RESUMEN
BACKGROUND/AIM: The pathogenesis of cardio-vascular disease (CVD) in hemodialysis (HD) patients involves inflammation and oxidative stress. High-sensitivity C-reactive protein (hs-CRP) is an established inflammatory biomarker associated with CVD. Several studies have suggested that the inflammatory biomarker pentraxin-3 (PTX-3) and the oxidative stress-related biomarker soluble lectin-like low-density lipoprotein receptor-1 (sLOX-1) are novel biomarkers for CVD in non-HD populations. This study aimed to clarify the association of these established and novel biomarkers with future cardiovascular (CV) events in HD patients. PATIENTS AND METHODS: This was a single-center prospective cohort study that included 255 HD patients. The primary outcome was the composite of nonfatal and fatal CV events. The event-free survival rate between the two groups according to the median plasma level of each biomarker at baseline was evaluated using the Kaplan-Meier method. The risk for CV events at elevated levels of each biomarker was estimated using Cox proportional hazard model. RESULTS: We observed 44 CV events during the median follow-up period of 743 days. The event-free survival rate significantly differed between the two groups in hs-CRP but not in PTX-3 or sLOX-1. The unadjusted hazard ratio (HR) for CV events in patients with hs-CRP levels above the median was 2.63 [95% confidence interval (CI)=1.37-5.02]. The HR remained significant after adjusting for age, sex, history of CVD, and diabetes (HR=2.30; 95%CI=1.20-4.43). CONCLUSION: In HD patients, hs-CRP may have a predictable role for future CV events, whereas PTX-3 and sLOX-1 do not.
Asunto(s)
Biomarcadores , Proteína C-Reactiva , Enfermedades Cardiovasculares , Diálisis Renal , Humanos , Proteína C-Reactiva/metabolismo , Masculino , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/sangre , Femenino , Biomarcadores/sangre , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Componente Amiloide P Sérico/metabolismo , Factores de Riesgo , Modelos de Riesgos Proporcionales , Estimación de Kaplan-Meier , PronósticoRESUMEN
OBJECTIVES: The current study aimed to examine the incidence of perioperative infections and graft viability in ABO-compatible and ABO-incompatible renal transplant recipients. METHODS: We included 643 living donor renal transplant recipients registered in the Michinoku Renal Transplant Network from 1998 to 2021. Patients were divided into the ABO-compatible and ABO-incompatible kidney transplantation groups. We compared the characteristics of the two groups and evaluated the incidence of postoperative viral infections (cytomegalovirus and BK virus), graft loss-free survival, and overall survival between the two groups. RESULTS: Of 643 patients, 485 (75%) and 158 (25%) were ABO-compatible and ABO-incompatible renal transplant recipients, respectively. Postoperative viral infections, rituximab use, and plasma exchange were significantly more common in ABO-incompatible than in ABO-compatible transplant recipients. However, there were no significant differences in terms of other background characteristics. The ABO-incompatible group was more likely to develop viral infections than the ABO-compatible group. Graft loss-free survival and overall survival did not significantly differ between the two groups. According to the multivariate Cox regression analysis, ABO compatibility was not significantly associated with graft loss-free survival and overall survival. CONCLUSION: Although the incidence of postoperative viral infections in ABO-incompatible renal transplant recipients increased, there was no significant difference in terms of rejection events, graft loss-free survival, and overall survival.
