Transition of patients with metabolic bone disease from paediatric to adult healthcare services: current situation and proposals for improvement.

BACKGROUND: There are currently no models for the transition of patients with metabolic bone diseases (MBDs) from paediatric to adult care. The aim of this project was to analyse information on the experience of physicians in the transition of these patients in Spain, and to draw up consensus recommendations with the specialists involved in their treatment and follow-up. METHODS: The project was carried out by a group of experts in MBDs and included a systematic review of the literature for the identification of critical points in the transition process. This was used to develop a questionnaire with a total of 48 questions that would determine the degree of consensus on: (a) the rationale for a transition programme and the optimal time for the patient to start the transition process; (b) transition models and plans; (c) the information that should be specified in the transition plan; and (d) the documentation to be created and the training required. Recommendations and a practical algorithm were developed using the findings. The project was endorsed by eight scientific societies. RESULTS: A total of 86 physicians from 53 Spanish hospitals participated. Consensus was reached on 45 of the 48 statements. There was no agreement that the age of 12 years was an appropriate and feasible point at which to initiate the transition in patients with MBD, nor that a gradual transition model could reasonably be implemented in their own hospital. According to the participants, the main barriers for successful transition in Spain today are lack of resources and lack of coordination between paediatric and adult units. CONCLUSIONS: The TEAM Project gives an overview of the transition of paediatric MBD patients to adult care in Spain and provides practical recommendations for its implementation.

Treatment and long-term outcome in primary nephrogenic diabetes insipidus.

BACKGROUND: Primary nephrogenic diabetes insipidus (NDI) is a rare disorder and little is known about treatment practices and long-term outcome. METHODS: Paediatric and adult nephrologists contacted through European professional organizations entered data in an online form. RESULTS: Data were collected on 315 patients (22 countries, male 84%, adults 35%). Mutation testing had been performed in 270 (86%); pathogenic variants were identified in 258 (96%). The median (range) age at diagnosis was 0.6 (0.0-60) years and at last follow-up 14.0 (0.1-70) years. In adults, height was normal with a mean (standard deviation) score of -0.39 (±1.0), yet there was increased prevalence of obesity (body mass index >30 kg/m2; 41% versus 16% European average; P < 0.001). There was also increased prevalence of chronic kidney disease (CKD) Stage ≥2 in children (32%) and adults (48%). Evidence of flow uropathy was present in 38%. A higher proportion of children than adults (85% versus 54%; P < 0.001) received medications to reduce urine output. Patients ≥25 years were less likely to have a university degree than the European average (21% versus 35%; P = 0.003) but full-time employment was similar. Mental health problems, predominantly attention-deficit hyperactivity disorder (16%), were reported in 36% of patients. CONCLUSION: This large NDI cohort shows an overall favourable outcome with normal adult height and only mild to moderate CKD in most. Yet, while full-time employment was similar to the European average, educational achievement was lower, and more than half had urological and/or mental health problems.

Complications of Phosphate and Vitamin D Treatment in X-Linked Hypophosphataemia.

Conventional treatment of X-linked hypophosphataemia (XLH) consists in the oral administration of phosphate plus calcitriol supplements. Although this therapy has reduced bone deformities and even achieved adequate patient growth, overtreatment or low adherence could lead to subsequent consequences that may compromise the efficacy of the therapy. Some of the complications associated with phosphate and vitamin D treatment are abdominal discomfort, diarrhoea, hypokalaemia, hyperparathyroidism, hypercalcaemia or hypercalciuria, nephrocalcinosis or nephrolithiasis, and ectopic calcifications. Therefore, constant multidisciplinary monitoring of patients with XLH is necessary to prevent the manifestation of these complications and to deal with them as soon as they appear. The main objective of this article is to review the main complications arising from conventional treatment of XLH and how to deal with them.

