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1.
Biometals ; 37(3): 721-737, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38642266

RESUMO

BACKGROUND: In kidney damage, molecular changes can be used as early damage kidney biomarkers, such as Kidney Injury Molecule-1 and Neutrophil gelatinase-associated lipocalin. These biomarkers are associated with toxic metal exposure or disturbed homeostasis of trace elements, which might lead to serious health hazards. This study aimed to evaluate the relationship between exposure to trace elements and early damage kidney biomarkers in a pediatric population. METHODS: In Tlaxcala, a cross-sectional study was conducted on 914 healthy individuals. The participants underwent a medical review and a socio-environmental questionnaire. Five early damage kidney biomarkers were determined in the urine with Luminex, and molybdenum, copper, selenium, nickel, and iodine were measured with ICP-Mass. RESULTS: The eGFR showed a median of 103.75 mL/min/1.73 m2. The median levels for molybdenum, copper, selenium, nickel, and iodine were 24.73 ng/mL, 73.35 ng/mL, 4.78 ng/mL, 83.68 ng/mL, and 361.83 ng/mL, respectively. Except for molybdenum and nickel, the other trace elements had significant associations with the eGFR and the early kidney damage biomarkers. Additionally, we report the association of different exposure scenarios with renal parameters. DISCUSSION: and Conclusions. Among the explored metals, exposure to Cu and iodine impairs renal function. In contrast, Se may manifest as a beneficial metal. Interactions of Mo-Se and Mo-Iodine seem to alter the expression of NGAL; Mo-Cu for CLU; Mo-Cu, Mo-Se, and Mo-iodine for Cys-C and a-1MG; and Mo-Cu and Mo-iodine for KIM-1; were noticed. Our study could suggest that trace element interactions were associated with early kidney damage biomarkers.


Assuntos
Biomarcadores , Exposição Ambiental , Oligoelementos , Humanos , Biomarcadores/urina , Biomarcadores/metabolismo , Criança , Masculino , Feminino , Oligoelementos/análise , Oligoelementos/urina , Exposição Ambiental/efeitos adversos , Estudos Transversais , Adolescente , Lipocalina-2/urina , Taxa de Filtração Glomerular , Cobre/urina , Cobre/análise , Selênio/urina , Selênio/análise , Nefropatias/induzido quimicamente , Nefropatias/urina , Nefropatias/metabolismo , Rim/metabolismo , Pré-Escolar , Níquel/urina
2.
Pediatr Transplant ; 27(3): e14460, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36582125

RESUMO

BACKGROUND: Despite the common use of mycophenolate in pediatric renal transplantation, lack of effective therapeuic drug monitoring increases uncertainty over optimal drug exposure and risk for adverse reactions. This study aims to develop a novel urine test to estimate MPA exposure based using metabolomics. METHODS: Urine samples obtained on the same day of MPA pharmacokinetic testing from two prospective cohorts of pediatric kidney transplant recipients were assayed for 133 unique metabolites by mass spectrometry. Partial least squares (PLS) discriminate analysis was used to develop a top 10 urinary metabolite classifier that estimates MPA exposure. An independent cohort was used to test pharmacodynamic validity for allograft inflammation (urinary CXCL10 levels) and eGFR ratio (12mo/1mo eGFR) at 1 year. RESULTS: Fifty-two urine samples from separate children (36.5% female, 12.0 ± 5.3 years at transplant) were evaluated at 1.6 ± 2.5 years post-transplant. Using all detected metabolites (n = 90), the classifier exhibited strong association with MPA AUC by principal component regression (r = 0.56, p < .001) and PLS (r = 0.75, p < .001). A practical classifier (top 10 metabolites; r = 0.64, p < .001) retained similar accuracy after cross-validation (LOOCV; r = 0.52, p < .001). When applied to an independent cohort (n = 97 patients, 1053 samples), estimated mean MPA exposure over Year 1 was inversely associated with mean urinary CXCL10:Cr (r = -0.28, 95% CI -0.45, -0.08) and exhibited a trend for association with eGFR ratio (r = 0.35, p = .07), over the same time period. CONCLUSIONS: This urinary metabolite classifier can estimate MPA exposure and correlates with allograft inflammation. Future studies with larger samples are required to validate and evaluate its clinical application.


