The identification of pathogenic antigens in membranous nephropathy (MN) is a hot topic in the research field of kidney diseases. In recent years, the widespread application of mass spectrometry has brought a breakthrough in the identification of MN-pathogenic antigens. As the antigen spectrum continues to be refined, the diagnosis of MN has evolved from morphological level to molecular level. This article reviewed the research progress of currently identified antigens of MN, such as phospholipase A2 receptor (a major pathogenic antigen of primary MN), thrombospondin type 1 domain-containing 7A (a potential tumor-associated antigen), neural epidermal growth factor-like protein 1 (an antigen associated with various secondary factors), semaphorin 3B (an antigen specific to pediatric MN) and so on, and the pathogenic mechanisms and clinical significance of these antigens.

Objective:To explore the role of prostacyclin (PGI 2) in the development of kidney and vascular system in mice. Methods:The prostacyclin synthase ( PGIS) knockout model was established in C57BL/6J mice. The effects of PGIS knockout on the survival rate of mice were observed by genotyping analysis. The effects of PGIS knockout on the development of kidney and vascular system in mice were observed by hematoxylin and eosin staining and periodic acid-Schiff staining. The morphological changes of kidneys in PGIS knockout mice were observed. Blood urea nitrogen was tested to evaluate the function of kidney in mice. Real-time quantitative PCR was used to analyze the effect of PGIS knockout on the mRNA expression of prostaglandin synthetase PGES and TXAS. The expression of PGIS in vascular system was observed by immunofluorescence staining. The blood pressure and heart rate of mice were measured by the tail-cuff method. Results:Most of the systemic complete PGIS knockout ( PGIS-/-) fetal mice sacrificed. The kidneys of PGIS-/- fetal mice developed abnormally, which showed sparse interstitial, abnormal tissue differentiation, lengthened renal vesicle, and significant decrease in the number of "S" -shape bodies ( P<0.01). The kidneys of PGIS-/- mice showed tissue atrophy, surface irregularities and cyst formation. Blood urea nitrogen level in the PGIS-/- mice was significantly higher than that in the wild type ( PGIS+/+) mice [(36.89±5.39) mmol/L vs (5.07±0.69) mmol/L, n=3, P<0.01]. There was no significant difference in the mRNA expression of PGES and TXAS between PGIS+/+ mice and PGIS-/-mice. PGIS was widely expressed in renal vascular endothelial cells and smooth muscle cells of PGIS+/+ mice. Vascular system developed abnormally, which showed loss of smooth muscle layer, width of subendothelial loose layer, thinning of the pipe wall, and discontinuity of the inner elastic plate in PGIS+/- mice. There was no significant difference in the blood pressure and heart rate between PGIS systemic half-knockout ( PGIS+/-) mice and PGIS-/- mice. Conclusion:PGIS plays an important role in the development of kidney and vascular system in mice.

