Objective:Through the investigation of the pathogenicity of COL4A4 heterozygous splicing mutations and the genotype-phenotype correlation in autosomal dominant Alport syndrome (ADAS), to better understand the impact of COL4A4 heterozygous splicing mutations on ADAS. Methods:The study was a case series analysis. Patients from 5 ADAS families with COL4A4 heterozygous splicing mutations detected by whole exome sequencing were recruited by three hospitals. In vivo transcriptional analysis and/or in vitro minigene splicing assay were conducted to determine the splicing patterns and assess the pathogenicity of COL4A4 heterozygous splicing mutations. Results:In the five ADAS pedigrees carrying COL4A4 heterozygous splicing mutations, four novel ADAS splicing patterns were described. In pedigree 1-4, most patients presented with continuous hematuria or/and microalbuminuria. Otherwise,the proband in pedigree 4 presented with macroalbuminuria and the proband in pedigree 1 had progressed to chronic kidney disease stage 2 at the age of 70 years old. In pedigree 5, all patients developed end-stage renal disease between 28 and 41 years old. c.735+3A>G detected in pedigree 1 and pedigree 2 and c.694-1G>C detected in pedigree 3 both led to exon 12 skipping in COL4A4, resulting in 42 nucleotides in-frame deletion (c.694_735del). c.2056+3A>G detected in pedigree 4 led to COL4A4 exon 26 skipping, which caused in-frame deletion of 69 nucleotides (c.1988_2056del). c.2716+5G>T detected in pedigree 5 led to a 360 nucleotides large in-frame deletion, including 100 bp sequence at the 3'end of exon 29,the whole sequence of exon 30 and 89 bp sequence at the 5'end of exon 31 (c.2446_2805del). Conclusions:Renal prognosis differs significantly for patients with small in-frame deletions versus large in-frame deletion splicing abnormalities. Determination of the pathogenicity and the splicing patterns of COL4A4 heterozygous splicing mutations using in vivo and in vitro transcriptional analysis may provide renal prognostic information.

Objectives:To analyze the clinical features of microscopic polyangiitis (MPA), and observe the clinical outcomes of different pathological types.Methods:The clinical data of 61 patients with MPA in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2010 to December 2019 were analyzed retrospectively. According to age, the patients were divided into ≥ 60 years old group (46 cases) and<60 years old group (15 cases). According to the initial serum creatinine, the patients were divided into ≥ 500 μmol/L group (18 cases) and<500 μmol/L group (43 cases). The basic data and laboratory examination results of the patients were recorded, and the disease activity was evaluated by Birmingham systemic vasculitis activity score (BVAS). Twenty-three patients with complete pathological data were pathologically classified and followed up to assess their clinical outcomes. The progression to end-stage renal disease (ESRD) or death was defined as the endpoint.Results:Ferritin in ≥60 years old group was significantly higher than that in<60 years old group: 452 (289, 792) μg/L vs. 210 (119, 451) μg/L, and there was statistical difference ( P<0.05). The fever rate, hemoglobin and platelets in creatinine ≥ 500 μmol/L group were significantly lower than those in creatinine<500 μmol/L group: 3/18 vs. 48.8% (21/43), 77.5 (62.8, 86.0) g/L vs. 85.0 (77.0, 104.0) g/L and 192 (147, 234) × 10 9/L vs. 257 (208, 365) × 10 9/L, the gastrointestinal involvement and BVAS in creatinine ≥ 500 μmol/L group were significantly higher than those in creatinine<500 μmol/L group: 16/18 vs. 25.6% (11/43) and 20.0 (16.0, 23.3) scores vs. 15.0 (12.0, 19.0) scores, and there were statistical differences ( P<0.05 or<0.01). Pearson correlation analysis result showed that BVAS was positively correlated with creatinine ( r = 0.42, P<0.01), negatively correlated with hemoglobin ( r = -0.42, P<0.01), but it had no correlation with erythrocyte sedimentation rate and platelets ( r = 0.05 and 0.04, P>0.05). Among the 23 patients with completed the clinical outcome statistics, endpoint events occurred in 5 of 6 patients with crescent renal pathology, and in 7 of 12 patients with severe renal interstitial injury. Kaplan-Meier survival curve analysis result showed that the average survival time in ESRD MPA patients was significantly shorter than that in non ESRD MPA patients (41.2 months vs. 63.5 months), and there was statistical difference ( χ2 = 0.48, P = 0.028). Conclusions:The clinical manifestations of elderly MPA patients are similar to those of young MPA patients. Creatinine≥500 μmol/L or anemia at initial onset indicate higher vasculitis activity in MPA. The prognosis of MPA patients with pathological manifestations of crescent or severe interstitial injury is poor, and the survival rate of ESRD is lower than that of non ESRD patients.

