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1.
Pediatr Transplant ; 25(8): e14096, 2021 12.
Article in English | MEDLINE | ID: mdl-34327777

ABSTRACT

BACKGROUND: Steroid use in renal transplant is related to multiple adverse effects. Long-term effects of early withdrawal steroids in pediatric renal transplant were assessed. METHODS: Renal transplant children with low immunological risk treated on basiliximab, tacrolimus, and mycophenolate with steroid withdrawal or steroid control were evaluated between 2003 and 2019. Clinical variables, treatment adherence, acute rejection, graft loss, and death were analyzed through hazard ratios, and Kaplan-Meier and multivariate analyses. RESULTS: The study included 152 patients, 71.1% steroid withdrawal, mean follow-up 8.5 years, 64.5% structural abnormalities, and 81.6% deceased donor. At 12 years of transplant, event-free survival analysis for graft loss or death showed no significant difference between steroid withdrawal and control steroid treatment (85.9% vs. 80.4%, p = .36) nor in acute rejection at 10 years (18.5% vs. 20.5%, p = .78) or in donor-specific antibody appearance (19.6% vs. 21.4%, p = .98). Delta height Z-score was increased in the steroid withdrawal group (p < .01). The main predictor of graft loss or death was non-adherence to treatment (p = .001; OR: 17.5 [3.3-90.9]). CONCLUSIONS: Steroid withdrawal therapy was effective and safe for low-risk pediatric renal transplant in long-term evaluation. Non-adherence was the main predictor of graft loss or death.


Subject(s)
Immunosuppressive Agents/therapeutic use , Kidney Transplantation , Steroids/administration & dosage , Child , Female , Graft Rejection , Humans , Kidney Transplantation/mortality , Male , Medication Adherence
2.
Front Pharmacol ; 12: 653525, 2021.
Article in English | MEDLINE | ID: mdl-33967795

ABSTRACT

Background: Tacrolimus (TAC) and mycophenolic acid (MPA) are the main immunosuppressive drugs used in pediatric kidney transplantation. Single nucleotide polymorphisms (SNPs) in metabolizing enzymes and transporters might influence plasma levels of these drugs. Herein, we sought to determine the influence of SNPs on CYP3A5, MRP2 and UGT1A9 genes in Chilean pediatric kidney recipients using TAC and MPA. Patients and Methods: A prospective study was performed on 104 pediatric kidney recipients that used TAC and MPA for immunosuppression. The median age at the time of transplantation was 8.1 years [Q1-Q3 4.5-11.6 years] and the main clinical diagnosis was a structural anomaly. In a subgroup of patients, a complete steroid withdrawal was made at day 7. The CYP3A5 polymorphism (ancestral allele *1; variant allele *3) was determined in the entire cohort, while MRP2 -24G > A, UGT1A9 -275T > A, and UGT1A9 -2152C > T polymorphisms were determined in 53 patients. Genotypes were associated with trough drug concentrations (C0), dose requirements normalized by weight (TAC-D mg/kg) or body surface (MPA-D mg/m2), trough levels normalized by dose requirements (C0/D), and area under the curve in 12 h normalized by dose requirements (AUC0-12h/D). Results: The frequencies of the variant alleles CYP3A5*3, MRP2-24A, UGT1A9-275A, and UGT1A9-2152T were 76.9, 22.1, 6.6, and 2.9%, respectively. AUC0-12h/TAC-D were 1.6-fold higher in CYP3A5*3/*3 patients than in CYP3A5*1 carriers (CYP3A5*1/*3 and CYP3A5*1/*1). When analyzing patients with steroid withdrawal, CYP3A5*3/*3 patients had 1.7-fold higher AUC0-12h/TAC-D than the other genotypes. Patients carrying the CYP3A5*3/*3 genotype had higher TAC-C0, lower TAC-D and higher TAC-C0/D, consistently in a 6-months follow-up. Creatinine clearance was stable during the follow-up, regardless of the genotype. No significant differences between MRP2 and UGT1A9 genotypes were observed in MPA-C0, MPA-D or MPA-C0/D. However, patients carrying the UGT1A9-275A allele had lower AUC0-12h/MPA-D than those carrying the UGT1A9-275T ancestral allele. Conclusions: These results support that CYP3A5 and UGT1A9 genotyping in pediatric recipients might be useful and advisable to guide TAC and MPA dosing and monitoring in children that undergo kidney transplantation.

3.
Rev. chil. pediatr ; 90(6): 662-667, dic. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1058198

ABSTRACT

INTRODUCCIÓN: El síndrome de CLOVES se caracteriza por sobrecrecimiento lipomatoso asociado a malformaciones vasculares, representando un desafío diagnóstico y terapéutico. La rapamicina, un inhibidor de la vía mTOR, ha demostrado ser una buena alternativa terapéutica en un grupo de anomalías vasculares. Reportamos dos casos de síndrome de CLOVES con buena respuesta al tratamiento con rapamicina oral. OBJETIVO: Reportar la experiencia del uso de rapamicina oral en el tratamiento de dos pacientes con síndrome de CLOVES. CASOS CLÍNICOS: Caso 1: preescolar femenino de tres años de edad con sín drome de CLOVES e historia de hospitalizaciones reiteradas por infección severa de malformaciones linfáticas macroquísticas y episodios trombóticos. Evoluciona con mala calidad de vida, múltiples hospitalizaciones, riesgo quirúrgico y progresión de las lesiones, por lo que se indicó rapamicina oral. A los 6 meses de tratamiento se evidenció reducción clínica y radiológica del tamaño de las masas lipomatosas y linfáticas, ausencia de linforrea cutánea y mejoría significativa de la calidad de vida, sin requerir nuevas hospitalizaciones. Caso 2: escolar femenino de diez años de edad, portadora de síndrome de CLOVES, que desarrolló escoliosis y deterioro de su capacidad motora, haciéndose dependiente del uso de silla de ruedas. Se indicó rapamicina oral, evidenciándose a los cuatro meses de tratamiento mejoría en su capacidad física, independencia y autovalencia, con desaparición de la linforrea. CONCLUSIÓN: Proponemos la rapamicina oral para el tratamiento de pacientes con sín drome de CLOVES que presenten complicaciones y deterioro de la calidad de vida producto de su enfermedad.


