Objective To investigate the clinical and pathological features of patients with a combination of Sjogren's syndrome (SS) and antineutrophil cytoplasmic antibody (ANCA) associated vasculitis with renal involvement. Methods By searching the Peking Union Medical College Hospital medical database and literature between January 1990 and June 2017, patients had a combination of SS and ANCA associated vasculitis with renal involvement were included. Data of clinical information, autoimmune antibodies, renal manifestations and renal pathology were retrieved and analyzed. Results Eighteen patients were enrolled: 4 from our hospital and 14 from literature. SS was diagnosed no later than ANCA associated vasculitis in all the patients, among which 83.3%(15/18) of patients had extra-glandular and extra-renal organs involved. All the patients were tested positive for myeloperoxidase (MPO)-ANCA, and only two were protein 3 (PR3)-ANCA positive concurrently. The positivity rates of antinuclear antibody (ANA), rheumatoid factor (RF), anti-SSA antibody, and anti-SSB antibody were 83.3%(15/18), 55.6%(10/18), 77.8%(14/18), and 38.9%(7/18), respectively. The renal manifestations were characterized by renal insufficiency with a median serum creatinine of 174 μmol/L, hematuria, moderate proteinuria with a median 24 hour urine protein of 1.70 g, and necrotizing vasculitis with oligo-immune complex and varying degrees of interstitial damage in pathology. Conclusions A combination of Sjogren's syndrome and ANCA associated vasculitis with renal involvement is rare in clinical setting, and almost all of the patients are MPO-ANCA positive, with high probability of ANA positivity and extra-glandular involvement. Physicians should beware of ANCA associated glomerulonephritis in SS patients with inexplicable renal dysfunction and renal biopsy should be carried out in time.

Objective To investigate the relationship between the incipient serum C-reactive protein (CRP) and clinicopathologic features in anti-neutrophil cytoplasmic antibody associated vasculitis (AAV). Methods Data of 138 consecutive AAV patients were collected. According to their serum CRP levels, patients were divided into group 1 with normal CRP, group 2 with slightly increased CRP and group 3 with severely increased CRP. Clinical features of AAV and histopathologic features of the kidney injury were compared among groups. Results CRP levels increased in 77.53% AAV patients on admission. Patients in the group of severely increased CRP had the highest levels of BVAS, serum C3, serum ANCA titer, leukocyte counts and the lowest levels of hemoglobin and albumin among the 3 groups (all P＜0.05). The mortality during the stage of therapy was highest in patients with severely increased CRP (P＜0.05). The focal kidney damage was more obvious in patients with severely increased CRP. There was no significant difference in renal prognosis among patients with different CRP levels. Conclusion The levels of incipient serum C-reactive protein of AAV vary in different patients and are positively correlated with patients' inflammation status as well as the disease activity, but are not correlated with the severity of kidney injury.

Objective To investigate the clinical manifestations, renal pathology and prognosis of antineutrophil cytoplasmic antibody-associated small-vessel vasculitis (AAV) accompanied with renal glomerular IgA deposition. Methods A retrospective analysis was performed at the First Affiliated Hospital of Zhejiang University College of Medicine. Patients diagnosed with AAV associated renal injury by renal biopsy from February 2004 to February 2017 were enrolled. Patients with antiglomerular basement membrane antibody-mediated nephritis, systemic lupus erythematosus nephritis, Henoch Schonlein purpura nephritis, hepatitis B virus associated nephritis and other known etiology were excluded. According to immunofluorescence examination, the patients were divided into IgA deposition group and pauci-immune complex deposition group. The differences in clinical manifestation, pathological features and prognosis were compared between groups. Results A total of 150 AAV cases were included, among which 25 cases were with IgA deposition and 125 cases with pauci-immune complex deposition. The level of serum albumin in IgA deposition group was higher than that in pauci-immune complex deposition group [(35.0±6.2) g/L vs (32.6±5.3) g/L, P=0.049], but the titer of MPO-ANCA was lower [24.8(10.4, 71.8) U/ml vs 63.0(21.9, 100.0) U/ml, P=0.044] in IgA deposition group. There was no significant difference between two groups in other laboratory indexes and renal pathological findings. The median follow-up time was 15.2 months in IgA deposition group and 8.9 months in pauci immune complex deposition group. During the follow-up there were 8 patients (32.0%) in IgA deposition group and 29 patients (23.2%) in pauci immune complex deposition group on maintaining dialysis; 2 patients (8.0%) in IgA deposition group and 7 patients (5.6%) in pauci immune complex deposition group died. There was no significant difference between two groups in patients' outcomes. Conclusions AAV patients with glomerular IgA deposition and AAV patients with typical glomerular immunoglobulin complex deposition are similar as regards clinical appearance and prognosis.