Estudio longitudinal del manejo renal del agua en pacientes diagnosticados de hipercalciuria idiopática en la infancia / Longitudinal study of kidney water management in patients diagnosed with idiopathic hypercalciuria in childhood

Existe controversia si la hipercalciuria idiopática (HI) produce alteraciones en el manejo renal del agua. Por primera vez en la literatura, llevamos a cabo un estudio longitudinal del manejo renal del agua (MRA) en pacientes diagnosticados de HI en edad pediátrica y con seguimiento hasta la edad adulta (media de seguimiento de 17,7 ± 1,4 años). MÉTODOS: Veintinueve pacientes (7 M, 22 F) mayores de 24 años (media 28,2 ± 2,9 años, rango: 24,1-35,9) que fueron diagnosticados de HI en la edad pediátrica (media 7,6 ± 3,2 años, rango: 1-14) fueron incluidos. Se determinaron la osmolaridad urinaria máxima (OsU) y/o el volumen urinario ajustado para 100 ml de tasa de filtrado glomerular (V/TFG) en ambos tiempos (pediátrico y adulto). Además, siempre que fue posible, en ambas edades se recogieron los niveles plasmáticos de creatinina, sodio plasmático, ácido úrico, cociente citrato/creatinina y calcio/citrato y, además, se realizó una ecografía renovesical. RESULTADOS: El MRA estuvo alterado en edad pediátrica en 9/29 casos (31%) (4 con OsU máxima reducida y 5 con V/TFG elevado). En la edad adulta, 7/29 (24,1%) presentaron alteración del MRA (6 OsU reducidos y uno con V/TFG elevado). En comparación con el grupo de edad pediátrica, los pacientes adultos mostraron valores reducidos de V/TFG, cociente calcio/creatinina y citrato/creatinina, así como aumento de creatinina plasmática, ácido úrico y del cociente calcio/citrato. No hubo diferencias en la OsU máxima en ambos tiempos. Sin embargo, la OsU en la edad adulta fue significativamente menor en aquellos que tenían cólicos renales comparado con aquellos que no los tuvieron (p = 0,04). CONCLUSIONES: La alteración del MRA ocurrió en aproximadamente un tercio de los pacientes con HI, y no se alteró tras 20 años después de su diagnóstico. Nosotros pensamos que estos resultados pueden ser debido a un cierto cumplimiento de la dieta protectora recomendada y al tratamiento farmacológico administrado en el diagnóstico de HI en la edad pediátrica

INTRODUCTION: There is much debate about whether idiopathic hypercalciuria (IH) affects kidney water management. For the first time in the literature, we carried out a longitudinal study of kidney water management (KWM) in patients diagnosed with IH in childhood and followed-up until adulthood (mean follow-up 17.7 ± 1.4 years). Methods; Twenty-nine patients (7 M, 22 F) over the age of 24 years (mean 28.2 ± 2.9 years, range: 24.1-35.9) who were diagnosed with IH in childhood (mean 7.6 ± 3.2 years, range: 1-14) were included. Maximum urine osmolality (UO) and/or urine volume adjusted for 100ml of glomerular filtration rate (V/GFR) in both age groups (paediatric and adult) were determined. Moreover, whenever possible, in both age groups plasma creatinine levels, plasma sodium levels, uric acid levels, the citrate/creatinine ratio and the calcium/citrate ratio were recorded and a renal and bladder ultrasound was performed. RESULTS: In the paediatric age group, KWM was altered in 9/29 cases (31%) (4 with reduced maximum UO and 5 with elevated V/GFR). In adulthood, KWM was found to be affected in 7/29 cases (24.1%) (6 with reduced UO and one with elevated V/GFR). Compared to the paediatric age group, adult patients had lower V/GFR, calcium/creatinine and citrate/creatinine values, as well as higher plasma creatinine, uric acid and calcium/citrate. There were no differences in the maximum UO in both age groups. However, UO in adulthood was significantly lower in subjects who had renal colic compared to those who did not (P = .04). CONCLUSIONS: KWM was affected in approximately one third of patients with IH, which persisted 20 years after diagnosis. We think that these results may be due to adherence to the recommended protective diet and to the pharmacological treatment administered at the diagnosis of IH during childhood

Longitudinal study of kidney water management in patients diagnosed with idiopathic hypercalciuria in childhood. / Estudio longitudinal del manejo renal del agua en pacientes diagnosticados de hipercalciuria idiopática en la infancia.