Objective:To investigate the clinical practice of chronic kidney disease-mineral and bone disorder (CKD-MBD) in maintenance hemodialysis patients in Shanghai, and to better understand the changes of clinical practice for CKD-MBD.Methods:Sixty-four hospitals with qualified dialysis center in Shanghai were selected for questionnaire survey as of March 2019. The survey questionnaire included the number of hemodialysis and peritoneal dialysis patients, the implementation of CKD-MBD guidelines, the learning of CKD-MBD guidelines, the detection and distribution of CKD-MBD biochemical indicators, the treatment of hyperphosphatemia, the treatment of secondary heperparathyroidism (SHPT) and renal bone disease, and the concentration of calcium ion in dialysate. The results were compared with previous survey data in 2011.Results:There were sixty-three hospitals included in this study, with 10 168 maintenance hemodialysis patients and 4 610 maintenance peritoneal dialysis patients in Shanghai. 84.1%(53/63) hospitals implemented the guidelines smoothly, which increased by 28.5% compared with the rate (55.6%) of 2011. The successful implementation rates for guidelines in secondary and tertiary hospitals were 83.3%(25/30) and 84.8%(28/33) , which increased by 44.0% and 11.7% respectively (39.3% of secondary hospitals and 73.1% of tertiary hospitals in 2011). All hospitals carried out the detection for serum calcium and phosphorus. The rate for parathyroid hormone (PTH), total alkaline phosphatase (AKP), bone specific alkaline phosphatase (BAP), 25-hydroxy vitamin D[25(OH)D], and other bone metabolism-related biomarkers were 98.4%(62/63), 90.5%(57/63), 19.0%(12/63), 90.5%(57/63) and 42.9%(27/63), respectively; coronary artery CT, lumbar lateral X-ray plain, echocardiography, bone mineral density, and vascular ultrasound were carried out in 68.3%(43/63), 74.6%(47/63), 100.0%(63/63), 68.3%(43/63)and 69.8%(44/63), respectively. Compared with 2011, the proportion of detection for PTH, AKP, BAP, 25(OH)D, coronary artery CT, lumbar lateral film and echocardiography increased by 2.1%, 1.6%, 0.5%, 47.9%, 14.6%, 20.9% and 1.9%, respectively. The proportion of patients with serum phosphorus ranging in 0.80-1.45 mmol/L(KDIGO guideline), serum phosphorus ranging in 0.80-1.78 mmol/L(KDOQI guideline), calcium ranging in 2.10-2.54 mmol/L, and PTH ranging in 150-600 ng/L were 37.0%(3 323/8 969), 50.7%(4 571/9 018), 60.2%(5 568/9 244) and 33.2%(3 018/9 087). Compared with 2011(39.6%, 53.5% and 34.1%), the proportion of patients with ideal serum phosphorus (0.80-1.78 mmol/L) and calcium (2.10-2.54 mmol/L) levels increased by 11.1% and 6.7% respectively, and the proportion with PTH 150-300 ng/L decreased by 0.9%. The proportion of hospitals for using non-calcium phosphate binders (lanthanum carbonate from 1.9% to 87.3% and sevelamer carbonate from 14.8% to 63.5%) and surgical treatment (from 38.9% to 68.3%) for SHPT dramatically increased.Conclusions:Through the availability of medicine increases, and nephrologists gain deeper understanding in management and treatment of CKD-MBD, the detection rate for CKD-MBD indicators and the eligible rate have significantly improved compared with those in 2011. However, the comprehensive management of CKD-MBD in Shanghai still faces great challenges. It is still necessary to further improve eligible rate for serum phosphorus and iPTH, so as to provide more evidences and management strategies for integrated management of end-stage renal disease and prevention of abnormal calcium and phosphorus metabolism in patients.

Objective To report the spontaneous remission and induced remission of phospholipase A2 receptor (PLA2R)-associated idiopathic membranous nephropathy (IMN) in adults,as well as to explore the potential prognostic factors.Methods A total of 120 patients with IMN in Huashan Hospital during 2012 and 2017 were enrolled and their clinical data were collected.Results PLA2R-associated IMN patients accounted for 89.2％ of the IMN patients.Spontaneous remission occurred in 35.5％ of PLA2R-associated IMN patients.The patients with higher serum albumin and lower level of PLA2R antibody were more likely to achieve spontaneous remission (both P ＜ 0.05).Multivariate logistic regression analysis showed that male was an independent risk factor for spontaneous remission in PLA2R-associated IMN patients (OR=0.060,95％CI 0.007-0.493,P=0.009),while higher serum albumin at baseline (OR=1.480,95％ CI 1.144-1.932,P=0.004) and the improvement of serum albumin after 3 months' non-immunosuppressive treatment (OR=2.040,95％CI 1.322-3.151,P=0.001) were independent protective factors for spontaneous remission.About 42.1％ PLA2R-associated IMN patients had received immunosuppressive therapy,with induced remission rate being 70.7％.High serum albumin before treatment was an independent protective factor for induced remission (OR=1.268,95％ CI 1.014-1.585,P=0.038).Conclusions PLA2R-associated IMN accounts for most of the IMN patients,with a spontaneous remission rate of 35.5％,during the follow-up period,which is even higher in patients with higher baseline serum albumin and lower PLA2R antibody titer.Induced remission rate is 70.7％ in patients in need of immunosuppresants.The serum albumin level may be helpful in predicting spontaneous remission and response to immunosuppressive therapy.