Objective To analyze the correlation between the pathological types of parathyroid and clinical manifestations in patients with renal secondary hyperparathyroidism (SHPT), so as to improve the efficacy and safety of treatment. Methods The pathological and clinical data of 130 patients with renal SHPT and maintenance hemodialysis (MHD) who had undergone total parathyroidectomy with autotransplantation (TPTX+AT) were collected. A total of 545 parathyroid glands were obtained and 998 slices were made and read. According to the pathological types of parathyroid hyperplasia, the patients were divided into diffuse hyperplasia (DH) group, diffuse between hyperplasia and nodular hyperplasia (DH/NH) group as well as nodular hyperplasia (NH) group. The clinical and biochemical characteristics of different groups before and after operation (1-, 3-, 6-, 9-, 12-month) were compared and analyzed by statistical tests. Results (1) The preoperative status: the dialysis age, serum calcium as well as incidence of bone pain, skin itching and shorten height in the NH group were significantly higher than those in the DH group (all P＜0.05), and the serum phosphorus and iPTH in the NH group were significantly higher than those in DH and DH/NH group (all P＜0.05). (2) The postoperative status: the serum calcium of the NH group at 1-month was lower than that of the DH group, and the incidence of hypocalcemia of the NH group at 1-month was higher than that of the DH group (P＜0.05); the serum phosphorus at 3-, 6-, 9-month and iPTH at 1-, 3-month of the NH group were significantly lower than that of the DH group (all P＜0.05), and the serum phosphorus at 3-month and iPTH at 1-month of the NH group were lower than that of the DH/NH group (all P＜0.05). Among the 3 groups the serum phosphorus change from 1 to 12 months had difference (F=3.241, P=0.042), while the differences of serum calcium and iPTH changes were statistically insignificant. Conclusions The clinical manifestations, serum calcium, phosphorus and iPTH in patients with renal SHPT before and after TPTX+AT are closely related to the pathological types of parathyroid hyperplasia. Compared with the DH patients, before the operation the NH patients have longer dialysis age, more serious the clinical symptoms such as bone disease, higher calcium, phosphorus and iPTH, while greater reduction of the serum calcium, phosphorus and iPTH in the short term after operation.

Objective To observe the expression of ChemR23 induced by Angiotensin Ⅱ (AngⅡ) in podocyte and its role in renal injury. Methods Conditionally immortalized mice podocytes were cultured in vitro. Immunofluorescence was used to observe the sub-cellular location of ChemR23. The expressions of ChemR23, Nephrin and Podocin stimulated by different concentrations of AngⅡ were detected by qRT-PCR and Western blotting. Lentivirus targeting ChemR23 was used. The expressions of Nephrin and Podocin and the phosphorylation state of NF-κB P65 were detected by Western Blot. The inhibitor of NF-κB P65 was added to the cultural medium for 2 h before AngⅡ stimulation. The effect of NF-κB P65 inhibitor on AngⅡ-induced expression of Nephrin and Podocin was detected by Western Blot. Results It is showed that ChemR23 was located in cytosol and membrane. Compared with the normal control, the expression of ChemR23 was significantly increased by AngⅡ in mRNA and protein level, while the expressions of Nephrin and Podocin were decreased (P＜0.05). When using Lentivirus vector to interfere the expression of ChemR23, AngⅡ-repressed expressions of Nephrin and Podocin were restored (P＜0.05). Western Blot showed the level of phosphorylated NF-κB P65 was significantly increased by AngⅡ stimulation (P＜0.05), which could be inhibited by interfering the expression of ChemR23. When adding the NF-κB P65 inhibitor, the low expression of Nephrin and Podocin induced by AngⅡ stimulation was restored (P＜0.05). Conclusions AngⅡ can induce ChemR23 expression, which activates NF-κB P65 signaling pathway, and then inhibits the expressions of Nephrin and Podocin. Targeting ChemR23 is a potential way to alleviate podocyte injury caused by AngⅡ.

