Mineral Metabolism in Children: Interrelation between Vitamin D and FGF23.

Fibroblast growth factor 23 (FGF23) was identified at the turn of the century as the long-sought circulating phosphatonin in human pathology. Since then, several clinical and experimental studies have investigated the metabolism of FGF23 and revealed its relevant pathogenic role in various diseases. Most of these studies have been performed in adult individuals. However, the mineral metabolism of the child is, to a large extent, different from that of the adult because, in addition to bone remodeling, the child undergoes a specific process of endochondral ossification responsible for adequate mineralization of long bones' metaphysis and growth in height. Vitamin D metabolism is known to be deeply involved in these processes. FGF23 might have an influence on bones' growth as well as on the high and age-dependent serum phosphate concentrations found in infancy and childhood. However, the interaction between FGF23 and vitamin D in children is largely unknown. Thus, this review focuses on the following aspects of FGF23 metabolism in the pediatric age: circulating concentrations' reference values, as well as those of other major variables involved in mineral homeostasis, and the relationship with vitamin D metabolism in the neonatal period, in vitamin D deficiency, in chronic kidney disease (CKD) and in hypophosphatemic disorders.

Nutritional Assessment and Support in Children with Chronic Kidney Disease: The Benefits of Working with a Registered Dietitian.

BACKGROUND: An unbalanced dietary pattern, characterized by high animal protein content: may worsen metabolic control, accelerate renal deterioration and consequently aggravate the stage of the chronic kidney disease (CKD) in pediatric patients with this condition. AIM: to assess the effect of a registered dietitian (RD) intervention on the CKD children's eating habits. METHODS: Anthropometric and dietetic parameters, obtained at baseline and 12 months after implementing healthy eating and nutrition education sessions, were compared in 16 patients (50% girls) of 8.1 (1-15) years. On each occasion, anthropometry, 3-day food records and a food consumption frequency questionnaire were carried out. The corresponding relative intake of macro- and micronutrients was contrasted with the current advice by the European Food Safety Authority (EFSA) and with consumption data obtained using the Spanish dietary guidelines. Student's paired t-test, Wilcoxon test and Mc Nemar test were used. RESULTS: At Baseline 6% were overweight, 69% were of normal weight and 25% were underweight. Their diets were imbalanced in macronutrient composition. Following nutritional education and dietary intervention 63%, 75% and 56% met the Dietary Reference Values requirements for fats, carbohydrates and fiber, respectively, but not significantly. CKD children decreased protein intake (p < 0.001), increased dietary fiber intake at the expense of plant-based foods consumption (p < 0.001) and a corresponding reduction in meat, dairy and processed food intake was noticed. There were no changes in the medical treatment followed or in the progression of the stages. CONCLUSIONS: RD-led nutrition intervention focused on good dieting is a compelling helpful therapeutic tool to improve diet quality in pediatric CKD patients.

Fenotipos inesperados en el síndrome de Alport: la necesidad del estudio genético / Unexpected phenotypes in Alport syndrome: the need for genetic testing

El diagnóstico del síndrome de Alport supone un reto en la edadpediátrica, debido a la ausencia de fenotipos clínicos esperados de la enfermedad, su clásica caracterización de entidad rara y la práctica muy restringida de biopsias renales con análisis rutinario de la muestra por microscopía electrónica durante la infancia. Se presentan las características clínicas y genéticas de 6 pacientes pediátricos (4 mujeres) diagnosticados de síndromede Alport en dos centros hospitalarios entre 2018 y 2021. Todos los pacientes presentaron un debut clínico claramente diferente y ninguno presentó complicaciones auditivas nioftalmológicas. La mitad carecía de antecedentes familiares de enfermedad renal crónica. Ninguna biopsia renal realizada confirmó el diagnóstico. Todos los pacientes fueron confirmadosgenéticamente y fueron el caso índice del estudio familiar. Esta serie ilustra la presencia de fenotipos clínicos inesperados en el síndrome de Alport y refleja la necesidad de incorporar el estudio genético para su diagnóstico.