Asunto(s)
Sistema del Grupo Sanguíneo ABO , Virus BK , Incompatibilidad de Grupos Sanguíneos , Infecciones por Citomegalovirus , Trasplante de Riñón , Infecciones por Polyomavirus , Complicaciones Posoperatorias , Infecciones Tumorales por Virus , Humanos , Trasplante de Riñón/efectos adversos , Incidencia , Masculino , Infecciones por Polyomavirus/epidemiología , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Infecciones por Citomegalovirus/epidemiología , Complicaciones Posoperatorias/epidemiología , Sistema del Grupo Sanguíneo ABO/inmunología , Adulto , Infecciones Tumorales por Virus/epidemiología , Rechazo de Injerto/epidemiología , Supervivencia de InjertoRESUMEN
BACKGROUND: Cardiovascular diseases are still highly prevalent after kidney transplantation. However, little is known about the impact of the timing of rejection episodes on cardiovascular disease. The study aimed to analyze the influence of the timing of rejection episodes on cardiovascular events in recipients of living donor kidney transplantation. METHODS: We studied 572 living donor kidney transplant recipients from the Michinoku Renal Transplant Network (MRTN), which includes 6 centers in the Tohoku region of Japan. Fine-Gray proportional hazards regression analysis with time-dependent variables was used to assess the effect of rejection episode on cardiovascular events. Recipients were divided into three groups: those without rejection (non-rejection, 370 patients), rejection within 6 months after transplantation (early rejection, 99 patients), and rejection after 6 months (late rejection, 103 patients). The effect of timing on cardiovascular events was evaluated using Fine-Gray proportional hazards regression analysis. RESULTS: During a median follow-up of 77 months, 70 patients experienced cardiovascular events. Rejection episodes were significantly associated with cardiovascular events (hazard ratio [HR]: 2.08, 95% confidence interval [CI]: 1.26-3.43, P = 0.004), along with age and dialysis vintage. The 5-year cumulative incidence of cardiovascular events was significantly higher in the late rejection group than in the early rejection group (15% vs. 3.3%, P = 0.021). However, no significant difference in 5-year cumulative cardiovascular event incidence was observed between the early rejection and non-rejection groups. Late rejection was significantly associated with cardiovascular events (HR: 2.40, 95% CI: 1.38-4.18, P = 0.002), whereas early rejection was not significantly correlated with cardiovascular event risk (HR: 1.18, P = 0.670). CONCLUSIONS: Rejections occurring more than 6 months after transplantation is significantly associated with risk of cardiovascular events. TRIAL REGISTRATION NUMBER: 2019-099-1, date of registration; 3 Dec. 2019, retrospectively registered.
Asunto(s)
Enfermedades Cardiovasculares , Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Donadores Vivos , Estudios Retrospectivos , Diálisis Renal/efectos adversos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/epidemiología , Supervivencia de InjertoRESUMEN
We aimed to evaluate the humoral response after the second and third doses of SARS-CoV-2 mRNA vaccine in ABO blood type incompatible kidney transplant (KT) recipients treated with rituximab. This retrospective study conducted between June 2021 and June 2022 included 131 KT recipients and 154 nontransplant controls who had received mRNA vaccines. We compared the seropositivity (anti-SARS-CoV-2 spike IgG antibody titer ≥ 0.8 U/mL) after the second and third vaccinations. Furthermore, we evaluated the impact of pretransplant vaccination for seropositivity. Of the 131 KT recipients, 50 had received the third dose of mRNA vaccine. The antibody titer was significantly increased after the third dose of mRNA vaccine. The seropositivity rate after the third dose of mRNA vaccine increased from 36 to 70%. We observed no significant difference in seropositivity after the third dose of mRNA vaccine in ABO incompatibility, rituximab use, mycophenolate mofetil use, and age at KT. Of the nine recipients who had received the second or third dose of the mRNA vaccine prior to the KT, eight of the recipients were seropositive both before and after the KT. Our results suggest that ABO incompatibility or rituximab use was not significantly associated with seropositivity.
