Showing papers in "International Urology and Nephrology in 2018"
TL;DR: Novel biomarkers seem to be more helpful to early detect AKI and/or predict the need for renal replacement, and mortality compared to serum creatinine, but more comprehensive studies are still required to determine their clinical utility.
Abstract: Acute kidney injury (AKI) consists of a rapid renal function decline which usually increases serum urea and creatinine levels. Since kidney injury begins by inducing biological and molecular changes which evolve to cellular damage, biomarkers could be used as tools for monitoring early AKI appearance, and predicting its recovery. Among the main AKI biomarkers the neutrophil gelatinase-associated lipocalin, cystatin C, kidney injury molecule-1, monocyte chemotactic peptide-1, N-acetyl-β-D-glucosaminidase, interleukin-18, liver-type fatty acid-binding protein, netrin-1, cycle arrest markers, endogenous ouabain, selenium-binding protein 1, and BPIFA2 marker, have been described. Even though novel biomarkers seem to be more helpful to early detect AKI and/or predict the need for renal replacement, and mortality compared to serum creatinine, more comprehensive studies are still required to determine their clinical utility.
117 citations
TL;DR: The causal interconnection between the gut microbial dysbiosis and CKD is demonstrated and favorable modification of the composition and function of the gut microbiome represents an appealing therapeutic target for prevention and treatment of CKD.
Abstract: Chronic kidney disease (CKD) has been shown to result in profound changes in the composition and functions of the gut microbial flora which by disrupting intestinal epithelial barrier and generating toxic by-products contributes to systemic inflammation and the associated complications. On the other hand, emerging evidence points to the role of the gut microbiota in the development and progression of CKD by provoking inflammation, proteinuria, hypertension, and diabetes. These observations demonstrate the causal interconnection between the gut microbial dysbiosis and CKD. The gut microbiota closely interacts with the inflammatory, renal, cardiovascular, and endocrine systems via metabolic, humoral, and neural signaling pathways, events which can lead to chronic systemic inflammation, proteinuria, hypertension, diabetes, and kidney disease. Given the established role of the gut microbiota in the development and progression of CKD and its complications, favorable modification of the composition and function of the gut microbiome represents an appealing therapeutic target for prevention and treatment of CKD. This review provides an overview of the role of the gut microbial dysbiosis in the pathogenesis of the common causes of CKD including hypertension, diabetes, and proteinuria as well as progression of CKD.
102 citations
TL;DR: The results support previous findings on the possibility of discriminating prostate cancer patients from healthy controls by detecting miRNA (miR-141-3p, miR-21, and miR -375) and further insights into miRNA abundance and characteristics are necessary to validate the panel of miRNA as surrogate markers in diagnosis of prostate cancer.
Abstract: Prostate cancer (PCa) is a common tumor disease in western countries and a leading cause of cancer-driven mortality in men Current methods for prostate cancer detection, like prostate-specific antigen screening, lead to significant overtreatment The purpose of the study was to analyze circulating microRNAs in serum as non-invasive biomarkers in patients with diagnosis of prostate cancer and healthy individuals This preliminary study included a population of 20 patients with mean age of 686 years and mean PSA of 213 ng/ml Eight healthy patients were used as control MiRNAs were quantified in the total RNA fraction extracted from serum and levels of five microRNAs (miR-106b, miR-141, miR-21, mir-34a, and miR-375) were quantified by RT-qPCR Statistical analyses evaluated correlation between clinicopathological data and miRNAs expression levels Relative expression ratios of miR-106b, miR-141-3p, miR-21, and miR-375 were significantly increased (18-, 19-, 24-, and 26-fold, respectively) in the PCa group compared to healthy control Using receiver operating characteristics, the highest area under the curve equal to 0906 was obtained for miR-357 and indicates a very good diagnostic properties of this biomarker We found expression level of mir-34a not related with PCa Our results support previous findings on the possibility of discriminating prostate cancer patients from healthy controls by detecting miRNA (miR-141-3p, miR-21, and miR-375) Further insights into miRNA abundance and characteristics are necessary to validate the panel of miRNA as surrogate markers in diagnosis of prostate cancer
88 citations
TL;DR: Current evidence based on careful review of published studies confirms the effectiveness of varicocelectomy as a means of both reducing oxidatively induced sperm DNA damage and potentially improving fertility.
Abstract: Varicocele, the leading cause of male infertility, can impair sperm quality and fertility via various oxidative stress mechanisms. An imbalance between excessive reactive oxygen species production and antioxidant protection causes alterations in nuclear and mitochondrial sperm DNA, thus rendering a subset of varicocele men less fertile. In particular, sperm DNA fragmentation is usually elevated in men with clinical varicocele in both abnormal and normal semen parameters by the current World Health Organization criteria. In this review, we discuss the evidence concerning the association between varicocele, oxidative stress, and SDF, and the possible mechanisms involved in infertility. Furthermore, we summarize the role of varicocele repair as a means of alleviating SDF and improving fertility. Lastly, we critically appraise the evidence-based algorithm recently issued by the Society for Translational Medicine aimed at guiding urologists on the use of SDF testing in men with varicocele seeking fertility. Current evidence based on careful review of published studies confirms the effectiveness of varicocelectomy as a means of both reducing oxidatively induced sperm DNA damage and potentially improving fertility. Varicocele repair should be offered as part of treatment option for male partners of infertile couples presenting with palpable varicoceles.
67 citations
TL;DR: A review of existing studies on physical activity in chronic kidney disease and end-stage renal disease patients tried to critically summarize the existing studies, to explore mechanisms and describe future perspectives regarding physical activity.