INTRODUCTION: CLOVES syndrome is characterized by lipomatous overgrowth associated with vascular malforma tions, representing a diagnostic and a therapeutic challenge. Rapamycin, an mTOR inhibitor, has proved to be a good therapeutic option in some vascular anomalies. In this article, we report two ca ses of CLOVES syndrome with good response to oral rapamycin treatment. OBJECTIVE: To report the outcome of two patients with CLOVES syndrome treated with oral rapamycin. CLINICAL CASES: Case 1: A three-year-old female preschooler with CLOVES syndrome and history of repeated hospita lizations due to severe infections resulting from macrocystic lymphatic malformations and due to thrombotic episodes. The patient evolved with poor quality of life, multiple hospitalizations, surgical risk and progression of the lesions, therefore, oral rapamycin was indicated. After six months of treatment, clinical and radiological reduction in the size of the lipomatous and lymphatic masses, cutaneous lymphorrhea absence and a significant improvement of her quality of life were observed, without requiring new hospitalizations. Case 2: a ten-year-old female schooler with CLOVES syndro me, who developed scoliosis and deterioration of her motor skills, becoming wheelchair-dependent. Oral rapamycin was indicated, showing improvement in her physical capacity, independence and au tonomy, and absence of lymphorrhea after four months of treatment. CONCLUSION: We propose oral rapamycin for the treatment of patients with CLOVES syndrome who present with complications and deterioration in the quality of life as a result of the disease.


Subject(s)
Humans , Female , Child, Preschool , Child , Sirolimus/therapeutic use , Vascular Malformations/drug therapy , Lipoma/drug therapy , Antibiotics, Antineoplastic/therapeutic use , Musculoskeletal Abnormalities/drug therapy , Nevus/drug therapy , Administration, Oral , Sirolimus/administration & dosage , Antibiotics, Antineoplastic/administration & dosage
4.
Rev Chil Pediatr ; 90(3): 336-342, 2019 Jun.
Article in Spanish | MEDLINE | ID: mdl-31344195

ABSTRACT

Hypertension (HTN) in children and adolescents is an important pathology, of, guarded prognosis, associated with modifiable and non-modifiable factors. The estimated prevalence is around 3.5% which increases progressively with age. The ideal method for its diagnosis is the measurement of blood pressure (BP) with auscultatory instruments. According to the American Academy of Pedia trics (AAP), BP should be measured in children older than three years of age once a year, and in children younger than three years of age if they present risk factors. Once the HTN is confirmed, the evaluation should be directed towards the detection of a causative disease and/or the search for risk factors associated with a primary HTN. The objective of treating primary and secondary HTN in pediatrics is to achieve a BP level that decreases the risk of target organ damage. Therapeutic op tions include treatment according to specific etiology, non-pharmacological and pharmacological one. This paper presents the position of the Chilean Society of Pediatrics Nephrology Branch with the aim of guiding pediatricians and pediatric nephrologists in the correct management of HTN in childhood. In this second part, recommendations on antihypertensive treatment are presented with an emphasis on lifestyle changes.


Subject(s)
Antihypertensive Agents/administration & dosage , Hypertension/therapy , Life Style , Adolescent , Age Factors , Blood Pressure/physiology , Blood Pressure Determination , Child , Child, Preschool , Chile , Humans , Hypertension/diagnosis , Practice Guidelines as Topic , Risk Factors
5.
Rev. chil. pediatr ; 90(3): 336-342, jun. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1013842

ABSTRACT

Resumen: La hipertensión arterial (HTA) en niños y adolescentes es una importante patología, de reservado pronóstico, asociada a factores modificables y no modificables. La prevalencia estimada es de apro ximadamente un 3,5%, la cual va aumentando progresivamente con la edad. El método ideal para su diagnóstico es la medición de la presión arterial (PA) con instrumentos auscultatorios. De acuerdo a la Academia Americana de Pediatría (AAP) la PA debe ser medida en niños mayores de 3 años una vez al año, y en niños menores de 3 años, si presentan factores de riesgo. Una vez confirmada la HTA, la evaluación debe dirigirse hacia la detección de una enfermedad causal y/o a la búsqueda de factores de riesgo asociados a una HTA primaria. El objetivo del tratamiento de la HTA primaria y secundaria en pediatría es lograr un nivel de PA que disminuya el riesgo de daño de los órganos blanco. Las opciones terapéuticas incluyen: tratamiento según etiología específica, no farmacológico y farmacológico. En esta Guia se presenta la posición de la Rama de Nefrología de la Sociedad Chile na de Pediatría con el objetivo de orientar a pediatras y nefrólogos infantiles en correcto manejo de la HTA en la infancia. En esta segunda parte se presentan las recomendaciones sobre el tratamiento antihipertensivo, haciendo énfasis en los cambios de estilo de vida.


Abstract: Hypertension (HTN) in children and adolescents is an important pathology, of, guarded prognosis, associated with modifiable and non-modifiable factors. The estimated prevalence is around 3.5% which increases progressively with age. The ideal method for its diagnosis is the measurement of blood pressure (BP) with auscultatory instruments. According to the American Academy of Pedia trics (AAP), BP should be measured in children older than three years of age once a year, and in children younger than three years of age if they present risk factors. Once the HTN is confirmed, the evaluation should be directed towards the detection of a causative disease and/or the search for risk factors associated with a primary HTN. The objective of treating primary and secondary HTN in pediatrics is to achieve a BP level that decreases the risk of target organ damage. Therapeutic op tions include treatment according to specific etiology, non-pharmacological and pharmacological one. This paper presents the position of the Chilean Society of Pediatrics Nephrology Branch with the aim of guiding pediatricians and pediatric nephrologists in the correct management of HTN in childhood. In this second part, recommendations on antihypertensive treatment are presented with an emphasis on lifestyle changes.