The diagnosis of Alport syndrome is a challenge in the pediatric age, due to the absence of expected clinical phenotypes of the disease, its classic characterization of a rare disease and the very restricted practice of renal biopsies with routine analysis of the sample by electron microscopy during infancy. The clinical and genetic characteristics of 6 pediatric patients (4 women) diagnosed with Alport syndrome in two hospital centers between 2018 and 2021 are reported. All patients presented a clearly different clinical debut and none presented auditory or ophthalmological complications. Half had no family history of chronic kidney disease. No kidney biopsy performed confirmed the diagnosis. All patients were genetically confirmed and were the index case in the family study. This series illustrates the presence of unexpected clinical phenotypes in Alport syndrome and reflects the need for the incorporation of the genetic study for its diagnosis.

[Unexpected phenotypes in Alport syndrome: the need for genetic testing]. / Fenotipos inesperados en el síndrome de Alport: la necesidad del estudio genético.

The diagnosis of Alport syndrome is a challenge in the pediatric age, due to the absence of expected clinical phenotypes of the disease, its classic characterization of a rare disease and the very restricted practice of renal biopsies with routine analysis of the sample by electron microscopy during infancy. The clinical and genetic characteristics of 6 pediatric patients (4 women) diagnosed with Alport syndrome in two hospital centers between 2018 and 2021 are reported. All patients presented a clearly different clinical debut and none presented auditory or ophthalmological complications. Half had no family history of chronic kidney disease. No kidney biopsy performed confirmed the diagnosis. All patients were genetically confirmed and were the index case in the family study. This series illustrates the presence of unexpected clinical phenotypes in Alport syndrome and reflects the need for the incorporation of the genetic study for its diagnosis.

El diagnóstico del síndrome de Alport supone un reto en la edad pediátrica, debido a la ausencia de fenotipos clínicos esperados de la enfermedad, su clásica caracterización de entidad rara y la práctica muy restringida de biopsias renales con análisis rutinario de la muestra por microscopía electrónica durante la infancia. Se presentan las características clínicas y genéticas de 6 pacientes pediátricos (4 mujeres) diagnosticados de síndrome de Alport en dos centros hospitalarios entre 2018 y 2021. Todos los pacientes presentaron un debut clínico claramente diferente y ninguno presentó complicaciones auditivas ni oftalmológicas. La mitad carecía de antecedentes familiares de enfermedad renal crónica. Ninguna biopsia renal realizada confirmó el diagnóstico. Todos los pacientes fueron confirmados genéticamente y fueron el caso índice del estudio familiar. Esta serie ilustra la presencia de fenotipos clínicos inesperados en el síndrome de Alport y refleja la necesidad de incorporar el estudio genético para su diagnóstico.

Rituximab treatment in pediatric patients with steroid-dependent nephrotic syndrome: A tertiary hospital.

BACKGROUND: Corticosteroids have had a central role in the treatment of nephrotic syndrome. The management of these patients who become dependent to steroids is complex, involving different immunosuppressive drugs patterns. The monoclonal antibody anti CD20, Rituximab, is likely to have beneficial effects in cases of steroid-dependent nephrotic syndrome patients with no easy resolution, even when we cannot make a statement about the specific role in the impact. We bring our personal experience in pediatric patients treated with this medication during the last years, to provide a thorough overview and useful information about the role of Rituximab in this pathology. METHODS: Retrospective study in patients with steroid-dependent idiopathic nephrotic syndrome controlled in the division of Pediatric Nephrology of a Spanish tertiary hospital in those patients who had received at least one treatment cycle of Rituximab, at any moment along the evolution of the disease. RESULTS: The study involved 8 patients. All of them previously received immunosuppressive therapy. The Rituximab were administered as an intravenous infusion, in a dose of 375 mg/m2, and all doses were administered in a period during which the disease was in remission. The depletion of lymphocytes B (CD19, 0%) were confirmed after the first dose of Rituximab except for one, with a lymphocyte count of 1%. The period of depletion lasts 10,3 months (median; range 6,5-16 months), and only one of the patients registered a relapse of the disease in this period. A reduction of relapses suffered by patients has been shown after the treatment began (3,6 relapses/year in the previous year to the start of the treatment versus 0,1 relapses/year during the first year post-rituximab). The relapse-free survival in the first year reached 83,3% in patients who suffered more than one relapse (75% of patients), and without a relapse after the treatment began in 2 cases. One or more drugs could be removed in 87,5% of patients after the first cycle of rituximab. After the rituximab treatment, we reached a 96,5% decrease in the corticosteroids doses administered (28,5 mg/m2/day during the 3 months pre-treatment versus 1 mg/m2/day in the last 3 months of patient monitoring). Not a significant observed adverse effect attributed to the drug after the post-rituximab monitoring period (median 46,5 months, range 5-97 months). CONCLUSION: The favorable results reported after rituximab treatment in our patients seems to confirm the effectiveness of this drug in the steroid-dependent nephrotic syndrome, making that therapeutic option into consideration and legitimating the use of the drug in complex cases involving pediatric patients. Even so, it seems recommendable to design pertinent studies to clarify, among others, the optimum regimen of the treatment (dose, interval and cycles), clinical repercussion and potential adverse effects in long terms.