INTRODUCTION: There is much debate about whether idiopathic hypercalciuria (IH) affects kidney water management. For the first time in the literature, we carried out a longitudinal study of kidney water management (KWM) in patients diagnosed with IH in childhood and followed-up until adulthood (mean follow-up 17.7±1.4 years). METHODS: Twenty-nine patients (7 M, 22 F) over the age of 24 years (mean 28.2±2.9 years, range: 24.1-35.9) who were diagnosed with IH in childhood (mean 7.6±3.2 years, range: 1-14) were included. Maximum urine osmolality (UO) and/or urine volume adjusted for 100ml of glomerular filtration rate (V/GFR) in both age groups (paediatric and adult) were determined. Moreover, whenever possible, in both age groups plasma creatinine levels, plasma sodium levels, uric acid levels, the citrate/creatinine ratio and the calcium/citrate ratio were recorded and a renal and bladder ultrasound was performed. RESULTS: In the paediatric age group, KWM was altered in 9/29 cases (31%) (4 with reduced maximum UO and 5 with elevated V/GFR). In adulthood, KWM was found to be affected in 7/29 cases (24.1%) (6 with reduced UO and one with elevated V/GFR). Compared to the paediatric age group, adult patients had lower V/GFR, calcium/creatinine and citrate/creatinine values, as well as higher plasma creatinine, uric acid and calcium/citrate. There were no differences in the maximum UO in both age groups. However, UO in adulthood was significantly lower in subjects who had renal colic compared to those who did not (P=.04). CONCLUSIONS: KWM was affected in approximately one third of patients with IH, which persisted 20 years after diagnosis. We think that these results may be due to adherence to the recommended protective diet and to the pharmacological treatment administered at the diagnosis of IH during childhood.

Renal tubular markers as screening tools for severe vesicoureteral reflux.

Severe (grades IV and V) vesicoureteral reflux (VUR) is a risk factor for acute pyelonephritis, renal scars, and renal failure. This study evaluates albumin and N-acetylglucosaminidase (NAG) urinary excretion, and renal concentrating ability as screening tools to select patients for voiding cystourethrogram (VCUG). Children (111 M, 52 F) aged 10.97 ± 21.17 months (mean + SD), diagnosed with UTI, and who had undergone renal ultrasound and a VCUG, underwent a desmopressin test and had albumin/creatinine and NAG/creatinine urinary excretion measured. Urine osmolality was significantly lower in 27 children with severe VUR (375.3 ± 171.8 mOsm/kg; mean + SD) compared to 100 patients with normal VCUG (611.5 ± 175.8 mOsm/kg), p < 0.001, and to 36 patients with VUR grades I to III (636.2 ± 180.2 mOsm/kg), p < 0.001. NAG/creatinine ratio was significantly elevated in 20 children with severe VUR (26.4 (28.3) U/g); median and interquartile range compared to 67 children with normal VCUG (10.8 (17.9) U/g), p = 0.003, and to 20 patients with VUR grades I to III (7.6 (21.1) U/g), p = 0.009.Conclusions: Urinary osmolality is significantly decreased and urinary excretion of NAG is significantly increased in patients with severe VUR. These tests could select patients for VCUG to assess for severe VUR. What is Known: • Severe vesicoureteral reflux (SVUR) may contribute to renal damage. Severe vesicoureteral reflux is diagnosed by voiding cystourethrogram and represents about 10% of all patients with VUR. Currently, there are no reliable tests used prior to VCUG to help on the decision of obtaining a VCUG to diagnose SVUR. What is New: • This study shows that renal tubular markers (concentrating ability and N-acetylglucosaminidase (NAG) excretion) are useful tests prior to voiding cystourethrogram to screen for severe vesicoureteral reflux. • This study suggests the use of renal concentrating ability and urinary N-acetylglucosaminidase (NAG) excretion to screen for severe vesicoureteral reflux before requesting a voiding cystourethrogram.