Subject(s)
Humans , Child, Preschool , Child , Adolescent , Hypertension/therapy , Life Style , Antihypertensive Agents/administration & dosage , Blood Pressure/physiology , Blood Pressure Determination , Risk Factors , Age Factors , Practice Guidelines as Topic , Hypertension/diagnosis
6.
Rev Chil Pediatr ; 90(2): 209-216, 2019 Apr.
Article in Spanish | MEDLINE | ID: mdl-31095238

ABSTRACT

Hypertension (HT) in children and adolescents is an important pathology, associated with modi fiable and non-modifiable factors. In the pediatric, the prevalence of HT is around 3.5%, and it in creases progressively with age. The ideal method for diagnosis is the measurement of blood pressure (BP) with auscultatory instruments. As published by the American Academy of Pediatrics (AAP), BP should be measured in children over 3 years of age once a year, and in children under 3 years of age, if it presents risk factors. Once HT has been confirmed, the evaluation should be directed towards the detection of a causative disease and the search for risk factors associated with primary HTN. The goal of treating primary and secondary HTN in pediatrics is to achieve a level of BP that decreases the risk of target organ damage. The therapeutic options include: treatment according to specific etiology, non-pharmacological and pharmacological. This document is the product of a collaborative effort of the Nephrology Branch of the Chilean Society of Pediatrics with the aim of helping pediatricians and pediatric nephrologists in the diagnosis and treatment of hypertension in childhood. In this first part, the recommendations of the diagnosis and study are presented.


Subject(s)
Hypertension/diagnosis , Hypertension/therapy , Adolescent , Antihypertensive Agents/therapeutic use , Blood Pressure Determination/methods , Child , Combined Modality Therapy , Humans , Hypertension/etiology , Medical History Taking , Physical Examination , Risk Factors
7.
J Bone Miner Res ; 34(10): 1851-1861, 2019 10.
Article in English | MEDLINE | ID: mdl-31099911

ABSTRACT

Renal transplantation (RTx) is an effective therapy to improve clinical outcomes in pediatric patients with terminal chronic kidney disease. However, chronic immunosuppression with glucocorticoids (GCs) reduces bone growth and BMD. The mechanisms causing GC-induced growth impairment have not been fully clarified. Fibroblast growth factor 23 (FGF23) is a peptide hormone that regulates phosphate homeostasis and bone growth. In pathological conditions, FGF23 excess or abnormal FGF receptors (FGFR) activity leads to bone growth impairment. Experimental data indicate that FGF23 expression is induced by chronic GC exposure. Therefore, we hypothesize that GCs impair bone growth by increasing FGF23 expression, which has direct effects on bone growth plate. In a post hoc analysis of a multicentric randomized clinical trial of prepubertal RTx children treated with early GC withdrawal or chronic GC treatment, we observed that GC withdrawal was associated with improvement in longitudinal growth and BMD, and lower plasma FGF23 levels as compared with a chronic GC group. In prepubertal rats, GC-induced bone growth retardation correlated with increased plasma FGF23 and bone FGF23 expression. Additionally, GC treatment decreased FGFR1 expression whereas it increased FGFR3 expression in mouse tibia explants. The GC-induced bone growth impairment in tibiae explants was prevented by blockade of FGF23 receptors using either a pan-FGFR antagonist (PD173074), a C-terminal FGF23 peptide (FGF23180-205) which blocks the binding of FGF23 to the FGFR-Klotho complex or a specific FGFR3 antagonist (P3). Finally, local administration of PD173074 into the tibia growth plate ameliorated cartilage growth impairment in GC-treated rats. These results show that GC treatment partially reduces longitudinal bone growth via upregulation of FGF23 and FGFR3 expression, thus suggesting that the FGF23/Klotho/FGFR3 axis at the growth plate could be a potential therapeutic target for the management of GC-induced growth impairment in children.


Subject(s)
Bone Development/drug effects , Bone and Bones/metabolism , Fibroblast Growth Factors/metabolism , Glucocorticoids/administration & dosage , Kidney Transplantation , Receptor, Fibroblast Growth Factor, Type 3/metabolism , Signal Transduction/drug effects , Animals , Bone Density/drug effects , Bone and Bones/pathology , Child , Female , Fibroblast Growth Factor-23 , Follow-Up Studies , Glucocorticoids/adverse effects , Humans , Kidney Failure, Chronic/metabolism , Kidney Failure, Chronic/pathology , Kidney Failure, Chronic/surgery , Klotho Proteins , Male , Membrane Proteins , Mice , Rats , Rats, Sprague-Dawley
8.
Rev. chil. pediatr ; 90(2): 209-216, abr. 2019. tab
Article in Spanish | LILACS | ID: biblio-1003739

ABSTRACT

Resumen: La hipertensión arterial (HTA) en niños y adolescentes es una patología importante, asociada a fac tores modificables y no modificables. En la edad pediátrica, la prevalencia de la HTA es de alrededor de un 3,5%, y va aumentando progresivamente con la edad. El método ideal para su diagnóstico es la medición de la presión arterial (PA) con instrumentos auscultatorios. Según lo publicado por la Academia Americana de Pediatría (AAP) la PA debe ser medida en niños mayores de 3 años una vez al año, y en niños menores de 3 años, si presenta factores de riesgo. Una vez confirmada la HTA, la evaluación debe dirigirse hacia la detección de una enfermedad causal y a la búsqueda de factores de riesgo asociados a una HTA primaria. El objetivo del tratamiento de la HTA primaria y secundaria en pediatría es lograr un nivel de PA que disminuya el riesgo de daño de órgano blanco. Las opcio nes terapéuticas incluyen: tratamiento según etiología específica, no farmacológico y farmacológico. Este documento es producto de un esfuerzo colaborativo de la Rama de Nefrología de la Sociedad Chilena de Pediatría con el objetivo de ayudar a los pediatras y nefrólogos infantiles en el diagnóstico y tratamiento de la HTA en la infancia. En esta primera parte, se presentan las recomendaciones del diagnóstico y estudio.