Assuntos
Transplante de Rim , Humanos , Criança , Feminino , Masculino , Estudos Prospectivos , Ácido Micofenólico/uso terapêutico , Imunossupressores/uso terapêutico , Imunossupressores/farmacocinética , Metabolômica , Área Sob a Curva
3.
Pediatr Nephrol ; 38(2): 593-604, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35748941

RESUMO

BACKGROUND: Various definitions used to describe cisplatin nephrotoxicity potentially lead to differences in determination of risk factors. This study evaluated incidence of kidney injury according to commonly used and alternative definitions in two cohorts of children who received cisplatin. METHODS: This retrospective cohort study included children from Vancouver, Canada (one center), and Mexico City, Mexico (two centers), treated with cisplatin for a variety of solid tumors. Serum creatinine-based definitions (KDIGO and Pediatric RIFLE (pRIFLE)), electrolyte abnormalities consisted of hypokalemia, hypophosphatemia and hypomagnesemia (based on NCI-CTCAE v5), and an alternative definition (Alt-AKI) were used to describe nephrotoxicity. Incidence with different definitions, definitional overlap, and inter-definition reliability was analyzed. RESULTS: In total, 173 children (100 from Vancouver, 73 from Mexico) were included. In the combined cohort, Alt-AKI criteria detected more patients with cisplatin nephrotoxicity compared to pRIFLE and KDIGO criteria (82.7 vs. 63.6 vs. 44.5%, respectively). Nephrotoxicity and all electrolyte abnormalities were significantly more common in Vancouver cohort than in Mexico City cohort except when using KDIGO definition. The most common electrolyte abnormalities were hypomagnesemia (88.9%, Vancouver) and hypophosphatemia (24.2%, Mexico City). The KDIGO definition provided highest overlap of cases in Vancouver (100%), Mexico (98.6%), and the combined cohort (99.4%). Moderate overall agreement was found among Alt-AKI, KDIGO, and pRIFLE definitions (κ = 0.18, 95% CI 0.1-0.27) in which KDIGO and pRIFLE showed moderate agreement (κ = 0.48, 95% CI 0.36-0.60). CONCLUSIONS: Compared to pRIFLE and KDIGO criteria, Alt-AKI criteria detected more patients with cisplatin nephrotoxicity. pRIFLE is more sensitive to detect not only actual kidney injury but also patients at risk of cisplatin nephrotoxicity, while KDIGO seems more useful to detect clinically significant kidney injury. A higher resolution version of the Graphical abstract is available as Supplementary information.


Assuntos
Injúria Renal Aguda , Hipofosfatemia , Neoplasias , Humanos , Criança , Cisplatino/efeitos adversos , Estudos Retrospectivos , Injúria Renal Aguda/etiologia , Reprodutibilidade dos Testes , Neoplasias/complicações , Fatores de Risco , Eletrólitos
4.
Calcif Tissue Int ; 111(6): 597-610, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36152042

RESUMO

Strength and muscle mass are important determinants of health status, and reference values for pediatric populations from every country or geographic region are needed. The aim of this study was to develop age- and sex-specific reference values of muscle strength and evaluate the correlation between muscle strength and appendicular lean mass in Mexican children and adolescents. A cross-sectional study was conducted in 1111 healthy subjects ages 5 to 19 years of age participating in the "Body Composition Reference Values in Mexican Children and Adolescents" study. Smoothed reference values for the 1, 3, 5, 15, 25, 50, 75, 85, 95, 97, and 99 percentiles of muscle strength for upper and lower limbs were developed based on age and sex using Jamar® and Microfet2® dynamometers. Mean values were derived using the Generalized Additive Models for Location, Scale and Shape (GAMLSS), and lean mass was determined using dual-energy X-ray absorptiometry. Highly positive correlations of muscle strength with lean mass in upper limbs were found r-values 0.87-0.92 for boys and r = 0.80-0.86 for girls. High and moderate positive correlations for lower limbs were also noted for upper limbs: r = 0.74-0.86 for boys and r = 0.67-0.82 for girls. The reference values for appendicular muscle strength established in this study demonstrated a high and positive correlation between appendicular mass and muscle strength. These data will be useful when evaluating conditions and diseases affecting muscle or sports.


