Objective To investigate the urate-lowering efficacy and renal effect of febuxostat in hyperuricemic patients with chronic kidney disease (CKD) stages 3-5. Methods A prospective, randomized, controlled trial of CKD stages 3-5 patients with hyperuricemia was conducted from June 2015 to June 2016. Patients were randomly assigned to either febuxostat group (treatment group) or allopurinol group (control group). Patients in treatment group received febuxostat 40 mg/d after study initiation, and the dosage was changed to 20 mg/d if serum uric acid (sUA)＜360 μmol/L. Patients in control group were administered a dose of 100 mg/d of allopurinol. Serum uric acid, serum creatinine and other clinical parameters were measured at baseline and 1-6 months after treatment. The rate of achieving target sUA level and the change of eGFR in two groups were performed using SPSS 21.0. Results A total of 98 patients met the inclusion criteria and completed the trial. The treatment group and the control group had 51 cases and 47 cases, respectively. There was no significant difference between the two groups in age, sex, body mass index (BMI), blood pressure, serum creatinine, eGFR, sUA and renal diseases (P＞0.05). At month 1-6, there were significant differences between treatment group and control group in the rate of achieving target sUA level (P＜0.01). At month 1 and month 3, no statistical difference was observed in the change of eGFR between the two groups (P=0.624, P=0.319). At month 6, the changes in eGFR were +2.23 ml?min-1?(1.73 m2)-1 and -4.36 ml?min-1?(1.73 m2)-1 in the treatment and control group, respectively, and the difference between the two groups was significant (P=0.037). In patients with CKD stages 3-5, generalized estimating equation showed that after adjusting for confounding variables, the eGFR increased 1.149 ml?min-1?(1.73 m2)-1 (P=0.003) and 24-hour urinary protein decreased 0.019 g/d (P=0.037) when per 60 μmol/L decreased in sUA. Febuxostat 20 mg/d was able to keep target sUA levels in 90.2% patients with CKD stages 3-5 within half a year and no serious adverse effects appeared. Conclusions Febuxostat performs better than allopurinol in lowering urate and delaying progression of renal function in patients with CKD stages 3-5 and HUA. Febuxostat 20 mg/d may be the effective and safe maintenance dose to maintain target sUA level in patients with CKD stages 3-5, but whether it can be used as the best long-term maintenance dose needs to be further studied.

Objective To investigate the characteristics and outcome of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in patients with renal injury. Methods AAV patients with renal injury diagnosed in the Department of Nephrology, Renmin Hospital of Wuhan University, from January 2012 to January 2017 were included into this study. Patients were divided into MPO-ANCA positive and PR3-ANCA positive groups for further study. The clinical characteristics, pathological and laboratory indexes, treatment and prognosis were retrospectively analyzed. Results A total of 68 cases were enrolled, among which 52 cases (76.5%) were MPO-ANCA positive and 16 cases (23.5%) were PR3-ANCA positive, and 41 patients (60.3%) were over 65 years old. The incidences of interstitial lung disease, digestive and nervous system damage in PR3-ANCA positive group were significantly higher than those MPO-ANCA positive group (P＜0.05). There were significant differences of hemoglobin, complement C3, complement C1q, IgE, 24 h urinary protein, erythrocyte sedimentation rate, procalcitonin, BVAS score and eGFR in two groups (P＜0.05). 19 cases had done renal biopsy，among them 14 cases were MPO-ANCA positive and 5 cases were PR3-ANCA positive. Incidence of crescentic necrotizing glomerulonephritis in PR3-ANCA positive group was significantly higher than that in MPO-ANCA positive group, and incidence of diffuse global glomerulosclerosis in MPO-ANCA positive group was significantly higher than that in PR3-ANCA positive group (all P＜0.05). At the median follow-up time of 32 months, the relapse rate at 6 month of MPO-ANCA-positive and PR3-ANCA-positive patients were 46.2% and 75.0%, respectively (P＜0.05). Multivariate logistic regression analysis showed that PR3-ANCA positive, age≥65 years old, baseline eGFR＜30 ml?min-1?(1.73 m2)-1, and combined with pulmonary interstitial lesions were all independent risk factors for relapse. And the incidence of ESRD were 42.3% and 75.0% during the follow-up period and 10 patients (14.7%) died. COX regression analysis showed that patients older than 65 years old, BVAS score≥18 points, eGFR＜30 ml?min-1?(1.73 m2)-1 and complicated with pulmonary interstitial disorders at the onset were independent risk factors causing ESRD or death. Conclusion The PR3-ANCA-positive patients had more severe renal injury than those with MPO-ANCA-positive patients, and the injury of extrarenal organs was more serious, recurrence rate was higher, and the prognosis was worse.

