ABSTRACT
Chronic kidney disease （CKD） is a global health problem， and its incidence increases year by year. Studies have revealed that the progression of CKD into end-stage renal disease （ESRD） is related to its inability to effectively eliminate toxins due to decreased renal function. Additionally， intestinal microflora produces a large amount of gut-derived uremic toxins （GDUTs） during protein fermentation. The theory of gut-kidney axis holds that gut and kidney interact with each other， and CKD reduces the ability to remove uremic toxins （UTs）， resulting in the accumulation of UTs in the blood. The accumulation of UTs also accelerates the deterioration of renal function， leading to a vicious circle. This paper focused on the sources of indoxyl sulfate and p-cresol sulfate in GDUTs and their mechanisms against CKD （such as inducing renal tubular cell death， oxidative stress and endothelial injury， promoting renal fibrosis and down-regulating renal protective protein） as well as the sources of trimethylamine oxide and its mechanisms against CKD （such as promoting renal fibrosis and inflammation）. Moreover， starting from gut-kidney axis， this paper summarized the ways of diet and nutrition regulation， toxin adsorption， enhanced dialysis to increase the clearance， inhibiting the sources of gut-derived toxins and traditional Chinese medicine （TCM） therapy （TCM preparations and TCM active ingredients） to regulate intestinal microecology and reduce the generation of GDUTs， aiming to provide new therapeutic ideas for delaying the progression of CKD.
ABSTRACT
At present, clinical interventions for chronic kidney disease are very limited, and most patients rely on dialysis to sustain their lives for a long time. However, studies on the gut-kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease. This study showed that berberine, a natural drug with low oral availability, significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins, including p-cresol. Furthermore, berberine reduced the content of p-cresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine-p-cresol pathway of the intestinal flora. Meanwhile, berberine increased the butyric acid producing bacteria and the butyric acid content in feces, while decreased the renal toxic trimethylamine N-oxide. These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut-kidney axis.
ABSTRACT
Resumen Antecedentes: existe actualmente un interés creciente, a nivel mundial, por las posibilidades que ofrece la hemodiálisis domiciliaria, la cual se encuentra más extendida en países del norte de Europa, Canadá, Reino Unido, Estados Unidos, Australia y Nueva Zelanda. En España, ha crecido de manera muy lenta, excepto en determinadas regiones como la provincia de Castellón, donde hemos puesto especial interés en la expansión de las técnicas dialíticas domiciliarias. Objetivo: describir la experiencia en el programa de hemodiálisis domiciliaria del Hospital General de Castellón. Metodología: estudio descriptivo de los pacientes incluidos en el programa de hemodiálisis domiciliaria del Hospital General de Castellón, desde su inicio en enero del 2008 hasta diciembre del 2017. Resultados: en su conjunto, entrenamos a 41 pacientes, de los que 36 llegaron a hemodializarse en casa (régimen corto-diario). La edad de los pacientes era 58,3±13,4 años; y el índice de Charlson, 4,1±1,6. 62 % de los pacientes eran hombres, 25,6 % padecían diabetes mellitus; 15,4 % tenían diagnóstico de insuficiencia cardíaca y 32 % eran portadores de fístula de hemodiálisis. El 38,5 % de los pacientes en edad laboral estaba activo. Obtuvimos una supervivencia técnica considerando el evento muerte+fallo técnico, censurando el trasplante, del 79,4 % al año, 75,2 % a los 2 años y 42,1 % a los 5 años. En el análisis univariante, resultaron determinantes la edad, la presencia de diabetes mellitus y la presencia de insuficiencia cardíaca. En el análisis multivariante, solo se mantuvo la insuficiencia cardíaca. Las reducciones semanales de fósforo y beta-2-microglobulina fueron significativamente mayores con hemodiálisis corta diaria, en comparación con la hemodiafiltración on-line. La hemodiafiltración on-line fue superior en la reducción semanal a partir de los 17 800 daltons para la mioglobina. Conclusiones: la hemodiálisis domiciliaria es una técnica posible que ofrece al paciente una adecuada reinserción sociolaboral, buenos niveles de reducción semanal de toxinas urémicas y una aceptable supervivencia técnica en el tiempo.
Abstract Background: There is currently a growing interest, worldwide, for the possibilities offered by home hemodialysis, which is more widespread in northern European countries, Canada, the United Kingdom, the United States, Australia and New Zealand. In Spain, it has grown very slowly, except in certain regions such as the province of Castellón, where we have placed special interest in the expansion of home dialysis techniques. Objective: To describe the experience in the Home Hemodialysis program of the Hospital General de Castellón. Methodology: Descriptive study of the patients included in the home hemodialysis program of the Hospital General de Castellón, from its beginning in January 2008 to December 2017. Results: As a whole, we trained 41 patients, of whom 36 came to hemodialysis at home (short-day regimen). Age 58,3±13,4 years, Charlson index 4,1±1,6, 62 % men, 25,6 % with diabetes mellitus, 15,4 % with diagnosis of heart failure, 32 % with hemodialysis fistula, 38,5 % of working-age patients were active. We obtained a technical survival considering the event death+technical failure, censoring transplant of 79,4 % a year, 75,2 % at 2 years and 42,1 % at 5 years, resulting determinants of the event in the univariate analysis: age, presence of diabetes mellitus and presence of heart failure, and only heart failure in the multivariate. The weekly reductions of phosphorus and beta-2-microglobulin were significantly greater with daily short hemodialysis with respect to on-line haemodiafiltration. Being the on-line hemodiafiltration superior in the weekly reduction from the 17800 daltons of myoglobin. Conclusions: Home hemodialysis is a possible technique that offers the patient an adequate social-labor reintegration with good levels of weekly reduction of uraemic toxins and an acceptable technical survival over time.
