Recursos y Material didactico
Para que no te pierdas (en) nada
Publicaciones científicas
RenalTube: a network tool for clinical and genetic diagnosis of primary tubulopathies
Mejía N, Santos F, Claverie-Martín F, García-Nieto V, Ariceta G, Castaño L; RenalTube group. RenalTube: a network tool for clinical and genetic diagnosis of primary tubulopathies. Eur J Pediatr. 2013 Jun;172(6):775-80. doi: 10.1007/s00431-013-1934-6. Epub 2013 Feb 7. PMID: 23389821.
The main purpose was to build a database while facilitating access to genotyping in order to improve the clinical and molecular knowledge of primary tubulopathies. Three tertiary referral centers of Spain collect clinical data through the site http://www.renaltube.com, while offering the analysis of 22 genes corresponding to 23 primary tubulopathies. There are three ways of collaboration: option 1 consists of adding patients to the database with clinical and biochemical information and requesting for genetic study, option 2 requires the payment of a fee for genetic analysis exclusively, and option 3 allows the enrollment of patients with a previously confirmed mutation. After 2 years of activity, RenalTube has collected data from 222 patients, the majority from Spain and Latin America (85.3 %). The most common tubulopathies are distal renal tubular acidosis (22.5 %) and classical Bartter syndrome (19.3 %) followed by familial hypomagnesemia with hypercalciuria and nephrocalcinosis (15.7 %) and Gitelman syndrome (15 %). Option 1 is the collaborating method preferred by doctors (62.3 %) followed by option 3 (36.3 %).
Conclusion: RenalTube is a network-based registry that can be easily reached and filled out worldwide. A web-based approach with a multilateral collaboration scheme enhances the recruitment of data and promotes the understanding of underlying mechanisms of rare inherited diseases, defines more accurate diagnostic and follow-up criteria, develops new molecular techniques and will improve the overall care of the patients.
Kidney function in patients with primary distal renal tubular acidosis
Forero-Delgadillo JM, Gil-Peña H, Alonso-Varela M, Santos F; RenalTube Group. Kidney function in patients with primary distal renal tubular acidosis. Pediatr Nephrol. 2021 Jul;36(7):1931-1935. doi: 10.1007/s00467-021-05068-x. Epub 2021 Apr 8. PMID: 33834289
Background: Recent reports indicate that chronic reduction of glomerular filtration rate (GFR) is common in patients with distal renal tubular acidosis (DRTA). Factors responsible for decreased GFR need clarification.
Methods: We reviewed records of 25 patients with genetically confirmed DRTA included in the RenalTube database. Patients < 18 years at diagnosis and having at least one annual follow-up were selected and classified in two groups according to GFR ≥ 90 (normal GFR) or < 90 mL/min/1.73 m2 (low GFR) after median follow-up of 8.8 years.
Results: Eighteen and seven patients had normal and low GFR (X ± SEM, 121.16 ± 28.87 and 71.80 ± 10.60 mL/min/1.73 m2, respectively, p < 0.01). At diagnosis, these 2 subgroups did not differ in sex, age, underlying mutated gene, GFR, height SDS, or percentage of ultrasound nephrocalcinosis. Serum creatinine (SCr) was different but likely due to median ages of presentation being 0.6 and 4.0 in normal and low GFR patients, respectively. On the last recorded visit, no differences between both groups were found in serum bicarbonate, serum potassium, or alkali dosage. Height SDS of patients with normal GFR was – 0.15 ± 0.47 whereas it was – 1.06 ± 0.60 in the low GFR group (p = 0.27). Interestingly, 23% of the whole group had low birth weight (LBW; < 2500 g), equating to 20% and 29% in the normal and low GFR patients, respectively (p = 0.65).
Conclusions: Our findings confirm the risk of kidney function reduction in patients with DRTA of pediatric age onset, suggesting that low GFR is related with less favorable growth outcome and discloses the high frequency of LBW in primary DRTA, a hitherto unrecognized feature.