Historia familiar de litiasis renal en pacientes diagnosticados de infección del tracto urinario por Escherichia coli / A family history of renal lithiasis in children diagnosed of urinary tract infection by Escherichia coli

INTRODUCCIÓN: Las infecciones de la vía urinaria (IVU) causadas por Escherichia coli (E. coli) son frecuentes en pacientes con hipercalciuria idiopática. Al ser tanto IVU como hipercalciuria (prelitiasis) de origen genético, planteamos si la historia familiar de urolitiasis es más frecuente en niños con IVU causada por E. coli. Secundariamente, planteamos si las cicatrices renales son más frecuentes en niños con prelitiasis. MATERIAL Y MÉTODOS: Estudio ambispectivo con datos de 104 pacientes (40 masculinos y 64 femeninos) seguidos tras haber sido diagnosticados, al menos una vez, de IVU por E. coli. Se preguntó por la existencia de urolitiasis en familiares (primer y segundo grado). En 80 pacientes se determinó la eliminación urinaria de calcio y citrato. RESULTADOS: En toda la muestra, la historia familiar de urolitiasis fue positiva en una frecuencia significativamente mayor de estos niños (n = 71; 68,3%) que en la población de control del mismo área (el 29,7% según datos previos publicados). La frecuencia de prelitiasis en niños con IVU fue del 47,5% (38/80). Se observó asociación entre prelitiasis tanto con la historia familiar de urolitiasis (p = 0,030) como con el reflujo vesicoureteral (p = 0,034). Además, los pacientes que desarrollaron cicatrices renales tenían más prelitiasis (OR 5,3; p = 0,033). CONCLUSIONES: La frecuencia de historia familiar de urolitiasis en niños con IVU causada por E. coli es muy alta. Basándonos en nuestros resultados, sugerimos la hipótesis de que la predisposición a litiasis involucra una defensa alterada contra E. coli y, consecuentemente, una mayor posibilidad de cicatrices renales

INTRODUCTION: Urinary tract infections (UTI) caused by Escherichia coli (E. coli) are common in patients with idiopathic hypercalciuria. As both UTI and hypercalciuria (prelithiasis) have a genetic basis, we wanted to know whether the family history of urolithiasis is more common in children with UTIs caused by E. coli. Secondarily, we wondered if the renal scars are more common in children with prelithiasis. MATERIAL AND METHODS: Ambispective study with collected data from 104 patients (40 male, 64 female) followed after having been diagnosed of UTI by E. coli at least once. These patients were asked about the existence of urolithiasis in relatives. The calcium and citrate urinary elimination was qunatified in 80 children. RESULTS: In the total sample, family history was positive for urolithiasis in a significantly higher frequency in those children (n = 71; 68.3%) than in the control population in our area (29.7%; previously published data). Prelithiasis frequency in children with UTI was 47.5% (38/80). An association was observed between the diagnosis of prelithiasis both with family history of urolithiasis (P=.030) and the diagnosis of vesicoureteral reflux (P=.034). Children who developed renal scarring had an increased risk of prelithiasis (OR 5.3; P=.033). CONCLUSIONS: The frequency of family history of urolithiasis in children with UTI caused by E. coli is very high. Based on our results we hypothesize that the predisposition to lithiasis can involve a constitutively altered defense to E. coli and, therefore, a greater possibility for renal scars

[A family history of renal lithiasis in children diagnosed of urinary tract infection by Escherichia coli]. / Historia familiar de litiasis renal en pacientes diagnosticados de infección del tracto urinario por Escherichia coli.

INTRODUCTION: Urinary tract infections (UTI) caused by Escherichia coli (E. coli) are common in patients with idiopathic hypercalciuria. As both UTI and hypercalciuria (prelithiasis) have a genetic basis, we wanted to know whether the family history of urolithiasis is more common in children with UTIs caused by E. coli. Secondarily, we wondered if the renal scars are more common in children with prelithiasis. MATERIAL AND METHODS: Ambispective study with collected data from 104 patients (40 male, 64 female) followed after having been diagnosed of UTI by E. coli at least once. These patients were asked about the existence of urolithiasis in relatives. The calcium and citrate urinary elimination was qunatified in 80 children. RESULTS: In the total sample, family history was positive for urolithiasis in a significantly higher frequency in those children (n=71; 68.3%) than in the control population in our area (29.7%; previously published data). Prelithiasis frequency in children with UTI was 47.5% (38/80). An association was observed between the diagnosis of prelithiasis both with family history of urolithiasis (P=.030) and the diagnosis of vesicoureteral reflux (P=.034). Children who developed renal scarring had an increased risk of prelithiasis (OR 5.3; P=.033). CONCLUSIONS: The frequency of family history of urolithiasis in children with UTI caused by E. coli is very high. Based on our results we hypothesize that the predisposition to lithiasis can involve a constitutively altered defense to E. coli and, therefore, a greater possibility for renal scars.