Objective To evaluate the effect of over-expression of phosphatase and tensin homolog does on chromosome ten (PTEN) in podocytes on kidney under high fat diet (HFD) in vivo and clarify the mechanism how PTEN regulates scavenger receptor A (SR-A) expression exposed to oxidized low density lipoprotein (ox-LDL) in podocytes in vitro. Methods The podocyte-specific PTEN knock-in (PPKI) mice were fed with HFD to establish mouse model of lipid-induced renal injury. Mice were divided into four groups: ND+Ctrl group, ND+PPKI group, HFD+Ctrl group and HFD+PPKI group. After 24 weeks of dietary intervention, all mice were tested for clinical and biochemical parameters, including serum creatinine (Scr) as well as urine albumin excretion rate (UAER); renal lipid content was measured by oil red O staining and cholesterol quantitative analysis; the pathological changes of glomeruli were observed by PAS staining and electron microscope. Podocyte injury was induced by ox-LDL in vitro. Western blotting was used to detect the changes of SR-A expression induced by ox-LDL after YAP-siRNA interfering (si-YAP), as well as YAP phosphorylation induced by ox-LDL after interfering by PTEN-siRNA (si-PTEN) and PTEN phosphatase inhibitor (Bpv-PTEN), and over-expressing by recombinant adenovirus (ad-PTEN). Results Compared with ND+Ctrl group, HFD+Ctrl group significantly aggravated the levels of Scr and UAER, the expression of SR-A in podocytes, renal lipid content, mesangial matrix expansion, effacement of podocyte foot processes, and incrassation of glomerular basement membrane (all P＜0.05). Conversely, compared with HFD+Ctrl group, HFD+PPKI group obviously alleviated the above lipid-induced renal damage (all P＜0.05). In vitro, the expression of SR-A in podocytes was up-regulated when stimulated with ox-LDL (P＜0.05), and the knockout of YAP significantly down-regulated the expression of SR-A induced by ox-LDL (P＜0.05). Exposed to ox-LDL, the expression of p-YAP increased in podocytes (P＜0.05); over-expression of PTEN inhibited p-YAP up-regulation induced by ox-LDL (P＜0.05), while either knockdown of PTEN or inhibition of PTEN phosphatase activity displayed opposite effect (all P＜0.05). Conclusions Over-expression of PTEN in podocytes protected the kidney against damage from HFD in vivo and PTEN might suppress SR-A mediated lipid uptake via dephosphorylating p-YAP to prevent podocyte injury from ox-LDL.

Objective To investigate the effects of protein expressions and the urea transport activity of aldosterone on urea transporter A1 (UT-A1) and urea transporter A3 (UT-A3) in HEK293 cells and Xenopus laevis oocytes. Methods (1) Western Blot was used to investigate the protein expressions of UT-A1 and UT-A3. (2) Cell surface biotinylation was used to investigate the protein expressions of UT-A1 and UT-A3 on the cell surface of Xenopus laevis oocytes. (3) 14C-urea transport experiment was conducted to investigate the transport activity of UT-A1 and UT-A3 in Xenopus laevis oocytes. Results (1) Compared with UT-A1 or UT-A3 high expression groups, the total protein levels of UT-A1 and UT-A3 were all significantly reduced in aldosterone treatment groups (all P＜0.01). (2) Compared with UT-A1 or UT-A3 high expression groups, the levels of protein expression on cell surface were all significantly reduced in aldosterone groups (all P＜0.01). (3) Compared with UT-A1 or UT-A3 high expression groups, 14C-urea transport experiment results showed that aldosterone treatment groups had significantly reduced the urea transporter activity of UT-A1 (1 min: 94.32±9.044 vs 40.68±4.274, P＜0.01, n=6; 3 min: 165.0±4.7 vs 80.3±0.6, P＜0.01, n=6), and UT-A3 (1 min: 204.6±3.1 vs 176.7±9.1, P＜0.05, n=6; 3 min: 371.4±14.9 vs 318.8±12.0, P＜0.05, n=6). Conclusion Aldosterone can directly down-regulate the protein expressions of UT-A1 and UT-A3 in both total protein and cell surface level, which reduces their urea transport activity.

Objective To investigate the possible mechanism of sclerostin/Lrp4 in calcification of VSMC induced by high phosphorus and the protective effect of Ginkgo biloba extract. Methods Aortic vascular smooth muscle cells (VSMCs) of SD rats were extracted and identified. VSMCs were divided into normal control group, high phosphorus induced calcification group (10 mmol/L β-glycerophosphate+50 μg/ml ascorbic acid), and high phosphorus induced calcification+Ginkgo biloba extract intervention group (10 mmol/L β-glycerophosphate+50 μg/ml ascorbic acid+0.5 mg/ml GBE), cultured in different mediums for 14 days. Vonkossa staining and alizarin red staining were used to detect the calcification of VSMCs. The mRNA level of BGP was detected by real time PCR, and the protein expressions of sclerostin and Lrp4 were detected by Western blot. Results Compared with normal control group, vonkossa staining and alizarin red staining showed significant calcium deposition in calcification group. Compared with calcification group, calcium salt deposition was significantly reduced in GBE treatment group. Real time PCR results showed β-catenin and BGP mRNA expressions in VSMC calcification group were higher than those in normal control group (P＜0.05). mRNA expressions of β-catenin and BGP in GBE treatment group were lower than those in calcification group (all P＜0.05). Compared with normal control group, the protein expression of sclerostin was increased, but the protein expression of Lrp4 was decreased in calcified group (all P＜0.05). Compared with calcification group, the protein expression of sclerostin decreased and the protein expression of Lrp4 increased in GBE treatment group (all P＜0.05). Conclusions High phosphorus can induce VSMC calcification by activating Wn/β-catenin signaling pathway. Sclerostin/Lrp4 is involved in hyperphosphine-induced VSMC calcification. GBE can reduce the high phosphorus induced VSMC calcification by regulating the Wnt/β-catenin signaling pathway.