Assuntos
Composição Corporal , Força Muscular , Criança , Masculino , Feminino , Humanos , Adolescente , Pré-Escolar , Adulto Jovem , Adulto , Valores de Referência , Estudos Transversais , Absorciometria de Fóton , Composição Corporal/fisiologia , Músculos , Músculo Esquelético/fisiologia , Índice de Massa Corporal
5.
J Pediatr Nurs ; 62: 129-135, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34801325

RESUMO

PURPOSE: We evaluated disease knowledge/self-management skills among low-income Mexican young adults maintained on dialysis and to test the effectiveness of the A.L.L. Y.O.U. N.E.E.D. I.S. L.O.V.E (AYNIL) Manual - Spanish Version on patient-reported outcomes. This is a low literacy teaching tool designed with patients and educators' input. DESIGN AND METHODS: A quasi-experimental study was conducted in 17 chronic dialysis patients at Mexico City's Hospital General de México, Dr. Eduardo Liceaga. Ages 18-30-year-old completed disease knowledge/self-management and quality of life measures before the intervention and 6 weeks later. RESULTS: Significant increases were observed on disease knowledge/self-management scores in the STARx questionnaire from 47 (IQ: 40,51) to 50 (IQ: 48,54) p = 0.04. The UNC-TRxANSITION Index increased significantly from 4.8 (IQ: 3.9,5.7) to 7.7 (IQ: 7.5,8.2) p ≤0.001. Significant increases in scores were detected in the "Burden of kidney disease" (p = 0.008), "Effects of kidney disease" " (p = 0.03) and " Dialysis staff encouragement" (p = 0.027) based on the KDQoL survey. CONCLUSIONS: In this vulnerable population, the Spanish version of the A.L.L. Y.O.U. N.E.E.D. I.S. L.O.V.E. - AYNIL Manual improved CKD/ESRD disease knowledge/self-management skills and HRQoL. This study highlighted the need for low-literacy educational tools to improve patient-reported outcomes. PRACTICE IMPLICATIONS: Young adults with CKD/ESRD can benefit from patient-centered educational interventions to enhance their autonomy and the development of self-management behaviors that improve patient-reported outcomes and potential complications of the disease. Special attention is needed in low-income patients with low rates of adherence to treatments and poor self-management skills.


Assuntos
Autogestão , Adolescente , Adulto , Estudos de Viabilidade , Humanos , México , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Diálise Renal , Adulto Jovem
6.
J Ren Nutr ; 30(3): 232-241, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31597621

RESUMO

OBJECTIVE: Decreased serum concentrations of 25-hydroxyvitamin D (25(OH)D) affect people with chronic kidney disease (CKD); lower concentrations of 25(OH)D have been associated with decrease in nutritional status indicators. On the other hand, muscle resistance exercise has improved the nutritional status of patients with CKD.The aim of this study was to evaluate the effect of resistance exercise and dietary supplementation with cholecalciferol on nutritional status indicators in adults with stage 4 CKD. METHODS: Patients with an estimated glomerular filtration rate between 15 and 29 mL/min/1.73 m2 in an open-label clinical trial were followed for 12 weeks. The intervention group received exercise resistance training sessions three times per week with oral cholecalciferol supplementation each day. The control group only received standard medical care. The outcomes were anthropometric measurements, handgrip strength, and bioelectrical impedance analysis. RESULTS: Thirty-nine patients of a median age of 48 (36-52) years had an estimated glomerular filtration rate of 21.8 ± 6.5 mL/min/1.73 m2. A total of 57.5% of the patients were women. In 41% of the patients, the etiology of CKD was diabetes. After 12 weeks, in the intervention group, the adherence to the resistance training was 77%, and the adherence to the supplementation with cholecalciferol was 96.2%. Significant improvements in 25(OH)D serum concentrations and in handgrip strength were detected in the intervention group (P < .05). In the control group, a decrease in 25(OH)D serum concentrations and a loss in handgrip strength were observed, although the difference was not statistically significant. Anthropometrics and biochemical and dietary indicators, but not bioelectrical impedance data, exhibited changes. CONCLUSION: Supplementation with cholecalciferol improves serum concentrations of 25(OH)D and, when combined with resistance exercise, improved muscle function as measured by handgrip strength in a study of patients with CKD not on dialysis.