Can acetazolamide be used to treat diseases involving increased bone mineral density?

Sclerosing bone dysplasias are a series of clinically and genetically heterogeneous diseases characterized by functional failure of the osteoclasts in bone resorption, leading to an excessive amount of bone mineral density (BMD) which could have serious clinical consequences. We treated three children affected with seriously high levels of BMD with acetazolamide, with the intention of inducing metabolic acidosis, thus increasing bone resorption and reducing BMD. All our patients tolerated and followed the treatment well and the clinical response was satisfactory in all cases.

Utilidad de las pruebas básicas de estudio de la función renal en la toma de decisiones en niños con pérdida de parénquima renal o dilatación de la vía urinaria / Usefulness of basic renal function tests in decision-making in children with loss of renal parenchyma and/or dilation of the urinary tract

Las pruebas básicas de estudio de la función renal como la osmolalidad urinaria máxima y la eliminación urinaria de albúmina y de N-acetil-glucosaminidasa se alteran con mucha frecuencia en situaciones clínicas que cursan con hiperpresión en la vía urinaria o con pérdida de parénquima renal. No obstante, en todos los algoritmos que se pueden consultar dedicados al estudio de los niños con infección urinaria o dilatación de la vía urinaria nunca se menciona el beneficio del uso de esos parámetros funcionales. En esta revisión, ofrecemos información acerca de la utilidad práctica que conlleva la determinación de los parámetros básicos de estudio de la función renal. A partir de esos datos proponemos un algoritmo destinado a realizar una petición razonada de la cistografía conjuntando parámetros morfológicos y funcionales (AU)

Basic renal function tests such as maximum urine osmolality and urinary elimination of albumin and N-acetyl-glucosaminidase often reveal abnormalities in clinical cases involving hyperpressure in the urinary tract or loss of renal parenchyma. However, in all the available algorithms dedicated to the study of children with urinary tract infection or dilation, the benefit of using these functional parameters is not mentioned. In this review, we provide information about the practical usefulness of assessing the basic renal function parameters. From these data, we propose an algorithm that combines morphological and functional parameters to make a reasoned case for voiding cystourethrography (AU)

Usefulness of basic renal function tests in decision-making in children with loss of renal parenchyma and/or dilation of the urinary tract. / Utilidad de las pruebas básicas de estudio de la función renal en la toma de decisiones en niños con pérdida de parénquima renal o dilatación de la vía urinaria.

Basic renal function tests such as maximum urine osmolality and urinary elimination of albumin and N-acetyl-glucosaminidase often reveal abnormalities in clinical cases involving hyperpressure in the urinary tract or loss of renal parenchyma. However, in all the available algorithms dedicated to the study of children with urinary tract infection or dilation, the benefit of using these functional parameters is not mentioned. In this review, we provide information about the practical usefulness of assessing the basic renal function parameters. From these data, we propose an algorithm that combines morphological and functional parameters to make a reasoned case for voiding cystourethrography.

Water renal management is altered more frequently than albuminuria in children in the G1 stage of the 2012 KDIGO Guideline / El manejo renal del agua se ve alterado con más frecuencia que la albuminuria en niños en el estadio G1 de la Guía KDIGO de 2012

Background: The G1 stage of chronic kidney disease (CKD) is defined in the 2012 KDIGO Guideline as kidney damage characterized by structural or functional kidney abnormalities without deterioration of glomerular filtration rate. Albuminuria and electrolyte abnormalities due to tubular disorders are considered functional markers of kidney damage. Changes in renal water handling are not explicitly cited in these guidelines. A large sample of children with abnormal dimercaptosuccinic acid (DMSA) scan located in the G1 stage was used in this study. Methods: Ambispective, cross-sectional study to evaluate the clinical histories of 116 pediatric patients. 100 patients were included in the first group (G1 stage) and 16 patients in the G2-G5 stages according to the classification of CKD Guideline KDIGO. All the patients had a renal pathologic DMSA scan. GFR, maximum urine osmolality and albumin/creatinine and NAG/creatinine ratios were determined. Results: The patients with normal GFR, in relation to those with reduced GFR, had significantly higher values of maximum urine osmolality and significantly reduced values of urine volume and albumin/creatinine and NAG/creatinine ratios. The most frequently observed alterations in children in the KDIGO G1 stage were those involving the water renal management such as urinary concentrating ability defect (29%) and increased urinary volume (20%). The frequency of children with increased urinary elimination of albumin (12%) and NAG (3%) was more lower. All children in KDIGO G2-G5 stages had alterations in water renal management. Conclusions: The parameters related with the water renal management are affected more frequently than albumin urinary excretion in children who have loss of parenchyma and normal GFR (AU)

