Protocol for a randomized controlled multicenter trial assessing the efficacy of leuprorelin for severe polycystic liver disease: the AGAINST-PLD study.

BACKGROUND: In patients with severe polycystic liver disease (PLD), there is a need for new treatments. Estrogens and possibly other female sex hormones stimulate growth in PLD. In some patients, liver volume decreases after menopause. Female sex hormones could therefore be a target for therapy. The AGAINST-PLD study will examine the efficacy of the GnRH agonist leuprorelin, which blocks the production of estrogen and other sex hormones, to reduce liver growth in PLD. METHODS: The AGAINST-PLD study is an investigator-driven, multicenter, randomized controlled trial. Institutional review board (IRB) approval was received at the University Medical Center of Groningen and will be collected in other sites before opening these sites. Thirty-six female, pre-menopausal patients, with a very large liver volume for age (upper 10% of the PLD population) and ongoing liver growth despite current treatment options will be randomized to direct start of leuprorelin or to 18 months standard of care and delayed start of leuprorelin. Leuprorelin is given as 3.75 mg subcutaneously (s.c.) monthly for the first 3 months followed by 3-monthly depots of 11.25 mg s.c. The trial duration is 36 months. MRI scans to measure liver volume will be performed at screening, 6 months, 18 months, 24 months and 36 months. In addition, blood will be drawn, DEXA-scans will be performed and questionnaires will be collected. This design enables comparison between patients on study treatment and standard of care (first 18 months) and within patients before and during treatment (whole trial). Main outcome is annualized liver growth rate compared between standard of care and study treatment. Secondary outcomes are PLD disease severity, change in liver growth within individuals and (serious) adverse events. The study is designed as a prospective open-label study with blinded endpoint assessment (PROBE). DISCUSSION: In this trial, we combined the expertise of hepatologist, nephrologists and gynecologists to study the effect of leuprorelin on liver growth in PLD. In this way, we hope to stop liver growth, reduce symptoms and reduce the need for liver transplantation in severe PLD. Trial registration Eudra CT number 2020-005949-16, registered at 15 Dec 2020. https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-005949-16 .

Plan PrEFiNE: Plan estratégico para la enfermedad de Fabry en Nefrología / PrEFiNe Plan: Strategic plan for Fabry diseases in Nephrology

Justificación: La enfermedad renal es una de las principales causas de muerte entre los pacientes con enfermedad de Fabry (EF). Al tratarse de una enfermedad de baja prevalencia, se realizan con frecuencia diagnósticos erróneos y retrasados, que a menudo se dan cuando ya se ha producido daño orgánico. El reconocimiento temprano de la enfermedad permitiría evitar las complicaciones graves y la muerte prematura en estos pacientes. Objetivo: Presentamos en este artículo un resumen del plan PrEFiNE, que incluye un abanico amplio de actividades con el objetivo de mejorar el conocimiento y reconocimiento de la EF entre los nefrólogos. Este proyecto está patrocinado por Shire Ibérica (http://shireiberica.com/). Métodos: Desde enero de 2016 y hasta finales del 2017 se iniciarán distintas actividades, comenzando por una evaluación del grado de conocimiento que existe actualmente sobre la EF. Se incluyen 3 estudios de prevalencia de la EF, que abarcan el espectro de los pacientes con enfermedad renal crónica (pacientes en diálisis, pacientes trasplantados renales y un estudio piloto en pacientes con enfermedad renal crónica en estadio 3-5 prediálisis) y un estudio farmacoeconómico, centrado en el impacto de la carga de la enfermedad. Paralelamente, se realizarán actividades formativas tanto presenciales como on line, y un amplio plan de comunicación mediante publicaciones y difusión a medios. El proyecto culminará con la publicación de un libro blanco de la EF en Nefrología, que recoja el resultado de todas las actividades y que proponga recomendaciones en respuesta a los resultados y a las necesidades detectadas. El plan PrEFiNE estará coordinado por distintos comités científicos, uno nacional y 10 regionales que garantizarán el desarrollo de las acciones con el máximo rigor científico y será supervisado por un comité asesor. Discusión: El plan PrEFiNE nos permitirá evaluar la utilidad de un proyecto dirigido a mejorar el conocimiento de una enfermedad minoritaria como la EF a nivel nacional, y a partir del cual se podrán establecer las recomendaciones necesarias para mejorar su reconocimiento, además de planes enfocados a mejorar las necesidades no cubiertas detectadas durante su desarrollo (AU)

