ABSTRACT
INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is the commonest inherited disorder of the kidneys. A vasopressin V2-receptor antagonist (tolvaptan) was recently approved for the treatment of ADPKD. This study aims to analyze the safety and tolerability of tolvaptan for the management of ADPKD patients in a real-world setting. METHODS: We conducted a descriptive retrospective study in ADPKD patients in an outpatient clinic setting in Spain from 2018 to 2019. Descriptive statistical analysis of demographics and clinical data, at baseline and one year after tolvaptan initiation, was assessed. Data are presented as median and interquartile range, and as frequencies for categorical variables. RESULTS: Ten patients with ADPKD were identified. At baseline median age was 49.5 (38.5-63.5) years and 60% were males. During treatment with tolvaptan, no significant aquaresis-related symptoms or hepatotoxicity were described. No serious adverse events, discontinuation, or deaths were reported during the study. CONCLUSION: Tolvaptan was well-tolerated without severe adverse events in patients with ADPKD who showed rapid disease progression criteria. Longer follow-up is required to learn about the long-term effects of this treatment.
ABSTRACT
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Subject(s)
Female , Humans , Middle Aged , Hemoperfusion/methods , Charcoal/therapeutic use , Valproic Acid/adverse effects , Suicide, Attempted , Renal DialysisSubject(s)
Charcoal , Drug Overdose/therapy , Hemoperfusion/methods , Psychotropic Drugs/poisoning , Valproic Acid/poisoning , Benzodiazepines/poisoning , Combined Modality Therapy , Depressive Disorder/drug therapy , Drug Overdose/drug therapy , Female , Flumazenil/therapeutic use , Humans , Hyperammonemia/chemically induced , Hyperammonemia/therapy , Middle Aged , Naloxone/therapeutic use , Olanzapine , Paranoid Disorders/drug therapy , Psychotropic Drugs/blood , Respiration, Artificial , Suicide, Attempted , Valproic Acid/bloodABSTRACT
Introducción: El objetivo de dicho estudio fue evaluar los cambios en la acetatemia durante la hemodiálisis (HD) en pacientes con líquido de diálisis (LD) convencional con acetato y en pacientes con LD con clorhídrico (HCl) y analizar sus efectos sobre la clínica y sobre distintos parámetros analíticos. Material y métodos: 14 pacientes en programa de HD estable (11 hombres) de 61 ± 15 años de edad fuerondializados durante 1 mes con el LD convencional con acetato y durante el segundo mes con el LD con HCl (sin acetato). Se obtuvieron análisis pre y post-diálisisla tercera sesión de las semanas 1 y 4 en cada uno de los períodos (con y sin acetato).Resultados: Las medias de los acetatos pre-diálisis fueron similares en ambos grupos, mientras que las medias de los acetatos post-diálisis fueron significativamente superiores en el grupo tratado con el LD convencional (0,48 ± 0,64 vs 0,18 ±0,23 mmol/L, p = 0,024). Tampoco hallamos diferencias significativas entre los 2 grupos en cuanto a la presencia de valores de acetato pre-diálisis patológicos, mientras sí hallamos un mayor porcentaje valores patológicos de acetato post-diálisis enel grupo tratado con LD convencional respecto al grupo del HCl (67% vs 21%, p = 0,001). Los niveles plasmáticos de IL-6 fueron significativamente superiores en el periodo de diálisis con acetato (31,7 ± 24,7 vs 18,7 ± 10,3 pg/ml, p = 0,014), aunque no se acompañaron de un aumento de otros marcadores inflamatorios como la LBP,el TNF-alfa o la PCR dializante el mismo periodo. No hallamos diferencias estadísticamente significativas en los otros parámetros evaluados excepto en la variación de las concentraciones de sodio, cloro y bicarbonato. Conclusiones: El LD sin acetato no expone a los pacientes a concentraciones elevadas de acetato consiguiendo que la mayoría de pacientes (79%) termine la HD con una acetatemia dentro del rango fisiológico.El uso de LD sin acetato es seguro y bien tolerado por los pacientes en hemodiálisis, aunque su traducción clínica debe ser evaluada en estudios prospectivosa más largo plazo (AU)