Asunto(s)
COVID-19 , Trasplante de Riñón , Humanos , Rituximab/uso terapéutico , Vacunas contra la COVID-19 , Estudios Retrospectivos , COVID-19/prevención & control , SARS-CoV-2 , Vacunas de ARNm , Anticuerpos Antivirales , Incompatibilidad de Grupos SanguíneosRESUMEN
We aimed to evaluate the seroprevalence and investigated factors associated with seropositivity after the second SARS-CoV-2 mRNA vaccination in kidney transplant (KT) recipients. This retrospective study conducted between June and November 2021 included 106 KT recipients and 127 healthy controls who received the second dose of the BNT162b2 mRNA vaccine at least 7 days before the measurement of antibody titers. The antibody titer against the receptor-binding domain of SARS-CoV-2 spike (S) protein was determined. We compared seroprevalence rates (immunoglobulin G [IgG] level of ≥ 0.8 or ≥ 15 U/mL) between the healthy controls and KT recipients and identified factors associated with impaired humoral response. The seroprevalence rate of the healthy controls and KT recipients was 98% and 22%, respectively. Univariate logistic regression analysis revealed that age > 53 years, rituximab use, mycophenolate mofetil use, and KT vintage < 7 years were negatively associated with the rate of anti-SARS-CoV-2 S IgG ≥ 15 U/mL in KT recipients. ABO blood type incompatible KT was not significantly associated with seroprevalence. Humoral response after the second BNT162b2 mRNA vaccine was greatly hindered by immunosuppression therapy in KT recipients. Older age, rituximab use, mycophenolate mofetil use, and KT vintage may play key roles in seroconversion.
Asunto(s)
COVID-19 , Trasplante de Riñón , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Inmunoglobulina G , Japón , Persona de Mediana Edad , Ácido Micofenólico , Estudios Retrospectivos , Rituximab , SARS-CoV-2 , Estudios Seroepidemiológicos , Receptores de Trasplantes , Vacunas Sintéticas , Vacunas de ARNmRESUMEN
BACKGROUND: Although a shortage in organ donation is a critical problem in Japan, understanding of and attitude toward organ transplantation in medical students have not been sufficiently reported. METHODS: Between 2013 and 2018, we surveyed 702 medical students in the fifth-year clinical training in our urology department. The survey concerned (1) knowledge of Japanese transplantation law, which was amended in 2010, and (2) whether the respondents had an organ donor card and had agreed to be a brain-dead donor or a living donor in kidney transplantation with specific reasons for their choices. RESULTS: All 702 students answered the survey. Of 657 students who provided valid answers to the first section, 402 (61%) recognized the amendment to the Japanese transplantation law, and only 11 (1.7%) fully understood its contents. Of 702 students, 194 (28%) had a donor card, 384 (55%) agreed to be a brain-dead donor, and 529 (75%) agreed to be a living donor in kidney transplantation. As the specific reasons for their choices, only a few medical students wrote reasons based on their medical standpoint, and more students wrote emotional reasons. CONCLUSIONS: The understanding of and attitude toward organ transplantation were not remarkably high in the fifth-year medical students in Japan. To solve the donor shortage problem, education about organ transplantation may need to be more effective.
Asunto(s)
Actitud , Muerte Encefálica , Trasplante de Riñón/legislación & jurisprudencia , Donadores Vivos/provisión & distribución , Estudiantes de Medicina/estadística & datos numéricos , Adulto , Estudios Transversales , Emociones , Humanos , Japón , Estudiantes de Medicina/psicología , Obtención de Tejidos y Órganos , Adulto JovenRESUMEN
We prospectively validate the efficacy of the frailty discriminant score (FDS) in individuals with urological cancers, as there has been growing importance in evaluating frailty in clinical practice. A prospective, multicenter study was conducted from February 2017 to April 2019. We enrolled 258 patients with urological cancers and 301 community-dwelling participants who were assessed for frailty. Frailty was assessed using FDS that includes ten items, such as physical, mental, and blood biochemical tests. The primary outcome was the non-inferiority (margin 5%) of FDS in discriminating patients with urological cancers from controls (Ctrl). The sensitivity, specificity, and area under the receiver operating characteristic (AUROC) curve for each predictive test were calculated. The secondary endpoints included the prediction of overall survival between patients with urological cancer who have high and low FDS. FDS was significantly higher in patients with urological cancers than that in the Ctrl. The AUROC curves for individuals with non-prostate cancers (such as bladder cancer, upper tract urothelial carcinoma, and renal cell carcinoma; 0.942) and those with prostate cancer (0.943) were within the non-inferior margin. The overall survival values were significantly lower in patients with higher FDS score than in those with lower FDS score. The study met its primary and secondary endpoints. The FDS is a reliable and valid tool for assessing frailty and prognosis in patients with urological cancers.
