Efficacy and safety of febuxostat for treating hyperuricemia in patients with chronic kidney disease and in renal transplant recipients: A systematic review and meta-analysis.

Febuxostat is potent and well-tolerated in the management of chronic gout. However, its clinical efficacy and safety in the treatment of hyperuricemia in patients with chronic kidney disease (CKD) and in renal transplant recipients have remained to be fully determined. The MEDLINE, EMBASE and Cochrane Library databases were searched for relevant articles. Data were extracted and pooled results were estimated from the standard mean difference (SMD) with 95% confidence intervals (95% CIs). The quality of the studies included was assessed, and their publication bias was examined. Four prospective randomized controlled trials and two retrospective observational studies were included in the systematic review and meta-analysis. Febuxostat administration significantly reduced the serum uric acid concentration in patients with CKD and in renal transplant recipients when compared with allopurinol or placebo in the short-term (1 month: SMD, -2.24; 95% CI, -3.59 to -0.89; P-value of SMD=0.001; I2, 92.4%; 3 months: SMD, -1.20; 95% CI, -2.04 to -0.36; P-value of SMD=0.005; I2, 88.9%; 6 months: SMD, -1.49; 95% CI, -2.68 to -0.30; P-value of SMD=0.014; I2, 92.9%). Furthermore, the increase in the estimated glomerular filtration rate in the febuxostat group was significantly higher than that in the control group (SMD, 0.30; 95% CI, 0.031 to 0.58; P-value of SMD=0.029; I2, 0.0%). No significant difference in the changes in serum creatinine (Scr), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) was identified between the two groups (Scr: SMD, -0.17; 95% CI, -0.97 to 0.63; P-value of SMD=0.67; I2, 79.2%; LDL: SMD, -0.21; 95% CI, -0.49 to 0.07; P-value of SMD=0.13; I2, 34.1%; HDL: SMD, -0.05; 95% CI, -0.70 to 0.61; P-value of SMD=0.89; I2, 69.2%). In conclusion, febuxostat is a potent and well-tolerated agent for the short-term management of hyperuricemia in patients with CKD and in renal transplant recipients. However, these data should be interpreted with caution due to the varied design of the studies included in the present meta-analysis.

The MMP2 rs243865 polymorphism increases the risk of prostate cancer: A meta-analysis.

Prostate cancer is a common cancer in men. However, the association between the rs243865 single-nucleotide polymorphisms in the matrix metalloproteinase 2 gene (MMP2) and the risk for prostate cancer is inconclusive. We searched the PubMed, EMBASE, Cochrane Library, and the Chinese CNKI and WANFANG databases for the relevant literature. Data were extracted and pooled results were estimated from odds ratios (OR) with 95% confidence intervals (95% CIs). The quality of included studies was assessed, and publication bias of all included studies was examined. A total five studies involving 1895 patients with prostate cancer and 1918 controls were included. There was a significant association between rs243865 polymorphisms and higher risk of prostate cancer in the co-dominant model, dominant model, and allele model (CC vs. CT+TT, OR: 1.60, 95% CI: 1.22-2.11, P = 0.001; CC vs. CT, OR: 1.80, 95% CI: 1.34-2.42, P < 0.001; C vs. T, OR: 1.32, 95% CI: 1.05-1.66, P = 0.016, respectively). However, there was no significant difference between the co-recessive model and recessive model. Our meta-analysis results suggest that MMP2 rs243865 polymorphisms are significantly associated with higher risk of prostate cancer.

Association between TGFB1 genetic polymorphisms and chronic allograft dysfunction: a systematic review and meta-analysis.