Abstract: The prevalence of chronic kidney disease (CKD) and end-stage renal disease (ESRD) is increasing steadily. CKD does not only relate to morbidity and mortality but also has impact on quality of life, depression and malnutrition. Such patients often have significantly decreased physical activity. Recent evidence suggests that low physical activity is associated with morbidity, mortality, muscle atrophy, quality of life impairment, cardiovascular outcomes and depression. Based on this, it is now recommended to regularly improve the physical activity of these patients. Furthermore, studies have shown the beneficial effects of various exercise programs with respect to outcomes such as low physical activity muscle atrophy, quality of life, cardiovascular outcomes and depression. Despite these encouraging findings, the subject is still under debate, with various aspects still unknown. In this review, we tried to critically summarize the existing studies, to explore mechanisms and describe future perspectives regarding physical activity in CKD/ESRD patients.
58 citations
TL;DR: MDC can lower the all-cause mortality of patients with CKD, reduce temporary catheterization for patients receiving dialysis, decrease the hospitalization rate, and slow the eGFR decline.
Abstract: To assess the efficacy of the multidisciplinary care (MDC) model for patients with chronic kidney disease (CKD). The MDC model has been used in clinical practice for years, but the effectiveness of the MDC model for patients with CKD remains controversial. Embase, PubMed, Medline, the Cochrane Library, and China National Knowledge Infrastructure databases were used to search for relevant articles. Only randomized controlled trials and cohort studies were pooled. Two independent authors assessed all articles and extracted the data. The efficacy was estimated from the odds ratios and corresponding 95% confidence intervals. A random effects model was used according to the heterogeneity. Twenty-one studies including 10,284 participants were analyzed. Compared with the non-MDC group, MDC was associated with a lower risk of all-cause mortality and lower hospitalization rates for patients with CKD. In addition, MDC also resulted in a slower eGFR decline and reduced temporary catheterization for patients receiving dialysis. However, according to the subgroup analysis, the lower rates of all-cause mortality in the MDC group were observed only in patients in stage 4–5 and when the staff of the MDC consisted of nephrologists, nurse specialists and professionals from other fields. The most prominent effect of reducing the hospitalization rates was also observed in patients with stage 4–5 but not in patients with stage 4–5 CKD. MDC can lower the all-cause mortality of patients with CKD, reduce temporary catheterization for patients receiving dialysis, decrease the hospitalization rate, and slow the eGFR decline. Moreover, the reduction in all-cause mortality crucially depends on the professionals comprising the MDC staff and the stage of CKD in patients. In addition, the CKD stage influences the hospitalization rates.
57 citations
TL;DR: Emodin showed an anti-fibrosis effect in surgery-induced renal fibrotic rats and this effect was potentially achieved via down- Regulating expressions of TGF-β1 and Smurf 2 and up-regulating Smad7 expression.
Abstract: Emodin is a natural active component extracted from Chinese herbs. In this study, we investigated the therapeutic effect of emodin on surgery-induced renal fibrosis in rat. Moreover, the function of Smad ubiquitination regulatory factor 2 (Smurf 2) was further studied in vitro. The renal fibrosis rat model was established via 5/6 renal mass reduction. The histopathological abnormalities of renal tissues in rats were tested via staining method and microscopic examination. Renal function indicators, the serum creatinine, blood urea nitrogen and total urinary protein were measured via spectrophotometric method. The renal tissues were tested via Western blotting and real-time quantitative PCR. Moreover, Smurf 2 protein expression under different conditions and its regulatory function in vitro was measured via Western blotting. Our results showed that the histopathological abnormalities, the decrease in rat body weight and the abnormal renal function caused by renal fibrosis were improved by emodin. Further, mRNA expression of TGF-β1 was decreased by emodin. Furthermore, extracellular matrix (ECM) components as well as TGF-β1/Smad signaling-related Smurf 2 were decreased by emodin both in vivo and in vitro. The protein level of mothers against decapentaplegic homolog 7 (Smad7) was up-regulated. In addition, ECM components were increased by Smurf 2 over-expression and these effects were weakened by emodin co-treatment in vitro. Emodin showed an anti-fibrosis effect in surgery-induced renal fibrotic rats. And this effect was potentially achieved via down-regulating expressions of TGF-β1 and Smurf 2 and up-regulating Smad7 expression.
48 citations
TL;DR: In this article, the exact pathophysiological mechanism of urolithiasis is not yet clear, as these calculi are of various types and too complex for simple understanding, therefore, different theories are presented in various times for its explanation like free particle, fixed particle, Randall's plaque theory.
Abstract: The formation of urinary stone, urolithiasis, is one the oldest known disease affecting human throughout different civilizations and times. The exact pathophysiological mechanism of urolithiasis is not yet clear, as these calculi are of various types and too complex for simple understanding. A single theory cannot explain its formation; therefore, different theories are presented in various times for its explanation like free particle, fixed particle, Randall’s plaque theory. In addition, various factors and components are identified that play an important role in the formation of these urinary calculi. In this review, composition of kidney stones, its prevalence/incidence, explanation of pathophysiological mechanisms and role of various factors; urinary pH, uric acid, parathyroid hormone, citrate, oxalate, calcium and macromolecules; osteopontin, matrix Gla protein, kidney injury molecules, urinary prothrombin fragment-1, Tamm–Horsfall protein, inter-α-inhibitors, have been discussed in detail.
44 citations
TL;DR: Depression and anxiety were significantly associated with females, low level of education, increased patients’ age, retirement, poor financial situation, marital status and co-morbidities.
