Showing papers in "International Urology and Nephrology in 2015"
TL;DR: Since the diagnosis and treatment of frailty and sarcopenia is crucial in geriatrics and all CKD patients, it would be very important to incorporate these evaluations in pre-dialysis, peritoneal dialysis, hemodialysis, and kidney transplant patients in order to detect and consequently treat the frailty phenotype in these groups.
Abstract: Frailty is a construct originally coined by gerontologists to describe cumulative declines across multiple physiological systems that occur with aging and lead individuals to a state of diminished physiological reserve and increased vulnerability to stressors. Fried et al. provided a standardized definition for frailty, and they created the concept of frailty phenotype which incorporates disturbances across interrelated domains (shrinking, weakness, poor endurance and energy, slowness, and low physical activity level) to indentify old people who are at risk of disability, falls, institutionalization, hospitalization, and premature death. Some authors consider the presence of lean mass reduction (sarcopenia) as part of the frailty phenotype. The frailty status has been documented in 7 % of elderly population and 14 % of not requiring dialysis CKD adult patients. Sarcopenia increases progressively along with loss of renal function in CKD patients and is high in dialysis population. It has been documented that prevalence of frailty in hemodialysis adult patients is around 42 % (35 % in young and 50 % in elderly), having a 2.60-fold higher risk of mortality and 1.43-fold higher number of hospitalization, independent of age, comorbidity, and disability. The Clinical Frailty Scale is the simplest and clinically useful and validated tool for doing a frailty phenotype, while the diagnosis of sarcopenia is based on muscle mass assessment by body imaging techniques, bioimpedance analysis, and muscle strength evaluated with a handheld dynamometer. Frailty treatment can be based on different strategies, such as exercise, nutritional interventions, drugs, vitamins, and antioxidant agents. Finally, palliative care is a very important alternative for very frail and sick patients. In conclusion, since the diagnosis and treatment of frailty and sarcopenia is crucial in geriatrics and all CKD patients, it would be very important to incorporate these evaluations in pre-dialysis, peritoneal dialysis, hemodialysis, and kidney transplant patients in order to detect and consequently treat the frailty phenotype in these groups.
89 citations
TL;DR: Pregabalin is an effective alternative for treatment of uraemic pruritus in dialysis patients and absolutely disappeared in two patients following renal transplantation, suggesting a larger sample size may be needed to demonstrate the effect of ondansetron in uraemia.
Abstract: Pruritus is common among patients with end-stage renal disease undergoing dialysis, and the pathogenesis can be explained by several mechanisms. However, there is no definite evidence supporting them, which limits the relative efficacy of any individual treatment option. In this paper, we aimed to compare pregabalin with ondansetron in treatment of uraemic pruritus (UP) in dialysis patients. In this 12-week prospective, randomized, and double-blind trial, we assessed the efficacy and side effects in UP patients undergoing dialysis. Patients were randomly assigned to receive 12 weeks of 75 mg twice-weekly pregabalin or 8 mg/day ondansetron or a placebo. Visits were scheduled at 0, 2, 4, 6, 8, and 12 weeks after treatment. The severity of pruritus was evaluated using Visual Analogue Scale and modified Duo’s VAG Scale. Quality of sleep was evaluated using the Pittsburgh sleep quality index. The effect of UP on health-related quality of life was assessed using the Chinese version of the 12-item short-form (SF-12) general health survey. Baseline laboratory data and demographic characteristics were recorded from patient charts. Finally, 179 (108 males, 71 females, aged 54.7 ± 11.3 years old) out of the 188 patients completed the 12-week study. Of five patients who stopped pregabalin treatment due to side effects, two patients reported an improvement in nausea and vomiting among those receiving ondansetron. Two patients dropped out for renal transplantation. The 179 patients included 62 cases from the pregabalin group, 60 from the ondansetron group, and 57 from the placebo group. Over the 12 weeks, only pregabalin improved UP significantly. The severity of pruritus was reduced significantly in the pregabalin group compared with the ondansetron and the placebo groups. The final pruritus scores were not different between the ondansetron and the placebo groups. Pruritus absolutely disappeared in two patients following renal transplantation. Pregabalin is an effective alternative for treatment of uraemic pruritus. Ondansetron has negligible effect on uremic pruritus and is expensive. A larger sample size may be needed to demonstrate the effect of ondansetron in uraemic pruritus.
84 citations
TL;DR: Although DDS is not pathognomonic of varicocele, the DDSi is a useful noninvasive biomaker to identify infertile individuals withvaricocele when examining sperm DNA damage during a routine semen analysis.
Abstract: Varicocele is a frequent cause of impaired testicular function that has been associated with increased levels of sperm DNA fragmentation (SDF). Sperm with degraded DNA (DDS), as observed using the sperm chromatin dispersion (SCD) test, represent a subpopulation of spermatozoa with extensive DNA and nuclear protein damage. The aim of this work was to determine the usefulness of sperm DNA degradation index (DDSi) as a novel noninvasive biomarker to identify infertile men with varicocele. A total of 593 semen samples obtained from men attending infertility clinics were analyzed for SDF and DDS with the SCD test. These samples were classified as: (1) fertile donors; (2) infertile patients with least two failed assisted reproduction cycles; (3) leukocytospermia; (4) Chlamydia trachomatis infection; (5) testicular cancer, and (6) infertile men with varicocele. The DDSi was obtained by determining the proportion of DDS in the whole sperm population presenting with fragmented DNA. The diagnostic accuracy of DDSi was evaluated by correlation coefficient and receiver operating characteristics analyses. A positive correlation (r ≥ 0.52) was observed between the SDF and the frequency of degraded sperm in all patient groups. The sperm DNA degradation index (DDSi) was at least twice as higher in infertile men with varicocele (mean: 0.54) compared with other clinical conditions and fertile donors (means ranging from 0.02 to 0.21; P < 0.0001). A DDSi ≥ 0.33 identified patients with varicocele with 94 % accuracy. Although DDS is not pathognomonic of varicocele, the DDSi is a useful noninvasive biomaker to identify infertile individuals with varicocele when examining sperm DNA damage during a routine semen analysis. This finding may alert practitioners and laboratories performing semen analysis that in the presence of an abnormal DDSi it is likely that a given patient has varicocele. It is therefore strongly recommended that such patients be referred to urologists in order to undergo a full andrological examination and be properly counseled.