BACKGROUND: Epidemiological studies have investigated the role of transforming growth factor-ß1 (TGF-ß1) in chronic allograft dysfunction (CAD) following kidney transplantation. TGFB1 gene polymorphisms (SNP rs1800470 and rs1800471) may be associated with the risk of CAD. In this meta-analysis, the relationship between these two variations and the risk of CAD was explored. MATERIALS AND METHODS: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, the Chinese CNKI and WANFANG databases were searched. Data were extracted and pooled results were estimated from odds ratios (ORs) with 95% confidential intervals (95% CIs). Quality assessments were performed, and publication bias of all eligible studies examined. RESULTS: Eight studies with 1038 subjects were included in our analysis. According to the effects on TGF-ß1 secretion, haplotypes were categorized as "HIGH", "INTERMEDIATE" and "LOW". The combined results showed a statistically significant difference of TGFB1 haplotypes between the CAD recipients and control subjects when "HIGH" with "INTERMEDIATE" and "LOW" ("HIGH" vs. "INTERMEDIATE" + "LOW": OR: 3.56, 95% CIs: 2.20, 5.78, P < 0.001) were compared. No significant association was found between the TGFB1 codon 10 or codon 25 and the CAD risk in all five genetic models. CONCLUSIONS: Our meta-analysis has found the haplotype of TGFB1 codon 10/25 T/T G/G and T/C G/G genotypes, associated with increased production of TGF-ß1, was linked with CAD risk following kidney transplantation. Moreover, no significant difference was found between TGFB1 codon 10 or codon 25 and the development of CAD.

Comparison of the efficacy and safety of URSL, RPLU, and MPCNL for treatment of large upper impacted ureteral stones: a randomized controlled trial.

BACKGROUND: There are three minimally invasive methods for the management of large upper impacted ureteral stones: mini-percutaneous nephrolithotomy (MPCNL), transurethral ureteroscope lithotripsy (URSL), and retroperitoneal laparoscopic ureterolithotomy (RPLU). This study aimed to compare MPCNL, URSL, and RPLU, and to evaluate which one is the best choice for large upper impacted ureteral stones. METHODS: Between January 2012 and December 2015, at the Department of Urology, Huai'an First People's Hospital, 150 consecutively enrolled patients with a large upper impacted ureteral stone (>15 mm) were included. The patients were randomly divided (1:1:1) into the MPCNL, URSL, and RPLU groups. The primary endpoint was success of stone removal measured 1 month postoperatively and the secondary endpoints were intraoperative and postoperative parameters and complications. RESULTS: Fifteen patients needed auxiliary ESWL after URSL, and 3 patients after MPCNL, but none after RPLU. The stone clearance rate was 96% (48/50) in the MPCNL group and 72% (33/46) in the URSL group. In the RPLU group the stones were completely removed and the stone clearance rate was 100% (48/48) (P = 0.021 vs. URSL; P = 0.083 vs. MPCNL). Operation-related complications were similar among the three groups (all P > 0.05). Hospital stay was shorter in the URSL group compared with MPCNL (P = 0.003). Operation time was the shortest with URSL and the longest with MPCNL (all P < 0.05). CONCLUSIONS: MPCNL and RPUL are more suitable for upper ureteral impacted stones of >15 mm. URSL could be considered if the patient is not suitable for general anesthesia, or the patient requests transurethral uretroscopic surgery. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry (Registration number: ChiCTR-INR-17011507 ; Registration date: 2017-5-22).

LINC00312 inhibits the migration and invasion of bladder cancer cells by targeting miR-197-3p.

To investigate the influence of the long non-coding RNA LINC00312 on bladder cancer (BC) cell invasion and metastasis by targeting miR-197-3p. BC and corresponding adjacent tissues were collected. LINC00312 and miR-197-3p were measured, and their correlation was detected through quantitative real-time PCR (qRT-PCR). BC cell line T24 was transfected and grouped (five groups) according to different transfection conditions. A scratch test was applied to analyze cell migration, and a Transwell assay was used to test cell invasion ability. Western blotting was to measure matrix metalloproteinase (MMP)-2, MMP-9, and the tissue inhibitor of metalloproteinase 2 (TIMP2) protein levels. qRT-PCR indicated that LINC00312 expression was lower but miR-197-3p expression was higher in BC tissues compared with adjacent tissues; LINC00312 was negatively correlated with miR-197-3p. The migration test revealed that the downregulation of miR-197-3p and overexpression of LINC00312 inhibited cell migration and invasion abilities, while the overexpression of miR-197-3p and the upregulation of LINC00312 promoted cell migration and invasion. BC cells with downregulated miR-197-3p or upregulated LINC00312 had low MMP-2 and MMP-9 levels but high TIMP2. LINC00312 inhibited BC cell invasion and metastasis through mediating miR-197-3p.

