Evaluation of limited-sampling strategies to calculate AUC(0-24) and the role of CYP3A5 in Chilean pediatric kidney recipients using extended-release tacrolimus.

Background: Kidney transplantation (KTx) requires immunosuppressive drugs such as Tacrolimus (TAC) which is mainly metabolized by CYP3A5. TAC is routinely monitored by trough levels (C0) although it has not shown to be a reliable marker. The area-under-curve (AUC) is a more realistic measure of drug exposure, but sampling is challenging in pediatric patients. Limited-sampling strategies (LSS) have been developed to estimate AUC. Herein, we aimed to determine AUC(0-24) and CYP3A5 genotype in Chilean pediatric kidney recipients using extended-release TAC, to evaluate different LSS-AUC(0-24) formulas and dose requirements. Patients and methods: We analyzed pediatric kidney recipients using different extended-release TAC brands to determine their trapezoidal AUC(0-24) and CYP3A5 genotypes (SNP rs776746). Daily TAC dose (TAC-D mg/kg) and AUC(0-24) normalized by dose were compared between CYP3A5 expressors (*1/*1 and *1/*3) and non-expressors (*3/*3). We evaluated the single and combined time-points to identify the best LSS-AUC(0-24) model. We compared the performance of this model with two pediatric LSS-AUC(0-24) equations for clinical validation. Results: Fifty-one pharmacokinetic profiles were obtained from kidney recipients (age 13.1 ± 2.9 years). When normalizing AUC(0-24) by TAC-D significant differences were found between CYP3A5 expressors and non-expressors (1701.9 vs. 2718.1 ng*h/mL/mg/kg, p < 0.05). C0 had a poor fit with AUC(0-24) (r 2 = 0.5011). The model which included C0, C1 and C4, showed the best performance to predict LSS-AUC(0-24) (r 2 = 0.8765) and yielded the lowest precision error (7.1% ± 6.4%) with the lowest fraction (9.8%) of deviated AUC(0-24), in comparison to other LSS equations. Conclusion: Estimation of LSS-AUC(0-24) with 3 time-points is an advisable and clinically useful option for pediatric kidney recipients using extended-release TAC to provide better guidance of decisions if toxicity or drug inefficacy is suspected. The different CYP3A5 genotypes associated with variable dose requirements reinforce considering genotyping before KTx. Further multi-centric studies with admixed cohorts are needed to determine the short- and long-term clinical benefits.

[Ambulatory Blood Pressure Monitoring (ABPM): Statement from chilean pediatric nephrology committee]. / Monitorización Ambulatoria de Presión Arterial (MAPA): Recomendaciones de la rama de nefrología pediátrica.

Ambulatory blood pressure monitoring (ABPM) is a useful clinical tool for the diagnosis and confir mation of arterial hypertension in pediatrics, and also allows the diagnosis of special conditions such as white coat hypertension and masked hypertension. There are international recommendations for its implementation and interpretation, however, there are still unresolved questions. This guide summarizes the available literature and attempts to standardize, through consensus of national specia lists, the application of this technique. More research studies are needed that provide new reference values and determine the relationship of alterations in ABPM with long-term clinical results.

Monitorización ambulatoria de presión arterial (MAPA): recomendaciones de la rama de nefrología pediátrica / Ambulatory blood pressure monitoring (ABPM): statement from chilean pediatric nephrology committee

Resumen: La monitorización ambulatoria de la presión arterial (MAPA) es una herramienta clínica útil para el diagnóstico y confirmación de hipertensión arterial en pediatría y permite igualmente el diagnóstico de condiciones especiales como la hipertensión de delantal blanco e hipertensión enmascarada. Exis ten recomendaciones internacionales para su realización e interpretación, sin embargo, aún quedan interrogantes por resolver. En esta guía se resume la bibliografía disponible y se intenta estandarizar, a través de consenso de especialistas nacionales, la aplicación de esta técnica. Se necesitan más estudios de investigación en niños que aporten nuevos valores de referencia y que determinen la relación de alteraciones en MAPA con resultados clínicos a largo plazo.

Abstract: Ambulatory blood pressure monitoring (ABPM) is a useful clinical tool for the diagnosis and confir mation of arterial hypertension in pediatrics, and also allows the diagnosis of special conditions such as white coat hypertension and masked hypertension. There are international recommendations for its implementation and interpretation, however, there are still unresolved questions. This guide summarizes the available literature and attempts to standardize, through consensus of national specia lists, the application of this technique. More research studies are needed that provide new reference values and determine the relationship of alterations in ABPM with long-term clinical results.

Riesgo de trastornos alimentarios en adolescentes obesos de la Región Metropolitana / Eating disorders risk among obese adolescents

Background: Preliminary research suggests that eating disorders (ED) are common among overweight teenagers. Missing the diagnosis is a poor prognostic factor. Aim: To quantify the risk of ED and the effects of age, sex and severity of obesity in obese adolescents. Patients and Methods: We studied 99 obese adolescents with a body mass index (BMI) > percentile 95 of CDC-NCHS, 51% females, aged between 11 and 19 years, attending an obesity clinic. The Eating Disorders Inventory-2 (EDI-2) was used to evaluate the risk of ED. A score equal or higher than 110, corresponding to the 85th percentile, was considered as risky. Results: Sixteen percent of studied adolescents had EDI scores > 110. No statistically significant differences were observed by age, sex or severity of obesity. EDI-2 scores in participants with a BMI z score over and under 4 were 93.6 ± 33.9 and 78.2 ± 38.8 respectively (p = 0.02). A high percentage of participants had body dissatisfaction (BD) and drive for thinness. Bulimic symptoms, inefficacy, fear of maturity, and impulsivity scores were significantly higher among participants with a high risk of developing ED. Conclusions: Obese adolescents have a high risk for ED, regardless of their age and sex. The risk increases along with higher BMI. The routine use of screening tests is fundamental for an early detection of ED.

[Eating disorders risk among obese adolescents]. / Riesgo de trastornos alimentarios en adolescentes obesos de la Región Metropolitana.

BACKGROUND: Preliminary research suggests that eating disorders (ED) are common among overweight teenagers. Missing the diagnosis is a poor prognostic factor. AIM: To quantify the risk of ED and the effects of age, sex and severity of obesity in obese adolescents. PATIENTS AND METHODS: We studied 99 obese adolescents with a body mass index (BMI) > percentile 95 of CDC-NCHS, 51% females, aged between 11 and 19 years, attending an obesity clinic. The Eating Disorders Inventory-2 (EDI-2) was used to evaluate the risk of ED. A score equal or higher than 110, corresponding to the 85th percentile, was considered as risky. RESULTS: Sixteen percent of studied adolescents had EDI scores > 110. No statistically significant differences were observed by age, sex or severity of obesity. EDI-2 scores in participants with a BMI z score over and under 4 were 93.6 ± 33.9 and 78.2 ± 38.8 respectively (p = 0.02). A high percentage of participants had body dissatisfaction (BD) and drive for thinness. Bulimic symptoms, inefficacy, fear of maturity, and impulsivity scores were significantly higher among participants with a high risk of developing ED. CONCLUSIONS: Obese adolescents have a high risk for ED, regardless of their age and sex. The risk increases along with higher BMI. The routine use of screening tests is fundamental for an early detection of ED.