Background: the purpose of this study was to evaluate blood acetate levels and its correlation with clinical and analytical changes in hemodialysis patients treated with standard bicarbonate dialysate compared to treatment with acetate-free bicarbonate dialysate. Methods: Fourteen patients on hemodialysis (11 male) with mean age of 61 ± 15 years were treated with conventional bicarbonate dialysate for 1 month andthen switched to acetate-free bicarbonate dialysate for another month. Blood samples were drawn at the third session of first and fourth week of each type of dialysis.Results: Pre-dialysis blood acetate levels were similar in both groups, whereas postdialysis blood acetate levels were higher in patients treated with conventional bicarbonate dialysate (0.48 ± 0.64 vs 0.18 ± 0.23 mmol/L, p = 0.024). Moreover, both periods had similar percentage of patients with pre-dialysis blood acetate levels in the pathologic range, whereas this percentage was higher in post-dialysis samples from patients treated with conventional bicarbonate dialysate respect to acetate-free dialysate (67% vs 21%, p = 0.001). Serum levels of interleukin-6 were statistically higher in the period with conventional bicarbonate dialysate (31.7 ± 24.7 vs 18,7 ± 10,3 pg/ml, p = 0,014), even though other inflammatory markers such as LBP, TNF-alfa and CRP failed to increase in the same period. We didnt found significant differences in the other parameters studied except for the changes in serum concentrationsof sodium, chloride and bicarbonate. Conclusions: Acetate-free bicarbonate dialysate does not expose patients to a big amount of acetate and allows that the majority of patients finished hemodialysis with blood acetate levels in the physiologic ranges. Acetate-free dialysate was safe and well tolerated by our hemodialysis patients, although clinical advantages derived from its use should be evaluated in long-termprospective studies (AU)
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Acetates/pharmacology , Hydrochloric Acid/pharmacology , Dialysis Solutions/pharmacology , Acetates/blood , Hydrochloric Acid/blood , Dialysis/methods , Hypotension/chemically inducedABSTRACT
BACKGROUND AND PURPOSE: CGS-26303 inhibits endothelin converting enzyme (ECE)-1 more specifically than phosphoramidon. We have studied the effect of CGS-26303 on ECE-1 expression in bovine aortic endothelial cells. METHODS: ECE-1 activity and big endothelin (ET)-1 levels were measured by ELISA, ECE-1 expression using western and northern blot and promoter activity using transfection assays. KEY RESULTS: ECE-1 activity was completely inhibited by CGS-26303 25 microM and phosphoramidon 100 microM. CGS-26303 and phosphoramidon, though not thiorphan, a neutral endopeptidase (NEP) inhibitor, stimulated ECE-1 expression in cells (maximal effect at 16 h, 25 microM). Cycloheximide abolished that effect. CGS-26303 induced ECE-1 mRNA expression and ECE-1 promoter activity. CGS-35066, a selective ECE-1 inhibitor, mimicked the effects of CGS-26303, suggesting that the effect was specific to ECE-1 inhibition. Big ET-1 accumulated in the cells and in the supernatants after CGS-26303 treatment. Neither exogenously added ET-1 nor the blockade of their receptors with bosentan modified ECE-1 protein. When big ET-1 was added to cells, significant increases in ECE-1 protein content and ECE-1 promoter activity were found. Bosentan did not block those effects. CGS-26303 did not modify prepro-ET-1 expression. CGS-26303 and big ET-1 induced the same effects in human endothelial cells, at lower doses. CONCLUSIONS: These results suggest that the accumulation of big ET-1 is responsible for the effects of CGS-26303 on ECE-1 and they did not depend on NEP blockade. Changes in ECE-1 protein after the administration of CGS-26303 could lead to a decreased response in long-term treatments.
