Safety and Tolerability of Tolvaptan in an Autosomal Dominant Polycystic Kidney Disease Spanish Cohort: A Real-World Experience.

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.

The peptidase inhibitor CGS-26303 increases endothelin converting enzyme-1 expression in endothelial cells through accumulation of big endothelin-1.

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.

[Clinical and analytical changes in hemodialysis without acetate]. / Cambios clínicos y analíticos al sustituir el líquido de diálisis convencional por uno sin acetato.

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.

[Prolonged acute renal failure and severe polyradiculopathy in ethylene glycol intoxication]. / Fracaso renal agudo prolongado y polirradiculopatía severa en paciente intoxicado con etilenglicol.

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.