Gout associated with reduced renal excretion of uric acid. Renal tubular disorder that nephrologists do not treat
García-Nieto VM, Claverie-Martín F, Moraleda-Mesa T, Perdomo-Ramírez A, Tejera-Carreño P, Córdoba-Lanus E, Luis-Yanes MI, Ramos-Trujillo E; en representación del Grupo RenalTube. Gout associated with reduced renal excretion of uric acid. Renal tubular disorder that nephrologists do not treat. Nefrologia (Engl Ed). 2021 Sep 6:S0211-6995(21)00142-9. English, Spanish. doi: 10.1016/j.nefro.2021.03.013. Epub ahead of print. PMID: 34503865
Abstract:
Gout is recurrent inflammatory arthritis caused by the deposition of monosodium urate crystals in the joints. The risk factors that predispose to suffering from gout include non-modifiable factors such as gender, age, ethnicity and genetics, and modifiable factors such as diet and lifestyle. It has been shown that the heritability of uric acid levels in the blood is greater than 30%, which indicates that genetics play a key role in these levels. Hyperuricaemia is often a consequence of reduced renal urate excretion since more than 70% is excreted by the kidneys, mainly through the proximal tubule. The mechanisms that explain that hyperuricaemia associated with reduced renal urate excretion is, to a large extent, a proximal renal tubular disorder, have begun to be understood following the identification of two genes that encode the URAT1 and GLUT9 transporters. When they are carriers of loss-of-function mutations, they explain the two known variants of renal tubular hypouricaemia. Some polymorphisms in these genes may have an opposite gain-of-function effect, with a consequent increase in urate reabsorption. Conversely, loss-of-function polymorphisms in other genes that encode transporters involved in urate excretion (ABCG2, ABCC4) can lead to hyperuricaemia. Genome-wide association study (GWAS) methods have made it possible to locate new gout-related loci associated with reduced renal urate excretion (NIPAL1, FAM35A).
Proyectos
Investigación de estrategias terapéuticas para la enfermedad de Dent-1 y adaptación de RenalTube a las necesidades de los pacientes con tubulopatías primarias
Nº expediente: PI20/00652
Entidad Financiadora: Instituto de Salud Carlos III y Fondo Europeo de Desarrollo Regional
Año de inicio y de finalización: 2021-2023
Investigador Principal: Félix Claverie Martín
Este proyecto busca mejorar la eficiencia del diagnóstico genético de varias tubulopatías renales incluidas en el proyecto coordinado RenalTube, investigar estrategias terapéuticas, y lograr una mayor aplicabilidad de RenalTube a las necesidades de los pacientes y sus familiares.
En este proyecto continuaremos el análisis genético de pacientes con tubulopatías, estudiaremos el potencial terapéutico del ácido tauroursodeoxicólico y el ácido docosahexaenoico en nuestro modelo de ratón knock-in (KI), valoraremos el efecto de oligos antisentido en el tratamiento de algunas enfermedades, examinaremos el posible efecto fundador de una mutación frecuente en los pacientes españoles con hipouricemia renal tipo 2, y en colaboración con las asociaciones de pacientes pretendemos conseguir una mayor aplicabilidad de RenalTube a las necesidades de los pacientes con enfermedad de Dent e hipomagnesemias familiares mediante la confección de acciones de transferencia entre RenalTube y dichas asociaciones.
Aplicación de RenalTube a las necesidades de los pacientes e investigación clínico-experimental sobre la acidosis tubular renal distal y el raquitismo hipofosfatémico ligado al X
Nº expediente: PI20/00922
Entidad Financiadora: Instituto de Salud Carlos III y Fondo Europeo de Desarrollo Regional
Año de inicio y de finalización: 2021-2023
Investigador Principal: Helena Gil Peña
Este proyecto busca, en coordinación con el proyecto PI20/00652, adecuar RenalTube a las necesidades de los pacientes y mantener su explotación como base de datos clínico-genética. Individualmente profundizará sobre: i) Las bases y posibles métodos diagnósticos para la acidosis tubular renal distal incompleta (iATRD). ii) La existencia de afectación cardíaca derivada de la normalización de los niveles de fósforo sérico en pacientes pediátricos con hipofosfatemia hereditaria ligada al X (XLH). Metodología: RenalTube abordará sus acciones hacia los pacientes: valorando la carga diaria que supone la enfermedad; desarrollando actividades formativas y educativas, en torno a las tubulopatías primarias; buscando iniciativas para ejercer influencia sobre entidades y organizaciones europeas e internacionales destinadas al estudio de estas enfermedades raras. El mantenimiento de su actividad como web y base de datos clínico-genética, se realizará como se viene haciendo desde su origen. Para profundizar sobre la iATRD y sus implicaciones, se desarrollará un estudio clínico prospectivo sobre la acidificación urinaria y la eliminación de NH4+en población pediátrica sana y con situaciones favorecedoras de urolitiasis, nefrocalcinosis, nefropatías intersticiales y/o hipocrecimiento de causa no aclarada. A aquellos casos que manifiesten resultados anormales se les evaluará su capacidad de concentración urinaria, prueba que también se realizará a padres (portadores de variantes patogénicas) de hijos con ATRD. Para valorar si en el XLH hay afectación cardíaca relacionada con la normalización de la fosfatemia, se llevará a cabo un estudio en pacientes pediátricos, con XLH y bajo tratamiento, incluidos en RenalTube, valorando: monitorización Holter, ecocardiograma y parámetros relacionados con la enfermedad. Además, se hará un protocolo con el modelo murino de XLH, analizando si el tratamiento con fosfato o anti-FGF23 se relaciona con procesos de hipertrofia ventricular.