Tratamiento con rituximab en pacientes pediátricos con síndrome nefrótico córtico-dependiente. Experiencia en un hospital terciario / Rituximab treatment in pediatric patients with steroid-dependent nephrotic syndrome: a tertiary hospital

Introducción: La corticoterapia continúa siendo la piedra angular en el tratamiento del síndrome nefrótico. El manejo de los pacientes que desarrollan dependencia a esteroides es complejo, implicando distintas pautas de fármacos inmunosupresores. El rituximab, anticuerpo monoclonal anti-CD20, parece tener efectos beneficiosos en pacientes con síndrome nefrótico córtico-dependiente de difícil manejo clínico, si bien aún no está bien definido su papel en esta entidad. Con el fin de aportar información útil sobre el papel del rituximab en esta patología, presentamos nuestra experiencia personal en pacientes pediátricos tratados con este fármaco en los últimos años. Materiales y métodos: Estudio retrospectivo en pacientes con síndrome nefrótico idiopático córtico-dependiente controlados en la Sección de Nefrología Pediátrica de un hospital terciario español, y que habían recibido, al menos, un ciclo de tratamiento con rituximab durante cualquier momento de la evolución de la enfermedad. (AU)

Background: Corticosteroids have had a central role in the treatment of nephrotic syndrome. The management of these patients who become dependent to steroids is complex, involving different immunosuppressive drugs patterns. The monoclonal antibody anti CD20, Rituximab, is likely to have beneficial effects in cases of steroid-dependent nephrotic syndrome patients with no easy resolution, even when we cannot make a statement about the specific role in the impact. We bring our personal experience in pediatric patients treated with this medication during the last years, to provide a thorough overview and useful information about the role of Rituximab in this pathology. Methods: Retrospective study in patients with steroid-dependent idiopathic nephrotic syndrome controlled in the division of Pediatric Nephrology of a spanish tertiary hospital in those patients who had received at least one treatment cycle of Rituximab, at any moment along the evolution of the disease. (AU)

Evolución de tubulopatías renales primarias diagnosticadas en edad pediátrica / Outcome of primary tubular tubulopathies diagnosed in pediatric age

ANTECEDENTES Y OBJETIVO: Las tubulopatías primarias son raras y se presentan habitualmente en la edad pediátrica. Avances recientes en diagnóstico genético y tratamiento han cambiado su historia natural. Este estudio presenta el espectro clínico de una serie de tubulopatías primarias diagnosticadas en una Unidad de Nefrología Pediátrica y ofrece datos de seguimiento a largo plazo sobre crecimiento, filtrado glomerular estimado y complicaciones intercurrentes. PACIENTES Y MÉTODOS: Estudio observacional en 53 pacientes con tubulopatías primarias y defecto genético identificado: síndrome de Gitelman (36%), acidosis tubular renal distal (15%), cistinuria (11%), raquitismo hipofosfatémico ligado al X (7%), síndrome de Dent-Lowe (7%), cistinosis (6%), y uno o 2 casos de otras tubulopatías. Se recogieron datos demográficos, analíticos y clínicos al diagnóstico, durante la evolución y en el momento del estudio. RESULTADOS: La edad (mediana y rango intercuartílico) al diagnóstico fue de 5,08 años (1,33-8,50). Las manifestaciones de presentación más frecuentes fueron descompensaciones metabólicas asociadas a procesos intercurrentes (40%) y talla baja (38%). La talla (media ± DE) fue de -1,39 ± 1,49 al diagnóstico y 1,07 ± 1,54 tras un seguimiento de 18,92 (6,25-24,33) años. Dieciséis (32%) desarrollaron filtrado glomerular estimado < 90 mL/min/1,73 m2. Tres pacientes requirieron reemplazo renal sustitutivo. Once enfermos tuvieron descompensaciones metabólicas que requirieron hospitalización, 9 cólicos nefríticos y/o cálculos renales y 10 problemas mentales. Seis de 8 pacientes con acidosis tubular renal desarrollaron sordera neurosensorial. CONCLUSIONES: Las tubulopatías primarias son un grupo heterogéneo de enfermedades que ocasionan afectación del crecimiento, reversible en gran medida con tratamiento, riesgo de reducción de filtrado glomerular estimado e importantes complicaciones extrarrenales derivadas o asociadas