Objective:To investigate the role of survival motor neuron ( SMN) gene knockout in mice with cisplatin-induced acute kidney injury (AKI). Methods:A mouse model (C57BL/6) of cisplatin-induced AKI was constructed. Twenty male wild type (WT) and SMN+/- mice weighing 22-24 g were randomly divided into four groups: WT mice with saline injection group (WT vehicle, n=5), SMN+/- mice with saline injection group ( SMN+/- vehicle, n=5), WT mice with cisplatin injection group (WT cisplatin, n=5) and SMN+/- mice with cisplatin injection group ( SMN+/- cisplatin, n=5). Mice were injected intraperitoneally with 20 mg/kg cisplatin or 0.9% saline. 72 hours later, the mice were sacrificed, and serum and kidney tissues were collected. The real time PCR and Western blotting were used to measure the expression levels of SMN mRNA and protein. The sarcosine oxidation and urease method were used to measure serum creatinine (Scr) and blood urea nitrogen (BUN) levels. Renal pathologic changes were observed by PAS staining. TUNEL immunofluorescence assay was used to detect the level of apoptosis. Western blotting and immunohistochemistry were used to detect the protein expression levels of apoptosis index poly (ADP-ribose) polymerase (PARP) and endoplasmic reticulum stress index CHOP. Results:Compared with WT mice, SMN mRNA and protein expression levels were lower in SMN+/- mice, and the expression level of SMN mRNA and protein was further decreased after intraperitoneal cisplatin injection (all P<0.05). Compared with WT mice with saline injection group, WT mice with cisplatin injection group had higher levels of Scr, BUN, tubular damage scores, TUNEL positive cell numbers, PARP and CHOP, while the expression levels of above indexes in the SMN+/- mice with cisplatin injection group were higher than those in the WT mice with cisplatin injection group (all P<0.05). Conclusions:SMN gene knockout can aggravate renal pathological damage and apoptosis of renal tubular epithelial cell in cisplatin-induced AKI mice. SMN may be a potential therapeutic target of AKI.

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.

Teaching rounds is an important part of clinical teaching practice, therefore, we established a demonstration team for teaching ward rounds. By formulating standard operation procedure for teaching rounds and encouraging innovation on teaching models, the team played a demonstration role in the clinical teaching rounds, which not only made up the shortcomings in teaching, but also improved the teaching level of clinical teachers and the quality of clinical training.

Objective To investigate the efficacy of leflunomide combined with prednisone in the induction therapy of proliferative lupus nephritis (LN).Methods A prospective,multicenter,randomized controlled clinical trial was conducted in patients with biopsy-proved proliferative lupus nephritis recruited from 15 renal centers from 2013 to 2015.Patients were randomized to two groups.Oral leflunomide or intravenous cyclophosphamide was given to patients in each group.Both groups received a tapering course of oral prednisone therapy.All patients were followed up for 24 weeks.The blood biochemistry,urine index,clinical curative effect and adverse reaction were recorded and analyzed statistically.Results A total of 100 patients were enrolled in this clinical trial,including 48 patients in leflunomide group and 52 patients in cyclophosphamide group.After 24 weeks,the overall response rate was 79％ (95％ CI 67％-90％) in the leflunomide group and 69％ (95％ CI 56％-82％) in the cyclophosphamide group.23％ (95％CI 11％-35％) of patients in leflunomide group showed complete remission compared with 27％ (95％CI 24％-30％) in cyclophosphamide group (P=0.35).The levels of 24-hr urine protein excretion,SLEDAI and anti-dsDNA antibody titers were decreased in patients treated with leflunomide group after 24-weeks treatment.And the levels of serum albumin and complement 3 after treatment were significantly higher compared with these before treatment.There was also no significant difference in changes of 24-hr urine protein excretion,SLEDAI score,anti-dsDNA antibody titers,serum albumin and complement C3 levels after treatment between two groups.Incidence of adverse events did not differ between the leflunomide and cyclophosphamide group.Conclusions Leflunomide combined with prednisone showed same efficacy compared with cyclophosphamide as induction therapy for lupus nephritis.Leflunomide might be an useful medicine in the induction therapy of lupus nephritis.