Abstract: Hypertension (HT) in children and adolescents is an important pathology, associated with modi fiable and non-modifiable factors. In the pediatric, the prevalence of HT is around 3.5%, and it in creases progressively with age. The ideal method for diagnosis is the measurement of blood pressure (BP) with auscultatory instruments. As published by the American Academy of Pediatrics (AAP), BP should be measured in children over 3 years of age once a year, and in children under 3 years of age, if it presents risk factors. Once HT has been confirmed, the evaluation should be directed towards the detection of a causative disease and the search for risk factors associated with primary HTN. The goal of treating primary and secondary HTN in pediatrics is to achieve a level of BP that decreases the risk of target organ damage. The therapeutic options include: treatment according to specific etiology, non-pharmacological and pharmacological. This document is the product of a collaborative effort of the Nephrology Branch of the Chilean Society of Pediatrics with the aim of helping pediatricians and pediatric nephrologists in the diagnosis and treatment of hypertension in childhood. In this first part, the recommendations of the diagnosis and study are presented.


Subject(s)
Humans , Child , Adolescent , Hypertension/diagnosis , Hypertension/therapy , Physical Examination , Blood Pressure Determination/methods , Risk Factors , Combined Modality Therapy , Hypertension/etiology , Medical History Taking , Antihypertensive Agents/therapeutic use
9.
Rev Chil Pediatr ; 90(6): 662-667, 2019 Dec.
Article in English, Spanish | MEDLINE | ID: mdl-32186590

ABSTRACT

INTRODUCTION: CLOVES syndrome is characterized by lipomatous overgrowth associated with vascular malforma tions, representing a diagnostic and a therapeutic challenge. Rapamycin, an mTOR inhibitor, has proved to be a good therapeutic option in some vascular anomalies. In this article, we report two ca ses of CLOVES syndrome with good response to oral rapamycin treatment. OBJECTIVE: To report the outcome of two patients with CLOVES syndrome treated with oral rapamycin. CLINICAL CASES: Case 1: A three-year-old female preschooler with CLOVES syndrome and history of repeated hospita lizations due to severe infections resulting from macrocystic lymphatic malformations and due to thrombotic episodes. The patient evolved with poor quality of life, multiple hospitalizations, surgical risk and progression of the lesions, therefore, oral rapamycin was indicated. After six months of treatment, clinical and radiological reduction in the size of the lipomatous and lymphatic masses, cutaneous lymphorrhea absence and a significant improvement of her quality of life were observed, without requiring new hospitalizations. Case 2: a ten-year-old female schooler with CLOVES syndro me, who developed scoliosis and deterioration of her motor skills, becoming wheelchair-dependent. Oral rapamycin was indicated, showing improvement in her physical capacity, independence and au tonomy, and absence of lymphorrhea after four months of treatment. CONCLUSION: We propose oral rapamycin for the treatment of patients with CLOVES syndrome who present with complications and deterioration in the quality of life as a result of the disease.


Subject(s)
Antibiotics, Antineoplastic/therapeutic use , Lipoma/drug therapy , Musculoskeletal Abnormalities/drug therapy , Nevus/drug therapy , Sirolimus/therapeutic use , Vascular Malformations/drug therapy , Administration, Oral , Antibiotics, Antineoplastic/administration & dosage , Child , Child, Preschool , Female , Humans , Sirolimus/administration & dosage
10.
Pediatr Nephrol ; 31(6): 965-74, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26747624

ABSTRACT

BACKGROUND: Chronic kidney disease (CKD) in children is characterized by severe growth failure. The growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis in uremic animals shows a post-receptor impaired phosphorylation of Janus kinase 2/signal transducer and activator of transcription (JAK-STAT) proteins. The objective of our study was to characterize the intracellular phosphorylation of JAK-STAT signaling in fibroblasts from children with CKD on chronic peritoneal dialysis (PD). METHODS: Serum GH-binding protein (GHBP), IGF-1 and IGFBP3 were measured in 15 prepubertal CKD stage-5 children on PD. Cytoplasmic JAK2, cytoplasmic/nuclear STAT5b and nuclear IGFBP3, acid-labile subunit (ALS) and IGF-1 mRNA expression were quantified in fibroblasts obtained from skin biopsies before and after stimulation with 200 ng/ml recombinant human growth hormone (rhGH). Phosphorylation activity at both the cytoplasmic and nuclear level was expressed as the ratio phosphorylated (p)/total (t) abundance of the product (p/t) at 30 and 60 min. Fifteen healthy children were recruited as the control group. Values were expressed in arbitrary units (AU) and normalized for comparison. Significance was defined as p < 0.05. RESULTS: Thirty minutes after rhGH stimulus, the cytoplasmic (p/t) JAK2 ratio was significantly lower in patients than in controls [median and interquartile range (IQR): 7.4 (4.56) vs. 20.5 (50.06) AU]. At 60 min after rhGH stimulation, median JAK2 phosphorylation activity was still significantly lower in the patients [7.14 (IQR 3.8) vs. 10.2 (IQR 29.8) AU; p < 0.05]. The increase in the cytoplasmic (p/t) STAT5b/ß-actin ratio was lower at both measurement points in the patients compared to the controls, without reaching statistical significance between groups. Median IGFBP3 mRNA abundance was significantly decreased in fibroblasts from uremic patients 24 h after rhGH stimulation compared to the healthy controls [1.27 (IQR 0.83) vs. 2.37 (IQR 0.80) AU]. Median ALS and IGF-1 mRNA expression changed in response to rhGH stimuli at 24 and 48 h. CONCLUSION: In this study, children with CKD undergoing PD therapy showed an impaired phosphorylation of JAK2/STAT5b signaling in fibroblasts after GH stimulation, as well as impaired IGFBP3 mRNA abundance. Both impairments may be partially responsible for the observed resistance to the growth-promoting actions of GH in chronic kidney failure.