BACKGROUND AND OBJECTIVE: Primary tubulopathies are rare and usually present at pediatric age. Recent advances in genetic diagnosis and treatment have changed its natural history. This study provides the clinical spectrum of a series of primary tubulopathies diagnosed in a Pediatric Nephrology Unit and to offer long-term follow-up data regarding growth, estimated glomerular filtration and intercurrent complications. PATIENTS AND METHODS: Observational study in 53 patients with primary tubulopathies and identified genetic defect: Gitelman syndrome (36%), distal renal tubular acidosis (15%), cystinuria (11%), X-linked hypophosphatemic rickets (7%), Dent-syndrome Lowe (7%), cystinosis (6%), and 1-2 cases of other tubulopathies. Demographic, analytical and clinical data were collected at diagnosis, during evolution and at the time of the study. RESULTS: The age (median and interquartile range) at diagnosis was 5.08 years (1.33-8.50). The most frequent presentation manifestations were metabolic decompensations associated with intercurrent processes (40%) and short stature (38%). Height (mean±SD) was - 1.39 ± 1.49 at diagnosis and 1.07 ± 1.54 after a follow-up of 18.92 (6.25-24.33) years. Sixteen (32%) developed an estimated glomerular filtration < 90 ml / min / 1.73 m2. Three patients required replacement renal replacement. Eleven patients had metabolic decompensations that required hospitalization, 9 renal colic and / or kidney stones and 10 mental problems. Six of 8 patients with distal renal tubular acidosis developed sensorineural deafness. CONCLUSIONS: Primary tubulopathies are a heterogeneous group of diseases that cause growth impairment, largely reversible with treatment, risk of estimated glomerular filtration reduction and significant extrarenal complications derived or associated

[Rituximab treatment in pediatric patients with steroid-dependent nephrotic syndrome: a tertiary hospital]. / Tratamiento con rituximab en pacientes pediátricos con síndrome nefrótico córtico-dependiente. Experiencia en un hospital terciario.

BACKGROUND: Corticosteroids have had a central role in the treatment of nephrotic syndrome. The management of these patients who become dependent to steroids is complex, involving different immunosuppressive drugs patterns. The monoclonal antibody anti CD20, Rituximab, is likely to have beneficial effects in cases of steroid-dependent nephrotic syndrome patients with no easy resolution, even when we cannot make a statement about the specific role in the impact. We bring our personal experience in pediatric patients treated with this medication during the last years, to provide a thorough overview and useful information about the role of Rituximab in this pathology. METHODS: Retrospective study in patients with steroid-dependent idiopathic nephrotic syndrome controlled in the division of Pediatric Nephrology of a spanish tertiary hospital in those patients who had received at least one treatment cycle of Rituximab, at any moment along the evolution of the disease. RESULTS: The study involved 8 patients. All of them previously received immunosuppressive therapy. The Rituximab were administered as an intravenous infusion, in a dose of 375 mg/m2, and all doses were administered in a period during which the disease was in remission. The depletion of lymphocytes B (CD 19%) were confirmed after the first dose of Rituximab except for one, with a lymphocyte count of 1%. The period of depletion lasts 10.3 months (median; range 6.5-16 months), and only one of the patients registered a relapse of the disease in this period. A reduction of relapses suffered by patients has been shown after the treatment began (3.6 relapses/year in the previous year to the start of the treatment vs. 0.1 relapses/year during the first year post-rituximab). The relapse-free survival in the first year reached 83.3% in patients who suffered more than one relapse (75% of patients), and without a relapse after the treatment began in 2 cases. One or more drugs could be removed in 87.5% of patients after the first cycle of rituximab. After the rituximab treatment, we reached a 96.5% decrease in the corticosteroids doses administered (28.5 mg/m2/day during the 3 months pre-treatment vs. 1 mg/m2/day in the last 3 months of patient monitoring). Not a significant observed adverse effect attributed to the drug after the post-rituximab monitoring period (median 46.5 months, range 5-97 months). CONCLUSION: The favorable results reported after rituximab treatment in our patients seems to confirm the effectiveness of this drug in the steroid-dependent nephrotic syndrome, making that therapeutic option into consideration and legitimating the use of the drug in complex cases involving pediatric patients. Even so, it seems recommendable to design pertinent studies to clarify, among others, the optimum regimen of the treatment (dose, interval and cycles), clinical repercussion and potential adverse effects in long terms.