Asunto(s)
Fragilidad/fisiopatología , Neoplasias Urológicas/patología , Neoplasias Urológicas/fisiopatología , Anciano , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/fisiopatología , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/fisiopatología , Estudios de Evaluación como Asunto , Femenino , Anciano Frágil , Evaluación Geriátrica/métodos , Humanos , Neoplasias Renales/patología , Neoplasias Renales/fisiopatología , Masculino , Pronóstico , Estudios Prospectivos , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/fisiopatología , Curva ROC , Sensibilidad y Especificidad , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/fisiopatologíaRESUMEN
BACKGROUND: The impact of distance between donor and recipient hospitals on outcomes in cadaveric kidney transplantations is unknown. We investigated the association between inter-hospital distance and outcomes in cadaveric kidney transplantations in Japan. METHODS: We retrospectively analyzed 363 cadaveric kidney transplantations between 2002 and 2017 in Japan. Inter-hospital distance, graft transport time, total ischemic time (TIT), and graft survival were compared between our hospital and national transplantation cohort in Japan. Estimated glomerular filtration rate (eGFR) 1 month and 1 year after transplantation was compared between cadaveric and living-donor kidney transplantations in our hospitals. Additionally, inter-hospital distances among the seven geographical regions in Japan were assessed. RESULTS: There were 12 and 351 cadaveric kidney transplantations at our hospital and in Japan, respectively. Mean inter-hospital distance at our hospital (217 ± 121 km) was significantly longer than that of the national cohort (53 ± 80 km; P < 0.001). Mean TIT and graft survival for our hospital and national cohort were 539 ± 200 min and 91% and 491 ± 193 min and 81%, respectively. Mean eGFRs 1 year after cadaveric and living-donor transplantations at our hospitals were comparable (47 ± 16 vs. 47 ± 15 mL/min/1.73 m2). The comparison among seven regions in Japan indicated a regional difference in inter-hospital distance with an association between area (km2) and inter-hospital distance (km). CONCLUSIONS: Despite the longer inter-hospital distance at our hospital, TIT and transplant outcomes were acceptable in our cases. In addition, geographical inequity in graft allocation in Japan was suggested.
Asunto(s)
Isquemia Fría , Trasplante de Riñón/estadística & datos numéricos , Transportes/estadística & datos numéricos , Adulto , Anciano , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: The impact of nail abnormalities on prognosis in hemodialysis patients is unknown. This study investigated whether toenail opacity as a readout of nail abnormalities predicted prognosis in hemodialysis patients. METHODS: In this observational study, 494 eligible hemodialysis patients who received hemodialysis at Oyokyo Kidney Research Institute between September 2010 and December 2015 were included. The presence of nail abnormalities was objectively evaluated by big toenail opacity ratio measurement. Primary endpoint was overall survival, and secondary endpoints were lower limb amputation and determination of risk factors for poor prognosis among patient demographics, comorbidities, blood tests, and big toenail opacity. Overall survival and lower limb survival were evaluated using the Kaplan-Meier method with log-rank test. Multivariate Cox regression analyses assessed predictors for poor prognosis. RESULTS: Big toenail opacity was found in 259 (52%) patients. Patients with big toenail opacity were significantly older, had shorter duration of dialysis, higher prevalence rates of diabetes mellitus (DM), cardiovascular disease (CVD), and higher mortality rates than those without opacity. Presence of big toenail opacity predicted poor prognosis for both overall and lower limb survival. Multivariate Cox regression analyses revealed serum albumin, the presence of DM and big toenail opacity were independent risk factors for both poor overall and lower limb survivals. CONCLUSION: The prevalence of big toenail opacity was high in hemodialysis patients. Despite the short observation period, our findings indicated that big toenail opacity had significant predictive power for poor overall and lower limb survival.