Objectives To compare the clinical characteristics, long-term survival and associated risk factors of automated peritoneal dialysis (APD) patients and continuous ambulatory peritoneal dialysis (CAPD) patients. Methods As a retrospectively study, adult patients started peritoneal dialysis in Peking Union Medical College Hospital (PUMCH) from September 1st, 2002 to September 30th, 2016 were enrolled. Baseline information and dialysis associated parameters were collected. The primary outcome was death and the secondary outcome was technical failure. The risk factors of death were analyzed in APD patients by Cox's regression model. Homochromous gender and age matched CAPD patients were analyzed as control. Results The baseline condition of 69 APD patients were similar to those of 138 CAPD patients. The survival rates of APD patients at 1-year、3-year and 5-year were 95.4%, 88.0% and 73.0% respectively, which were superior to CAPD patients. No significant difference in technical survival was found between APD and CAPD patients. Single-factor Cox's regression analysis showed that all-cause mortality of CAPD patients was 2.2 times higher than that of APD patients (95% CI 1.221-3.837). In the multi-factor Cox regression analysis model, adjusted by age, complications (including cardiovascular disease and diabetes), nPCR and serum creatinine, dialysis modality was not an independent risk factor of dialysis patients. Age (HR=1.077, 95%CI 1.016-1.142, P=0.013), diabetes (HR=3.608, 95%CI 1.117-11.660, P=0.032) and serum albumin (HR=0.890, 95%CI 0.808-0.982, P=0.020) were independently associated with all-cause death of APD patients. Conclusions Dialysis modality was not an independent risk factor for the all-cause mortality of peritoneal dialysis patients. Age, diabetic nephropathy and hypoalbuminemia were independently associated with the death of APD patients.

Objective To investigate the efficacy and safety of neurotropin in the treatment of restless legs syndrome and sleep disorder in patients with maintenance hemodialysis. Methods Sixty eight patients who met the inclusion criteria were randomly assigned to control group (n=34) and treatment group (n=34). The trial lasted for 16 weeks, and all patients undergone thorough dialysis. 7.2 units (2 branches) neurotropin were slowly injected to the patients in the treatment group at the end of each hemodialysis and they were stopped after 8 weeks. The patients in the control group had no treatment for restless leg syndrome on the basis of adequate dialysis. All patients were assessed regularly as regards their biochemical indexes, restless legs syndrome rating scale and Pittsburgh sleep quality index. Results All the patients completed the experiment, and restless legs syndrome scores were decreased in two groups. Compared with the baseline, the restless legs syndrome scores decreased significantly in patients treated with neurotropin, and the differences between two groups were significant (P＜0.01). In the Pittsburgh sleep quality index scores, the patients in the treatment group decreased in all scores and the difference was statistically significant (P＜0.01). Conclusions Neurotropin can relieve the symptoms of restless legs syndrome and sleep disturbance in patients on maintenance hemodialysis and is safe, but symptoms may occur again after withdrawal.

Objective To study shortdated postoperative variation characteristics of bone turnover markers (BTMs) in uremic patients with secondary hyperparathyroidism (SHPT) underwent parathyroidectomy (PTX). Methods A total of 19 uremic patients with SHPT underwent successful PTX, hospitalized in the Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University from January 2017 to April 2017, were enrolled in the study. The operative model for all enrolled patients was total parathyroidectomy with forearm autotransplantation. The baseline epidemiological and clinical data before PTX and the levels of serum intact parathyroid hormone (iPTH) and serum BTMs after PTX (in the 1st, 3rd and 7th postoperative day) were collected. The correlations between serum iPTH and serum BTMs before PTX and the trend analysis of serum BTMs after PTX were studied. Results The levels of serum iPTH, serum alkaline phosphatase (ALP), serum type Ⅰcollagen cross-linked C-telopeptides (CTX) and serum tartrate-resistant acid phosphatase 5b (TRACP-5b) before PTX were increased, in turn, (1512.4±612.0) ng/L, 267.4(153.1, 424.2) U/L, (5.78±1.15) μg/L and (8.79±4.61) IU/L. Positive correlations between ALP and iPTH (r=0.577, P=0.010), TRACP-5b and iPTH (r=0.640, P=0.003), and ALP and TRACP-5b (r=0.698, P=0.001) were found. The serum levels of ALP increased, while the serum levels of CTX and TRACP-5b decreased within 7 days after PTX. Conclusions Renal osteodystrophy (ROD) with high bone turnover rate is common in uremic patients with severe SHPT. The activities of osteoblast and osteoclast are up-regulated in coupling with positive correlations to serum levels of iPTH. Increased activities of osteoblast and decreased activities of osteoclast were found shortdated postoperatively.