Background: Renal failure is one of the main causes of death in patients with Fabry disease (FD). Due to the low prevalence of FD, delayed diagnosis and misdiagnosis, often the correct diagnosis is made when organ damage is already present. Early recognition of the disease would allow the prevention of severe complications and the premature death of patients with FD. Objective: We present here the PrEFiNE project, which includes a wide spectrum of activities with the aim of improve knowledge and diagnosis of FD. The project is sponsored by Shire Iberia (http://shireiberica.com/) Methods: From January 2016 to the end of 2017 several activities will be carried out, starting with a survey to evaluate current FD knowledge among nephrologists; in addition some studies to assess prevalence of this disease will be performed. One study will include patients receiving dialysis, another study will cover kidney transplant patients, and a pilot study in chronic kidney disease in stage 3-5 predialysis. Also planned is a pharmacoeconomic study to focus on burden of FD. At the same time medical education activities will be conducted both on line and on site. Plan for dissemination will include medical publications and diffusion to media. PrEFiNE Project will finish with the publication of a compilation book on FD in Nephrology including all planned activities and proposing recommendations based on results and detected unmet needs. PrEfiNE Plan will be coordinated by severa scientific committees, one at national level and 10 other regionals comittees, tha will be responsible to ensure the maximum scientific quality of proposed activities. An advisory board will supervise the project. Discussion: PrEfiNE project will evaluate an action plan focused on improving FD knowledge to make necessary recommendations for an early recognition of the disease. In addition will generate a plan to improve previously undetected needs (AU)

PrEFiNe Plan: Strategic plan for Fabry diseases in Nephrology. / Plan PrEFiNE: Plan estratégico para la enfermedad de Fabry en Nefrología.

BACKGROUND: Renal failure is one of the main causes of death in patients with Fabry disease (FD). Due to the low prevalence of FD, delayed diagnosis and misdiagnosis, often the correct diagnosis is made when organ damage is already present. Early recognition of the disease would allow the prevention of severe complications and the premature death of patients with FD. OBJECTIVE: We present here the PrEFiNE project, which includes a wide spectrum of activities with the aim of improve knowledge and diagnosis of FD. The project is sponsored by Shire Iberia (http://shireiberica.com/) METHODS: From January 2016 to the end of 2017 several activities will be carried out, starting with a survey to evaluate current FD knowledge among nephrologists; in addition some studies to assess prevalence of this disease will be performed. One study will include patients receiving dialysis, another study will cover kidney transplant patients, and a pilot study in chronic kidney disease in stage 3-5 predialysis. Also planned is a pharmacoeconomic study to focus on burden of FD. At the same time medical education activities will be conducted both on line and on site. Plan for dissemination will include medical publications and diffusion to media. PrEFiNE Project will finish with the publication of a compilation book on FD in Nephrology including all planned activities and proposing recommendations based on results and detected unmet needs. PrEfiNE Plan will be coordinated by severa scientific committees, one at national level and 10 other regionals comittees, tha will be responsible to ensure the maximum scientific quality of proposed activities. An advisory board will supervise the project. DISCUSSION: PrEfiNE project will evaluate an action plan focused on improving FD knowledge to make necessary recommendations for an early recognition of the disease. In addition will generate a plan to improve previously undetected needs.

Autosomal dominant policystic kidney disease, more than a renal disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a systemic disorder mainly involving the kidney. It affects one in 400-1000 live births. Early hypertension and progressive renal failure due to massive enlargement of cysts and fibrosis are hallmarks of the disease. ADPKD accounts for ~5-10% of cases requiring renal replacement therapy. But not only the kidneys are affected in ADPKD: cysts also occur in other organs such as the liver, pancreas, arachnoid membrane and seminal vesicles. Non-cystic manifestations of the diseases are intracranial aneurysms, hernias and valvular abnormalities. Complications in ADPKD usually result from kidney involvement and include cyst bleeding and cyst infection. However, serious extrarenal features such as subarachnoid haemorrhage can also occur. There is no specific treatment for ADPKD currently, but many molecules targeting up- or downregulated molecules in the renal epithelial cells are being tested. A clinical trial using tolvaptan (a vasopressin receptor antagonist) has demonstrated efficacy, while mTOR inhibitors have shown no positive effect in ADPKD. ACEIs and ARBs are the drugs of choice for treating hypertension in ADPKD. Until a specific therapy becomes available, early treatment of hypertension and lifestyle changes are encouraged.