81 citations
TL;DR: This meta-analysis indicated that HER2 expression is associated with poor prognosis in patients with BCa, and could serve as a useful biomarker for clinical prediction.
Abstract: The prognostic role of human epidermal growth factor receptor 2 (HER2) in bladder cancer (BCa) remains controversial. Thus, we conducted a meta-analysis to assess the prognostic significance of HER2 for patients with BCa. Systematically computerised searching in PubMed, Scopus database, Embase and Cochrane Library Database was conducted. Published studies comparing the prognosis in patients with BCa stratified by HER2 status were included, and relationships between HER2 positivity and gender, stage, grade, lymph node metastasis and survival were analysed. Nine studies with 2,242 eligible patients were identified. HER2 expression was significantly correlated with poor disease-specific survival [pooled hazard ratio (HR) 2.00; 95 % confidence interval (CI) 1.22–3.29; P = 0.006] and disease-free survival (pooled HR 1.68; 95 % CI 1.33–2.14; P < 0.0001) of patients with BCa. The positive rates of HER2 ranged from 27.8 to 85.2 % with a pooled positive rate of 41.2 % (1,006/2,442). HER2 expression was significantly associated with tumour grade [high grade vs. low grade: odds ratio (OR) 4.08; 95 % CI 1.29–12.93] and lymph node metastasis (positive vs. negative: OR 1.71; 95 % CI 1.07–2.75). This meta-analysis indicated that HER2 expression is associated with poor prognosis. Thus, HER2 could serve as a useful biomarker for clinical prediction.
68 citations
TL;DR: In this article, the authors systematically identified and reviewed the methods and consistency of recommendations of recently developed clinical practice guidelines (CPG) and best practice statements (BPS) on the evaluation of the infertile male.
Abstract: We systematically identified and reviewed the methods and consistency of recommendations of recently developed clinical practice guidelines (CPG) and best practice statements (BPS) on the evaluation of the infertile male. MEDLINE and related engines as well as guidelines’ Web sites were searched for CPG and BPS written in English on the general evaluation of male infertility published between January 2008 and April 2015. Four guidelines were identified, all of which reported to have been recently updated. Systematic review was not consistently used in the BPS despite being reported in the CPG. Only one of them reported having a patient representative in its development team. The CPG issued by the European Association of Urology (EAU) graded some recommendations and related that to levels (but not quality) of evidence. Overall, the BPS issued respectively by the American Urological Association and American Society for Reproductive Medicine concurred with each other, but both differed from the EAU guidelines with regard to methods of collection, extraction and interpretation of data. None of the guidelines incorporated health economics. Important specific limitations of conventional semen analysis results were ignored by all guidelines. Besides variation in the methodological quality, implementation strategies were not reported in two out of four guidelines. While the various panels of experts who contributed to the development of the CPG and BPS reviewed should be commended on their tremendous efforts aiming to establish a clinical standard in both the evaluation and management of male infertility, we recognized inconsistencies in the methodology of their synthesis and in the contents of their final recommendations. These discrepancies pose a barrier in the general implementation of these guidelines and may limit their utility in standardizing clinical practice or improving health-related outcomes. Continuous efforts are needed to generate high-quality evidence to allow further development of these important guidelines for the evaluation and management of males suffering from infertility.
59 citations
TL;DR: The home-based aerobic exercise program was feasible, safe and effective for the improvement in the cardiopulmonary and functional capacities of overweight NDD-CKD patients.
Abstract: Home-based exercise has been shown to provide benefits in terms of physical capacity in the general population, but has been scarcely investigated in patients with chronic kidney disease (CKD). To evaluate the impact of a home-based aerobic training on the cardiopulmonary and functional capacities of overweight non-dialysis-dependent patients with CKD (NDD-CKD). Twenty-nine sedentary patients (55.1 ± 11.6 years, BMI = 31.2 ± 6.1 kg/m2, eGFR = 26.9 ± 17.4 mL/min/1.73 m2) were randomly assigned to a home-based exercise group (n = 14) or to a control group (n = 15) that remained without performing exercise. Aerobic training was performed three times per week for 12 weeks. A cardiopulmonary exercise test, functional capacity and clinical parameters were evaluated. A significant increase, ranging from 8.3 to 17 %, was observed in the cardiopulmonary capacity parameters, such as maximal ventilation (p = 0.005), VO2peak (p = 0.049), ventilatory threshold (p = 0.040) and respiratory compensation point (p < 0.001), of the exercise group. A simultaneous improvement in the functional capacity tests [6-min walk test (p < 0.001), time up and go test (p < 0.001), arm curl test (p < 0.001), sit and stand test (p < 0.001), 2-min step test (p < 0.001) and back scratch test (p = 0.042)] was also found in patients who were submitted to the exercise. Exercised patients experienced a decrease in systolic and diastolic blood pressure, average 10.6 % (p < 0.001) and 9.2 % (p = 0.007), respectively, and a trend toward improved renal function (p = 0.1). No change in any parameter was found in the control group during the follow-up. The home-based aerobic exercise program was feasible, safe and effective for the improvement in the cardiopulmonary and functional capacities of overweight NDD-CKD patients.