Asunto(s)
Fallo Renal Crónico/patología , Uñas/patología , Anciano , Índice Tobillo Braquial , Femenino , Humanos , Japón/epidemiología , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Curva ROC , Estudios RetrospectivosRESUMEN
Muscle invasive bladder cancer is an aggressive type of epithelial tumor with a high rate of metastasis. For bladder cancer cells to reach the muscle layer, cells must invade through an urothelial cell monolayer (transurothelial invasion) and basement membrane. However, the process by which transurothelial invasion occurs has not been fully characterized. In this study we developed a novel method to evaluate the transurothelial invasion capacity and investigated its cellular and molecular processes using primary culture cells from bladder cancer patients. The analysis revealed that compared with the prognosis for patients with nonmuscle invasive bladder cancer that of patients with muscle invasive bladder cancer was particularly poor due to metastatic recurrence. Cancer cells from patients with muscle invasive bladder cancer exhibited a higher invasive capacity through the urothelial cell monolayer compared with those from noninvasive bladder cancer patients. Furthermore, muscle invasive bladder cancer cells demonstrated a greater ability to form invadopodia, the filamentous actinbased membrane protrusions required for matrix degradation and invasion compared with noninvasive cells. Bladder cancer cell lines were established with reduced invadopodia formation by silencing the expression of cortactin, an essential component of invadopodia. The cortactin knockdown bladder cancer cells with reduced invadopodia formation demonstrated a markedly reduced ability to invade through the urothelial cell monolayer, indicating that invadopodia are essential for transurothelial invasion. The results indicate that invadopodia formation is required for muscle invasion of aggressive bladder cancer cells.
Asunto(s)
Músculo Liso/patología , Neoplasias de la Vejiga Urinaria/patología , Línea Celular Tumoral , Humanos , Metaloendopeptidasas/metabolismo , Invasividad Neoplásica , Pronóstico , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
Invasive cancer cells form the filamentous actinbased membrane protrusions known as invadopodia. Invadopodia are thought to play a critical role in cancer cell invasion and metastasis due to their ability to degrade the extracellular matrix. The present study assessed whether invadopodia formation is essential in extravasation of circulating bladder cancer cells and lung metastasis. To analyze the importance of invadopodia, bladder cancer cell lines with reduced invadopodia formation were established by silencing the expression of cortactin, an essential component of invadopodia, using cortactin short hairpin RNA. Bladder cancer cells with cortactin knockdown demonstrated a markedly decreased ability to form invadopodia, secrete matrix metalloproteinases and invade the extracellular matrix. In addition, the knockdown cells exhibited a reduced transendothelial invasion capacity and decreased formation of metastatic foci in the lungs. The present study demonstrated that bladder cancer cells with cortactin knockdown have a reduced capacity to extravasate into the lung from the circulation, due to the decreased invasive character of invadopodia. This suggests that invadopodia formation is a critical process for cancer cell extravasation.
Asunto(s)
Cortactina/metabolismo , Neoplasias Pulmonares/secundario , Seudópodos/metabolismo , Seudópodos/patología , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Animales , Línea Celular Tumoral , Técnicas de Silenciamiento del Gen , Humanos , Neoplasias Pulmonares/patología , Metaloproteinasas de la Matriz/metabolismo , Ratones , Ratones Desnudos , Invasividad Neoplásica/patología , Neoplasias de la Vejiga Urinaria/enzimologíaRESUMEN
Although the number of elderly patients requiring dialysis has increased, data regarding the prognosis of elderly patients undergoing hemodialysis are limited. In the present study, prognosis in Japanese hemodialysis patients aged ≥80 years was evaluated. From January 1988 to July 2013, 1144 consecutive patients with end-stage renal disease required renal replacement therapy at our institution; of these, 141 were aged ≥80 years. These patients' charts were retrospectively reviewed for relevant clinical variables and survival time. The life expectancies table from the National Vital Statistics database was used, and prognostic factors were assessed by multivariate analysis. In total, 107 deaths (76%) were recorded during the study period. The median survival time and estimated life-shortening period in the patients were 2.6 years and -5.3 years, respectively. Eastern Cooperative Oncology Group Performance Status and hemoglobin level were revealed as prognostic factors in the multivariate analysis. Estimates of prognosis and prognostic factors may provide useful information for physicians as well as elderly patients with end-stage kidney disease.