Assuntos
Insuficiência Renal Crônica , Treinamento Resistido , Adulto , Colecalciferol/uso terapêutico , Suplementos Nutricionais , Feminino , Força da Mão , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Insuficiência Renal Crônica/complicações , Vitamina D
7.
Pediatr Transplant ; 23(8): e13595, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31571392

RESUMO

TDM of tacrolimus is usually performed with trough levels (C0h ). However, in pediatric patients, C0h may not be an adequate marker. The AUC is considered a more suitable indicator of drug exposure. As several blood samples are needed for the estimation of AUC, and LSS for predicting tacrolimus AUC and optimizing the dose adjustment have been proposed. Moreover, in emerging countries such as Mexico, non-innovator formulations, which bioequivalence has not been demonstrated, are frequently used. Hence, the aim of this study was to develop and validate a LSS to predict the tacrolimus AUC0-12h in Mexican pediatric kidney transplant recipients who received either Prograf® or non-innovator tacrolimus formulations. A total of 56 pharmacokinetic profiles were randomized into two groups: model development (n = 28) and model validation (n = 28). The limited sampling equations were obtained after a stepwise multiple regression using AUC as the dependent variable and tacrolimus blood concentrations, quantified by CMIA, at different time points as the independent variables. The final equation included observed concentrations at 1 hour (C1h ) and 4 hours (C4h ) after dose administration. The predictive performance of the model was adequate in terms of both, bias and precision. Results strongly suggest that the clinical use of this LSS could provide an ethical, cost-, and time-effective method in the TDM of tacrolimus in pediatric patients with kidney transplant. The model proved to be adequate with either Prograf® or non-innovator tacrolimus formulations of dubious bioequivalence.


Assuntos
Área Sob a Curva , Imunossupressores/farmacocinética , Transplante de Rim , Tacrolimo/farmacocinética , Adolescente , Animais , Bovinos , Criança , Pré-Escolar , Estudos Transversais , Previsões , Humanos , Masculino , México , Estudos Retrospectivos , Adulto Jovem
9.
J Pediatr ; 202: 171-178.e3, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30268401

RESUMO

OBJECTIVE: We sought to assess worldwide differences among pediatric patients undergoing hemodialysis. Because practices differ widely regarding nutritional resources, treatment practice, and access to renal replacement therapy, investigators from the Pediatric Investigation and Close Collaboration to examine Ongoing Life Outcomes, the pediatric subset of the MONitoring Dialysis Outcomes Cohort (PICCOLO MONDO) performed this cross-sectional study. We hypothesized that growth would be better in developed countries, possibly at the expense of bone mineral disease. STUDY DESIGN: In this cross-sectional study, we analyzed growth by height z score and recommended age-specific bone mineral metabolism markers from 225 patients <18 years of age maintained on hemodialysis, between the years of 2000 to 2012 from 21 countries in different regions. RESULTS: The patients' median age was 16 (IQR 14-17) years, and 45% were females. A height z score less than the third percentile was noted in 34% of the cohort, whereas >66% of patients reported normal heights, with patients from North America having the greatest proportion (>80%). More than 70% of the entire cohort had greater than the age-recommended levels of phosphorus, particularly in the Asia-Pacific and North America, where we also observed the greatest body mass index z score (0.99 ± 1.6) and parathyroid hormone levels (557.1 [268.4-740.5]). Below-recommended parathyroid hormone levels were noted in 26% and elevated levels in 61% of the entire sample, particularly in the Asia Pacific region. Lower-than-recommended calcium levels were noted in 36% of the entire cohort, particularly in Latin America. CONCLUSIONS: We found regional differences in growth- and age-adjusted bone mineral metabolism markers. Children from North America had the best growth, received the most dialysis, but also had the worst phosphate control and body mass index z scores.