55 citations
TL;DR: Patients with BPS/IC are at risk of development of anxiety, depression, and insomnia, and these findings can help guide urologists, urogynecologists, and psychiatrists toward early identification and treatment of psychological complications that may develop in B PS/IC patients.
Abstract: To explore the association between bladder pain syndrome/interstitial cystitis (BPS/IC) and the risk of subsequent healthcare-seeking behavior for common mental disorders in Taiwan using a population-based administrative database. Both BPS/IC subjects and their age- and sex-matched non-BPS/IC control subjects who had no previous insomnia and mental diseases, including anxiety, depression, were subsequent serviced for these mental disorders by psychiatrists from the recruited date between 2002 and 2010. The risk of outcomes was assessed with Kaplan–Meier curves; and the impact of BPS/IC was estimated with Poisson regression analysis and Cox proportional hazards models.
We included 16,185 BPS/IC subjects and 32,370 non-BPS/IC subjects, with a mean age of 46 years and 73.5 % of women. Difference of the prevalence of hypertension, diabetes, chronic kidney disease, and hyperlipidemia between groups was not significant difference. Subjects with BPS/IC had a significant higher incidence rate of anxiety, depression, and insomnia than the matched controls (92.9 vs 38.4, 101.0 vs 42.2, 47.5 vs 23.0; per 10,000 person-year). After adjusting for age, sex, and common comorbidities in multivariable analysis, BPS/IC remained a significant predictor with hazard ratio and 95 % confidence incidence, 2.4 (2.2–2.7), 2.4 (2.2–2.6), and 2.1 (1.8–2.4) for anxiety, depression, and insomnia, respectively. Patients with BPS/IC are at risk of development of anxiety, depression, and insomnia. These findings can help guide urologists, urogynecologists, and psychiatrists toward early identification and treatment of psychological complications that may develop in BPS/IC patients.
53 citations
TL;DR: All evaluated scoring systems are capable of pointing out worse prognosis including mechanical ventilation requirement and mortality, and NLR has the advantage of its rapid, simple and low-cost characteristics.
Abstract: To evaluate the mortality and morbidity prediction capability of three different scoring systems: Fournier’s gangrene severity index (FGSI), Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) and neutrophile–lymphocyte ratio (NLR) with this retrospective cohort study. Medical records of all patients treated for FG with the final histopathological diagnosis between October 2008 and January 2013 were retrospectively evaluated. Data were collected from medical history, physical examination findings, biochemical and microbiological tests and tissue cultures. FGSI and LRINEC scores and NLR were determined for all patients. Then, it was explored whether higher FGSI (<4 vs. ≥4), LRINEC (<6 vs. ≥6) or NLR (<10 vs. ≥10) were associated with worse prognosis. A total of 33 patients were evaluated; 3 died (9.1 %) and 30 (90.9 %) survived. Mean age was 57.6 ± 13.2 years. Survivors were younger than nonsurvivors (56 ± 12.8 vs. 72.9 ± 7.3, p < 0.05). Diabetes mellitus was the most encountered predisposing factor with 66.7 % prevalence. All patients with localized disease (100 %) and 8/11 patients (72.7 %) with extended disease survived (p < 0.05). Patients with higher FGSI scores, LRINEC scores and NLR were more likely to require mechanical ventilation in intensive care unit and longer hospitalization times and were more likely to die compared to patients with lower scores. In conclusion, all evaluated scoring systems, FGSI, LRINEC and NLR, are capable of pointing out worse prognosis including mechanical ventilation requirement and mortality. NLR has the advantage of its rapid, simple and low-cost characteristics.
52 citations
TL;DR: Fosfomycin could be an alternative treatment option for UTI related to ESBL-producing E. coli spp.
Abstract: Purpose
The appearance of extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacteria in urinary tract infection (UTI) constitutes an important therapeutic challenge. The aim of this study was to describe drug susceptibility profiles of ESBL-producing bacteria isolated from urine samples. We also determined the antimicrobial co-resistance to several agents, including fosfomycin.
50 citations
TL;DR: PTNS therapy with adhesive skin surface electrodes is an effective method to treat NDO secondary to SCI and is not only no difference comparing to SS therapy but also noninvasive and easily managed by patients.
Abstract: To compare the effectiveness of percutaneous tibial nerve stimulation (PTNS) using adhesive skin surface electrodes versus solifenacin succinate (SS) in patients with neurogenic detrusor overactivity (NDO) secondary to spinal cord injury (SCI). A randomized controlled study involving 100 patients with NDO secondary to SCI was conducted. Patients were randomized into two groups. In group A, patients received PTNS using adhesive skin surface electrodes for 4 weeks. In group B, patients underwent SS treatment for 4 weeks. Bladder diaries and incontinence quality of life questionnaire were reviewed before treatment and 2 and 4 weeks after treatment. Improvement in all bladder diary parameters was statistically significant within each group 2 and 4 weeks after treatment compared to baseline (p 0.05). Compared to SS, PTNS was not associated with any unanticipated adverse events. PTNS therapy with adhesive skin surface electrodes is an effective method to treat NDO secondary to SCI. This therapy is not only no difference comparing to SS therapy but also noninvasive and easily managed by patients.
46 citations
TL;DR: The renoprotective effect of sildenafil against renal I/R might be due to the activation of antioxidant genes (Nrf2, HO-1 and NQO-1) and antiapoptotic gene (Bcl2) and attenuation of proinflammatory cytokines (TNF-a, IL-1β and ICAM-1).