Upregulation of microRNA-96 and its oncogenic functions by targeting CDKN1A in bladder cancer.

BACKGROUND: Genome-wide miRNA expression profile has identified microRNA (miR)-96 as one of upregulated miRNAs in clinical bladder cancer (BC) tissues compared to normal bladder tissues. The aim of this study was to confirm the expression pattern of miR-96 in BC tissues and to investigate its involvement in carcinogenesis. METHODS: Quantitative real-time PCR was performed to detect the expression levels of miR-96 in 60 BC and 40 normal control tissues. Bioinformatics prediction combined with luciferase reporter assay were used to verify whether the cyclin-dependent kinase inhibitor CDKN1A was a potential target gene of miR-96. Cell counting kit-8 and apoptosis assays were further performed to evaluate the effects of miR-96-CDKN1A axis on cell proliferation and apoptosis of BC cell lines. RESULTS: We validated that miR-96 was significantly increased in both human BC tissues and cell lines. According to the data of miRTarBase, CDKN1A might be a candidate target gene of miR-96. In addition, luciferase reporter and Western blot assays respectively demonstrated that miR-96 could bind to the putative seed region in CDKN1A mRNA 3'UTR, and significantly reduce the expression level of CDKN1A protein. Moreover, we found that the inhibition of miR-96 expression remarkably decreased cell proliferation and promoted cell apoptosis of BC cell lines, which was consistent with the findings observed following the introduction of CDKN1A cDNA without 3'UTR restored miR-96. CONCLUSIONS: Our data reveal that miR-96 may function as an onco-miRNA in BC. Upregulation of miR-96 may contribute to aggressive malignancy partly through suppressing CDKN1A protein expression in BC cells.

[Impact of preoperative nutritional risk on complications after radical cystectomy].

OBJECTIVE: To evaluate whether urological patients at nutritional risk are at higher risk for complications after radical cystectomy than those not at nutritional risk. METHODS: We performed a retrospective observational study in the consecutive patients undergoing radical cystectomy between 2010 and 2013. A total of 147 patients were enrolled in this study. The nutritional risk score was assessed preoperatively by a specialized study nurse. The patients with NRS (nutritional risk screening, NRS2002)scores≥3 were considered to have nutritional deficiency. Postoperative complications were defined using the standardized Clavien-Dindo classification. Univariate and multivariate analyses were performed to identify the predictors of complications. RESULTS: The patients aged ≥70 years(50.57%) were more prone to nutritional risk than those aged <70 years (31.67%, P=0.023). Of the 63 patients at nutritional risk, 39 (61.90%) presented with at least 1 complication compared with 29 of the 84 controls (34.52%, P=0.001). The patients at nutritional risk were at threefold risk for complications on binary Logistic analysis (OR=3.128,95%CI 1.538-6.361,P=0.002). The length of hospital stay of the patients at higher nutritional risk was longer than that of those without nutritional risk [(12.9±5.7) d vs. (10.4±4.3) d, P=0.003]. CONCLUSION: The patients aged ≥70 years are at higher nutritional risk than that of those aged <70 years. Patients at nutritional risk are more prone to complications after radical cystectomy.

[Changes of miRNA-17-5p, miRNA-21 and miRNA-106a level during rat kidney ischemia-reperfusion injury].