Abstract: Depression and anxiety have high prevalence in patients on hemodialysis and are strongly associated with socio-economic factors. The aim of this study was to evaluate the prevalence of depression and anxiety in hemodialyzed patients in Greece and its association with socio-demographic factors. Four hundred and fourteen (414) patients on hemodialysis (262 males and 152 females) from 24 dialysis centers in Greece participated in this observational cross-sectional study. Mean age was 63.54 (54.06–72.41), and mean time of dialysis treatment was 36 (16–72) months. Depression and anxiety were assessed by the state–trait anxiety inventory (STAI), the beck depression inventory (BDI) and the hospital anxiety and depression scale (HADS). Multinomial logistic regression was performed to estimate the factors being independently associated with anxiety and depression levels (HADS scale). Multiple linear regression was performed to estimate the factors being independently associated with BDI and STAI. From a total of 414 participants, (29.4%, n = 122) had depression and 35.9% (n = 149) had anxiety. Depression and anxiety were significantly associated with females, low level of education, increased patients’ age, retirement, poor financial situation, marital status and co-morbidities. The overall study findings indicated a significant correlation between the levels of anxiety and depression in patients on hemodialysis. Patients with high levels of anxiety had higher levels of depression and those with high depression scores had higher anxiety scores.
42 citations
TL;DR: Intradialytic exercise appears to be clinically beneficial in improving daily physical activity and sleep quality in maintenance hemodialysis patients.
Abstract: Physical inactivity and sleep disturbance are frequently observed and relate to poor clinical outcomes in maintenance hemodialysis patients. We aimed to investigate the effect of intradialytic exercise on daily physical activity and sleep quality, measured by an accelerometer, in maintenance hemodialysis patients. This study randomly assigned ambulatory maintenance hemodialysis patients aged ≥ 20 years on dialysis ≥ 6 months, without a hospitalization history for the previous 3 months to 4 groups: aerobic exercise (AE), resistance exercise (RE), combination exercise (CE), and control. A stationary bike was used for AE and a TheraBand®/theraball for RE. A 12-week intradialytic exercise program (3 times/week) was completed in the AE (n = 11), RE (n = 10), and CE (n = 12) groups. The control group (n = 13) received only warm-up stretching. At baseline and 12-week follow-up, daily physical activity and sleep quality were measured with a triaxial accelerometer (wActiSleep-BT; ActiGraph, Pensacola, FL) during a continuous 7-day wear period. We observed a significant increase in metabolic equivalent (MET; kcal/h/kg) in the AE (1.02 ± 0.03 vs 1.04 ± 0.04, P = 0.04) and CE (1.06 ± 0.05 vs 1.09 ± 0.08, P = 0.01) groups at 12 weeks compared with baseline. When comparing between-group changes in MET, there was a significant increase in METs in the CE group (0.03 ± 0.03 vs − 0.01 ± 0.04, P = 0.02) compared with the control group. The total number of sedentary bouts (per week) decreased significantly in the AE (200 ± 37 vs 174 ± 36, P = 0.01), RE (180 ± 31 vs 130 ± 49, P = 0.03), and CE groups (180 ± 45 vs 152 ± 46, P = 0.04) at 12 weeks compared with baseline. The average sleep fragmentation index, indicating poor sleep quality, decreased significantly at 12 weeks compared with baseline in the AE (51.4 ± 8.0 vs 44.5 ± 9.6, P = 0.03) and RE groups (52.3 ± 7.3 vs 40.0 ± 15.4, P = 0.01). Intradialytic exercise appears to be clinically beneficial in improving daily physical activity and sleep quality in maintenance hemodialysis patients.
42 citations
TL;DR: MiR-15a expression measured in urine may be used as diagnostic molecular biomarker for RCC, and differentiated RCC from benign renal tumors with 98.1% specificity, 100% sensitivity at a cut-off value of 5.00E−06 RFU.
Abstract: Currently, there is no accurate diagnostic molecular biomarker for renal cell carcinoma (RCC). The aim of this study was to assess the expression of microRNA-15a (miR-15a) in urine of patients with RCC and to evaluate its potential as a diagnostic molecular biomarker. In total, 67 patients with solid renal tumors were enrolled: clear-cell RCC (ccRCC, n = 22), papillary RCC (pRCC, n = 16), chromophobe RCC (chRCC, n = 14), oncocytoma (n = 8), papillary adenoma (n = 2) and angiomyolipoma (n = 5). MiRNA-15a expression levels measurement in urine were performed using qPCR. Urine of 15 healthy volunteers without kidney pathology was used as control. We observed a difference in mean miR-15a expression values in groups of pre-operative patients with RCC, benign renal tumors and healthy persons (2.50E−01 ± 2.72E−01 vs 1.32E−03 ± 3.90E−03 vs 3.36E−07 ± 1.04E−07 RFU, respectively, p 0.05). Direct association between RCC size and miR-15a expression values was obtained (Pearson correlation coefficient—0.873). On the 8th day after nephrectomy, mean expression value in patients with RCC decreased by 99.53% (p < 0.01). MiR-15a expression differentiated RCC from benign renal tumors with 98.1% specificity, 100% sensitivity at a cut-off value of 5.00E−06 RFU, with AUC—0.955. MiR-15a expression measured in urine may be used as diagnostic molecular biomarker for RCC.
TL;DR: Although the primary efficacy finding was inconclusive, these results inform future trial design of AMDC-USR to identify clinically meaningful efficacy endpoints based on IEF reduction, understanding of placebo response rate, and refinement of subject selection criteria to more appropriately align with AMDC -USR’s proposed mechanism of action.