Abstract: To study the possible renoprotective effect of sildenafil against renal ischemia/reperfusion (I/R) injury and its effect on the expression of some antioxidant, antiapoptotic gene and proinflammatory cytokine genes in rat model of renal I/R injury. One hundred and twenty male Sprague Dawley rats were subdivided into three equal groups: sham (underwent right nephrectomy without ischemia), control (underwent right nephrectomy and left ischemia for 45 min) and study [as control with 1 mg/kg sildenafil (per oral) 60 min before anesthesia]. Serum creatinine and BUN were measured at the baseline and the study endpoints (2, 24, 48 h and 7 days), and the left kidney was harvested at study endpoints for histopathological examination as well as for assessment of the expression of antioxidant genes (Nrf-2, HO-1 and NQO-1), antiapoptotic gene (Bcl-2) and inflammatory cytokines, e.g., TNF-a, IL-1β and ICAM-1. I/R caused significant increase in serum creatinine, BUN, histopathological damage score (p < 0.001) and significant reduction in antioxidant genes (nrf2, HO-1 and NQO-1) and antiapoptotic gene (Bcl2) with significant increase in TNF-a, IL-1β and ICAM-1 genes in kidney tissues. Pretreatment with sildenafil caused significant attenuation of serum creatinine and BUN as well as significant increase in the expression of antioxidant genes and Bcl-2 genes with significant reduction in the expression of proinflammatory cytokine genes (p value < 0.001). The renoprotective effect of sildenafil against renal I/R might be due to the activation of antioxidant genes (Nrf2, HO-1 and NQO-1) and antiapoptotic gene (Bcl2) and attenuation of proinflammatory cytokines (TNF-a, IL-1β and ICAM-1).
TL;DR: ESRD patients undergoing any one of the three dialysis modalities studied had a high prevalence of sleep disorders and patients on HD had a lower proportion of OSAS than those on CAPD and APD, which is most likely attributed to their lower body mass indices.
Abstract: Sleep disorders for patients on dialysis are significant causes of a poorer quality of life and increased morbidity and mortality. No study has evaluated patients undergoing automated peritoneal dialysis (APD) to assess their sleep disorders compared to hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). A total of 166 clinically stable patients who had been on dialysis for at least 3 months were randomly selected for the study and divided into HD, CAPD or APD. Socio-demographic, clinical and laboratory parameters and self-administered questionnaires were collected for the investigation of insomnia, restless legs syndrome (RLS), bruxism, rapid eye movement sleep behavior disorder, excessive daytime sleepiness (EDS), obstructive sleep apnea syndrome (OSAS), sleepwalking, sleep hygiene, depression and anxiety. Insomnia was detected in more than 80 % of patients on the three modalities. OSAS was lower for patients on HD (36 %) than on CAPD (65 %) (p < 0.01) or APD (60 %) (p < 0.04). Patients on APD were more likely to have RLS compared to those on HD or CAPD (p < 0.04) (50 vs. 23 vs. 33 %). No differences among the modalities were found in bruxism, EDS, sleepwalking, sleep hygiene, depression or anxiety. ESRD patients undergoing any one of the three dialysis modalities studied had a high prevalence of sleep disorders. Patients on HD had a lower proportion of OSAS than those on CAPD and APD, which is most likely attributed to their lower body mass indices. The possible causes of higher RLS rates in APD patients have not been established.
TL;DR: A behavioral and educational strategy addressing the patient’s perceptions and knowledge about the anti-rejection drugs significantly improved the short-term adherence to immunosuppressive therapy.
Abstract: Solid-organ transplant recipients present a high rate of non-adherence to drug treatment. Few interventional studies have included approaches aimed at increasing adherence. The objective of this study was to evaluate the impact of an educational and behavioral strategy on treatment adherence of kidney transplant recipients. In a randomized prospective study, incident renal transplant patients (n = 111) were divided into two groups: control group (received usual transplant patient education) and treatment group (usual transplant patient education plus ten additional weekly 30-min education/counseling sessions about immunosuppressive drugs and behavioral changes). Treatment adherence was assessed using ITAS adherence questionnaire after 3 months. Renal function at 3, 6, and 12 months, and the incidence of transplant rejection were evaluated. The non-adherence rates were 46.4 and 14.5 % in the control and treatment groups (p = 0.001), respectively. The relative risk for non-adherence was 2.59 times (CI 1.38–4.88) higher in the control group. Multivariate analysis demonstrated a 5.84 times (CI 1.8–18.8, p = 0.003) higher risk of non-adherence in the control group. There were no differences in renal function and rejection rates between groups. A behavioral and educational strategy addressing the patient’s perceptions and knowledge about the anti-rejection drugs significantly improved the short-term adherence to immunosuppressive therapy.
TL;DR: The sensitivity of AR immunohistochemistry for prostate cancer is 94.8 %.
Abstract: Androgen receptor (AR) is a recognized immunohistochemical marker of prostate cancer. However, the sensitivity and specificity of AR for prostate cancer in the setting of other genitourinary neoplasms has not been rigorously studied. We employed tissue microarrays containing prostate carcinomas, urothelial carcinomas, renal cell carcinomas, and testicular neoplasms. Slides were stained immunohistochemically for AR. Androgen receptor was positive in 95 % of prostate carcinomas (n = 230), but 19 % of invasive urothelial carcinomas of the bladder (n = 190) and 33 % of non-invasive bladder urothelial carcinomas were also AR positive (N = 107). Furthermore, 16 % of renal pelvis urothelial carcinomas (n = 43) were positive. Of primary renal cell carcinomas, 19 % were AR positive (n = 307). From a metastatic renal cell carcinoma cohort, 28 % of metastases were AR positive (N = 126). Six percent of non-teratomatous testicular germ cell tumors stained for AR (n = 103). Our data show that the sensitivity of AR immunohistochemistry for prostate cancer is 94.8 %. However, the specificity of AR is only 81.4 %, among our cohort of invasive genitourinary tumors. Thus, we find the specificity of AR suboptimal, yet AR may remain useful as a component of an immunostain panel.