OBJECTIVE: Ischemia-reperfusion (I/R) is a main cause of acute kidney injury (AKI). The renal expression profiles of microRNA (miRNA) and time course of their changes after renal I/R were explored to screen acute AKI prognostic-related microRNAs and biomarkers. METHODS: The expression profile of miRNA was analyzed for detecting miRNAs in kidney after renal I/R injury. Real-time polymerase chain reaction (PCR) was performed to validate the results of microarray. And the relationship was examined between kidney injury and time course of changes in selected miRNAs. RESULTS: Twenty-one miRNAs were differentially expressed in kidney of rats with renal I/R injury. And 5 miRNAs had prominent differences. miR-17-5p, miR-21 and miR-106a were selected for further confirmation by quantitative real-time-PCR. And the results were consistent with those of microarry. During early stage (4 h) after I/R, the expression level of miR-17-5p significantly increased (P < 0.05). And it occurred earlier than those of BUN level and plasma concentration of neutrophil gelatinase-associated lipocalin (NGAL). Renal expressions of miR-21 and miR-106a were significantly elevated in ischemia 20 min and 30 min groups at 12 h and 24 h post-reperfusion (P < 0.01). And the trend was in accordance with those of BUN and NGAL. CONCLUSIONS: miR-21, miR-17-5p and miR-106a are differentially expressed during different phases of renal I/R injury. And miR-17-5p is more sensitive than BUN and NGAL so that it is a more ideal biomarker for AKI.

Subcutaneous nephrovesical bypass: Treatment for ureteral obstruction in advanced metastatic disease.

The aim of the present study was to explore the value of subcutaneous nephrovesical bypass (SNVB) for the treatment of ureteral obstruction due to pelvic metastatic disease. SNVB stents (n=30) were implanted in 24 patients with advanced metastatic disease between January 2008 and December 2012. Urinalysis, serum creatinine (SCr), glomerular filtration rate (GFR), quality of life (QoL) scores, and renal ultrasonography were evaluated at follow-up. The SNVB procedures were successful in all 24 patients. Patient follow-ups occurred at an average of 10.6 months. Preoperative hydronephrosis was eliminated in 16 cases (53.3%) and reduced in the remaining patients. Following surgery, SCr levels reduced significantly from 256±46 to 124±23 µmol/l (P<0.001). GFRs increased from 25±4.8 to 45±5.3 ml/min (P<0.01). The mean QoL scores were 3.4±1.4 preoperatively and 7.6±1.0 postoperatively (P<0.001). The results showed that SNVB is a minimally invasive, effective and safe procedure for patients with ureteral obstruction resulting from advanced malignant disease. As an alternative procedure to percutaneous nephrostomy, SNVB offers patients a better QoL.

[Clinical efficacy and relative factors of dendritic cell-based tumor vaccination for prostate cancer: a systematic review and meta-analysis].

OBJECTIVE: To evaluate the efficacy and safety of dendritic cell (DC)-based vaccines in the treatment of prostate cancer, and investigate the factors that influence the clinical benefit rate (CBR) of the vaccines. METHODS: Based on pre-determined search criteria, we searched the Medline database for randomized controlled trials on DC-based vaccines immunotherapy of prostate cancer. We systematically analyzed the identified studies using RevMan 5.0 and SPSS 17.0 softwares. RESULTS: Ten randomized controlled trials involving 179 prostate cancer patients were identified and subjected to meta-analysis. The CBR of the DC vaccines for prostate cancer was 54.2% , and the objective response rate was 7.7%. Most adverse effects were local reactions at the injection site, fever and flu-like symptoms. The prostate cancer patients achieved cellular immune response (OR = 31.12, 95% CI = 5.52-175.6, P < 0.01) and reduction of log PSA slope (OR = 4.38, 95% CI = 1.17-16.35, P = 0.03) after administration of DC vaccines, which was positively correlated with CBR. The dose of DC vaccines had a significant correlation with CBR (OR = 5.98, 95% CI = 1.45-24.62, P = 0.01), but not the age of the patients (P = 0.53). Besides, density-enriched DCs achieved a higher CBR, while the route of administration had no effect on CBR. CONCLUSION: DC-based vaccines are effective, safe and well-tolerated in the treatment of prostate cancer. DC-mediated cellular immune response has a significant effect on CBR and can be used as an important index for the assessment of vaccines. More multi-centered randomized controlled trials of higher quality and larger sample size are needed to provide more valid evidence.

Overexpression of microRNA-100 predicts an unfavorable prognosis in renal cell carcinoma.