Assuntos
Estatura , Doenças Ósseas Metabólicas/epidemiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/epidemiologia , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Diálise Renal/métodos , Adolescente , Antropometria , Biomarcadores/sangue , Índice de Massa Corporal , Doenças Ósseas Metabólicas/diagnóstico , Criança , Pré-Escolar , Distúrbio Mineral e Ósseo na Doença Renal Crônica/diagnóstico , Estudos Transversais , Feminino , Saúde Global , Humanos , Internacionalidade , Falência Renal Crônica/diagnóstico , Masculino , Prognóstico , Medição de Risco , Taxa de Sobrevida
10.
Pediatr Nephrol ; 33(7): 1123-1131, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-28733752

RESUMO

Immunosuppressive drugs for solid organ transplantation are critical dose drugs with a narrow therapeutic index. Many of the most commonly used innovator drugs are off patent and have been replicated by generic counterparts, often at substantial cost-savings to the patient. However, serious adverse events caused by the transition from innovator to generic medications, specifically in pediatric solid organ transplant recipients, have questioned these autosubstitutions. The purpose of this review is to summarize the criteria set forth by the regulatory bodies, and to examine how major immunosuppressive drugs conform to these recommendations. Regulatory bodies have established inconsistent criteria to demonstrate bioequivalence between innovator and generic medications, causing approved generic variations to have varying levels of equivalence with the innovator drugs. In order to minimize the risk for under-immunosuppression, the following recommendations have been concluded. Brand prescribing of cyclosporine and tacrolimus are recommended due to evidence of adverse events after conversion to generic formulations and differences in dissolution parameters. Mycophenolate mofetil (MMF) shows better bioequivalence between innovator and generic formulations, however caution should be advised when switching between formulations. The institution of 'innovator only' policies may be appropriate at this time in order to minimize the risk of under-immunosuppressing patients until the evidence of more stringent bioequivalence has been established.


Assuntos
Medicamentos Genéricos/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Transplante de Órgãos/efeitos adversos , Ciclosporina/farmacocinética , Ciclosporina/normas , Ciclosporina/uso terapêutico , Substituição de Medicamentos/normas , Medicamentos Genéricos/farmacocinética , Medicamentos Genéricos/normas , Rejeição de Enxerto/imunologia , Humanos , Terapia de Imunossupressão/normas , Imunossupressores/farmacocinética , Imunossupressores/normas , Ácido Micofenólico/farmacocinética , Ácido Micofenólico/normas , Ácido Micofenólico/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tacrolimo/farmacocinética , Tacrolimo/normas , Tacrolimo/uso terapêutico , Equivalência Terapêutica , Resultado do Tratamento , Estados Unidos , United States Food and Drug Administration/normas
11.
Pediatr Nephrol ; 32(1): 21-29, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-26921212

RESUMO

We have reviewed current evidence on the therapeutic drug monitoring (TDM) of mycophenolic acid (MPA) in relationship to drug efficacy and safety. The relationship between actual MPA exposure and mycophenolate mofetil (MMF) dose has been shown to be weak in children and adolescents. The TDM of MPA exposure should ideally be performed using full pharmacokinetic profiles or limited sampling strategies. Recent evidence has provided some rationale for using the post-dose trough level as a single measure. In terms of short-term efficacy, there is strong evidence that a MPA area under the time-concentration curve of >30 mg × h/L reduces acute rejection episodes early after renal transplantation, and there is evolving evidence that aiming for the same exposure over the long term may be a viable strategy to reduce the formation of donor-specific antibodies. Strong evidence also supports the existence of important drug interactions and age/developmental dependent differences in drug metabolism that may necessitate the need for TDM of MMF therapy. Based on these findings and given the substantial inter- and intra-patient variability of MPA exposure, it would appear that MMF therapy should be subject to TDM to avoid over- and under-dosing. This may be a viable strategy to reduce treatment-emergent adverse events and to increase the effective pediatric transplant survival rates.


Assuntos
Monitoramento de Medicamentos , Imunossupressores/uso terapêutico , Transplante de Rim/métodos , Ácido Micofenólico/uso terapêutico , Adolescente , Criança , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/farmacocinética , Ácido Micofenólico/farmacocinética
12.
Histochem Cell Biol ; 145(1): 25-40, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26515056