TL;DR: PCL/silk fibroin/collagen electrospun nanofiber scaffold has appropriate pore size and porosity, is suitable for the growth of oral mucosal epithelial cells, has good cell compatibility, and is a good scaffold for tissue engineering urethral reconstruction.
Abstract: Purpose
To prepare polycaprolactone (PCL)/silk fibroin/collagen electrospun nanofiber scaffold and test its effects on growth and proliferation of oral mucosal epithelial cells.
TL;DR: Surgical smoke evacuation in the first few seconds of a cut is essential; however, using smoke evacuators such as a wall suction alone may not be enough.
Abstract: Introduction
Electrocautery, harmonic scalpel tissue dissection and other surgical techniques can generate surgical smoke with high proportion of ‘fine particles’ (PM2.5) <2.5 μm, which is known to have adverse effects on human health. The high-risk zone for PM2.5 during surgeries by time and by distance has not been well evaluated.
TL;DR: Prevalence of depressive symptoms in patients diagnosed with BPH is associated with severity of LUTS, erectile dysfunction, nocturia, BPH pharmacotherapy (5αRIs), sedentary life style, and comorbidities including obesity.
Abstract: Background
Symptoms of depression are common in patients diagnosed with benign prostatic hyperplasia (BPH) and are usually a reaction to deterioration of health, severity of lower urinary tract symptoms, and erectile dysfunction. The aim of this observational study was to evaluate the prevalence of depressive symptoms in patients diagnosed with BPH and factors affecting their occurrence in a large Polish cohort.
TL;DR: Estrogen-alone-induced inflammatory response could promote the expression of inflammatory markers; however, T supplementation reduces the expressionof inflammatory markers and E2-induced apoptosis occurs dependently on T manipulation in prostatitis.
Abstract: The age-related decline of the testosterone-to-estrogen (T-to-E2) ratio in serum is associated with the increased prevalence of prostatic inflammation. The goal of the study was to induce prostatic inflammation with E2 and androgen treatment and to explore the inflammatory markers and apoptosis on prostatitis.
Castrated SD rats were treated with E2 and different doses of androgens to achieve an elevated concentration of E2 and a wide range of the androgen-to-E2 ratio in serum. Inflammatory markers TNF-α, COX-2 and MIP-1α were immunohistochemically stained. Apoptosis detection was evaluated by TUNEL staining. E2, T and DHT concentrations in serum were measured, and the relative weight of the prostate and seminal vesicles were determined. T was anti-inflammatory at the doses which normalized or over stimulated the growth of the prostate and seminal vesicles. Experimentally, prostatitis induced by E2 alone increased the prostatic levels of the inflammatory markers TNF-a, COX-2 and MIP-1a. As signs of anti-estrogenic actions, androgens dose-dependently decreased the expression of TNF-α, COX-2 and MIP-1α. Prostatitis induced by E2 alone caused extensive apoptosis in the castrate-resistant cells and E2-induced apoptosis occurred dependently of T manipulation. Estrogen-alone-induced inflammatory response could promote the expression of inflammatory markers; however, T supplementation reduces the expression of inflammatory markers and E2-induced apoptosis occurs dependently on T manipulation in prostatitis.
TL;DR: EDA prevents LPS-induced AKI not only by reducing the production of inflammatory cytokines, but also by attenuating oxidative damage in renal mitochondria, mitochondrial fragmentation, and apoptosis of renal cells.
Abstract: Acute kidney injury (AKI) is a frequent complication of sepsis. The present work examined the therapeutic potential of edaravone (EDA), a free radical scavenger, for inhibiting sepsis-induced renal injury. Saline and lipopolysaccharide (LPS) were injected intraperitoneally at a dose of 10 mg/kg of body weight. EDA, 3-methyl-1-phenyl-pyrazolin-5-one, was administrated intravenously at a dose of 3 mg/kg of body weight to male Wistar rats. Wistar rats were divided into four groups: treatment with LPS alone, treatment with LPS followed by EDA administration, treatment with saline followed by EDA administration, and untreated controls. Administration of LPS caused a significant increase in BUN and serum creatinine levels with concurrent pathological alterations in kidney tissues. EDA treatment relieved all these changes. Moreover, EDA reduced LPS-induced elevation of serum TNF-α and IL-6 in rats. Furthermore, EDA could prevent mitochondrial membrane potential loss induced by LPS and reverse the changes in mitochondrial antioxidant (such as T-AOC, SOD, CAT, and GSH) and mitochondrial MDA levels. TUNEL staining of the kidney sections and immunoblot analysis on renal cortical lysates showed that EDA treatment resulted in reduced number of apoptotic cells, which occurred concomitantly with decreased levels of cytochrome c and cleaved caspase 3. Following LPS treatment of rat renal tubular cells, mitochondrial fragmentation was observed prior to apoptosis, which was inhibited by EDA. EDA prevents LPS-induced AKI not only by reducing the production of inflammatory cytokines, but also by attenuating oxidative damage in renal mitochondria, mitochondrial fragmentation, and apoptosis of renal cells.
TL;DR: The readily obtainable preoperative laboratory parameters including Ca, iPTH, P, and ALP will allow identification of a subgroup of patients who are at greater risk for the development of SH following PTX.