Subject(s)
Fibroblasts/metabolism , Janus Kinase 2/metabolism , Renal Insufficiency, Chronic/metabolism , STAT5 Transcription Factor/metabolism , Uremia/metabolism , Actins/metabolism , Biopsy , Carrier Proteins/blood , Child , Child, Preschool , DNA-Binding Proteins/metabolism , Female , Human Growth Hormone/pharmacology , Humans , Insulin-Like Growth Factor Binding Protein 3/blood , Insulin-Like Growth Factor Binding Protein 3/metabolism , Insulin-Like Growth Factor I/analysis , Insulin-Like Growth Factor I/metabolism , Male , Peritoneal Dialysis , Phosphorylation , Primary Cell Culture , Recombinant Proteins/pharmacology , Renal Insufficiency, Chronic/therapy , Signal Transduction , Skin/cytology , Skin/pathology
11.
Pediatr Transplant ; 19(7): 675-83, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26256468

ABSTRACT

The aim of the current study was to compare results in pediatric renal transplantation of patients with and without SBP. Between 2001 and 2013, a total of 168 kidney transplants were performed at our center. A retrospective analysis was performed and recipients were divided into two groups: NB and SBP. Incidence of surgical complications after procedure, and graft and patient survival were evaluated. A total of 155 recipients (92%) with complete data were analyzed, and 13 recipients that had had previous bladder surgeries were excluded (11 with VUR surgery and two with previous kidney transplants), of the 155 recipients: 123 (79%) patients had NB, and 32 (21%) patients had SBP, with a median follow-up of 60 (1-137) and 52 (1-144) months, respectively. Among post-transplant complications, UTI (68.8% vs. 23%, p < 0.0001) and symptomatic VUR to the graft (40.6% vs. 7.3%, p < 0.0001) were significantly higher in the SBP group. There was no significant difference in overall graft and patient survival between groups. Renal transplantation is safe in pediatric recipients with SBP; however, urologic complications such as UTI and VUR were significantly higher in this group. Graft and patient survival was similar in SBP and NB groups.


Subject(s)
Graft Survival , Kidney Transplantation/mortality , Postoperative Complications/etiology , Urinary Bladder Diseases/complications , Adolescent , Case-Control Studies , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Incidence , Infant , Male , Postoperative Complications/epidemiology , Retrospective Studies , Risk Factors
12.
Pediatr Nephrol ; 28(7): 1121-6, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23494552

ABSTRACT

BACKGROUND: Cardiovascular disease (CVD) in patients on chronic peritoneal dialysis (PD) is a major cause of death and is closely linked to hypertension and volume overload. The mini-Pet has been proposed as a useful tool to evaluate free-water transport (FWT) and characterize ultrafiltration across the peritoneum. Knowledge regarding FWT could be of great value to predict volume overload in PD patients. Our objective in this study was to characterize FWT through the peritoneum in children on PD. METHODS: We studied clinically stable patients with >2 months on PD. Exclusion criteria were a peritonitis episode up to 2 months prior to entrance into the study and active nephrotic syndrome. A 1-h mini-peritoneal equilibration test (mini-PET) was performed with 3.86 % glucose. Calculations (see text for full definitions) were: Dip Na (Na dial min60 - Na dial min1), Dip D/PNa (D/PNa60 - D/PNa1), total Na removal (NaR = total Na dial60 - Na dial1), ultrafiltration small pores [(UFSP = NaR × 1,000)/Nap], and FWT (UF-UFSP). Peritoneal equilibration test (PET), left ventricular mass index (LVMI, g/m(2)), daily UF, and residual renal function were evaluated. Pearson's correlation coefficient was used to establish correlation between variables. RESULTS: Sixteen patients were included, with a mean age of 11.8 ± 3.8 years. Free water transport normalized to body surface area (BSA) (FWTn) was 133.9 ± 85.7 ml/m(2); creatinine dialysate-to-plasma (D/P) and glucose dialysate at X dwell time-to-0 dwell time (Dx/D0) ratios were 0.38 ± 0.1 and 0.65 ± 0.09, respectively. LVMI was 46.6 ± 14.8 g/m(2); 2-h creatinine D/P and glucose Dx/D0 showed no correlation with FWTn, UF, and LVMI. FWTn showed a significant inverse correlation with LVMI (r 0.58, p 0.02). CONCLUSIONS: This study characterized FWT in PD children through the mini-PET. Left ventricular hypertrophy showed a high prevalence in this group, and a significant correlation between LVMI and FWT was found. FWT could be a useful tool to evaluate UF in PD children.


Subject(s)
Blood Volume , Body Water/metabolism , Dialysis Solutions/adverse effects , Hypertrophy, Left Ventricular/etiology , Peritoneal Dialysis/adverse effects , Peritoneum/metabolism , Adolescent , Age Factors , Biological Transport , Biomarkers/blood , Body Surface Area , Child , Child, Preschool , Creatinine/blood , Dialysis Solutions/metabolism , Female , Glucose/metabolism , Humans , Hypertrophy, Left Ventricular/blood , Hypertrophy, Left Ventricular/diagnosis , Hypertrophy, Left Ventricular/physiopathology , Hypertrophy, Left Ventricular/prevention & control , Male , Models, Biological , Permeability , Predictive Value of Tests , Prospective Studies , Sodium/blood , Time Factors
13.
Horm Res Paediatr ; 79(2): 88-96, 2013.
Article in English | MEDLINE | ID: mdl-23429258