Hipertensión arterial en el lactante. Un reto diagnóstico en pediatría / Infantile arterial hypertension: A diagnostic challenge in paediatrics

La prevalencia de la hipertensión arterial ha aumentado considerablemente en la edad pediátrica como consecuencia principal de su detección en niños mayores y adolescentes, en quienes predomina la causa esencial (primaria). En otras etapas de la edad pediátrica la HTA es menos frecuente, en especial en lactantes. En este grupo la hipertensión arterial obedece casi siempre a causas secundarias, en ocasiones potencialmente graves, por lo que resulta imprescindible detectarla, llevar a cabo un proceso diagnóstico etiológico adecuado y proporcionar al paciente un adecuado tratamiento, que suele requerir de un profesional especializado. A las dificultades técnicas propias de la medición de la presión arterial en los lactantes se añade la ausencia de recomendaciones específicas relacionadas con su identificación sistemática y de valores de normalidad bien establecidos en este rango de edad, por lo que su manejo constituye un reto diagnóstico y terapéutico para el profesional. A través de la exposición de 3 casos de hipertensión detectada en la etapa de lactante, se pretende sensibilizar al pediatra sobre esta enfermedad, así como proporcionar información sobre su orientación diagnóstica y terapéutica, incidiendo asimismo en las medidas farmacológicas

Arterial Hypertension prevalence (HTN) has significantly increased in paediatric patients, mainly in older children and teenagers. In these subjects the most common type is essential or primary HTN. However, in infants HTN prevalence is significantly lower and is almost always due to secondary causes, which can be potentially severe. Hence the importance of its detection, in order to establish an etiological diagnosis and provide an appropriate treatment, which usually requires a specialist physician. In addition to the technical difficulties of blood pressure measurement in infants, the lack of recommendations to perform a systematic screening in this age range and the absence of well-established normal values turns infancy-onset HTN into a diagnostic and therapeutic challenge for the physician. By means of the exposition of three infancy-onset HTN cases, the aim is to increase the paediatrician's awareness of this pathology and also to provide information about its diagnostic and therapeutic approach, dealing also with pharmacological measures of treatment

Acidosis tubular renal distal (ATRd): aspectos epidemiológicos, diagnósticos, de seguimiento clínico y terapéuticos. Resultados de una encuesta a un colectivo de nefrólogos / Distar Renal Tubular Acidosis (dRTA): Epidemiological, diagnostics, clinical follow-up and therapeutical issues. Nephrologists cohort survey outcome