Abstract: Hypocalcemia is one of the common complications after parathyroidectomy (PTX). Severe hypocalcemia (SH) can lead to tetany, cardiac arrhythmia and even sudden death. However, predictors for the development of SH in patients with secondary hyperparathyroidism demonstrated in some small-scale studies with a limited sample size remain inconclusive. A retrospective chart review of 420 consecutive dialysis patients who underwent PTX during a 12-year period was performed. We checked serum levels of calcium (Ca), phosphorus (P), alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH) for three consecutive days postoperatively. SH was defined as the minimum values of serum calcium lower than 1.875 mmol/L (7.5 mg/dL) within 3 days after operation. The mean (±SD) age of our study population was 53 ± 12 years, and more than half (57 %) were female. SH occurred in 37 % of the patients after PTX. Using a multivariate stepwise logistic regression analysis, lower preoperative levels of Ca (odds ratio 0.69, 95 % CI 0.60–0.79, P < 0.001), higher preoperative levels of iPTH (odds ratio 1.04, 95 % CI 1.00–1.07, P = 0.048), P (odds ratio 2.43, 95 % CI 1.49–3.95, P < 0.001) and ALP (odds ratio 1.08, 95 % CI 1.05–1.11, P < 0.001) were found to be independent predictors of occurrence of SH following PTX. The readily obtainable preoperative laboratory parameters including Ca, iPTH, P, and ALP will allow identification of a subgroup of patients who are at greater risk for the development of SH following PTX.
TL;DR: Specific characteristics of specialized therapies for refractory OAB that may significantly influence patient preferences are identified, which may be used to help inform treatment decision-making.
Abstract: To evaluate patient preferences for refractory overactive bladder (OAB) treatments: sacral neuromodulation (SNM), onabotulinum toxin A (Botox®), and percutaneous tibial nerve stimulation (PTNS) A cross-sectional Web survey was conducted with UK idiopathic OAB patients, recruited by a market research company Preference was explored using direct questioning, comparing SNM, Botox, and PTNS, and via best–worst scaling (BWS) In BWS, patients prioritized subsets of 13 treatment characteristics (attributes) across 13 choice tasks, identifying the attribute they considered best and worst in each task The attributes were those that were identified by patients in previous qualitative interviews as influential in treatment selection BWS scores for each attribute, ranging from 10 (most favourable) to −10 (most unfavourable), were calculated based on the rates they were identified as best and as worst To identify attributes that may influence treatment choice, BWS scores were compared among patients based on their most preferred treatment using analyses of variance; pairwise differences were assessed using Tukey’s multiple comparisons test The study population (N = 139) was 77 % female, had a mean age of 49 years, and were diagnosed a mean of 61 years ago All 13 attribute BWS scores were viewed positively (score > 00) or negatively (score < 00) Among the 127 (91 %) of patients who had experience with OAB medication only, most (≥80 %) were willing to try each of the three treatments; 57, 34, and 9 % most preferred PTNS, SNM, and Botox, respectively Preferences for the attributes differed based on which treatment that patients preferred Specifically, patients preferring SNM (PS) favoured ‘implanted device in upper buttock’ more than those preferring PTNS (PP) or Botox (PB) Compared to PB, PS also favoured ‘sends signals between bladder and brain to help restore bladder function’ and ‘test phase’ PB favoured ‘Botox (botulinum toxin) treatment’ and ‘treatment procedure delivered through the urethra’ more than PS and PP PP favoured the following more than PS and PB: ‘needle inserted into ankle’, ‘minimal side effects’ and ‘treatment requires repeated visits over time’ This study identified specific characteristics of specialized therapies for refractory OAB that may significantly influence patient preferences, which may be used to help inform treatment decision-making
TL;DR: This is the first study that demonstrates a relationship between tissue AGEs levels and sepsis-related mortality in PD-treated or diabetic ESRD patients and future studies are necessary to evaluate the non-cardiovascular effects of tissue A GEs in E SRD patients.
Abstract: The relation between tissue AGEs and mortality in end-stage renal disease (ESRD) is documented, but only in hemodialysis (HD) patients. This study aimed to measure and compare tissue AGEs levels in patients receiving either HD or peritoneal dialysis (PD) and to study the effect of these products on all-cause, cardiovascular or sepsis-related mortality. Tissue AGEs were noninvasively assessed in 304 dialysis patients (202 on chronic HD and 102 on continuous ambulatory PD) by measuring skin autofluorescence using a validated Autofluorescence Reader (AGE Reader, DiagnOptics b.v., Groningen, The Netherlands). There was no difference in regard to AGEs levels between the HD (3.6 ± 0.8 AU)- and PD (3.5 ± 0.7 AU, p = 0.2)-treated patients. Diabetic patients had higher AGEs values in the HD group (3.97 ± 0.81 vs. 3.52 ± 0.77, p = 0.002), but not in the PD group (3.68 ± 0.6 vs. 3.45 ± 0.70, p = 0.26). In PD patients, increasing AGEs levels were associated with an elevated risk of all-cause mortality (a 2.09-fold increase for each increment of 1 AU in AGEs values) and sepsis (a 3.44-fold increase for each increment of 1 AU in AGEs values)-related mortality. Performing a similar analysis in diabetic patients, AGEs was associated only with sepsis-related mortality (a 3.08-fold increase for each increment of 1 AU in AGEs values). This is the first study that demonstrates a relationship between tissue AGEs levels and sepsis-related mortality in PD-treated or diabetic ESRD patients. Future studies are necessary to evaluate the non-cardiovascular effects of tissue AGEs in ESRD patients.
TL;DR: This study highlights the important role of androgens in maintaining the integrity of the structure and function of corpus cavernosum in rats through counter-regulation of autophagy and apoptosis, mainly by regulating BECN 1–Bcl-2 interaction.