Objective To examine the effect and mechanism of high salt diet on the renal medullary cyclooxygenase 2 (COX2) expression and urinary sodium excretion. Methods Thirty male C57BL/6j mice were divided into four groups: (1) normal salt diet group (0.4％NaCl, n=5); (2) high salt diet group (8％NaCl, n=5);(3) Bortezomib+normal salt diet group (n=10);(4) Bortezomib+high salt diet group (n=10). The different groups were pre-treated with saline or bortezomib ,followed by normal salt diet or high salt diet for three days. All the mice were maintained on metabolic cage at the last day and allowed free access to water. Twenty-four hours urine was collected. Body weight, urine volumes were documented. At the end of experiments, mice were sacrificed under anesthesia and the kidneys were harvested for Western blotting and immunohistochemistry. The transgenic mice carrying a luciferase reporter driven by an NF-κB response promoter, HIV long terminal repeat (LTR) (HLL mice) were used to explore the effect of high salt diet on renal medullary NF-κB activity. HLL mice were fed with normal salt diet or high salt diet for 3 days, after which renal medullary luciferase activity was determined using a commercial luciferase assay kit. Luciferase activity was quantified with a luminometer and adjusted for the total amount of proteins. The cellular location of NF-κB was examined using immunohistochemistry of NF-κB p65 staining. Results (1) Western blotting results showed high salt diet significantly increased the COX2 expression in the renal medulla of C57BL/6j mice (P﹤0.05). (2) High salt diet significantly increased NF-κB luciferase reporter activity in the HLL mice renal medullary tissues when compared to normal salt diet (P﹤0.05). The immunohistochemistry of NF-κB p65 showed the expression of NF-κB was mainly in the renal interstitial cells. (3) Western blotting results showed bortezomib inhibited the renal medullar COX2 expression induced by high salt diet (P﹤0.05). (4) Bortezomib decreased the urinary sodium excretion of high salt diet mice (P﹤0.05), but had no change on urine volume. Conclusions High salt diet induce renal medullary COX2 over-expression and activate the activation of NF-κB in renal medullary. Bortezmoib can inhibit the renal medullar COX2 expression induced by high salt diet. The NF-κB pathway activation may involve in the regulation of renal medullar COX2 expression by high salt diet.

Objective To explore whether the stimulation effect of high phosphate on hyperplasia of human parathyroid cells and hyperparathyroidism through local cyclooxygenase 2 (COX2) up-regulation pathway. Methods Parathyroid glands were collected from 19 uremic patients undergoing parathyroidectomy.Expressions of COX1,COX2 and proliferative cell nuclear antigen (PCNA) of the glands were detected by immunohistochemistry.Primary parathyroid cells were cultured and treated with high or normal phosphate for 48 hours.Then expressions of COX2 and PCNA were detected by Western blotting and real-time PCR. Results Among 62 glands from above 19 patients,43 glands were nodular hyperplasia and 19 diffuse hyperplasia.Both high expressions of COX2 and PCNA were found in these blands.Expression of COX2 was found in both oxyphil and chief cells and was more in the diffuse hyperplasia glands than that in the nodular hyperplasia (P＜0.05).80.60％ and 85.20％ of COX2 positive cells in diffuse hyperplasia glands and nodular hyperplasia also expressed PCNA. High phosphate could stimulate iPTH secretion in vitro (P＜0.05).Expressions of COX2 and PCNA were higher in high phosphate group.(P＜0.05). Conclusion High phosphate may stimulate the hyperplasia of parathyroid cells by up-regulating the local COX2 expression.

Objective To evaluate the role of nutritional parameters in prognosis,especially in the early and late mortality of hospital-acquired acute kidney injury (AKI) patients.Methods This study was a prospective cohort study conducted in a hospital comprising 1500 beds in Shanghai, China. One hundred ninety-four patients with hospital-acquired AKI, as determined using the RIFLE staging criteria,were enrolled as subjects after obtaining informed consent.Patients with AKI caused by postrenal obstruction,glomerulonephritis,interstitial nephritis or vasculitis were excluded.Nutritional evaluation,including subjective global assessment (SGA),anthropometric and laboratory examination,was conducted. Other laboratory measurements and clinical data were recorded.The primary outcome was early mortality (≤ 7 days) and late mortality (8-28 days) after enrolling into the study. Results AKI patients at enrollment were characterized by a high prevalence of malnutrition as determined by SGA, anthropometric and laboratory examination.Univariate analysis showed that the SGA,the serum levels of prealbumin,cholesterol and total lymphatic cells, and the Maastricht index were significantly different among early mortality,late mortality and survival groups.The serum prealbumin and cholesterol levels in the early death group were significantly lower than those in the survival and late death groups (P＜0.05).Multivariate analysis revealed that SGA,albumin,prealbumin and cholesterol remained independently and significantly associated with early mortality after adjusting for age,sex,dialysis,ventilation,hemoglobin,platelets,bilirubin,and Glasgow coma score.The areas under the receiver operating characteristic curve to predict early mortality for albumin,prealbumin and cholesterol were 0.591,0.736 and 0.603,respectively,with that of prealbumin significantly higher than others (P＜0.05). Conclusion Low levels of serum prealbumin,albumin and cholesterol at enrollment are independtly associated with increased early mortality in hospital-acquired AKI patients.