Antecedentes: El estadio G1 de la enfermedad renal crónica (ERC) se define en la Guía KDIGO de 2012 como el daño renal caracterizado por anomalías estructurales o funcionales del riñón y sin deterioro del filtrado glomerular. Tanto la albuminuria como las anomalías que afectan a los electrolitos debido a trastornos tubulares se consideran marcadores de daños funcionales. No obstante, en esta guía no se explicitan cuáles son los cambios que se producen en el manejo renal del agua. En este estudio, se utilizó una muestra grande de niños en estadio G1 con gammagrafías con ácido dimercaptosuccínico (DMSA) anormales. Métodos: Llevamos a cabo un estudio transversal ambispectivo para evaluar las historias clínicas de 116 pacientes pediátricos. En el primer grupo, se incluyó a 100 pacientes en estadio G1 y a 16 pacientes en los estadios G2-G5 de la ERC de la clasificación de la Guía KDIGO. Las gammagrafías con DMSA de todos los pacientes revelaban patologías renales. Se calcularon las TFG, la osmolalidad urinaria máxima y los cocientes de albúmina/creatinina y de NAG/creatinina. Resultados: En comparación con los pacientes con TFG reducidas, los pacientes con TFG normales presentaron valores de osmolalidad urinaria máxima significativamente superiores, así como volúmenes urinarios y cocientes de albúmina/creatinina y de NAG/creatinina significativamente inferiores. Las alteraciones que se observaron con mayor frecuencia en los niños en estadio G1 de la Guía KDIGO afectaban al manejo renal del agua. Entre ellas, se encontraban fallos en la capacidad de concentración de la orina (29%) y un aumento del volumen urinario (20%). Sin embargo, se observó que la frecuencia de niños en los que aumentó la eliminación a través de la orina de albúmina (12%) y NAG (3%) era mucho menor. Por su parte, todos los niños en los estadios G2-G5 de la Guía KDIGO presentaban alteraciones en el manejo renal del agua. Conclusiones: Aquellos parámetros relacionados con el manejo renal del agua se ven afectados con más frecuencia que la albuminuria en niños con pérdidas de parénquima renal y TFG normales (AU)

Water renal management is altered more frequently than albuminuria in children in the G1 stage of the 2012 KDIGO Guideline.

BACKGROUND: The G1 stage of chronic kidney disease (CKD) is defined in the 2012 KDIGO Guideline as kidney damage characterized by structural or functional kidney abnormalities without deterioration of glomerular filtration rate. Albuminuria and electrolyte abnormalities due to tubular disorders are considered functional markers of kidney damage. Changes in renal water handling are not explicitly cited in these guidelines. A large sample of children with abnormal dimercaptosuccinic acid (DMSA) scan located in the G1 stage was used in this study. METHODS: Ambispective, cross-sectional study to evaluate the clinical histories of 116 pediatric patients. 100 patients were included in the first group (G1 stage) and 16 patients in the G2-G5 stages according to the classification of CKD Guideline KDIGO. All the patients had a renal pathologic DMSA scan. GFR, maximum urine osmolality and albumin/creatinine and NAG/creatinine ratios were determined. RESULTS: The patients with normal GFR, in relation to those with reduced GFR, had significantly higher values of maximum urine osmolality and significantly reduced values of urine volume and albumin/creatinine and NAG/creatinine ratios. The most frequently observed alterations in children in the KDIGO G1 stage were those involving the water renal management such as urinary concentrating ability defect (29%) and increased urinary volume (20%). The frequency of children with increased urinary elimination of albumin (12%) and NAG (3%) was more lower. All children in KDIGO G2-G5 stages had alterations in water renal management. CONCLUSIONS: The parameters related with the water renal management are affected more frequently than albumin urinary excretion in children who have loss of parenchyma and normal GFR.