RESUMO
Background:Volume overload is one of the most important factors associated with left ventricular hypertrophy (LVH) and cardiovascular disease in chronic peritoneal dialysis (PD) patients. MiniPET is a reliable tool to evaluate free water transport (FWT). In a clinical setting, the significance of FWT has not been evaluated in terms of outcome in children on PD. The objective was to define a FWT value of clinical significance in children on PD, fixing its relationship to left ventricular mass index (LVMI) as a well-known outcome parameter.Methods:MiniPET was performed with 3.86% glucose, 1-h long, to measure FWT in PD patients > 6 years old. An echocardiogram (ECG) was performed within 2 months of the MiniPET. Left ventricular hypertrophy was defined as LVMI ≥ 38.6 g/height2.7 (95th percentile). Receiver operating characteristic curve (ROC) analysis was used to determine the cut-off value of FWT searching the highest sensitivity and specificity to differentiate patients with normal/abnormal LVMI. A p < 0.05 was considered significant.Results:Forty-six studies were performed on 32 patients, 16 males; mean age 11.59 ± 3.07 years. Mean normalized FWT (nFWT) was 144.4 ± 84.8 mL/m2, corresponding to 46.7% of total ultrafiltration. Mean LVMI was 42 ± 11.3 g/m2.7 with a negative correlation to nFWT (p < 0.01). Eighteen out of 32 patients had LVH. The ROC analysis (nFWT vs LVMI) showed an area under the curve of 0.71 (95% confidence interval [CI], 0.53 - 0.89; p = 0.04), allowing a cut-off nFWT value of 110 mL/m2 to be defined, dividing the population into 2 groups of patients according to the LVMI cut-off value of 38,6 g/m2.7.Conclusions:The nFWT showed an inverse correlation to LVMI. A nFWT value < 110 mL/m2 was significantly associated with LVH. The negative relationship observed between nFWT and LVMI, and the cut-off level for nFWT according to the 95th percentile of LVMI, suggest that the regular evaluation of nFWT could become a useful tool in assessing the capacity of PD treatment to keep patients' volume status under control, avoiding cardiovascular impairment.
Assuntos
Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Absorção Peritoneal/fisiologia , Diálise Peritoneal/efeitos adversos , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/terapia , Adolescente , Transporte Biológico , Água Corporal , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Estudos Prospectivos , Curva ROC , Insuficiência Renal Crônica/complicaçõesRESUMO
ABSTRACT 6-Methylcoumarin (6MC) is a semisynthetic coumarin with important in vitro and in vivo anti-inflammatory activity. In order to continue the pre-clinical characterization of this molecule, in vitro intestinal permeability, plasma profile and tissue distribution after oral administration in rats were studied. The permeability of 6MC was evaluated by the Caco-2 cellular model in both the apical-basal (A-B) and basal-apical (B-A) directions. The pharmacokinetics and biodistribution were evaluated in rats after oral and intraperitoneal administration at doses of 200 mg/kg. Transport experiments with Caco-2 cells showed that 6MC presented high permeability at all concentrations evaluated. This finding suggested that 6MC could be transported across the gut wall by passive diffusion. The plasma concentration-time curve showed that the maximum concentration (Cmax) was 17.13 ± 2.90 µg/mL at maximum time (Tmax) of 30 min for the oral route and Cmax 26.18 ± 2.47 µg/mL at 6.0 min for the intraperitoneal administration, with elimination constant of (Ke ) 0.0070 min-1 and a short life half time of (T1/2 ) lower that 120 min. The distribution study showed that 6MC has high accumulation in the liver, and widespread distribution in all the organs evaluated.