Norovirus: a growing cause of gastroenteritis in catalonia (Spain)?

Infectious acute gastroenteritis (AGE) is a major health problem worldwide. Salmonella is a leading cause of AGE outbreaks, but viruses may be responsible for up to 80% of cases. We compared the frequency and characteristics of AGE out breaks in Catalonia due to norovirus and Salmonella and the changes in these outbreaks from 2000 through 2010. In 2006 through 2010, we also investigated the distribution by season, setting, and implicated food, the incidence rates of cases associated, and the hospitalization rates. Differences in proportions were estimated by Pearson's chi-square test, and the odds ratio (OR) and 95% confidence interval (CI) were calculated. In 2000 through 2010, the number of AGE outbreaks caused by Salmonella decreased and those caused by norovirus significantly increased. From 2006 onward, norovirus was the most common etiology in AGE outbreaks, but in foodborne outbreaks, Salmonella was the more common cause until 2010. The incidence rate per 10(5) inhabitants was greater for norovirus (20.81 versus 3.97, P < 0.001), and the hospitalization rate was lower for norovirus (0.84 versus 4.69, P < 0.001). Salmonella infections occurred more frequently in the warmer months, and norovirus infections were more common in the colder months, both in terms of total outbreaks (OR = 4.50; 95% CI, 2.85 to 7.11; P < 0.001) and foodborne outbreaks (OR = 4.38; 95% CI, 2.42 to 7.95; P < 0.001). Norovirus infections were less common in private homes (OR = 0.08; 95% CI, 0.04 to 0.14; P < 0.001) and more common in nursing homes (P < 0.001) and hospitals or long-term care facilities (OR = 14.09; 95% CI, 3.35 to 59.33; P < 0.001). Foods most frequently implicated in norovirus infection outbreaks were seafood (22% ; OR = 7.89; 95% CI, 2.59 to 24.3; P < 0.001), and those most common in Salmonella infection outbreaks were mayonnaise and similar items (30.2%; OR = 0.05; 95% CI, 0.01 to 0.22; P < 0.001). Foodborne outbreaks in which the vehicle was not identified were more frequent in cases of norovirus infection (OR = 4.59; 95% CI, 2.54 to 8.30; P < 0.001). Our results indicate that norovirus rather than Salmonella is the most common cause of AGE outbreaks in Catalonia. Foodborne AGE outbreaks were more commonly caused by norovirus than by Salmonella only in 2010, the last year of the study.

WT1 mutations may be a cause of severe renal failure due to nephroblastomatosis in Wilms' tumor patients.

Wilms' tumor suppressor gene (WT1) encodes a transcription factor required for normal development of the genitourinary system. Germline WT1 mutations have been described in a wide spectrum of pathological conditions, including kidney diseases, genital abnormalities and Wilms' tumor. Here we report a 4-year-old male patient who presented with bilateral cryptorchidism, Wilms' tumor, nephroblastomatosis and renal failure without nephrotic proteinuria. Sequence analysis of the WT1 gene demonstrated a constitutional heterozygous nonsense mutation in exon 7, which leads to a truncation of the WT1 protein at the zinc-finger 1. In the DNA of the tumor, we observed the same mutation in homo/hemizygosity. Given the requirement of WT1 for normal development, the WT1 mutation is likely to be responsible for the nephroblastomatosis and, in consequence, for the severe renal failure observed in our patient. This finding extends the spectrum of kidney diseases related to WT1 mutations and points to the need to screen for this gene in children with genitourinary abnormalities and Wilms' tumor because of the associated risk of nephroblastomatosis and renal failure in those carrying WT1 mutations.

Post-pancreaticoduodenectomy hemorrhage. Incidence, diagnosis, and treatment.