Asunto(s)
Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/rehabilitación , Esperanza de Vida , Diálisis Renal/mortalidad , Diálisis Renal/estadística & datos numéricos , Distribución por Edad , Anciano de 80 o más Años , Femenino , Anciano Frágil , Humanos , Japón/epidemiología , Masculino , Prevalencia , Pronóstico , Medición de Riesgo , Distribución por Sexo , Tasa de SupervivenciaRESUMEN
Hyperphosphatemia is an important determinant of morbidity and mortality in patients with chronic kidney disease (CKD). Patients with CKD are advised to consume a low phosphate diet and are often prescribed phosphate-lowering drug therapy. However, commercially processed food and drinks often contain phosphate compounds, but the phosphate level is not usually provided in the ingredient list, which makes it difficult for CKD patients to choose a correct diet. We conducted a survey of the awareness of food/beverages containing artificially added phosphate among CKD patients undergoing hemodialysis. The subjects were 153 patients (77 males and 76 females; average age 56±11 years) who were randomly selected from the Dialysis Center of Hirosaki City, Japan. The subjects were provided with a list of questions. The survey results showed that 93% of the subjects were aware of the presence of high sugar content in soda, whereas only 25% were aware of the presence of phosphate (phosphoric acid) in such drinks. Despite 78% of the subjects being aware of the detrimental effects of consumption of a high phosphate diet, 43% drank at least 1 to 5 cans of soda per week and about 17% consumed "fast food" once each week. We also assessed the immediate effects of high-phosphate containing carbonated soda consumption by determining urinary calcium, phosphate, protein and sugar contents in overnight fasted healthy volunteers (nâ=â55; average age 20.7±0.3 years old, 20 males and 35 females). Significantly higher urinary calcium (adjusted using urinary creatinine) excretion was found 2 h after consuming 350 ml of carbonated soda compared to the fasting baseline level (0.15±0.01 vs. 0.09±0.01, pâ=â0.001). Our survey results suggest that CKD patients undergoing hemodialysis are not adequately aware of the hidden source of phosphate in their diet, and emphasize the need for educational initiatives to raise awareness of this issue among CKD patients.
Asunto(s)
Bebidas Gaseosas/efectos adversos , Hiperfosfatemia/etiología , Fosfatos/efectos adversos , Insuficiencia Renal Crónica/complicaciones , Anciano , Estudios de Casos y Controles , Conducta Alimentaria , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto , Encuestas y Cuestionarios , Adulto JovenRESUMEN
BACKGROUND: Bixalomer (BXL) was developed to improve gastrointestinal symptoms and reduce constipation, relative to sevelamer hydrochloride, in hemodialysis patients. We prospectively evaluated the safety and effectiveness of switching maintenance dialysis patients from sevelamer hydrochloride to BXL. METHODS: Twenty-eight patients were switched from sevelamer hydrochloride to BXL (1:1 dose) from July to October 2012, whereas 84 randomly selected patients not treated with sevelamer hydrochloride were enrolled as a control group. The primary endpoint was improvement of gastrointestinal symptoms; secondary endpoints included improvement in metabolic acidosis, changes in blood biochemistry, and safety 12 weeks after the switch. We also surveyed patient satisfaction with switching to BXL 12 weeks after the switch. RESULTS: Before switching, symptoms of epigastric fullness were significantly worse in the switch than in the control group. Twelve weeks after the switch, reflux, epigastric fullness, and constipation had improved significantly in the switch group. Other factors, including stomach ache, diarrhea, and form of stool, did not change significantly. Blood gas analysis showed that metabolic acidosis was significantly improved by switching. Four patients (14%) experienced grade 1 adverse events, all of which improved immediately after stopping BXL. Major adverse events were diarrhea and abdominal discomfort. Mean satisfaction score was 3.1 ± 0.7, with 64% of patients reporting they were "neither satisfied nor dissatisfied" after switching. CONCLUSIONS: A switch from sevelamer hydrochloride to BXL improved symptoms of reflux, epigastric fullness, constipation, and metabolic acidosis in hemodialysis patients. TRIAL REGISTRATION: The study was registered as Clinical trial: (UMIN000011150).