Abstract: The purpose of the study was to assess safety and efficacy of autologous muscle derived cells for urinary sphincter repair (AMDC-USR) in female subjects with predominant stress urinary incontinence. A randomized, double-blind, multicenter trial examined intra-sphincteric injection of 150 × 106 AMDC-USR versus placebo in female subjects with stress or stress predominant, mixed urinary incontinence. AMDC-USR products were generated from vastus lateralis needle biopsies. Subjects were randomized 2:1 to receive AMDC-USR or placebo and 1:1 to receive 1 or 2 treatments (6 months after the first). Primary outcome was composite of ≥ 50% reduction in stress incontinence episode frequency (IEF), 24-h or in-office pad weight tests at 12 months. Other outcome data included validated subject-recorded questionnaires. Subjects randomized to placebo could elect to receive open-label AMDC-USR treatment after 12 months. Subject follow-up was up to 2 years. AMDC-USR was safe and well-tolerated with no product-related serious adverse events or discontinuations due to adverse events. Interim analysis revealed an unexpectedly high placebo response rate (90%) using the composite primary outcome which prevented assessment of treatment effect as designed and thus enrollment was halted at 61% of planned subjects. Post hoc analyses suggested that more stringent endpoints lowered placebo response rates and revealed a possible treatment effect. Although the primary efficacy finding was inconclusive, these results inform future trial design of AMDC-USR to identify clinically meaningful efficacy endpoints based on IEF reduction, understanding of placebo response rate, and refinement of subject selection criteria to more appropriately align with AMDC-USR’s proposed mechanism of action.
TL;DR: The potential efficacy of pre-, pro- and synbiotics in the restoration of healthy gut microbia is described in detail and the underlying mechanisms by which microbiota can influence kidney diseases and vice versa are discussed.
Abstract: The complicated communities of microbiota colonizing the human gastrointestinal tract exert a strong function in health maintenance and disease prevention. Indeed, accumulating evidence has indicated that the intestinal microbiota plays a key role in the pathogenesis and development of chronic kidney disease (CKD). Modulation of the gut microbiome composition in CKD may contribute to the accumulation of gut-derived uremic toxins, high circulating level of lipopolysaccharides and immune deregulation, all of which play a critical role in the pathogenesis of CKD and CKD-associated complications. In this review, we discuss the recent findings on the potential impact of gut microbiota in CKD and the underlying mechanisms by which microbiota can influence kidney diseases and vice versa. Additionally, the potential efficacy of pre-, pro- and synbiotics in the restoration of healthy gut microbia is described in detail to provide future directions for research.
TL;DR: The midstream voided urine microbiome of older adults with stage 3–5 non-dialysis-dependent chronic kidney disease is diverse and greater microbiome diversity is associated with higher eGFR.
Abstract: To examine the characteristics of the midstream urine microbiome in adults with stage 3–5 non-dialysis-dependent chronic kidney disease (CKD). Patients with non-dialysis-dependent CKD (estimated glomerular filtration rate [eGFR] 50% reads) by the genera Corynebacterium (n = 11), Staphylococcus (n = 9), Streptococcus (n = 7), Lactobacillus (n = 7), Gardnerella (n = 7), Prevotella (n = 4), Escherichia_Shigella (n = 3), and Enterobacteriaceae (n = 2); the rest lacked a dominant genus. The samples had high levels of diversity, as measured by the inverse Simpson [7.24 (95% CI 6.76, 7.81)], Chao [558.24 (95% CI 381.70, 879.35)], and Shannon indices [2.60 (95% CI 2.51, 2.69)]. Diversity measures were generally higher in participants with urgency urinary incontinence and higher estimated glomerular filtration rate (eGFR). After controlling for demographics and diabetes status, microbiome diversity was significantly associated with estimated eGFR (P < 0.05). The midstream voided urine microbiome of older adults with stage 3–5 non-dialysis-dependent CKD is diverse. Greater microbiome diversity is associated with higher eGFR.
TL;DR: LI-ESWT is safe as oral PDE5i in penile rehabilitation post nerve-sparing radical cystoprostatectomy and during last follow-up, 16% more patients in LI- ESWT group had recovery of potency as compared to the control group.
Abstract: To evaluate the role of low-intensity extra corporeal shock wave therapy (LI-ESWT) in penile rehabilitation (PR) post nerve-sparing radical cystoprostatectomy (NS-RCP). This study included 152 sexually active men with muscle invasive bladder cancer. After bilateral NS-RCP with orthotopic diversion by a single expert surgeon between June 2014 and July 2016, 128 patients were available categorized into three groups: LI-ESWT group (42 patients), phosphodiesterase type-5 inhibitors (PDE5i) group (43 patients), and control group (43 patients). Mean age was 53.2 ± 6.5 years. Mean ± SD follow-up period was 21 ± 8 months. During first follow-up FU1, all patients of the three groups had insufficient erection for vaginal penetration; with decrease of preoperative IIEF-EF mean score from 27.9 to 6.9. Potency recovery rates at 9 months were 76.2%, 79.1%, and 60.5% in LI-ESWT, PDE5i, and control groups, respectively. There was statistically significant increase in IIEF-EF and EHS scores during all follow-up periods in all the study groups (p < 0.001). However, there was no significant difference between the three groups during all follow-up periods. Statistical evaluation showed no significant difference in continence and oncological outcomes during all follow-up points among the three groups (p = 0.55 and 0.07, respectively). During last follow-up, 16% more patients in LI-ESWT group had recovery of potency as compared to the control group. Although the difference is not statistically significant, but of clinical importance. LI-ESWT is safe as oral PDE5i in penile rehabilitation post nerve-sparing radical cystoprostatectomy.
TL;DR: It is indicated that bilateral is superior to unilateral varicocelectomy in infertile males with left clinical and right subclinical varicocele, which is associated with greater improvements in sperm concentration, normal sperm morphology and progressive motility and spontaneous pregnancy rate after the surgery.