BACKGROUND: Although mortality post-pancreaticoduodenectomy (PD) has decreased, morbidity rates continue to be high, ranging from 30% to 50%. Among complications, hemorrhage stands out; it is associated with high mortality and there is no standard management. The aim of the present study was to analyze the incidence, diagnosis, and treatment of hemorrhage post-cephalic PD at our center. METHODS: From January 2005 to December 2008, 107 PDs were performed. A retrospective review of characteristics of patients with postoperative hemorrhage was made from our prospective database. Demographic data, diagnosis, treatment (medical, laparotomy, interventional radiology), association with fistula (pancreatic or biliary), intra- or extraluminal hemorrhage, bleeding time (early or late), severity (moderate/severe), and mortality were analyzed. RESULTS: Eighteen patients (18/107; 16.82%) hemorrhaged after PD. Hemorrhage appeared early (< 24 h) in 4 of these 18 patients (22.2%), and it was severe in 13/18 (72%). Hemorrhage-related mortality was 11% (2/18) and hospital mortality was 22.2% (4/18). Arteriography was performed in 8/18 patients (44.4%) and was effective in 6/8 (75%); laparotomy was performed in 8/18 (44.4%). Re-bleeding occurred in 5 of these 18 patients after the first treatment (27.8%). An association between hemorrhage and fistula was observed. CONCLUSIONS: Hemorrhage after pancreatic resection must be considered a complication with relatively high mortality. Diagnosis should be established and treatment applied rapidly. Pancreatic and/or biliary fistulae were significantly associated with a higher risk of postoperative hemorrhage. Interventional radiology is a good therapeutic option.

[Relationship between renal size and blood pressure profile in patients with autosomal dominant polycystic kidney disease without renal failure]. / Relación entre el tamaño renal y el perfil de presión arterial en pacientes con poliquistosis renal autosómica dominante sin insuficiencia renal.

BACKGROUND: Enlargement of renal size plays an important role in the development of hypertension in patients with autosomic dominant polycystic kidney disease (ADPKD) and normal renal function. METHODS: A 24h blood pressure monitoring (ABPM) and a renal echography have been performed in 37 patients with ADPKD and estimated glomerular filtration rate > 60 ml/min/1.73 m(2) to study the relationship between renal size and an altered blood pressure profile in prehypertension stages. RESULTS: 13 patients had normal blood pressure, 11 were diagnosed of masked hypertension, 4 had white coat hypertension and 9 had hypertension. We have found in the normotensive group with a dipper blood pressure profile a positive and statistically significant relationship between renal size and diastolic blood pressure variability. CONCLUSIONS: ABPM helps to make an early diagnosis of hypertension and to identify those patients with masked hypertension. This study suggests a relationship between renal size and a blood pressure profile linked to a major cardiovascular risk in normotensive patients with ADPKD.

Relación entre el tamaño renal y el perfil de presión arterial en pacientes con poliquistosis renal autosómica dominante sin insuficiencia renal / Relationship between kidney size and blood pressure profile in patients with autosomal dominant polycystic kidney disease without renal failure

Antecedentes: El aumento del tamaño renal desempeña un papel importante en el desarrollo de la hipertensión arterial (HTA) en pacientes con poliquistosis renal autosómica dominante (PQRAD) con función renal normal. Material y métodos: Se han practicado a 37 pacientes con PQRAD, filtrado glomerular estimado (FGe) por MDRD>60 ml/min/1,73 m2y supuestamente normotensos, una monitorización de la presión arterial (MAPA) y una ecografía renovesical para investigar la posible relación entre el aumento del tamaño renal y un perfil patológico de presión arterial (PA) en estadios de prehipertensión. Resultados: 13 pacientes resultaron ser normotensos, 11 presentaron HTA enmascarada, cuatro tuvieron HTA de bata blanca y nueve, HTA verdadera. Se ha observado en los pacientes normotensos con patrón reductor de la PA una correlación positiva y estadísticamente significativa entre el tamaño renal y la variabilidad de la presión arterial diastólica (PAD). Conclusiones: La MAPA permite realizar un diagnóstico precoz de la HTA e identificar apacientes con hipertensión enmascarada. Este trabajo sugiere que en pacientes normotensos con PQRAD existe una posible relación entre el tamaño renal y un perfil de PA con mayor riesgo cardiovascular (AU)