Subject(s)
Aspartic Acid Endopeptidases/drug effects , Aspartic Acid Endopeptidases/metabolism , Endothelin-1/drug effects , Metalloendopeptidases/drug effects , Metalloendopeptidases/metabolism , Organophosphonates/pharmacology , Protease Inhibitors/pharmacology , Tetrazoles/pharmacology , Animals , Aorta, Thoracic , Blotting, Northern , Blotting, Western , Cattle , Cells, Cultured , Dose-Response Relationship, Drug , Endothelin-1/metabolism , Endothelin-Converting Enzymes , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Enzyme-Linked Immunosorbent Assay , Gene Expression Regulation , Humans , Methyltransferases/drug effects , Methyltransferases/metabolism , Neprilysin/antagonists & inhibitors , Organophosphonates/administration & dosage , Promoter Regions, Genetic/drug effects , Protease Inhibitors/administration & dosage , Tetrazoles/administration & dosage , TransfectionABSTRACT
BACKGROUND: the purpose of this study was to evaluate blood acetate levels and its correlation with clinical and analytical changes in hemodialysis patients treated with standard bicarbonate dialysate compared to treatment with acetate-free bicarbonate dialysate. METHODS: fourteen patients on hemodialysis (11 male) with mean age of 61 15 years, were treated with conventional bicarbonate dialysate for 1 month and then switched to acetate-free bicarbonate dialysate for another month. Blood samples were drawn at the third session of first and fourth week of each type of dialysis. RESULTS: Pre-dialysis blood acetate levels were similar in both groups, whereas post-dialysis blood acetate levels were higher in patients treated with conventional bicarbonate dialysate (0.48+/- 0.64 vs. 0.18+/-0.23 mmol/L, p=0.024). Moreover, both periods had similar percentage of patients with pre-dialysis blood acetate levels in the pathologic range, whereas this percentage was higher in post-dialysis samples from patients treated with conventional bicarbonate dialysate respect to acetate-free dialysate (67% vs. 21%, p=0.001). Serum levels of interleukin-6 were statistically higher in the period with conventional bicarbonate dialysate (31.7+/- 24.7 vs. 18.7+/- 10.3 pg/ml, p=0.014), even though other inflammatory markers such as LBP, TNF- and CRP failed to increase in the same period. We didn't found significant differences in the other parameters studied except for the changes in serum concentrations of sodium, chloride and bicarbonate. CONCLUSIONS: Acetate-free bicarbonate dialysate does not expose patients to a big amount of acetate and allows that the majority of patients finished hemodialysis with blood acetate levels in the physiologic ranges. Acetate-free dialysate was safe and well tolerated by our hemodialysis patients, although clinical advantages derived from its use should be evaluated in long-term prospective studies.
Subject(s)
Kidney Failure, Chronic/blood , Kidney Failure, Chronic/therapy , Renal Dialysis , Acetates/blood , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle AgedABSTRACT
La intoxicación por etilenglicol se manifiesta con acidosis metabólica severa y fracaso renal agudo (FRA). La evolución del FRA puede ser prolongada pero la progresión hacia una insuficiencia renal crónica terminal (IRCT) ha sido descrita en muy pocos casos. Presentamos el caso de un paciente que tras ingestión de 920 ml de etilenglicol padeció un FRA de curso prolongado precisando hemodiálisis (HD) durante 37 días. La evolución posterior fue favorable con recuperación parcial de la función renal tras un año de seguimiento. El cuadro se acompañó de una grave afectación neurológica con polirradiculopatía sensitivo-motora y autonómica
Ethylene glycol intoxication involves acute renal failure and severe metabolic acidosis. Prolonged renal insufficiency can occur but terminal chronic renal failure has been reported in very few cases. We describe a patient who after ingestion of 920 ml of ethylene glycol developed prolonged acute renal failure needing hemodyalisis for 37 days and then he partly recovered renal function. The patient developed a severe sensitive-motor and autonomic polyradiculopathy
Subject(s)
Male , Adult , Humans , Ethylene Glycol/poisoning , Alcoholic Intoxication/complications , Acute Kidney Injury/chemically induced , Alcoholic Intoxication/therapy , Acute Kidney Injury/therapy , Renal Dialysis/methods , Clinical EvolutionABSTRACT
Ethylene glycol intoxication involves acute renal failure and severe metabolic acidosis. Prolonged renal insufficiency can occur but terminal chronic renal failure has been reported in very few cases. We describe a patient who after ingestion of 920 ml of ethylene glycol developed prolonged acute renal failure needing hemodialysis for 37 days and then he partly recovered renal function. The patient developed a severe sensitive-motor and autonomic polyradiculopathy.