Abstract: The purpose of this study is to compare the effect of bilateral versus unilateral varicocelectomy on seminal response and spontaneous pregnancy rates in infertile male patients with left clinical and right subclinical varicocele. A total of 358 infertile men with left clinical and right subclinical varicocele were randomized to group that underwent bilateral (n = 179) and group that underwent unilateral microsurgical subinguinal varicocelectomy (n = 179). Baseline data regarding male age, female partner age, grade of varicocele body mass index, bilateral testicular volume and serum follicle-stimulating hormone, luteinizing hormone, total testosterone levels and infertility duration and semen parameters were gathered. One year after the surgery, semen parameters including sperm volume, sperm concentration, normal sperm morphology, progressive motility and sperm DNA fragmentation index were recorded and any pregnancy was also documented via telephone calls and hospital visits. We found the baseline characteristics were comparable between the two groups. The seminal parameters had significant improvements 1 year postoperatively in both groups. However, the bilateral group showed significantly greater improvements than the unilateral group in sperm concentration, normal sperm morphology and progressive motility. Besides, the pregnancy rate was statistically higher in the bilateral group after the surgery (42.5 versus 26.0%, bilateral versus unilateral group). In conclusion, our study indicated that bilateral is superior to unilateral varicocelectomy in infertile males with left clinical and right subclinical varicocele, which is associated with greater improvements in sperm concentration, normal sperm morphology and progressive motility and spontaneous pregnancy rate after the surgery.
TL;DR: This population-based study provides the first evidence of improved CSM free survival and OM free survival in patients with de novo mPCa since the introduction of several systemic agents for CRPC patients.
Abstract: Over the past decade, several systemic agents as docetaxel, cabazitaxel, sipuleucel-T, abiraterone and enzalutamide have improved overall survival (OS) in metastatic prostate cancer (mPCa) patients. However, to date the OS benefit was not demonstrated in population-based analysis. Between 2004 and 2014, 19,047 men with de novo mPCa were identified within the Surveillance Epidemiology and End Results database. Median year of diagnosis resulted in two groups: historical (2004–2008) and contemporary (2009–2014). Due to potentially important differences according to year of diagnosis, we relied on propensity score matching. Propensity-score-matched Kaplan–Meier analyses and Cox regression models (CRMs) tested cancer-specific mortality (CSM) free survival and overall mortality (OM) free survival according to treatment period. The propensity-score-matched cohort consisted of 8596 patients with mPCa. Of those, 4298 (50.0%) were historical (2004–2008) and 4298 (50.0%) were contemporary (2009–2014). CSM free survival rates and OM free survival rate were 32 versus 36 months (p < 0.0001) and 26 versus 29 months (p < 0.0001) for, respectively, historical and contemporary patients. In multivariable CRMs, patients diagnosed in contemporary years had lower CSM (HR 0.88; CI 0.82–0.93) and OM (HR 0.88; CI 0.84–0.93) risks compared to historical counterpart (all p < 0.0001). This population-based study provides the first evidence of improved CSM free survival and OM free survival in patients with de novo mPCa since the introduction of several systemic agents for CRPC patients.
TL;DR: Uremic toxins may stimulate NF-κB mRNA and decrease Nrf2 expression in HD patients and, consequently, trigger inflammation and oxidative stress.
Abstract: Uremic toxins produced by gut microbiota (indoxyl sulfate—IS, p-cresyl sulfate—p-CS, and indole-3-acetic acid—IAA) accumulate in hemodialysis (HD) patients and exhibit potent inflammatory effects. However, the impact of these toxins on nuclear E2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB) expression in HD patients remains poorly defined. The aim of this study was to evaluate the association between uremic toxins and Nrf2/NF-κB expression in vitro (RAW 264.7 macrophage-like cells) and in peripheral blood mononuclear cells from HD patients.
Uremic toxins, C-reactive protein (CRP), interleukin-6 (IL-6) and malondialdehyde (MDA) levels were measured in fifteen HD patients and nine healthy individuals. RAW 264.7 macrophage-like cells were incubated with IS, as a prototype of protein-bound uremic toxin. Nrf2 and NF-κB expressions were analyzed by RT-qPCR.
HD patients presented high levels of inflammatory markers, MDA and uremic toxins. In addition, they presented high NF-κB and low Nrf2 expression. Uremic toxins were positively correlated with NF-κB expression (IS, ρ = 0.58, p < 0.003; p-CS, ρ = 0.71, p < 0.001; IAA, ρ = 0.62, p < 0.001) and negatively with Nrf2 (IS, ρ = − 0.48, p = 0.01; p-CS, ρ = − 0.46, p < 0.02). Uremic toxins also exhibited positive correlations with CRP and MDA levels. Multivariate analysis revealed that p-CS is a determinant factor of NF-κB expression. In RAW 264.7 culture, NF-κB mRNA expression was stimulated by IS, while Nrf2 was downregulated.
Thus, uremic toxins may stimulate NF-κB mRNA and decrease Nrf2 expression in HD patients and, consequently, trigger inflammation and oxidative stress.
TL;DR: This study identified possible PCa tumor markers to more accurately predict the occurrence, progression, and prognosis of PCa, and which could be used in the development of tumor drug therapy.