ANTECEDENTES Y OBJETIVOS: La acidosis tubular renal distal (ATRd) es una enfermedad minoritaria, de origen genético o adquirido, caracterizada por una incapacidad de excreción urinaria de hidrogeniones (H+), hipobicarbonatemia, hipercloremia, hipocitraturia y habitualmente hipokaliemia e hipercalciuria. Las formas genéticas suelen diagnosticarse en los primeros meses de vida y su tratamiento consiste en suplementos de álcali encaminados a evitar las consecuencias clínicas a largo plazo, sobre todo la enfermedad renal crónica (presente en algunas series hasta en el 82% de los pacientes) y la enfermedad ósea asociada. Se desarrolló una encuesta multirrespuesta cerrada de 10 preguntas encaminada a conocer aspectos epidemiológicos, diagnósticos, del manejo clínico y terapéutico, dentro del colectivo de nefrólogos españoles. MATERIALES Y MÉTODOS: Encuesta distribuida a los asistentes a un foro científico sobre ATRd durante el congreso de 2019 de la Sociedad Española de Nefrología (SEN); las respuestas se recogieron a la salida del mismo. Los resultados se analizaron con un test estadístico paramétrico estableciéndose el porcentaje de cada respuesta a las 10 preguntas. RESULTADOS: De entre los que respondieron a la encuesta, el 44,4 y el 37,7% no atendieron a ningún paciente con ATRd en el último año ni en los tres anteriores, respectivamente. Cuando se sospecha la patología, el diagnóstico genético confirmatorio se realiza solo en el 13,3% de los casos y el estudio familiar solo en el 11,1%. Solo el 26,6% afirman que el control metabólico es excelente, bueno o muy bueno, y el 69% piensan que el cumplimiento terapéutico es regular, malo o muy malo. CONCLUSIONES: La encuesta ha puesto de manifiesto el relativo desconocimiento de esta patología, así como la baja satisfacción con el control metabólico y el pobre cumplimiento terapéutico, lo cual puede conllevar una mayor severidad en la enfermedad renal y ósea asociadas a la ATRd

BACKGROUND AND OBJECTIVES: dRTA is a genetic or acquired rare disease, characterized by an unability to excrete hydrogens (H+) into urine, hypobicarbonatemia, hyperchloremia, and frequently hypercalciuria and hypokalaemia. Genetic forms are usually diagnosed during the first months of life and its treatment is based on providing alkali supplements in order to prevent long term clinical consequences, particularly chronic kidney disease (described in some cohorts up to 82% of dRTA patients) and the associated bone disease. A 10 queries multi choice closed response survey was designed to know more about epidemiological, diagnostics, clinical management and therapeutical issues of this disease among Spanish nephrologists. MATERIALS AND METHODS: This survey was delivered to the attendees to a scientific meeting on dRTA at the Spanish Nephrology Society congress in 2019. Surveys were collected at the end of this dRTA event. Results were analyzed by using a parametric statistical test, obtaining the percentage of each response for the 10 questions. RESULTS: Among the survey responders, 44.4% and 37.7% did not visit any dRTA patient during the 1st and 3rd last year respectively. When having a suspicious diagnose, confirming genetic diagnostic test is only performed on the 13.3% of cases and pedigree studies only on 11.1%. Only a 26.6% confirms that metabolic control is excellent, good or very good, and 69% of the responders believe that treatment compliance is not bad, bad or very bad. CONCLUSIONS: This survey enhances the fact that dRTA is not a well known entity, satisfaction with metabolic control is poor and compliance is low. All these factors can lead to a higher severity of renal and bone diseases associated to dRTA

Distar Renal Tubular Acidosis (dRTA): Epidemiological, diagnostics, clinical follow-up and therapeutical issues. Nephrologists cohort survey outcome. / Acidosis tubular renal distal (ATRd): aspectos epidemiológicos, diagnósticos, de seguimiento clínico y terapéuticos. Resultados de una encuesta a un colectivo de nefrólogos.

BACKGROUND AND OBJECTIVES: dRTA is a genetic or acquired rare disease, characterized by an unability to excrete hydrogens (H+) into urine, hypobicarbonatemia, hyperchloremia, and frequently hypercalciuria and hypokalaemia. Genetic forms are usually diagnosed during the first months of life and its treatment is based on providing alkali supplements in order to prevent long term clinical consequences, particularly chronic kidney disease (described in some cohorts up to 82% of dRTA patients) and the associated bone disease. A 10 queries multi choice closed response survey was designed to know more about epidemiological, diagnostics, clinical management and therapeutical issues of this disease among Spanish nephrologists. MATERIALS AND METHODS: This survey was delivered to the attendees to a scientific meeting on dRTA at the Spanish Nephrology Society congress in 2019. Surveys were collected at the end of this dRTA event. Results were analyzed by using a parametric statistical test, obtaining the percentage of each response for the 10 questions. RESULTS: Among the survey responders, 44.4% and 37.7% did not visit any dRTA patient during the 1st and 3rd last year respectively. When having a suspicious diagnose, confirming genetic diagnostic test is only performed on the 13.3% of cases and pedigree studies only on 11.1%. Only a 26.6% confirms that metabolic control is excellent, good or very good, and 69% of the responders believe that treatment compliance is not bad, bad or very bad. CONCLUSIONS: This survey enhances the fact that dRTA is not a well known entity, satisfaction with metabolic control is poor and compliance is low. All these factors can lead to a higher severity of renal and bone diseases associated to dRTA.