RESUMO

Hyperpolarization-activated cationic and cyclic nucleotide-gated channels (HCN) comprise four homologous subunits (HCN1-HCN4). HCN channels are found in excitable and non-excitable tissues in mammals. We have previously shown that HCN2 may transport ammonium (NH4 (+)), besides sodium (Na(+)), in the rat distal nephron. In the present work, we identified HCN1 and HCN3 in the proximal tubule (PT) and HCN3 in the thick ascending limb of Henle (TALH) of the rat kidney. Immunoblot assays detected HCN1 (130 kDa) and HCN3 (90 KDa) and their truncated proteins C-terminal HCN1 (93 KDa) and N-terminal HCN3 (65 KDa) in enriched plasma membranes from cortex (CX) and outer medulla (OM), as well as in brush-border membrane vesicles. Immunofluorescence assays confirmed apical localization of HCN1 and HCN3 in the PT. HCN3 was also found at the basolateral membrane of TALH. We evaluated chronic changes in mineral dietary on HCN3 protein abundance. Animals were fed with three different diets: sodium-deficient (SD) diet, potassium-deficient (KD) diet, and high-potassium (HK) diet. Up-regulation of HCN3 was observed in OM by KD and in CX and OM by HK; the opposite effect occurred with the N-terminal truncated HCN3 in CX (KD) and OM (HK). SD diet did not produce any change. Since HCN channels activate with membrane hyperpolarization, our results suggest that HCN channels may play a role in the Na(+)-K(+)-ATPase activity, contributing to Na(+), K(+), and acid-base homeostasis in the rat kidney.


Assuntos
Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Túbulos Renais Proximais/metabolismo , Alça do Néfron/metabolismo , Canais de Potássio/metabolismo , Potássio na Dieta/metabolismo , Animais , Membrana Celular/metabolismo , Hipopotassemia/patologia , Córtex Renal/metabolismo , Medula Renal/metabolismo , Masculino , Microvilosidades/metabolismo , Técnicas de Patch-Clamp , Ratos , Ratos Wistar , Sódio/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo
13.
Ther Drug Monit ; 38(3): 288-92, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27167176

RESUMO

BACKGROUND: Although tacrolimus therapy is not the first-line therapy for childhood nephrotic syndrome, it is often used instead of cyclosporine to ameliorate the side effects. The pharmacokinetics (PK) of tacrolimus (Tac) can be influenced by many conditions, and it has a high plasma protein binding. The Tac PK during relapse and remission of childhood nephrotic syndrome has not been well described. METHODS: We performed 14 PK profiles (with measurements before intake and 0.5, 1, 2, 4, and 12 hours postintake) in 7 children with steroid-resistant nephrotic syndrome at week 1 (all nephrotic) and week 16 after Tac therapy (all in remission). These data were compared with historical PK data of 161 PK profiles in 87 pediatric renal transplant recipients with measurements before intake and 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours postintake. Tac levels were measured using the Abbott Tacro II assay. We used descriptive statistics to generate percentiles and compared these with those of patients with steroid-resistant nephrotic syndrome. RESULTS: The median age of patients with nephrotic syndrome was 3.2 years (range 2.5, 17.2), male gender 71.4%, significantly younger than the control group. Median Tac dose was similar during both PK profiles (0.11 mg·kg·d at week 1 versus 0.13 mg·kg·d at week 16, P = 0.81). There were no statistically significant differences in median dose-normalized area-under-the-time-concentration profiles, peak concentration, time to reach peak concentration, and Tac trough levels. Individual dose-normalized Tac levels for each time point during the PK profile were also not different (P = 0.81). CONCLUSIONS: We conclude that Tac PK profiles are unaltered during relapse of nephrotic syndrome.


Assuntos
Imunossupressores/farmacocinética , Síndrome Nefrótica/tratamento farmacológico , Tacrolimo/farmacocinética , Adolescente , Área Sob a Curva , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Humanos , Imunossupressores/administração & dosagem , Masculino , Síndrome Nefrótica/fisiopatologia , Recidiva , Tacrolimo/administração & dosagem , Fatores de Tempo
14.
Br J Clin Pharmacol ; 80(4): 630-41, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25846845