Abstract: Prostate cancer (PCa) is a common malignant human tumor and one of the main causes of cancer-related deaths in men. At present, prostate-specific antigen levels are widely used to diagnose PCa in the clinic, but they are not sufficient for an accurate early diagnosis or prognosis. To identify potential molecular markers for PCa, we used real-time PCR to measure the expression levels of various microRNAs, including miR-1825, miR-484, miR-205, miR-141, and let-7b, in the serum of 72 PCa patients and 34 healthy controls. miR-1825, miR-484, miR-205, miR-141, and let-7b were shown to be highly specific for PCa, suggesting that they could be used as PCa tumor screening biomarkers. miR-205 may also be used as a biomarker for indicating bone metastasis in PCa patients, miR-1825 levels may help indicate tumor–node–metastasis classification, the evaluation of treatment effects, and determining prognosis, while let-7b levels may indicate potential tumor malignancy and the hormone resistance status and could be used as a basis to adjust individual treatments for the high-risk, early diagnosis of refractory PCa. This study identified possible PCa tumor markers to more accurately predict the occurrence, progression, and prognosis of PCa, and which could be used in the development of tumor drug therapy.
TL;DR: The PEG-based method for isolation urinary exosome is an inexpensive and easily performed approach and the application for cargo miRNA analysis is feasible and may present a promising diagnostic approach.
Abstract: To assess a new and highly specific, but low-cost, easily performed and suitable for large-scale applications method for renal fibrosis (RF) diagnostics. Thirty-five RF and twenty non-RF patients were enrolled in the study. An appropriate polyethylene glycol (PEG) was used to isolate urinary exosomes. The efficiency of isolation process was evaluated by the morphology and size observation, as well as the detection of specific markers (CD63, CD9). The expression level of exosomal miR-29c, miR-21 and the endogenous control snRNA-U6 were detected by qRT-PCR. The diagnostic potency of urinary exosomal miR-29c and miR-21 was estimated by the ROC method. Spearman’s rank-order correlations analysis was used to assess the correlation between the miRNAs and clinical parameters, including pathological index. PEG-based method for isolation urinary exosome was effective and could be completed with a relatively low-speed centrifugal machine. Exosomal miR-29c and miR-21 were detected in all samples. The analysis of miRNAs in urinary exosomes revealed significant dys-regulation of miR-29c and miR-21 associated with RF. Exosomal miR-29c and miR-21 could predict degree of RF with AUC of 0.8333 and 0.7639 (P < 0.05). Correlation analysis showed that the level of miR-29c had a significant negative relationship with eGFR and the interstitial relative area. The PEG-based method for isolation urinary exosome is an inexpensive and easily performed approach. The application for cargo miRNA analysis is feasible. Urinary exosomal miR-29c may present a promising diagnostic approach.
TL;DR: Proper urological follow-up of SCI patients should consist of medical history, clinical examination, renal laboratory tests, imaging surveillance of the upper urinary tract, urodynamic study, and cystoscopy/cytology.
Abstract: To review currently available guidelines and recommendations regarding urological follow-up of patients after spinal cord injury (SCI) and present an evidence-based summary to support clinicians in their clinical practice. Maximum data were collected according to different methods, including searches with multiple and specific keywords, reference checks, gray literature searches (congress reports, working papers, statement documents), and browsing-related Web site access. Obtained data were analyzed with the modified version of the Oxford grading system for recommendations using levels of evidence (LE) and grades of recommendation (GR). Different surveillance strategies exist, but there is no consensus among authors and organizations. As a result, practice patterns vary around the world. The present review indicates that proper urological follow-up of SCI patients should consist of medical history (LE 1-4, GR B-C), clinical examination (LE 4, GR C), renal laboratory tests (LE 1-3, GR B), imaging surveillance of the upper urinary tract (LE 1-3, GR A-B), urodynamic study (LE 2-4, GR B-C), and cystoscopy/cytology (LE 1-4, GR D). Clinicians agree that SCI patients should be followed up regularly with an individually tailored approach. A 1-year follow-up schedule seems reasonable in SCI patients without additional risk factors of renal deterioration (LE 3-4, GR C). In those who manifest risk factors, report changes in bladder behavior, or present with already developed complications of neurogenic bladder dysfunction, follow-up plans should be modified with more frequent checkups (LE 4, GR C). Urodynamic study should be repeated and considered as a routine monitoring strategy. Individuals with neurogenic lower urinary tract dysfunction are at increased risk of multiple complications. Nevertheless, proper follow-up after SCI improves the prognosis for these patients and their quality of life.
TL;DR: A significantly increased risk of incident CKD and ESRD among patients with psoriasis compared with individuals without Psoriasis was demonstrated in this study.
Abstract: Patients with psoriasis may have a higher risk of developing chronic kidney (CKD) and end-stage renal disease (ESRD) compared with general population. This systematic review and meta-analysis aimed to comprehensively investigate this association by reviewing all available evidence. A systematic review was performed using MEDLINE and EMBASE database from inception to January 2018 to identify all cohort studies that compared the risk of incident CKD and/or ESRD in patients with psoriasis versus individuals without psoriasis. Pooled risk ratio and 95% confidence interval were calculated using random-effect, generic inverse variance method. A total of four retrospective cohort studies with 199,808 patients with psoriasis were included. The risk of incident CKD and ESRD was significantly increased among patients with psoriasis with the pooled risk ratio of 1.34 (95% CI, 1.14–1.57) and 1.29 (95% CI, 1.05–1.60), respectively. A significantly increased risk of incident CKD and ESRD among patients with psoriasis compared with individuals without psoriasis was demonstrated in this study.
TL;DR: Docetaxel induces protective autophagy in CRPC cells by JNK pathway activation and then Bcl-2 phosphorylation and Beclin1 dissociation and TP activates mTOR pathway, which ultimately inhibits docetaxe-induced autophophagy and improves therapeutic efficacy of docentaxel inCRPC cells.