[Infantile arterial hypertension: A diagnostic challenge in paediatrics]. / Hipertensión arterial en el lactante. Un reto diagnóstico en pediatría.

Arterial Hypertension prevalence (HTN) has significantly increased in paediatric patients, mainly in older children and teenagers. In these subjects the most common type is essential or primary HTN. However, in infants HTN prevalence is significantly lower and is almost always due to secondary causes, which can be potentially severe. Hence the importance of its detection, in order to establish an etiological diagnosis and provide an appropriate treatment, which usually requires a specialist physician. In addition to the technical difficulties of blood pressure measurement in infants, the lack of recommendations to perform a systematic screening in this age range and the absence of well-established normal values turns infancy-onset HTN into a diagnostic and therapeutic challenge for the physician. By means of the exposition of three infancy-onset HTN cases, the aim is to increase the paediatrician's awareness of this pathology and also to provide information about its diagnostic and therapeutic approach, dealing also with pharmacological measures of treatment.

Outcome of primary tubular tubulopathies diagnosed in pediatric age. / Evolución de tubulopatías renales primarias diagnosticadas en edad pediátrica.

BACKGROUND AND OBJECTIVE: Primary tubulopathies are rare and usually present at pediatric age. Recent advances in genetic diagnosis and treatment have changed its natural history. This study provides the clinical spectrum of a series of primary tubulopathies diagnosed in a Pediatric Nephrology Unit and to offer long-term follow-up data regarding growth, estimated glomerular filtration and intercurrent complications. PATIENTS AND METHODS: Observational study in 53 patients with primary tubulopathies and identified genetic defect: Gitelman syndrome (36%), distal renal tubular acidosis (15%), cystinuria (11%), X-linked hypophosphatemic rickets (7%), Dent-syndrome Lowe (7%), cystinosis (6%), and 1-2 cases of other tubulopathies. Demographic, analytical and clinical data were collected at diagnosis, during evolution and at the time of the study. RESULTS: The age (median and interquartile range) at diagnosis was 5.08 years (1.33-8.50). The most frequent presentation manifestations were metabolic decompensations associated with intercurrent processes (40%) and short stature (38%). Height (mean±SD) was -1.39±1.49 at diagnosis and 1.07±1.54 after a follow-up of 18.92 (6.25-24.33) years. Sixteen (32%) developed an estimated glomerular filtration<90ml / min / 1.73m2. Three patients required replacement renal replacement. Eleven patients had metabolic decompensations that required hospitalization, 9 renal colic and / or kidney stones and 10 mental problems. Six of 8 patients with distal renal tubular acidosis developed sensorineural deafness. CONCLUSIONS: Primary tubulopathies are a heterogeneous group of diseases that cause growth impairment, largely reversible with treatment, risk of estimated glomerular filtration reduction and significant extrarenal complications derived or associated.

X-Linked Hypophosphataemic Rickets and Growth.

X-linked hypophosphataemia (XLH) is the most prevalent form of hereditary rickets characterized by an alteration of phosphate metabolism which frequently leads to the appearance of fractures, bone deformities and growth delay. Although the mechanism of growth impairment in patients with XLH still needs to be clarified, it is known that this alteration is not due to genetic or endocrine factors. A potential explanation for the impairment of growth in this disease is the alteration of the growth plate, a structure responsible for longitudinal growth of bones. Some of the findings in the growth plate of patients with XLH include atypical organization of chondrocytes due to low rates of proliferation and apoptosis and disturbance of chondrocyte hypertrophy, overactivation of the mitogen-activated protein kinase (MAPK) signalling pathway and upregulation of phosphorylated extracellular signal-regulated kinase (pERK). Conventional treatment of XLH (consisting of oral phosphate supplements and active vitamin D analogues) is often insufficient for the longitudinal growth of bone, but other strategies based on recombinant growth hormone or therapies targeting fibroblast growth factor 23 (FGF23) or its receptor, such as burosumab, have shown promising results. This article briefly describes the relationship between XLH and growth retardation, and how to address this alteration in patients with XLH.