Objective To analyze the role of telehealth?based dialysis registration systems in real?time and dynamic reflection of renal anemia in hemodialysis (HD) patients, and discuss the prospect of its application in dialysis registration management. Methods The Red China project was to build up a dialysis registration system based on the WeChat mobile terminal platform. Demographic and baseline laboratory parameters such as age, gender, primary disease, dialysis age, creatinine were recorded in this system. Hemoglobin (Hb) level was monthly recorded. The platform generated Hb statistics report for each HD center monthly, including the detection rate, target rate and the distribution level of Hb, and released it to physicians through the WeChat terminal of mobile phone. After that, physicians could change the treatment of anemia individually on basis of this report. Here the demographic and baseline laboratory parameters, the detection rate, target rate, the average level and the distribution of Hb from June 2015 to October 2017 after the project launched were analyzed. Results From June 2015 to October 2017, 8392 maintenance HD patients from 28 HD centers in Shanghai were enrolled, of whom 5059(60.3％) were male.The average rate age was (60.5 ± 13.7) years old. Baseline average Hb was (108.3±16.0) g/L. Baseline detection rate and target rate were 54.2％and 47.5％, respectively. After 28 months follow?up, the detection rate of Hb increased from 54.2％ to 73.6％ (P<0.001), the target rate of Hb increased from 47.5％ to 56.1％ (P<0.001), and the level of average Hb rose from (108.3±16.0) g/L to (110.7±16.0) g/L. The difference between average Hb in two consecutive months was less than 1.3 g/L. Conclusions The telehealth?based dialysis registration system can timely report the anemia situation of HD patients, which may improve the awareness rate of anemia, the degree of attention and the compliance of anemia monitoring, so as to improve the detection rate and target rate of Hb and reduce the fluctuation of Hb, which helps to maintain the HD patients to correct anemia in a timely, stable and long?term way. The telehealth?based dialysis registration system, as an improved mode of dialysis registration is a promising way for long?term management of renal anemia in dialysis patients.

Objectives By Oxford pathological classification and analysis of circulating complement complement 3 (C3),renal C3 deposition,and clinical laboratory tests,we discussed the correlation between complement C3 and immunoglobin A nephropathy (IgAN) in pathogenesis.Methods A retrospective study of 558 IgAN cases at Xinhua Hospital from January of 2000 through December of 2013 was performed.All 558 IgAN diagnoses were made and confirmed by renal needle biopsy.Results Compared to patients who had circulating C3 ＜ 0.9,patients with circulating C3 level ＞ 0.9 showed statistically significant decreases in serum creatinine [(100.92 ± 105.31) μmol/L vs (157.58 ± 208.39) μmol/L,t =-2.283,P =0.025],blood urea nitrogen [(5.69 ± 2.88) mmol/L vs (7.69 ± 5.90) mmoL/L,t =-2.81,P =0.006];besides,other parameters like IgA,body weight,body mass index (BMI),cholesterol,triglyceride,serum IgA/C3 ratio,albumin,and estimated glomeruli filtrate rate (eGFR) also presented statistically significant differences between two patient groups;no statistically significant differences were observed between two groups in glomerular mesangial cell proliferation,capillary endothelial proliferation,segmental glomerular sclerosis or adhesions,renal tubule atrophy,tubulointerstitial fibrosis,and formation of glomerular crescent;meanwhile,no statistically significant differences were observed between two groups in mesangial depositions of IgA,IgG,IgM,and complement C3;meanwhile the blood level of C3 between C3 deposition negative group,deposition 2 + and 3 + subgroup showed statistically significant differences (2.493 and 2.782;0.013 and 0.006),nevertheless,prognostic indices in Oxford classification,such as mesangial cell proliferation,capillary endothelial proliferation,segmental glomerular sclerosis or adhesions,renal tubule atrophy and tubulointerstitial fibrosis,were also statistically different between two patient groups (Pearson Square test result was 50.782,35.141,21.105,30.182,respectively;P ＜0.01).Conclusions Renal deposition of complement C3 or decrease in circulating C3 level may be associated with a poor prognosis of IgA nephropathy,and alteration in C3 dynamics may be implicated in the pathogenesis of IgAN through its involvement in humoral immunity.