Abstract: This study investigates the docetaxel-resistant mechanism and explores the effect of tea polyphenols (TP) on autophagy and its related mechanism in human castration-resistant prostate cancer (CRPC) cell lines PC3 and DU145. Immunofluorescence assay and annexin V-FITC/PI double staining flow cytometry were used to analyze the apoptosis and autophagy of PC3 and DU145 cells. The expression of autophagy-related proteins was detected by western bolt. Docetaxel could induce autophagy and apoptosis, together with the expression increase in p-JNK, p-Bcl-2 and Beclin1. The level of autophagy was remarkably decreased, but apoptosis was increased after combining with TP. In addition, the expression of p-mTOR was increased after combining with TP. Docetaxel induces protective autophagy in CRPC cells by JNK pathway activation and then Bcl-2 phosphorylation and Beclin1 dissociation. TP activates mTOR pathway, which ultimately inhibits docetaxel-induced autophagy and improves therapeutic efficacy of docetaxel in CRPC cells.
TL;DR: Markers of renal injury, such as proteinuria and tubular dysfunction, have been associated with outcomes among patients with sickle cell nephropathy and provide means for early detection of nephopathy and screening prior to progression to renal failure.
Abstract: Sickle cell nephropathy is a major complication of sickle cell disease. It manifests in different forms, including glomerulopathy, proteinuria, hematuria, and tubular defects, and frequently results in end-stage renal disease (ESRD). Different pathophysiologic mechanisms have been proposed to explain the development of nephropathy in SCD, where hemolysis and vascular occlusion are the main contributors in the manifestations of this disease. Markers of renal injury, such as proteinuria and tubular dysfunction, have been associated with outcomes among patients with sickle cell nephropathy and provide means for early detection of nephropathy and screening prior to progression to renal failure. In small-sized clinical trials, hydroxyurea has demonstrated to be effective in slowing the progression to ESRD. Dialysis and renal transplantation represent the last resort for patients with sickle cell nephropathy. Nevertheless, despite the availability of diagnostic and therapeutic strategies, sickle cell nephropathy remains a challenging and under-recognized complication for patients with sickle cell disease.
TL;DR: The SMN by up-regulating testicular TAC, SOD, GSH-px and TTM levels and the CEL by inhibiting COX2 and iNos expression as well as NO content could fairly ameliorate the VCL-decreased spermatogenesis.
Abstract: The present study was done to investigate the ameliorative effect of silymarin (SMN) and celecoxib (CEL) on varicocele (VCL)-induced detrimental impact in testicular tissue.
Mature Wistar rats were divided into control and test groups. Following VCL induction, the animals in test group were subdivided into non-treated VCL-induced, SMN-treated (50 mg/kg, orally), CEL-treated (10 mg/kg) and SMN + CEL-treated groups. Following 60 days, testicular total antioxidant capacity (TAC), malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), glutathione peroxidase (GSH-px), total thiol molecules (TTM), mRNA and protein levels of COX2 and mRNA level of iNos were analyzed. Moreover, the germinal cells apoptosis and mRNA damage were examined. Observations revealed that co-administration of SMN and CEL significantly (P < 0.05) up-regulated TAC, SOD, GSH-px and TTM levels and resulted in a remarkable (P < 0.05) reduction in iNos and COX2 expression, NO and MDA contents. The animals in SMN + CEL-treated group exhibited significantly (P < 0.05) lower number of apoptotic cells and cells with mRNA damage per one mm2.
The SMN by up-regulating testicular TAC, SOD, GSH-px and TTM levels and the CEL by inhibiting COX2 and iNos expression as well as NO content could fairly ameliorate the VCL-decreased spermatogenesis.
TL;DR: The current results demonstrated that transurethral en bloc resection with bipolar button electrode is an effective, feasible, and safe treatment for NMIBC.
Abstract: Transurethral resection of bladder tumor (TURBT) using a wire loop is considered the gold standard for staging and treating non-muscle invasive bladder cancer (NMIBC). TURBT is associated with serious disadvantages that facilitate tumor recurrence. The present study evaluated the safety and efficacy of the bipolar button electrode for en bloc resection of NMIBC. From January 2013 to July 2016, 82 consecutive patients newly diagnosed with NMIBC received transurethral en bloc resection with bipolar button electrode. Operative details, pathological result, and intraoperative and postoperative complications regarded as safety outcomes were documented. Each patient was followed up for ≥ 18 months. A total of 118 neoplasms were removed en bloc from 82 patients. The mean tumor diameter was 2.42 ± 1.34 cm. The average operation time was 35 ± 14 min. No complications such as bladder bleeding, vesicle perforation, and obturator nerve reflex occurred during the treatment. Pathological evaluations showed urothelial carcinoma with stage Ta low grade in 26 patients, T1 high grade in 51 patients, and T2 high grade in 5 patients. In addition, the bladder detrusor muscle layer was provided in all cases. The 18-month recurrence-free survival was 88.5% (23/26) and 74.5% (38/51) for Ta and T1 patients, respectively. The current results demonstrated that transurethral en bloc resection with bipolar button electrode is an effective, feasible, and safe treatment for NMIBC.
TL;DR: Findings indicate that miR-129-5p and Wnt5a may be novel therapeutic targets for overcoming gemcitabine resistance in bladder cancer treatment and could significantly increase cell sensitivity to gem citabine and promote cell apoptosis.