RESUMO

AIMS: The aims of this study were (i) to develop a population pharmacokinetic (PK) model of tacrolimus in a Mexican renal transplant paediatric population (n = 53) and (ii) to test the influence of different covariates on its PK properties to facilitate dose individualization. METHODS: Population PK and variability parameters were estimated from whole blood drug concentration profiles obtained at steady-state using the non-linear mixed effect modelling software NONMEM® Version 7.2. RESULTS: Tacrolimus PK profiles exhibited high inter-patient variability (IPV). A two compartment model with first order input and elimination described the tacrolimus PK profiles in the studied population. The relationship between CYP3A5 genotype and tacrolimus CL/F was included in the final model. CL/F in CYP3A5*1/*1 and *1/*3 carriers was approximately 2- and 1.5-fold higher than in CYP3A5*3/*3 carriers (non-expressers), respectively, and explained almost the entire IPV in CL/F. Other covariates retained in the final model were the tacrolimus dose and formulation type. Limustin® showed markedly lower concentrations than the rest of the formulations. CONCLUSIONS: Population PK modelling of tacrolimus in paediatric renal transplant recipients identified the tacrolimus formulation type as a significant covariate affecting the blood concentrations and confirmed the previously reported significant effect of CYP3A5 genotype on CL/F. It allowed the design of a proposed dosage based on the final model that is expected to help to improve tacrolimus dosing.


Assuntos
Citocromo P-450 CYP3A/genética , Imunossupressores/farmacocinética , Transplante de Rim , Tacrolimo/farmacocinética , Adolescente , Química Farmacêutica , Criança , Pré-Escolar , Cálculos da Dosagem de Medicamento , Feminino , Genótipo , Humanos , Imunossupressores/sangue , Masculino , México , Modelos Biológicos , Farmacogenética , Tacrolimo/sangue , Adulto Jovem
17.
Pediatr Transplant ; 19(1): E7-10, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25418869

RESUMO

PTE is defined as hematocrit >51% or hemoglobin >17 g/dL after renal transplantation. Risk factors include native kidneys with adequate erythropoiesis pretransplant, smoking, renal artery stenosis, and cyclosporine treatment. We report the case of a 14-yr-old female kidney transplant patient, with triple therapy immunosuppression and stable graft function who developed PTE at 12 months post-transplant with hemoglobin 17.3 g/dL, hematocrit 54.2%, stable graft function, and normotensive with normal cardiac echocardiogram and erythropoietin levels. The only risk factor found was tobacco use. As she had no spontaneous improvement, enalapril treatment was started at 19 months post-transplant with a hemoglobin level of 17.5 g/dL and hematocrit 53%; by 23 months post-transplant, hemoglobin lowered to 15 g/dL and hematocrit to 44.5% and continued to be in normal range thereafter. PTE is a rare condition in childhood and can be successfully treated with enalapril.


Assuntos
Transplante de Rim/efeitos adversos , Policitemia/etiologia , Adolescente , Feminino , Humanos
18.
J Pediatr Nurs ; 30(5): e71-81, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26202468

RESUMO

BACKGROUND: There is a lack of valid health care transition readiness (HCT) scales in Spanish. OBJECTIVE: To provide initial validation of the UNC TRxANSITION Scale™ among Mexican adolescents and young adults (youth) with chronic kidney disease (CKD). METHODS: We used the professionally translated/back translated, provider-administered UNC TRxANSITION Scale™ (Ferris et al., 2012). This 33-question scale measures HCT in ten sub-scales including knowledge about diagnosis or treatment, diet, reproductive health, school/work, insurance, ability to self-manage and looking for new health providers. Its maximum score is 10. We enrolled 163 Mexican adolescents (48.5% females) with CKD stage≥3, mean age of 15.1years (±2.1) and whose primary language is Spanish. There were 15 patients on hemodialysis (9.2%) and 30 transplant recipients (18.4%). Results were compared to those reported in adolescents with chronic conditions from the USA. RESULTS: Our cohort's overall median total score was 5.9. Patients≥16years old had a median total score of 6.4, whereas younger patients had median score of 5.6 (p<0.05). Transplant patients had greater scores in the total and the sub-scales of medication knowledge, issues of reproduction, insurance, trade/work and adherence (p<0.05). When comparing the total score (by age), results from our Mexican youth were similar to those reported in youth from the USA. CONCLUSIONS: In our Mexican cohort of youth with CKD, health care transition readiness is greater in older patients and in transplant recipients. Our cohort's overall score is low, indicating the need for a health care transition preparation program. The UNC TRxANSITION Scale™ results in Mexican youth with CKD are comparable to findings in youth from the USA.