Hemodialysis monitoring and information management software was used to establish an intelligent electronic system to manage hemodialysis patients' information,with hardware and software moderations.The electronic information management system for hemodialysis functioned steadily since 2008.This system changed not only the existing medical process of the center,but also contributed to safer treatments,more accurate operations of doctor’ s instructions,and better medical information records as well The results indicate that the electronic information management system in hemodialysis centers not only irnproves work efficiency and management quality significantly,but also effectively ensures the safety and caliber of hemodialysis treatment with less manpower costs.

Objective To report a simple formula to estimate phosphate removal by standard four-hour hemodialysis in Chinese patients.Methods A total of 165 MHD patients in Huashan Hospital were enrolled.Effluent dialysate samples were collected during treatment to estimate the total amount of phosphate removal.Pre-dialysis levels of serum phosphate,potassium (K+),hematocrit(Hct),parathyroid hormone(iPTH),carbon dioxide combining power(CO2CP),alkaline phosphatase (AKP),Kt/V,and ultrafiltration volume,age,gender,dry body weight,blood flow,phosphate clearance of dialyser,phosphate concentration of dialysate at 60 min after the start of HD were obtained.80％ observations were randomly selected for formula building by backward stepwise and the remaining 20％ observations were used to validate the formula.Results The formula was described as Tpo4 =88.6 ×C60-0.03 ×Age + 1.07 ×Gender +0.06 ×Clearance-4.59,where C60 was phosphate concentration in dialysate measured 60 min into HD and Clearance was the phosphate clearance of dialyser.Formula validation further suggested good predictive ability.Conclusion This study derives an approach to quantify phosphate removal by a simple formula,which will be helpful for clinicians to treat patient individually.

Objective To observe the changes of renin-angiotensin system (RAS) in cultured mesangial cells by serum from 3/4 nephrectomized rats feeding with low protein diet and α-keto acid. Methods Thirty male SD rats received 3/4 nephrectomy (Nx) were placed on 18%normal protein diet (NPD,n=10),6% low protein diet(LPD,n=10) or 5% low protein plus 1%α-keto acid diet (LK,n=10) flor 12 weeks.Ten male SD sham-operated rats fed with 18% normal protein diet were used as control (sham group).In addition,mesangial cells were cultured in sera (10%) collected from above animals treated with or without losartan (0.02 mmol/L)for 48 hours.ELISA was applied to detect the level of Ang II,TGF-β1 and fibronectin (FN) in cell medium.Westem blotting was used to determine the protein level of ATI receptor (AT1R)and real-time PCR was used to detect the mRNA level of AT1R,TGF-β1 and FN. Results (1) Nutritional indices including body weight,total protein and albumin had no significant difference in each group. (2) Serum creatinine and 24 h pruteinuria were significantly inceased in nephrectomized groups compared to sham group(P<0.05,respectively).24 h proteinuria was greatly lower in LK group than that in NPD and LPD groups(P<0.05,respectively).(3)LK greatly decteased the level of Ang II[NPD(12.70±0.12)mg/g protein;sham(8.04±0.62)mg/g protein]in supernatant as well as the protein and mRNA expression of AT1R in cultured mesangial cells (P<0.05).(4)NPD serum directly induced higher secretion[FN:sham(20.58±0.46)g/g protein,NPD (39.84±0.06)g/g protein;TGF-β1:sham(10.12±O.56)mg/g protein,NPD(83.85±3.58)mg/g protein] and mRNA expression of FN and TGF-β1 compared with sham group (P<0.05).LPD decreased these increment (P<0.05) and LK showed stronger inhibitory effect (P<0.05). (5)Losartan application sharply reduced FN and TGF-β1 production both in supematant and in mRNA expression in NPD serum treated cells (P<0.05,respectively). Conclusion Low protein diet with α-keto acids supplement directly inhibits the RAS in mesangial cells which may contribute to its beneficial effect on the kidney.