PURPOSE: Dysregulation of microRNA-100 (miR-100) has been reported to be involved in tumorigenesis and tumor progression of several cancer types. However, its expression patterns in tumors are controversial. The aim of this study was to investigate the expression and clinical significance of miR-100 in renal cell carcinoma (RCC). METHODS: Real-time quantitative PCR was performed to detect the expression levels of miR-100 in 96 paired samples of RCC and adjacent non-cancerous renal tissues. Then, statistical analysis was performed to determine the associations of miR-100 expression with the clinical features and the prognosis of RCCs. RESULTS: miR-100 expression was significantly higher in RCC tissues compared with adjacent non-cancerous renal tissues (5.3 ± 2.2 vs. 1.9 ± 0.8, P < 0.001). In addition, high miR-100 expression in RCC tissues was significantly associated with advanced tumor T stage (P = 0.005) and grade (P = 0.01), and the presence of metastasis (P = 0.008). Moreover, Kaplan-Meier analysis showed the significant differences in 5-year overall (50.0 vs. 83.3 %, P = 0.006) and tumor-specific survival (58.3 vs. 83.3 %, P = 0.008) for patients with high and low miR-100 expression, respectively. Furthermore, multivariable Cox regression analysis identified high miR-100 expression in RCC tissues as an independent poor prognostic marker of both overall (P = 0.01) and tumor-specific survival (P = 0.02) in patients with RCCs. CONCLUSION: Our data offer convincing evidence that miR-100 overexpression strongly associates with advanced tumor progression and unfavorable clinical outcome of patients with RCC. miR-100 expression may be a useful prognostic marker for this disease.

Comparative analysis of upper ureteral stones (> 15 mm) treated with retroperitoneoscopic ureterolithotomy and ureteroscopic pneumatic lithotripsy.

OBJECTIVE: To investigate an appropriate treatment for patients with upper ureteral stones, > 15 mm in size, by comparing the therapeutic outcomes for those undergoing retroperitoneoscopic ureterolithotomy (RPUL) and rigid ureteroscopic pneumatic lithotripsy (URSPL) retrospectively. PATIENTS AND METHODS: During the study period, 81 patients with a large upper ureteral stone (> 15 mm) were divided into two groups. RPUL was performed with retroperitoneal approach, and the stone was removed in group A. URSPL was conducted using a rigid ureteroscope, and pneumatic probe was used for lithotripsy in group B. The patient characteristics, success rate, stone-free rate, operation time, and complications were analyzed prospectively in the two groups. RESULTS: The success rates of operation were 94.5% (34/36) in group A and 88.8% (40/45) in group B, but there were no significant differences between two groups (P > 0.05). After 4 weeks of follow-up, the stone-free rate after RPUL (100%, 34/34) and URSPL (77.5%, 31/40) groups were statistically different (P = 0.006). Furthermore, simultaneous ureterolithotomy and ureteroplasty by retroperitoneal laparoscopic surgery were performed on four patients combined with ureteral stricture. However, the mean operation time and hospital staying time after surgery in group A were longer than that in group B, and the differences were statistically significant (P < 0.05). The complication rate after RPUL (17.6%, 6/34) was lower than that after URSPL (20%, 8/40), but the differences were not statistically significant (P > 0.05). CONCLUSION: RPUL is a safe and effective treatment technique for large, impacted, upper ureteral stones >15 mm in size when first-line treatments have failed or are unlikely to be effective. It can handle with combined pathologies simultaneously.

High bifurcation of abdominal aorta upon horseshoe kidney at the level of upper L2 vertebral body: a rare case report.

A high-positioned bifurcation of abdominal aorta upon a horseshoe kidney at the level of upper L2 vertebral body was detected during contrast enhanced abdominal computed tomography scan. The isthmus was clamped between the two elevated and extended common iliac arteries. The right renal artery arose from right common iliac artery supplying the superior and medium segments of right kidney. The left renal artery originated from right common iliac artery and branched off into three main arteries supplying the medium segment of right kidney, the inferior segment of right kidney and the lower half part of left kidney, respectively. The left accessory renal artery arose from abdominal aorta supplying the upper half part of left kidney. The inferior mesenteric artery arose from right common iliac artery. Lumbarization anomaly, scoliolosis, asymmetric pelvis and serious hydronephrosis of left kidney were also found. We describe this rare case of variations and discuss the possible embryonic development mechanism.