ABSTRACT

BACKGROUND: Glucocorticoid immunosuppressant therapy in pediatric kidney transplant (Tx) recipients does not allow the improvement of growth after Tx. OBJECTIVE: To determine the effect of early steroid withdrawal (SW) on longitudinal growth, insulin sensitivity (IS), and body composition (BC). METHODS: This was a prospective, randomized, multicenter study in Tx. Insulin-like growth factor (IGF)-I, IGF-binding protein 3 (IGFBP3), IS, and BC (DEXA/pQCT) were determined at baseline and up to 12 months after Tx. RESULTS: A total of 30 patients were examined; 14 patients were assigned to the SW group (7 male, 7 female; 12 in Tanner stage I) and 16 patients were assigned to the steroid control (SC) group (10 male, 6 female;12 in Tanner stage I). Their chronological age was 7.8 ± 4.3 years, height was -2.3 ± 0.99 SD scores (SDS), and body mass index -0.3 ± 1.2 SDS. After 1 year, the SW group showed an increase in height SDS (+1.2 ± 0.22 vs. +0.60 ± 0.13 SDS in the SC group, p < 0.02), lower IGFBP3 (p < 0.05), cholesterol (p < 0.05), and higher high-density lipoprotein cholesterol (p < 0.05). SW patients had lower trunk fat with no differences in IS. Only in prepubertal patients, the SW group had lower glycemia (p < 0.05), very low-density lipoprotein cholesterol (p < 0.01), triglycerides (p < 0.05), triglycerides/glycemia index (TyG; p < 0.02), and better lean mass. Both groups showed an improvement in lean mass after kidney Tx. CONCLUSIONS: SW improved longitudinal growth, lipid profile, and trunk and lean fat in Tx patients. In prepubertal recipients, the decrease in TyG suggests better IS.


Subject(s)
Adiposity , Body Height , Body Mass Index , Cholesterol/blood , Immunosuppressive Agents , Kidney Transplantation , Steroids , Child , Child, Preschool , Female , Humans , Insulin-Like Growth Factor Binding Protein 3/blood , Insulin-Like Growth Factor I/metabolism , Male , Prospective Studies , Time Factors , Transplantation, Homologous
14.
Educ. méd. (Ed. impr.) ; 15(3): 179-184, sept. 2012. tab
Article in Spanish | IBECS | ID: ibc-106427

ABSTRACT

Introducción. Los cursos de formación pedagógica pueden mejorar el desempeño de los docentes clínicos. Diseñamos un curso de diez sesiones para mejorar las competencias docentes de profesionales que tienen responsabilidades como tutores clínicos. En el año 2008 se realizaron tres cursos. Las actividades se programaron una vez a la semana, de 08:30 a 10:00 h de la mañana, para facilitar la asistencia. El curso se componía de tres módulos -currículo, metodología y evaluación- y se diseñó para centrarse en los alumnos. Fueron facilitadores de los cursos docentes clínicos con formación en docencia en ciencias de la salud (con diploma o maestría). Objetivo. Evaluar si los asistentes percibían haber realizado cambios en sus prácticas docentes a un año de haber finalizado el curso. Sujetos y métodos. Se administró de modo anónimo, mediante una plataforma informática, un cuestionario con 13 preguntas cerradas y espacio para comentarios. Se envió por correo electrónico una invitación a responder el cuestionario a los 55 tutores clínicos que fueron alumnos de los tres cursos realizados durante el año 2008. El cuestionario se remitió un año después de haber finalizado el curso respectivo. Resultados. El cuestionario fue respondido por 41 tutores clínicos (74,5%). Las respuestas apuntaron a cambios realizados en todos los aspectos consultados: programas (34%), metodología (83%) y evaluación (71%). Conclusiones. La mayoría de los participantes en estos cursos de formación docente perciben haber hecho cambios positivos en sus prácticas docentes. Actualmente se está dictando el noveno curso de estas características (AU)


Introduction. Faculty development courses can improve the performance of teachers. We designed a ten sessions course aimed to improve the teaching skills of professionals who have responsibilities as tutors in clinical settings. Three courses were given in year 2008. The courses were held in teaching hospitals once a week to make easier for tutors to attend. The courses included curriculum, methodology and evaluation modules. They were student centred, took place in the workplace and employed local teachers with a degree in health sciences education that were clinical tutors themselves. Aim. To assess whether clinical tutors perceived themselves as having made changes in their teaching practices one year after having finished the course. Subjects and methods. An anonymous online survey with thirteen closed questions and space for open comments was administered online. One year after finishing the respective course, an invitation to complete the survey was e-mailed to the fifty-five tutors who completed one of the year 2008 courses. Results. Forty-one tutors answered the survey (74.5%). Changes in teaching practices and in major aspects of the teaching process were declared in all the items consulted in the survey: teaching methodology 83%, assessment of students 71%, programs 34%. Conclusions. Clinical tutors perceive themselves as having made positive changes in their teaching practices after a faculty development course. Currently the ninth similar course is being given (AU)


Subject(s)
Humans , Faculty, Medical/statistics & numerical data , Education, Medical, Continuing/trends , Educational Measurement , Evaluation of the Efficacy-Effectiveness of Interventions
15.
Perit Dial Int ; 32(4): 437-43, 2012.
Article in English | MEDLINE | ID: mdl-22473035

ABSTRACT

BACKGROUND: Nephrotic syndrome (NS) in children has been associated with a systemic circulating permeability factor. Therefore, once peritoneal dialysis (PD) has been started, peritoneal protein losses should be higher in the nephrotic than in the non-nephrotic population. OBJECTIVE: We compared peritoneal protein losses in children with and without NS on PD. METHODS: Our retrospective 4-year study analyzed Hispanic patients with NS under PD. Data at dialysis entry and 6 months later were compared. Nutritional support was given according to recommended dietary allowances and recommendations from the Kidney Disease Outcomes Quality Initiative. Clinical and biochemical data were obtained, and 24-hour dialysate and urine samples were collected to measure protein losses. Dialysis dose (Kt/V), daily protein intake (DPI), normalized protein equivalent of nitrogen appearance (nPNA), peritoneal equilibration test (PET), and peritonitis rate were determined. All measurements took place at least 4 weeks after resolution of a peritonitis episode. All patients received automated PD using a HomeChoice PD System cycler (Baxter Healthcare Corporation, Deerfield, IL, USA), with an exchange volume of 1100 mL/m(2) and a dextrose concentration of 1.5% - 2.5%. A control group of non-NS children on PD matched by age and sex were also studied. Data are reported as mean ± standard deviation. Differences between groups were calculated using the Mann-Whitney U-test, and p < 0.05 was considered significant. RESULTS: Each study group consisted of 10 patients [NS patients: 4 boys, mean age of 7.3 ± 4.1 years; control patients: 6 boys, mean age of 7.2 ± 4.7 years (p = nonsignificant)]. In the group with NS, 8 patients were diagnosed by biopsy as having focal segmental glomerulosclerosis, and 2 as having minimal-change disease. At study entry, patients with NS had hourly urinary protein losses of 398 ± 313 mg/m(2) and daily peritoneal protein losses of 3.4 ± 1.9 g/m(2), compared with 29.9 ± 31 mg/m(2) and 1.5 ± 1.1 g/m(2) respectively in the control group (p < 0.05). The same statistical difference was found 6 months later. We observed no statistical differences in PET results, daily exchange volume, and mean dextrose concentration of dialysate. Similarly, no significant between-group differences were observed for Kt/V, DPI, nPNA, and biochemical parameters. CONCLUSIONS: Hispanic children with NS on PD show higher peritoneal protein losses than do their control counterparts. Such differences could be secondary to increased peritoneal permeability caused by a systemic permeability factor.