Background: Enlargement of renal size plays an important role in the development of hypertension in patients with autosomal dominant polycystic kidney disease (ADPKD)and normal renal function. Methods: A 24h blood pressure monitoring (ABPM) and a renal ecography have been performed in 37 patients with ADPKD and estimated glomerular filtration rate >60 ml/min/1,73 m2to study the relationship between renal size and an altered blood pressure profile in prehypertension stages. Results: 13 patients had normal blood pressure, 11 were diagnosed of masked hypertension, 4 had white coat hypertension and 9 had hypertension. We have found in the normotensive group with a dipper blood pressure profile a positive and statistically significant relationship between renal size and diastolic blood pressure variability. Conclusions: ABPM helps to make an early diagnosis of hypertension and to identify those patients with masked hypertension. This study suggests a relationship between renal size and a blood pressure profile linked to a major cardiovasular risk in normotensive patients with ADPKD (AU)

Preservation of renal function in a patient with Fabry nephropathy on enzyme replacement therapy.

Fabry disease is an X-linked recessive inborn error of glycosphingolipid metabolism caused by the deficient activity of the lysosomal enzyme, alpha-galactosidase A. Enzyme replacement therapy (ERT) for this disorder has been available in Europe since 2001. However, its effect on advanced renal failure remains controversial. We report the case of a patient whose decline in renal function was reduced by the administration of ERT (agalsidase-alpha). This reduction was more pronounced after doubling the dose of the enzyme. The rate of deterioration of eGFR went from 6.3 ml/min/year prior to the start of ERT (0.2 mg/kg) to 2 ml/min/year (0.4 mg/kg). To our knowledge, this is the first reported case of a patient with moderately impaired renal function treated with high doses of ERT and follow-up of 6 years. The data shown here suggest that ERT may have a very positive impact on renal function even in advanced stages. The role of proteinuria and its control seem to have a clear responsibility for this favorable outcome.

Síndrome nefrótico idiopático en el niño / Primary nephrotic syndrome in children

El síndrome nefrótico idiopático (SNI) es responsable de más del 80% de los síndromes nefróticos en la infancia y de un 20-25% en los adultos. Aun cuando puede presentarse a cualquier edad es una enfermedad típicamente pediátrica cuya mayor frecuencia de aparición se sitúa entre los 2-6 años y con mayor incidencia en el genero masculino. Dentro del síndrome nefrótico infantil debemos considerar de forma diferencial el que aparece en el primer año de vida. Igualmente, en el momento actual, los conocimientos genéticos identifican otras formas (que excluiríamos de la denominación SNI) las formas genéticas, ligadas a daños estructurales de los podocitos. En pediatría se define síndrome nefrótico una proteinuria superior a 40 mg/m2/hora con albúmina plasmática inferior a 2,5 g/dl. La histología subyacente en el SNI es mayoritariamente las lesiones mínimas, 76,6% en el Estudio Internacional de Enfermedades Renales en el niño (ISKDC). Otras variantes histológicas menos frecuentes, son la glomerulonefritis segmentaria y focal y la glomerulonefritis mesangial difusa, sin depósitos o con depósitos focales o difusos de IgM, no reconocida universalmente como entidad diferenciada por ser considerada por algunas escuelas como una variante de las lesiones mínimas. En niños, el SNI se caracteriza por su buena respuesta al tratamiento, alta tendencia a las recidivas y buen pronóstico final sin deterioro de la función renal. Siendo el curso de la enfermedad habitualmente prolongado, con mayor o menor número de recaídas, la elección del esquema terapéutico con corticoides y/o inmunosupresores deben plantearse con unos objetivos básicos: 1) Inducción lo más rápidamente posible de la remisión. 2) Prevención de las recaídas y 3) Evitar la iatrogenia farmacológica inducida por la inmunosupresión. Los corticoides siguen siendo el tratamiento de elección sin que se haya esclarecido su mecanismo de acción. Los protocolos empleados son múltiples y los únicos con alta evidencia son: la respuesta a los corticoides y la respuesta a la ciclofosfamida o clorambucil para modificar la corticodependencia en los casos que evolucionan de esta forma. El tratamiento inicial del SNI será: Prednisona 60 mg/m2/día 4-6 semanas, seguido de prednisona 40 mg/m2/48 h durante 4-6 semanas con supresión progresiva en 6 semanas (tabla I). El tratamiento de la recaída: 60 mg/m2/día hasta la desaparición de la proteinuria (Albustix negativo o indicios) durante 5 días consecutivos, seguido de prednisona 40 mg/m2/48 h durante 4-6 semanas y supresión en 6 semanas (tabla II). El tratamiento del SNI corticodependiente o corticorresistente (definición en texto) se recoge en las figuras 1 y 2. 33 Ante la falta de niveles altos de evidencia en el tratamiento de estas formas evolutivas, el esquema propuesto es solo recomendado, pudiendo ser aceptables otras alternativas terapéuticas. Junto al tratamiento de base: corticoides y/o inmunosupresores, debemos considerar el tratamiento general: dieta normocalórica y normoproteica, adecuada a la edad. No profilaxis antibiótica. Administración de vacunas cumpliendo el calendario vacunal completo y vacunación de varicela, neumococo y gripe. Aporte de calcio y vit. D. El tratamiento del edema será la restricción de sodio, no de agua, administrando seroalbúmina solo en situaciones especiales como hipovolemia sintomática o edema incapacitante. Consideración específica debe tenerse a las formas genéticas: NPHS1, NPHS2 y WT1 y a los síndromes nefróticos de comienzo durante el primer año de vida, por ser distinto el planteamiento dado su resistencia al tratamiento. En el SNI del niño dado el predominio de lesiones mínimas y corticosensibilidad, no está indicado proceder a una biopsia renal al inicio de la enfermedad sino instaurar un tratamiento esteroideo, realizándose la biopsia con criterios distintos según grupos, aun cuando existe unanimidad en realizarla en el síndrome nefrótico corticorresistente, en los de comienzo dentro del primer año de vida y en los casos con datos clínicos y/o analíticos que sugieran ser formas secundarias a una enfermedad sistémica. Dentro del primer año de vida tienen su manifestación la mayor parte de las formas genéticas; destacando el síndrome nefrótico finlandés (SNF), la esclerosis mesangial difusa aislada o asociada a otras anomalías y las infrecuentes causas infecciosas, aunque también puede observarse histología de lesiones mínimas, mesangial o membranosa más raramente. Por último es de señalar la posibilidad de recidiva postrasplante en las formas corticorresistentes, específicamente la esclerosis segmentaria y focal, con alto índice de recidivas, oscilando en las distintas series entre 10-80%, de tratamiento difícil, sin nivel de evidencia, y repercusión negativa en la evolución del injerto. Algunas formas genéticas, síndrome nefrótico finlandés o esclerosis segmentaria y focal en su forma genética también puede mostrar recidiva postrasplante aunque con menor frecuencia