Abstract: The aim of this study was to determine the changes and underlying mechanisms of erectile organ structure and function in castrated rats. In addition, the regulatory effects of an androgen on autophagy and apoptosis in corpus cavernosum smooth muscle cells (CCSMCs), especially the regulatory effect of androgen on the BECN 1–Bcl-2 interaction, were investigated. Male Sprague–Dawley rats were divided into three groups (30/group): control group, castration group, and castration with testosterone supplementation group. The erectile function was examined both in vivo and in vitro, by electric stimulation of the cavernous nerve and corpus cavernosum strip bath test, respectively. Transmission electron microscopy, TUNEL assay, Masson’s trichrome staining, immunohistochemistry, and western blotting were performed to determine the levels of autophagy and apoptosis, and the structural changes in corpus cavernosum. Compared with control group, the castration group showed (1) lower erectile function: lower intracavernosal pressure/mean arterial pressure ratio, lower systolic and diastolic capability of corporal strips, and reduced expressions of eNOS and nNOS; (2) greater fibrosis: decreased smooth muscle/collagen ratio, lower expression of α-SMA, and higher expression of TGF-β1; (3) inhibited autophagy: decreased autophagosomes, lower expressions of BECN1 and LC3-II; and (4) enhanced apoptosis: higher apoptotic index and decreased Bcl-2/Bax ratio. Testosterone supplementation partially improved the effects of castration. Castration attenuates erectile function and induces corporeal fibrosis by inhibiting autophagy and promoting apoptosis of CCSMCs in rats. Therefore, our study highlights the important role of androgens in maintaining the integrity of the structure and function of corpus cavernosum in rats through counter-regulation of autophagy and apoptosis, mainly by regulating BECN 1–Bcl-2 interaction.
TL;DR: EGCG treatment can decrease renal ischemia–reperfusion injury by suppressing inflammation and cell apoptosis, and may represent a potential strategy to reduce renal I/R injury.
Abstract: Background Renal ischemia–reperfusion (I/R) injury plays an important role in the acute kidney injury. The pathogenetic mechanisms potential I/R injury is involved in apoptosis and inflammation. Epigallocatechin gallate (EGCG), a major constituent of green tea, has been shown to have anti-inflammatory and anti-apoptotic activities. This study aimed to explore the underlying effects and mechanisms of EGCG on renal I/R injury in a rat model. Materials and methods We induced renal I/R injury in SD rats by clamping the left renal artery for 45 min followed by 24-h reperfusion, along with a contralateral nephrectomy. We randomly allocated 30 rats to three groups (n = 10): sham group, IRI group, and EGCG group. We preconditioned rats intraperitoneally with EGCG (50 mg/kg) or vehicle (50 mg/kg) 45 min before inducing renal ischemia. We collected serum and kidneys at 24 h after reperfusion. Renal function and histologic damage were assessed. We also determined markers of inflammation and apoptosis in kidneys or serum. Results EGCG pretreatment can significantly reduce renal dysfunction, histologic change and the expression of tumor necrosis factor-α, IL-1β, IL-6, Bax and cleavage caspase 3 induced by I/R injury and increase the expression of Bax and caspase 3. Moreover, EGCG pretreatment can further induce the activation of p38 mitogen-activated protein kinase in kidney, with no influence on the expression of p38.
TL;DR: Compliance to CPAP therapy is associated with a slower rate of progression of CKD in patients with CKD and OSA, and progressive decline of eGFR after CPAP prescription.
Abstract: Chronic kidney disease (CKD) is associated with a high incidence of obstructive sleep apnea (OSA). We assessed the effect of continuous positive airway pressure (CPAP) on renal function in patients with CKD and OSA. In this retrospective cohort study, 42 patients with Stage 3–5 CKD and OSA were stratified into two groups: patients who use CPAP more (average >4 h/night on >70 % of nights) and patients who use CPAP less (average ≤4 h/night on ≤70 % of nights). Median follow-up time was 2.3 (1.6–2.9) years for greater and 2.0 (0.6–3.5) years for lesser CPAP users. Chart reviews were carried out to record clinical characteristics, proteinuria measurements by urine dipstick, and eGFR values calculated by CKD–EPI equations. Univariate analyses were performed using Wilcoxon rank-sum and Kruskal–Wallis tests. Multivariate logistic regression models were applied to assess eGFR decline after CPAP prescription. Twelve (29 %) of the 42 subjects used CPAP more. Groups were similar with respect to age, body mass index, blood pressure, Charlson Comorbidity Index, and baseline eGFR and proteinuria. The median rate of decline of eGFR was significantly slower at −0.07 mL/min/1.73 m2/year (range −30 to 13) in those who used more CPAP compared to those who used it less at −3.15 mL/min/1.73 m2/year (range −27 to 7) (p = 0.027).Greater use of CPAP was also associated with a significantly reduced level of proteinuria at 0.15 (range 0.0–3.0) versus 0.70 g/L (range 0.0–3.0) (p = 0.046). Less compliant CPAP users were more likely to have progressive decline of eGFR (decline >3 mL/min/1.73 m2/year), with unadjusted OR 5.0 (95 % CI 0.93–26.8) and adjusted OR 8.9 (95 % CI 1.1–72.8), adjusting for CCI and baseline eGFR. Compliance to CPAP therapy is associated with a slower rate of progression of CKD in patients with CKD and OSA.
TL;DR: Intradetrusor injection of AMDC is safe, minimally invasive and a promising treatment option for the UAB.
Abstract: We conducted the first-regenerative medicine cellular therapy for underactive bladder (UAB) in an FDA-approved, compassionate-use IND trial to evaluate treatment safety and potential clinical efficacy of autologous muscle-derived stem cells (AMDC) on a patient with UAB. No study-related adverse events or side effects were reported. In the 1-year follow-up period, the subject denied any gross hematuria, urgency, frequency or infection. A reduction in maximum cystometric capacity from 844 to 663 mL was observed, and the patient was able to void small amounts but continues to require self-catheterization 1 year after AMDC injection. Intradetrusor injection of AMDC is safe, minimally invasive and a promising treatment option for the UAB.