Patrón de aislamiento bacteriano y sensibilidad antimicrobiana en urocultivos positivos obtenidos de una población pediátrica / Uropathogen pattern and antimicrobial susceptibility in positive urinary cultures isolates from paediatric patients

Introducción. El conocimiento de los uropatógenos y sus perfiles de sensibilidad antibiótica deben ser la base del tratamiento empírico racional en las infecciones urinarias. Material y métodos. Se analizaron retrospectivamente el patrón bacteriano y la sensibilidad antimicrobiana en los urocultivos positivos pediátricos identificados en un período de 5 años (2009-2013) de un Hospital de tercer nivel, y se compararon los resultados con un estudio previo realizado en el mismo Hospital entre 1995 y 1999. Resultados. Se aislaron un total de 2,762 cultivos de orina positivos en el período de estudio referido. Escherichia coli fue el microorganismo más frecuentemente aislado (58,9%), seguido de Enterococcus sp. (11,6%) y Proteus mirabilis (10,9%). Más del 95% de las cepas de E. coli no productoras de BLEE fueron sensibles a fosfomicina, nitrofurantoína, cefotaxima y aminoglucósidos. Por contra, el 56, 49 y 22% de los aislados de E. coli fueron resistentes a ampicilina, cefalosporinas orales de primera generación y cotrimoxazol, respectivamente. Ampicilina y amoxicilina/clavulánico fueron los antibióticos más eficaces para tratar Enterococcus sp. y P. mirabilis, respectivamente. La distribución porcentual de gérmenes y la sensibilidad antimicrobiana obtenidas en el estudio no presentaron cambios sustanciales respecto a las publicadas en el mismo hospital en la década de los noventa. Conclusiones. E. coli fue el germen mayoritariamente aislado, con un alto porcentaje de resistencias a ampicilina, cefalosporinas orales de primera generación y cotrimoxazol. Este patrón urinario de aislamientos y sensibilidad antimicrobiana fue similar al reportado en otros estudios pediátricos y tampoco se modificó respecto a una serie comparable de la década de los noventa, por lo que puede considerarse que las recomendaciones actuales del tratamiento antibiótico empírico en las infecciones urinarias se mantienen vigentes (AU)

Introduction. Knowledge of urophatogens and antibiotic susceptibility should be used to assist with empirical urinary tract infection treatment. Material and methods. We retrospectively analysed local bacterial pattern and antimicrobial susceptibility in positive urinary isolates from paediatric patients collected in the period 2009-2013. Results were compared with a previous study carried out in the same sanitary area between 1995 and 1999. Results. We identified 2,762 urinary isolates. Escherichia coli was the most common uropathogen (58.9%), followed by Enterococcus sp. (11.6%) and Proteus mirabilis (10.9%). More than 95% of non extended-spectrum beta-lactamase (ESBL)-producing E. coli were susceptible to nitrofurantoin, fosfomycin, cefotaxime and aminoglycosides. However, 56%, 49%, and 22% of the E. coli isolates were resistant to ampicillin, oral first-generation cephalosporins, and trimethoprim-sulfamethoxazole, respectively. Ampicillin and amoxicillin-clavulanate were the most effective antibiotics to treat Enterococcus sp. and P. mirabilis, respectively. Not significant modifications were found compared to results published at the same area in the ‘90s. Conclusions. E. coli was the mostly isolated uropathogen, with a high percentage of resistance to ampicillin, oral first-generation cephalosporins, and trimethoprim-sulfameth-oxazole. These urinary isolates and antimicrobial susceptibility patterns were similar to those reported in other paediatric studies and did not show significant changes compared to local previously published results. Thus, it can be considered that the current recommendations about empiric antibiotic therapy in paediatric urinary tract infections remain applicable nowadays (AU)