Abstract: Gemcitabine resistance is a major obstacle for effective treatment of bladder cancer. This study was aimed to investigate the potential role of miR-129-5p in the development of gemcitabine resistance in bladder cancer cells and its underlying mechanism. The IC50 for gemcitabine in 20 bladder cancer cells was first profiled from Genomics of Drug Sensitivity in Cancer. miR-129-5p level and gene mRNA expression were detected using quantitative real-time PCR (qRT-PCR). Cell viability, apoptosis, and gene protein level were assessed by MTT, flow cytometry, and Western blot, respectively. Regulatory relationship between Wnt5a and miR-129-5p was determined using luciferase reporter assay. We found that down-regulated miR-129-5p level contributed to gemcitabine resistance in bladder cancer cells and tissues. We also observed restoration of miR-129-5p could significantly increase cell sensitivity to gemcitabine and promote cell apoptosis. Mechanism analysis revealed that Wnt5a is a direct target gene of miR-129-5p and knock-down of Wnt5a reversed gemcitabine resistance. Taken together, our findings indicate that miR-129-5p and Wnt5a may be novel therapeutic targets for overcoming gemcitabine resistance in bladder cancer treatment.
TL;DR: Findings suggest that CXCL3 autocrine/paracrine pathways are involved in the development of prostate cancer by regulating the expression of the target genes that are related to the progression of malignancies.
Abstract: We have previously indicated that CXCL3 was upregulated in the tissues of prostate cancer, and exogenous administration of CXCL3 played a predominant role in the tumorigenicity of prostate cancer cells. In the present study, we further explored the role and the underlying mechanism of CXCL3 overexpression in the oncogenic potential of prostate cancer in an autocrine/paracrine fashion. CXCL3-overexpressing prostate cancer cell line PC-3 and immortalized prostate stromal cell line WPMY-1 were established by gene transfection. CCK-8, transwell assays and growth of tumor xenografts were conducted to characterize the effects of CXCL3 on PC-3 cells’ proliferation and migration. Western blotting was conducted to test whether CXCL3 could affect the expression of tumorigenesis-associated genes. The results showed that CXCL3 overexpression in PC-3 cells and the PC-3 cells treated with the supernatants of CXCL3-transfected WPMY-1 cells stimulated the proliferation and migration of PC-3 cells in vitro and in a nude mouse xenograft model. Western blotting revealed higher levels of p-ERK, Akt and Bcl-2 and lower levels of Bax in the tumor xenografts transplanted with CXCL3-transfected PC-3 cells. Moreover, the tumor xenografts derived from the PC-3 cells treated with supernatants of CXCL3-transfected WPMY-1 cells showed higher expression of ERK, Akt and Bcl-2 and lower expression of Bax. These findings suggest that CXCL3 autocrine/paracrine pathways are involved in the development of prostate cancer by regulating the expression of the target genes that are related to the progression of malignancies.
TL;DR: Allopurinol protects primary human glomerular endothelial cells from high glucose-induced ROS generation, p53 overexpression and endothelial dysfunction and provides a pathogenetic mechanism that supports the results of experimental and clinical studies about the beneficial effect of xanthine oxidase inhibitors on the development of diabetic nephropathy.
Abstract: Mitochondrial reactive oxygen species (ROS) overproduction in capillary endothelial cells is a prerequisite for the development of diabetic nephropathy. Inhibition of xanthine oxidase, another ROS generator, ameliorates experimental diabetic nephropathy. To test the hypothesis that the initial high glucose-induced ROS production by the mitochondria activates xanthine oxidase, which afterward remains as the major source of ROS, we cultured primary human glomerular endothelial cells (GEnC) under normal or high-glucose conditions, with or without the xanthine oxidase inhibitor allopurinol. ROS generation and nitric oxide synthase (NOS) activity were assessed by chemiluminescence or colorimetrically. Levels of intercellular adhesion molecule 1 (ICAM-1), p53 and phosphorylated p53 (p-p53) were assessed by western blotting. Allopurinol prevented high glucose-induced ROS generation indicating that xanthine oxidase is the major source of ROS. Allopurinol protected GEnC from endothelial dysfunction since it prevented the high glucose-induced decrease in NOS activity and increase in ICAM-1 expression. Allopurinol reduced p53 and p-p53 levels induced by high glucose suggesting an axis of xanthine oxidase-derived ROS, DNA damage, p53 stabilization and endothelial dysfunction that may contribute to the pathogenesis of diabetic nephropathy. Allopurinol protects GEnC from high glucose-induced ROS generation, p53 overexpression and endothelial dysfunction. These data provide a pathogenetic mechanism that supports the results of experimental and clinical studies about the beneficial effect of xanthine oxidase inhibitors on the development of diabetic nephropathy.
TL;DR: Exposure to exogenous renalase may be a promising strategy for slowing or halting the progression of CKD, and another mechanism of anti-fibrotic renal protection of renalase, which may be partly associated with inhibiting oxidative stress is prompt.
Abstract: Renal interstitial fibrosis (RIF) is a common pathway for progression of chronic kidney disease (CKD) to end-stage renal disease. In our previous study, it has been provided that renalase can ameliorate renal interstitial fibrosis in unilateral ureteral obstruction (UUO) rats. The other mechanism of renalase to alleviate renal fibrosis should be explored.
In this study, we evaluated the role of oxidative stress in UUO rats and epithelial–mesenchymal transition (EMT) in human proximal renal tubular epithelial (HK-2) cells and examined the association of renalase. Oxidative stress could induce EMT and fibrosis in HK-2 cells. In the UUO model, oxidative stress occurred and maintained at a high level leading to RIF. Administration of renalase by adenovirus significantly attenuated oxidative stress and further in vitro study showed that renalase can exert anti-fibrosis by inhibiting oxidative stress. Our results prompt another mechanism of anti-fibrotic renal protection of renalase, which may be partly associated with inhibiting oxidative stress. These data provided another theoretical basis that supplementation with exogenous renalase may be a promising strategy for slowing or halting the progression of CKD.