TL;DR: MRI is a useful tool to predict urinary incontinence after RP and the MUL and PV are well-identified structures that are involved in UI, and the study shows that UWT also influences UI.
Abstract: Prostate cancer can be treated by radical prostatectomy (RP) and provoke a troublesome side effect: urinary incontinence (UI). We propose a verification of the usefulness of MRI and an identification of which structures are involved in UI after RP. Between September 2002 and December 2011, 550 patients underwent RP. We performed MRI to evaluate extraprostatic disease before surgery. To evaluate patient status, we measured the following structures: length (LP), width (WP), height (HP) and volume (PV) of the prostate, membranous urethral length (MUL), urethral wall thickness (UWT), levator ani muscle (LAM) and obturator internus muscle (OIM) thickness, ratio of levator ani muscle/prostate volume (LAM/PV), volume of the urethra (VU). UI was defined according to ICS definition as the complaint of any involuntary leakage of urine and evaluated 1 year after surgery. Analyses were performed by mean comparisons, univariate and multivariate logistic regression with a 1000-resample bootstrapping. Means of measurements were: LP 4.46 cm, WP 5.15 cm, HP 3.9 cm, PV 49.3 cc; LAM 0.51 cm, OIM 1.46 cm; MUL 1.43 cm, UWT 1.38 cm; and LAM/PV 0.013 cm/cc, VU 2.33 cc. One hundred and twenty-two (22.2 %) patients complained of urine leakage. Univariate obtained differences in PV, OIM, MUL, and UWT. After adjusting by confounders, multivariate analysis showed: MUL: [OR 0.134; CI 95 % (0.022–0.493); P 0.006]; PV: [OR 1.016; CI 95 % (1.004–1.029); P 0.005]; UWT: [OR 6.03; CI 95 % (1.068–44.1); P 0.033]. MRI is a useful tool to predict UI after RP. The MUL and PV are well-identified structures that are involved in UI. Our study shows that UWT also influences UI.
TL;DR: PDE5 inhibitors’ utility in disease states and clinical conditions related to kidney disease such as systemic hypertension and acute and chronic kidney injury is summarized and the mechanisms explaining possible kidney protective roles of PDE5 inhibitor are discussed.
Abstract: Chronic kidney disease (CKD) represents a worldwide health problem. Traditionally, the nephroprotective treatment for CKD aims to slow progression to end-stage renal disease and includes dietary protein restriction, correction of metabolic acidosis, and renin–angiotensin system blockers. However, current standard therapeutic options may not be enough for preventing CKD progression in a subset of patients making necessary to develop novel therapeutic options to further slow renal function loss. Phosphodiesterase type 5 (PDE5) inhibitors represent a class of drugs traditionally used to treat erectile dysfunction and pulmonary hypertension. However, recent evidence suggests that PDE5 inhibitors may have additional therapeutic effects, such as cardioprotection and cerebrovascular protection. In the current review, we summarize PDE5 inhibitors’ utility in disease states and clinical conditions related to kidney disease such as systemic hypertension and acute and chronic kidney injury and discuss the mechanisms explaining possible kidney protective roles of PDE5 inhibitors. A recently completed phase 2 trials demonstrated that the long-acting PDE5 inhibitor PF-00489791 decreased albuminuria in patients with overt diabetic nephropathy when added on top of renin–angiotensin system blockade.
TL;DR: It is demonstrated that PN for T2 renal masses has no contraindicated effect on CSS, and the use of PN increased progressively between 2001 and 2011.
Abstract: Increasing popularity and improved technical feasibility of partial nephrectomy (PN) has encouraged urologists to treat larger renal masses with nephron-sparing surgery. We used a national database to characterize practice patterns for the surgical management of patients with T2 renal tumors and examined the effect of PN on cancer-specific survival in such patients. Between 2001 and 2011, 10,259 patients with primary tumor size >7 cm confined to the kidney (T2) were treated surgically for kidney cancer. PN trends were examined using annual percentage change (APC). Multivariate survival models were developed to identify independent determinants of PN use and cancer-specific survival (CSS) following surgical treatment of kidney cancer. Overall, 543 patients (5.29 %) were treated with PN versus 9716 (94.71 %) who underwent radical nephrectomy (RN). The use of PN increased progressively between 2001 and 2011 (APC +11.1 %, p 10 cm, localized disease, and papillary histology were all associated with improved CSS with PN (all p values <0.05). PN is increasingly utilized to treat T2 renal masses. Our analysis demonstrates that PN for T2 renal masses has no contraindicated effect on CSS.
TL;DR: The role of Smad in kidney disease, the molecular mechanisms, and the potential of Smads as a therapeutic target in chronic kidney disease are characterized and discussed.
Abstract: Smads are the key intermediates of canonical transforming growth factor-beta (TGF-β) signaling. These intermediates are divided into three distinct subgroups based on their role in TGF-β family signal transduction: Receptor-regulated Smads (R-Smads) 1, 2, 3, 5 and 8, common Smad4, and inhibitory Smads6 and 7. TGF-β signaling through Smad pathway involves phosphorylation, ubiquitination, sumoylation, acetylation, and protein-protein interactions with mitogen-activated protein kinases, PI3K-Akt/PKB, and Wnt/GSK-3. Several studies have suggested that upregulation or downregulation of TGF-β/Smad signaling pathways may be a pathogenic mechanism in the progression of chronic kidney disease. Smad2 and 3 are the two major downstream R-Smads in TGF-β-mediated renal fibrosis, while Smad7 also controls renal inflammation. In this review, we characterize the role of Smads in kidney disease, describe the molecular mechanisms, and discuss the potential of Smads as a therapeutic target in chronic kidney disease.