Objective To study the effcts of total parathyroidectomy with autotransplantation (tPTX+AT) on fibroblast growth factor -23 (FGF - 23) in maintenance hemodialysis (MHD) patients with severe secondary hyperparathyroidism (SPTH). Methods Maintenance hemodialysis patients with severe SPTH treated in our hospital from 2014 to 2016 were enrolled and divided into two groups: tPTX+AT group and non-surgical group. Two groups' biochemical indexes and FGF-23 level before and after 6 months treatment were compared. Results A total of 48 patients were included in the study, including 22 in the tPTX+AT group and 26 in the non-surgical group. Age, duration of dialysis, primary disease, rate of hypertension, parathyroid hormone (iPTH), FGF-23, cholesterol (TCH), triglyceride (TG), albumin (ALB), and hemoglobin (HGB) level showed no significant difference between the two groups (P＞0.05); but serum calcium and alkaline phosphatase (ALP) of that tPTX+AT group were significantly higher than those of the non-surgical group (P＜0.01). After 6 months the blood iPTH, calcium, phosphorus and the calcium-phosphorus product level of tPTX+AT group were significantly lower than those of non-surgical group (P＜0.05). Blood lipids, propagated, HGB, and ALP level had no statistical differences in the two groups (P＞0.05); serum FGF-23 progressive declined after 1 week, 1 month, 3 month and 6 month in tPTX+AT patients, and after 6 months, the level of FGF-23 was significantly lower than that of non-surgical patients[1462.9(903.7, 5826.9) ng/L vs 12 627.9(5488.9, 16 844.4) ng/L, P＜0.01]. Conclusion tPTX+AT can significantly alleviate calcium and phosphorus metabolism disorders and in 6 months gradually reduce FGF-23 level in patients receiving MHD.

Objective To investigate the frailty in maintenance hemodialysis (MHD) patients and its influence factors. Methods A total of 127 adults undergoing hemodialysis from January 2015 and January 2016 in our center were recruited. Their clinical data and blood biochemical data were collected. Frailty was assessed using Fried's Frailty Phenotype. Quantification of coronary artery calcification (CACs) was determined by multi-slice spiral computed tomography (MSCT). According to the frailty scores, patients were divided into non-frailty, pro-frailty and frailty group. Their in clinical and biochemical index as well as CACs were compared. The correlations of frailty scores with above index were assessed by Spearman's correlation. Multiple logistic regression analysis was applied to evaluate the effect factors of frailty on MHD patients. Results Among 127 selected patients, 46(36.22%) patients without frailty, 45(35.43%) patients with pro-frailty, and 36(28.35%) patients with frailty. The age, diabetes, haemoglobin, albumin, pre-albumin, C-reactive protein, fibroblast growth factor 23 (FGF23), CACs and left ventricular end-diastolic dimension (LVEDD) of the 3 groups had statistical differences (all P＜0.05). The degrees of calcification among 3 groups were also different statistically (F=31.769, P＜0.001). In patients with MHD, frailty was positively correlated with age (r=0.545, P＜0.001), diabetes (r=0.236, P=0.008), C-reactive protein (r=0.245, P=0.006), FGF23 (r=0.189, P=0.034) and CACs (r=0.396, P＜0.001), while negatively correlated with haemoglobin (r=-0.257, P=0.004), albumin (r=-0.380, P＜0.001), pre-albumin (r=-0.313, P＜0.001). Age (OR=1.076), C-reactive protein (OR=1.176), albumin (OR=0.796) and artery calcification (OR=2.465) were independent influence factors for frailty in MHD patients (all P＜0.05). Conclusions The prevalence of frailty is high among MHD patients. Frailty is associated with age, C-reactive protein, albumin and artery calcification in MHD patients.