Subject(s)
Dialysis Solutions/pharmacokinetics , Nephrotic Syndrome/therapy , Peritoneal Dialysis/methods , Peritoneum/metabolism , Proteins/metabolism , Child , Child, Preschool , Dietary Proteins/metabolism , Female , Glomerulosclerosis, Focal Segmental , Hispanic or Latino , Humans , Kidney Failure, Chronic/metabolism , Kidney Failure, Chronic/therapy , Male , Nephrotic Syndrome/ethnology , Nephrotic Syndrome/metabolism , Permeability , Retrospective Studies
16.
Rev Med Chil ; 139(3): 334-9, 2011 Mar.
Article in Spanish | MEDLINE | ID: mdl-21879165

ABSTRACT

BACKGROUND: Hypovitaminosis D has a high prevalence among patients with chronic kidney disease (CKD). AIM: To determine the prevalence of 25 hydroxy vitamin D (25(OH) D) insufficiency and deficiency in pediatric patients on dialysis and kidney transplantation. MATERIAL AND METHODS: Serum calcium and phosphorus, parathormone (PTH), alkaline phosphatases and 25 (OH)D were measured in 13 children on hemodialysis (HD), 18 on peritoneal dialysis (PD) and 53 that received an allograft (Tx), aged 9.8 ± 4.6 years (51% females). RESULTS: Fifty four percent of patients had height Z score less than -1.88. Patients on HD had the lowest values. The average time of replacement therapy was 2.9 ± 2.8 years. Mean 25(OH)D levels in all was 18.7 ± 10.7ng/ml (HD: 21 ± 16.8, PD: 18.9 ± 8.5, Tx: 18.1 ± 9.72 ng/ml). Eighty eight percent of patients had levels below 30 ng/ml. Mean of serum calcium was 9.5 ± 0.64 mg/dl, serum phosphorus 5.03 ± 1.02 mg/dl, calcium-phosphorus product 48 ± 11.8 mg/dl and alkaline phosphatases 300.5 ± 171.3 IU/L. Average PTH values in dialyzed and Tx patients were 724.6 ± 640.5 and 107.7 ± 56.2 pg/ml, respectively (p < 0.001). A positive correlation between 25 (OH) D and calcium levels among PD patients was observed (r = 0.490, p = 0.04). CONCLUSIONS: Hypovitaminosis D is highly prevalent among children on renal substitution therapy, regardless of the type of therapy used and the stage of renal failure.


Subject(s)
Kidney Failure, Chronic/complications , Renal Replacement Therapy , Vitamin D Deficiency/etiology , Alkaline Phosphatase/blood , Calcium/blood , Child , Cohort Studies , Female , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/therapy , Male , Parathyroid Hormone/blood , Phosphorus/blood , Prevalence , Vitamin D/analogs & derivatives , Vitamin D/blood
17.
Pediatr Nephrol ; 26(12): 2235-44, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21695450

ABSTRACT

This prospective, comparative trial investigated the impact on mean change in height standard deviation score (SDS), acute rejection rate, and renal function of early steroid withdrawal in 96 recipients with 5 years of follow-up. Recipients under basiliximab induction and steroid withdrawal (SW: TAC/MMF; n = 55) were compared with a matched steroid control group (SC: TAC/MMF/STEROID, n = 41). SW received steroids until Day 6, SC decreased to 10 mg/m(2) within 2 months post-transplant. Five years after SW, the longitudinal growth (SDS) gain was 1.4 ± 0.4 vs. 1.1 ± 0.3 for SC group (p < 0.02). Height benefits in prepubertal and pubertal status in both groups were demonstrated in the delta growth trends (mixed model; p < 0.01). Biopsy-proven acute rejection in SW was 11% and 17.5%, SC (p: ns). Mean eGFR (ml/min/1.73 m(2)) at 5 years post-transplant was SW 80.6 ± 27.8 vs. 82.6 ± 25.1 for SC (p: ns). The death-censored graft survival rate at 1 and 5 years was 99 and 90% for SW; 98 and 96% for SC (p = ns). PTLD incidence in SW 3.3 vs. 2.5% in SC (p: ns). Five years post-transplant, early steroid withdrawal showed positive impacts on growth, stable renal function without increased acute rejection risk, and PTLD incidence.


