their protein levels were tested by Western blotting. Results AM induced the redistribution of adhesion molecules, actin-associated proteins as well as the F-actin at cell-cell contacts between podocytes. This effect was similar to that of forskolin and could be blocked by H89. The levels of those proteins did not change significantly (P＞0.05). AM up-regulated the activities of RhoA, Rac1 and Cdc42 (P＜0.05), which were partially blocked by H89. The protein levels of Rho GTPases showed no difference compared with the control (P＞0.05). Conclusions AM may promote cell-cell contact formation of podocytes, probably through enhancing the activity of Rho GTPases and then resulting in the redistribution of adhesion molecules, actin-associated proteins and F-actin, which is partially mediated through cAMP-PKA signaling pathway.

Objective To investigate the role of increased microRNA-21 (miR-21) in the development of renal tubulointerstitial fibrosis secondary to aristolochic acid induced acute kidney injury. Methods C57BL/6J male mice were intraperitoneally injected with aristolochic acid at a dose of 10 mg/kg. Blood samples and kidneys were harvested at day 1, 3, 7, 14, 28 after aristolochic acid treatment. To assess the role of miR-21 in aristolochic acid induced acute kidney injury to chronic kidney disease progression, mice were intravenously injected with anti-miR-21 or anti-scramble (10 mg/kg) at 1 h before aristolochic acid dosing, as well as d5 and d10 after aristolochic acid dosing. Results Increased serum creatinine and severe kidney injury were found at d3 after aristolochic acid treatment. Renal tubulointerstitial fibrosis was developed at d14 after aristolochic acid treatment. Protein expression of α-SMA, vimentin and collagen I were significantly up-regulated at d7 and peaked at d14 (P＜0.01), while protein abundance of E-Cadherin decreased at d14 and lasted until d28 (P＜0.01). The abundance of miR-21 increased at d7 after aristolochic acid dosing, peaking at d14 and thereafter maintaining at a high level. Anti-miR-21 intervention relieved renal injury with reduced serum creatinine (P＜0.05) and attenuation of renal tubulointerstitial fibrosis. Besides, the protein expression of α-SMA, vimentin, and collagen I/IV was all down-regulated after anti-miR-21 treatment (P＜0.05). PTEN was up-regulated and the ratio of its downstream genes p-AKT/AKT was decreased. (P＜0.05) Conclusions A single high dose of aristolochic acid leads to acute kidney injury and the development of renal tubulointerstitial fibrosis secondary to AKI. Renal tubulointerstitial fibrosis could be partially reversed by inhibiting miR-21 via PTEN/ p-AKT pathway.