Subject(s)
Humans , Male , Female , Hemodialysis, Home , Ecological Momentary Assessment , Spain , UremiaABSTRACT
Chronic kidney disease (CKD) is a major disease that threatens human health. With the progression of CKD, the risk of cardiovascular death increases, which is associated with the elevated levels of uremic toxins (UTs). Representative toxins such as indoxyl sulfate and p-cresyl sulfate are involed in CKD progression and cardiovascular events inseparable from the key role of endothelial dysfunction. The therapeutic strategies of UTs are aimed at signaling pathways that target the levels and damage of toxins in modern medicine. There is a certain relevance between toxins and "turbid toxin" in the theory of Chinese medicine (CM). CM treatments have been demonstrated to reduce the damage of gut-derived toxins to the heart, kidney and blood vessels. Modern medicine still lacks evidence-based therapies, so it is necessary to explore the treatments of CM.
Subject(s)
Humans , Intestinal Mucosa , Metabolism , Medicine, Chinese Traditional , Renal Insufficiency, Chronic , Drug Therapy , Signal Transduction , Toxins, Biological , Metabolism , Uremia , MetabolismABSTRACT
Objective To observe the effects of long-term hemodialysis(HD) combined with hemoperfusion(HP) on the levels of protein-bound uremic toxins (PBUTs) in maintenance hemodialysis (MHD) patients.Methods Forty-six patients with MHD were selected and divided into HD +HP group and HD group .HD+HP group ( n=22 ) was treated with low-flux HD twice a week and HD combined with HP once a week ,while HD group(n=24) was treated with low-flux HD three times a week.The follow-up lasted 36 weeks.The pre-dialysis concentration of PBUTs was measured at week 12, 24, 36 and baseline.PBUTs included hippuric acid (HA), indoxyl sulphate (IS)and p-cresyl sulphate (PCS).High performance liquid chromatography-tandem mass spectrometry ( HPLC-MS/MS) was used for determination .Results After 36 weeks of follow-up, the concentration of the three toxins in the HD +HP group was lower than that in the HD group during the study.At the end of the study, the reduction rates of HA, IS and PCS were 33.5%,12.8% and 24.2%, respectively, in HD+HP group.The three toxins in HD group increased by 2.3%,21.8%and 2.8%.The clearance rate of HA, PCS and IS in the HP+HD group was higher than in HD group (P<0.05).Conclusion Long-term HD combined with HP can more effectively remove PBUTs , and keep them at a lower level .
ABSTRACT
Objective To observe the effects of long-term hemodialysis(HD) combined with hemoperfusion(HP) on the levels of protein-bound uremic toxins (PBUTs) in maintenance hemodialysis (MHD) patients.Methods Forty-six patients with MHD were selected and divided into HD +HP group and HD group .HD+HP group ( n=22 ) was treated with low-flux HD twice a week and HD combined with HP once a week ,while HD group(n=24) was treated with low-flux HD three times a week.The follow-up lasted 36 weeks.The pre-dialysis concentration of PBUTs was measured at week 12, 24, 36 and baseline.PBUTs included hippuric acid (HA), indoxyl sulphate (IS)and p-cresyl sulphate (PCS).High performance liquid chromatography-tandem mass spectrometry ( HPLC-MS/MS) was used for determination .Results After 36 weeks of follow-up, the concentration of the three toxins in the HD +HP group was lower than that in the HD group during the study.At the end of the study, the reduction rates of HA, IS and PCS were 33.5%,12.8% and 24.2%, respectively, in HD+HP group.The three toxins in HD group increased by 2.3%,21.8%and 2.8%.The clearance rate of HA, PCS and IS in the HP+HD group was higher than in HD group (P<0.05).Conclusion Long-term HD combined with HP can more effectively remove PBUTs , and keep them at a lower level .
ABSTRACT
Objective To study whether the uremic toxins accumulated long-term in uremia patients may be involved in oxidation of protein by forming advanced oxidative protein products (AOPPs). Methods Malonylaldehyde (MDA), hippuric acid (HA) and p-cresol were used as the representatives of uremic toxins. Human albumin serum (HSA), plasma specimens from normal or uremia patients were incubated respectively with MDA (10 retool/L), HA (20 mmol/L) and p-cresol (10 retool/L) or PBS (20 retool/L, pH 7.4, as control groups) at 37℃ for 30 minutes or 24 hours, respectively. Those indices such as AOPPs, protein thiol groups (Pt-SH) and dityrosine were used as biomarkers of protein injury. High performance liquid chromatography (HPLC) was employed to identify the aggregation and cross-links of modified proteins. Results AOPPs levels in all groups containing poison compounds were significantly increased by 121.5%(P<0.05) compared to that in control groups. Uremic toxins also resulted in over 14.7% loss in Pt-SH (P< 0.05) and 119.2% increment in dityrosine, respectively (P<0.05). Meanwhile, the formation of HMW-AOPPs in a time-dependent manner was observed by HPLC and cross-linked protein levels were significantly increased by 148.45%～333.3% in comparison with control groups. Conclusion Uremic toxins can directly mediate the damage of proteins by inducing the formation of HMW- AOPPs in a time-dependent manner, which is also one of the mechanism of AOPPs production in vivo besides the activation of the myeloperoxidase-H2O2-Cl pathway.