Assuntos
Avaliação de Resultados em Cuidados de Saúde , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Transição para Assistência do Adulto/organização & administração , Adolescente , Adulto , Fatores Etários , Feminino , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Transplante de Rim/métodos , Transplante de Rim/estatística & dados numéricos , Masculino , México , Avaliação de Programas e Projetos de Saúde , Diálise Renal/métodos , Diálise Renal/estatística & dados numéricos , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Tradução , Resultado do Tratamento , Adulto Jovem
19.
J Pediatr Nurs ; 30(5): 668-76, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26165785

RESUMO

INTRODUCTION: The STARx Questionnaire was designed with patient and provider input, to measure self-management and transition skills in adolescents and young adults (AYA) with chronic health conditions. With proven reliability and an empirically-based factor structure, the self-report STARx Questionnaire requires further validation to demonstrate its clinical and research utility. In this study we examine the concurrent, predictive, and discriminant validity of the STARx Questionnaire. METHODS: To examine concurrent validity, the STARx Questionnaire was compared to two other published transition readiness tools. Predictive validity was examined using linear regressions between the STARx Total Score and literacy, medication adherence, quality of life, and health services use. Discriminant validity was examined by comparing the performance of three chronic illness conditions on the STARx Total Score and associated subscales. RESULTS: The STARx Questionnaire and its subscales positively correlated with the scores for both transition readiness tools reflecting strong concurrent validity. The STARx Questionnaire also correlated positively with the literacy, self-efficacy, and adherence measures indicating strong predictive validity; however, it did not correlate with either quality of life or health care utilization. The performance of AYA across three different clinical conditions was not significant, indicating the clinical utility of this HCT tool for a variety of chronic health conditions. CONCLUSION: The strong validity of the STARx Questionnaire, in tandem with its strong reliability, indicated adequate psychometric properties for this generic self-report measure. These strong psychometric properties should contribute to the STARx being a viable measure of health care transition for both research and clinical purposes.


Assuntos
Doença Crônica/terapia , Autocuidado/métodos , Inquéritos e Questionários , Transição para Assistência do Adulto/organização & administração , Adolescente , Doença Crônica/psicologia , Feminino , Humanos , Masculino , Avaliação de Programas e Projetos de Saúde , Qualidade de Vida , Reprodutibilidade dos Testes , Adulto Jovem
20.
Rev Invest Clin ; 67(3): 170-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26202740

RESUMO

BACKGROUND: Peritoneal dialysis is the most frequent dialysis method in children, and peritonitis is a frequent complication. The responsible organisms differ between nosocomial and community acquired peritonitis, they cause longer hospitalization time, and can lead to dialysis failure. OBJECTIVE: The aim of the study was to describe the risk factors associated with nosocomial peritonitis in children with end-stage renal disease undergoing dialysis treatment. METHODS: A nested case-control study was conducted in an academic medical center. SUBJECTS: The basic cohort included all pediatric patients with end-stage renal disease undergoing continuous ambulatory peritoneal dialysis therapy and who were hospitalized for non-infectious causes during the study period, January 2008 to December 2009. Cases were subjects who developed nosocomial peritonitis during hospitalization, and controls were children free of nosocomial peritonitis. The final groups consisted of 10 cases and 35 controls. RESULTS: There were 11 episodes of nosocomial peritonitis in 10 subjects (incidence rate, 6.6 cases per year of hospitalization). By multiple logistic regression analysis, the presence of congenital abnormalities of the kidney and urinary tract was the only risk factor significantly associated with nosocomial peritonitis (OR: 11.54; 95% CI: 1.86-71.59). CONCLUSION: Congenital abnormality of the kidney and urinary tract was a significant risk factor for nosocomial peritonitis in pediatric patients with end-stage renal disease undergoing peritoneal dialysis.


Assuntos
Infecção Hospitalar/etiologia , Falência Renal Crônica/terapia , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Peritonite/etiologia , Centros Médicos Acadêmicos , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Infecção Hospitalar/epidemiologia , Feminino , Hospitalização , Humanos , Rim/anormalidades , Modelos Logísticos , Masculino , México , Diálise Peritoneal Ambulatorial Contínua/métodos , Peritonite/epidemiologia , Fatores de Risco , Sistema Urinário/anormalidades
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