Subject(s)
Adrenal Cortex Hormones/administration & dosage , Body Height , Graft Rejection/epidemiology , Immunosuppressive Agents/administration & dosage , Kidney Transplantation , Adolescent , Antibodies, Monoclonal/administration & dosage , Basiliximab , Body Height/drug effects , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Male , Recombinant Fusion Proteins/administration & dosage
18.
Pediatr Nephrol ; 26(8): 1303-10, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21416403

ABSTRACT

The short half-life of erythropoietin (rHuEPO) leads to repeated fluctuations in hemoglobin levels and the need for frequent administration. Continuous erythropoietin receptor activator (CERA) therapy has been approved for once or twice a month in adult dialysis patients. To evaluate the efficacy and safety of CERA therapy in the management of anemia in pediatric peritoneal dialysis (PD) stable PD children under twice-a-week EPO were converted to a subcutaneous CERA, scheduled every 2 weeks. The follow-up was 6 months. The primary efficacy parameter was hemoglobin > 11 g/dL. The exclusion criteria were ferritin <100 ng/ml and Hb saturation <20%. Sixteen children, aged 9.75 ± 3.6 years, including 11 boys, participated in the study. Mean Hb level at month 0 was 10.8 ± 1.9 g/dL. A decrease in hemoglobin to 10.38 ± 1 g/dL at month 2 was observed. The CERA dose was increased from 0.86 ± 0.33 to 1.67 ± 0.4 µg/kg at month 3. The target Hb level was reached by the 3rd month. The Hb level and CERA dose were 12.2 ± 1.2 and 1.6 ± 0.67 µg/kg respectively at the end of the study. No adverse events were observed during the protocol. CERA is an effective and safe therapy for maintaining hemoglobin levels when administered twice, up to once a month, in PD children. Doses required to reach target Hb were higher than published experiences in adult populations.


Subject(s)
Anemia/drug therapy , Erythropoietin/administration & dosage , Hemoglobins/analysis , Kidney Failure, Chronic/therapy , Peritoneal Dialysis/adverse effects , Polyethylene Glycols/administration & dosage , Anemia/etiology , Child , Dose-Response Relationship, Drug , Female , Humans , Male
19.
Rev. méd. Chile ; 139(3): 334-339, mar. 2011. ilus
Article in Spanish | LILACS | ID: lil-597622

ABSTRACT

Background: Hypovitaminosis D has a high prevalence among patients with chronic kidney disease (CKD). Aim: To determine the prevalence of 25 hydroxy vitamin D (25(OH) D) insufficiency and deficiency in pediatric patients on dialysis and kidney transplantation. Material and Methods: Serum calcium and phosphorus, parathormone (PTH), alkaline phosphatases and 25 (OH)D were measured in 13 children on hemodialysis (HD), 18 on peritoneal dialysis (PD) and 53 that received an allograft (Tx), aged 9.8 ± 4.6 years (51 percent females). Results: Fifty four percent of patients had height Z score less than -1.88. Patients on HD had the lowest values. The average time of replacement therapy was 2.9 ± 2.8 years. Mean 25(OH)D levels in all was 18.7 ± 10.7ng/ml (HD: 21 ± 16.8, PD: 18.9 ± 8.5, Tx: 18.1 ± 9.72 ng/ml). Eighty eight percent of patients had levels below 30 ng/ml. Mean of serum calcium was 9.5 ± 0.64 mg/dl, serum phosphorus 5.03 ± 1.02 mg/dl, calcium-phosphorus product 48 ± 11.8 mg/dl and alkaline phosphatases 300.5 ± 171.3 IU/L. Average PTH values in dialyzed and Tx patients were 724.6 ± 640.5 and 107.7 ± 56.2 pg/ml, respectively (p < 0.001). A positive correlation between 25 (OH) D and calcium levels among PD patients was observed (r = 0.490, p = 0.04). Conclusions: Hypovitaminosis D is highly prevalent among children on renal substitution therapy, regardless of the type of therapy used and the stage of renal failure.


Subject(s)
Child , Female , Humans , Male , Kidney Failure, Chronic/complications , Renal Replacement Therapy , Vitamin D Deficiency/etiology , Alkaline Phosphatase/blood , Calcium/blood , Cohort Studies , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/therapy , Parathyroid Hormone/blood , Phosphorus/blood , Prevalence , Vitamin D/analogs & derivatives , Vitamin D/blood
20.
Pediatr Nephrol ; 25(10): 2159-64, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20574772

ABSTRACT

The peritoneal equilibration test (PET) is the gold standard method for defining peritoneal membrane permeability and for prescribing peritoneal dialysis (PD) therapy on an individual basis. However, it is laborious, consumes nursing time, and requires many hours to be performed. Therefore, several authors have attempted to validate a short PET protocol, with controversial results. To evaluate the concordance between the 2-h (short) and 4-h (classical) peritoneal equilibrium test, a prospective observational protocol was applied in three PD centers (Mexico, Chile, and Uruguay) between July 1, 2008 and July 31 2009. PET protocol: the night prior to the test, each patient received five exchanges, 1 h each, at the same glucose concentration as previously used. Afterwards, a 2.5% glucose dialysis solution was used for a dwell time of 4 h. Exchange fill volume was 1,100 ml/m2 body surface area. The next morning, the 4-h dwell was drained, and Dianeal 2.5% was infused. Three dialysate samples at 0, 2, and 4 h were obtained. A single blood sample was obtained at 120 min. Creatinine D/P and glucose D/D0 ratios were calculated at hours 0, 2, and 4. Patients were categorized as low, low average, high average, or high transporters according creat D/P and gluc D/D0 results. Pearson and Kappa test were used for numerical and categorical correlations, respectively, and p<0.05 was considered significant. Eighty-seven PET studies were evaluated in 74 patients, 33 males, age 11.1+/-5.05 years old. A positive linear correlation of 92% between 2 and 4-h creat D/P and 80% between 2 and 4-h gluc D/D0 (p<0.001) was founded. The Kappa test showed a significant concordance between creat D/P and gluc D/D0 categories at 2 and 4 h (p<0.001). When analyzing cut-off-value categories, creat D/P was founded to be lower and gluc D/D0 higher than other experiences. This multicentric prospective study strongly suggests that PET obtained at 2 h and 4 h, based on either creatinine or glucose transport, provides identical characterization of peritoneal membrane transport capacity in PD children.


Subject(s)
Peritoneal Dialysis/methods , Peritoneal Dialysis/standards , Peritoneum/metabolism , Child , Female , Humans , Male
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