Asunto(s)
Acidosis/prevención & control , Quelantes/uso terapéutico , Enfermedades Gastrointestinales/prevención & control , Soluciones para Hemodiálisis/efectos adversos , Soluciones para Hemodiálisis/uso terapéutico , Hiperfosfatemia/tratamiento farmacológico , Poliaminas/efectos adversos , Poliaminas/uso terapéutico , Acidosis/inducido químicamente , Acidosis/diagnóstico , Quelantes/efectos adversos , Sustitución de Medicamentos , Femenino , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Gastrointestinales/diagnóstico , Humanos , Hiperfosfatemia/complicaciones , Masculino , Persona de Mediana Edad , Diálisis Renal , Sevelamer , Resultado del TratamientoRESUMEN
The majority of deaths associated with solid tumors are caused by tumor metastasis. To prevent metastasis, it is vital to understand its detailed process. In hematogenous metastasis of bladder cancer, some cancer cells disseminating into blood circulation extravasate into the lung tissues to form metastases. To study the molecular basis of the lung metastasis of bladder cancer, we employed an in vivo selection system that mimics hematogenous metastasis of bladder cancer on a low-metastatic bladder cancer cell line (KK-47). We have successfully isolated a high-metastatic bladder cancer subline, KK-47HM4, from KK-47 cells. We characterized KK-47HM4 in in vitro experimental systems. No significant difference in growth rate and susceptibility to NK cell attack between KK-47 and KK-47HM4 cells was observed. However, KK-47HM4 exhibited the higher capacities of Matrigel Matrix invasion and transendothelial invasion than KK-47. These results suggest that the extravasation of KK-47HM4 cells was enhanced among the multiple steps of the lung metastasis of bladder cancer. Our cDNA microarray analysis identified 67 genes whose expression was up- or downregulated in KK-47HM4 cells compared with KK-47 cells. This analysis data implied that one possible cause for enhanced extravasation of KK-47HM4 is its higher adhesion to extracellular matrix proteins. KK-47HM4 is the first bladder cancer subline with enhanced extravasation potential using the in vivo selection system. The information provided by our cDNA microarray analysis using KK-47HM4 will be useful for further investigation into the molecular basis of extravasation of cancer cells.
Asunto(s)
Línea Celular Tumoral/patología , Invasividad Neoplásica/patología , Neoplasias de la Vejiga Urinaria/patología , Animales , Humanos , Neoplasias Pulmonares/secundario , Ratones , Ratones Desnudos , Análisis de Secuencia por Matrices de OligonucleótidosRESUMEN
Aim. The objective of this study was to characterize coordinated molecular changes in the structure and composition of the walls of venous segments of arteriovenous (AV) fistulas evoked by overflow. Methods. Venous tissue samples were collected from 6 hemodialysis patients with AV fistulas exposed to overflow and from the normal cephalic veins of 4 other hemodialysis patients. Total RNA was extracted from the venous tissue samples, and gene expression between the 2 groups was compared using Whole Human Genome DNA microarray 44 K. Microarray data were analyzed by GeneSpring GX software and Ingenuity Pathway Analysis. Results. The cDNA microarray analysis identified 397 upregulated genes and 456 downregulated genes. Gene ontology analysis with GeneSpring GX software revealed that biological developmental processes and glycosaminoglycan binding were the most upregulated. In addition, most upregulation occurred extracellularly. In the pathway analysis, the TGF beta signaling pathway, cytokines and inflammatory response pathway, hypertrophy model, and the myometrial relaxation and contraction pathway were significantly upregulated compared with the control cephalic vein. Conclusion. Combining microarray results and pathway information available via the Internet provided biological insight into the structure and composition of the venous wall of overflow AV fistulas.