Objective To investigate whether the combination of maintenance hemodialysis (MHD) with hemoperfusion(HP) can improve the clearance rate of middle- and largemolecule uremic toxins so as to improve the quality of life and reduce the mortality in MHD patients. Methods A prospective, randomized and controlled clinical trial was carried out. One hundred MHD patients were selected and then randomly divided into two groups after four weeks of run-in period. HD+HP group received MHD alone 2 times a week and the combined treatment of HD with HP (HD+HP) once a week, whereas HD group received MHD alone 3 times a week. The follow up lasted for mean 2 years. The primary outcome was the death of patients. Secondary end points included clinical data, leptin, high sensitive C-reactive protein (hsCRP), interleukin 6 (IL-6),β2 microglobulin (β2-MG), parathyroid hormone (PTH), tumor necrosis factor α (TNF-α) and the indexes of dimensions of Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36Chinese Edition ). Results At the end of the two-year observation, the serum concentration of leptin, hsCRP, PTH, IL-6, β2-MG and TNF-α, systolic blood pressure (SBP), diastolic blood pressure(DBP), heart rate(HR), cardiothoracie ratio, left ventricular mass index (LVMI), EPO dose and the types of antihypertensive drugs used were lower in HD +HP group as compared to HD group (all P＜0.05). HD+HP group had higher hemoglobin (Hb), ejection fraction (EF) and body mass index (BMI) (all P＜0.05). No significant differences between two groups were found in terms of serum albumin (Alb), serum iron (SI), total iron binding capacity (TIBC), cardiac output (CO),Kt/V, early/atrial mitral inflow velocities (E/A) (all P＞0.05). Besides, the SF-36 indicated that the total score of overall dimensions in HD+HP group was higher (P＜0.05) and the quality of life of HD+HP group was evidently better as compared to HD group. The Kaplan-Meier survival curves for the 2-year observation period showed that patients in HD +HP group had obvious survival advantage, while Log-rank test results showed P＜0.05. No serious adverse incidents occurred during the HD+HP treatment. Conclusion HD+HP is superior to HD in eliminating regularly middleand large-molecules uremic toxins and has a potential role in improving the quality of life and survival rate of MHD patients.

Objective To evaluate the efficacy and safety of PES14LF polyethersulfone highflux dialyzer on maintenance hemodialysis(MHD)patients. Methods A total of 72 MHD patients from two hospitals in Shanghai were enrolled in a randomized parallel controlled study.Conventional hemodialysis was performed for 4 h with PES14LF dialyzer in trial group and with German F6 dialyzer in control group.For each patient the study lasted one week.The clearances of urea,creatinine and phosphate were calculated.Adverse event and adverse reaction were recorded.Results There were no significant difierences of urea and creatinine clearance and reduction ratio between trial and control group.The phosphate clearance in trial group was significantly higher than that in control group[(144.57±27.83)ml/min vs(117.15±22.77)ml/min,P＜0.051.There was no significant difference of phosphate reduction ratio between trial and control group.The efficiency of urea clearance and urea reduction ratio achieved clinic effective target in two groups and no significant differences in above indexes between two groups were found. Conclusion PES14LF dialyzer is effective and safe for clinical application.