Objective To observe the effect of recombinant adenovirus-mediated the fms-like tyrosine kinast-1 (FLT-1) gene promoter carrying protein C (PC) gene (Ad-FLT-1/PC) on apoptosis and oxidative stress in rat with diabetic nephropathy atherosclerosis. Methods High sugar, high fat diet and streptozotocin by intraperitoneal injection were used to establish diabetic nephropathy atherosclerosis rat model. The rats were randomly divided into Ad-FLT-1/PC group (n=23), Ad-GFP group (n=23) and normal saline group (n=22) and injected with 300 ul Ad-FLT-1/PC, Ad-GFP and normal saline by caudal vein. Another healthy rats (n=23) were control group. At day 1, 3, 7 and 14 after transfection, rats of each group were randomly executed to observe vascular apoptosis and assay the level of SOD and MDA in plasma by the kit method of WST and TBA. Results Vascular cell apoptosis was observed in Ad-FLT-1/PC group, Ad-GFP group and NS group, the apoptosis index showed no statistical difference between three groups at each time point (P＞0.05). At day 14 after transfection, Ad-FLT-1/PC group rats had higher concentration of the plasma SOD and lower MDA than Ad-GFP group and NS group. The difference were statistically significant (all P＜0.05). Conclusions The recombinant adenovirus Ad-FLT-1/PC can effectively regulate oxidative stress but not apoptosis.

Objective To investigate the effects of the erythropoietin (EPO) on ischemia reperfusion injury (IRI) in rats with nephron-sparing surgery (NSS). Methods Fifty-four Sprague Dawley rats were divided into 3 groups randomly after right kidney nephrectomy: Sham group, NSS group (PBS+NSS) and EPO group (EPO+NSS). During NSS, renal artery was clamped for 40 min to induce IRI. Sham group just adopted exposure renal artery without vascular clamped. Rats in NSS group were injected intraperitoneally with PBS for 3 days before NSS. Rats in EPO group were injected intraperitoneally with EPO for 3 days before NSS. After 12 h, 24 h, 72 h, blood sample and renal tissues were collected. The serum creatinine (Scr) and urea nitrogen (BUN) were evaluated. The pathology injury was evaluated by HE staining. The CD24/CD133 double-positived renal progenitor cells (RPCs) were tested by flow cytometry. The CD133 and PCNA protein were quantified by immunohistochemical staining. The expressions of Wnt7b and β-catenin protein were detected by Western blotting. Results Rats in NSS group had more elevated Scr, BUN and pathology injury scores 12 h, 24 h and 72 h after operation than those in Sham group (all P＜0.05). Compared with those in the NSS group, the Scr and BUN in the EPO group were significantly lower 24 h after the surgery (all P＜0.05), and the pathology injury score also decreased (P＜0.05). The proportion of RPCs, expressions of CD133 and PCNA, and expressions of Wnt7b and β-catenin protein were significantly higher after 24 h of the surgery in NSS group than those in the Sham group (all P＜0.05). While compared with those in the NSS group, the proportion of RPCs and expressions of CD133, PCNA, Wnt7b and β-catenin increased at the EPO group (all P＜0.05). Conclusions EPO can reduce the IRI after NSS, and its mechanism may be related to the mobilization of the RPCs by the Wnt7b/β-catenin signal pathway.

Objective To explore the impacts of NPHP1 knockdown on the phenotype of Madin-Darby canine kidney (MDCK) cells. Methods The expression of NPHP1 in MDCK cells was knockdown by siRNA interference. Cells were divided into normal control group, negative control group and siRNA group. The cellular morphology and migration were observed by light microscope. The mRNA expressions and activities of matrix metalloproteinases 2 and 9 (MMP2 and MMP9) were detected by real time PCR and gelatin zymography. The mRNA and protein expressions of E-cadherin, β-catenin, zonula occluden-1 (ZO-1), ZO-1-associated nucleic acid binding protein (ZONAB) and α-smooth muscle actin (α-SMA) were analyzed by real time PCR, Western blotting and immunocytochemistry. Results Compared with those in normal control group, in siRNA group the mRNA expressions of E-cadherin, β-catenin and ZO-1 decreased, and MMP9, MMP2, α-SMA and ZONAB increased after interfering NPHP1 24 h (all P＜0.05); the protein expressions of E-cadherin, β-catenin and ZO-1 decreased and ZONAB and α-SMA increased after 48 h (all P＜0.05), and MDCK cells became elongated with enhanced migration capacity; siRNA cells had decreased expressions of E-cadherin and β-catenin on the membrane, but increased expression of ZONAB in cytoplasm and nucleoplasm after 72 h, and α-SMA was also observed in some interfered cells. Conclusions NPHP1 knockdown induces epithelial-mesenchymal transition in MDCK cells, and ZO-1/ZONAB signaling pathway was activated. These changes may associate with renal interstitial fibrosis of Nephronophthisis type I.