RESUMEN
BACKGROUND: The aim of this study is to evaluate the usefulness of serum N-glycan profiling for prognosis in hemodialysis patients. METHODS: Serum N-glycan analysis was performed in 100 hemodialysis patients in June 2008 using the glycoblotting method, which allows high-throughput, comprehensive, and quantitative N-glycan analysis. All patients were longitudinally followed up for 5 years. To evaluate the independent predictors for prognosis, patients' background, blood biochemistry, and N-glycans intensity were analyzed using Cox regression multivariate analysis. Selected N-glycans and independent factors were evaluated using the log-rank test with the Kaplan-Meier method to identify the predictive indicators for prognosis. Each patient was categorized according to the number of risk factors to evaluate the predictive potential of the risk criteria for prognosis. RESULTS: In total, 56 N-glycan types were identified in the hemodialysis patients. Cox regression multivariate analysis showed cardiovascular events, body mass index, maximum intima media thickness, and the serum N-glycan intensity of peak number 49 were predictive indicators for overall survival. Risk classification according to the number of independent risk factors revealed significantly poor survival by increasing the number of risk factors. CONCLUSIONS: Serum N-glycan profiling may have a potential to predict prognosis in patients undergoing hemodialysis.
Asunto(s)
Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/mortalidad , Polisacáridos/sangre , Diálisis Renal , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/etiología , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
Core2 ß-1,6-N-acetylglucosaminyltransferase (C2GnT) forms an N-acetylglucosamine branch in the O-glycans (core2 O-glycans) of cell surface glycoproteins. We previously revealed that the expression of C2GnT is positively correlated with poor prognosis in prostate cancer patients. However, the detailed mechanisms underlying their poor prognosis remain unclear. In the current study, we report that the core2 O-glycans carried by the surface MUC1 glycoproteins of prostate cancer cells play an important role in the evasion of NK cell immunity. In C2GnTexpressing prostate cancer cells, the MUC1 core2 O-glycans are modified with poly-N-acetyllactosamine. MUC1 glycoproteins carrying poly-N-acetyllactosamine attenuated the interaction of the cancer cells with NK cells, resulting in decreased secretion of granzyme B by the NK cells. PolyNacetyllactosamine also interfered with the ability of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) to access the cancer cell surface. These effects of poly-N-acetyllactosamine on NK cells render C2GnT-expressing prostate cancer cells resistant to NK cell cytotoxicity. By contrast, C2GnT-deficient prostate cancer cells carrying a lower amount of poly-N-acetyllactosamine than the C2GnT-expressing prostate cancer cells were significantly more susceptible to NK cell cytotoxicity. Our results strongly suggest that C2GnT-expressing prostate cancer cells evade NK cell immunity and survive longer in the host blood circulation, thereby resulting in the promotion of prostate cancer metastasis.
Asunto(s)
Células Asesinas Naturales/inmunología , N-Acetilglucosaminiltransferasas/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Glicosilación , Granzimas/metabolismo , Humanos , Células Asesinas Naturales/citología , Masculino , Mucina-1/metabolismo , N-Acetilglucosaminiltransferasas/genética , Polisacáridos/metabolismo , Neoplasias de la Próstata/enzimología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacología , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Ligando Inductor de Apoptosis Relacionado con TNF/farmacologíaRESUMEN
BACKGROUND: Simple renal cysts usually have benign clinical features. We report a rare case of papillary renal cell carcinoma (RCC) associated with a large recurrent simple cyst following sclerotherapy. CASE PRESENTATION: A 47-year-old Japanese woman received minocycline sclerotherapy for a large (9 cm in diameter) simple left renal cyst in May 2005. The cyst regrew, and second-line sclerotherapy with ethanol was performed in November 2005. Three years later, she developed papillary RCC on the wall of the recurrent renal cyst. Radical nephrectomy was performed, but the patient died of metastatic disease 15 months after surgery. CONCLUSION: Malignant transformation from recurrent simple renal cyst to RCC may occur in the years following sclerotherapy, underscoring the need for long-term follow-up.