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[Collagen IV (alpha3-alpha4) nephropathy]. / La nefropatía del coláigeno IV (aalpha3-alpha4).

Recent evidence has shown that the COL4A3, COL4A4 and COL4A5 genes are involved in different renal manifestations. Mutations in these collagen type IV genes affect the glomerular basement membrane (GBM) giving rise to a nephropathy whose symptoms range from isolated hematuria to severe renal failure. This disorder has been traditionally considered to be different entities: Autosomal Dominant Alport syndrome, Familial Benign Hematuria, Autosomal Recessive Alport Syndrome carriers. But the increased knowledge of the molecular basis of this clinical diversity prompted us to agglutinate these entities under the name of "collagen type IV nephropathy". This fact has relevant implications in diagnosis, prognosis and management.

La nefropatía del colágeno IV (3-4) / Collagen IV (3-4) nephropathy

Se ha demostrado que los genes COL4A3, COL4A4 y COL4A5 están implicadosen distintas manifestaciones renales. Mutaciones en estos genes del colágenoIV afectan la estructura de la membrana basal glomerular (MBG) dando lugar auna nefropatía cuyos síntomas oscilan desde la hematuria aislada hasta la insuficienciarenal. Estas alteraciones renales han sido consideradas históricamente comodistintas entidades: síndrome de Alport autosómico dominante, hematuria familiarbenigna y portadores del síndrome de Alport autosómico recesivo. Pero el conocimientomolecular de estas enfermedades ha hecho que podamos agruparlas bajoel epígrafe de «nefropatía del colágeno IV». Este hecho tiene importantes implicacionesen el diagnóstico, pronóstico y seguimiento de la enfermedad

Recent evidence has shown that the COL4A3, COL4A4 and COL4A5 genes areinvolved in different renal manifestations. Mutations in these collagen type IV genesaffect the glomerular basement membrane (GBM) giving rise to a nephropathywhose symptoms range from isolated hematuria to severe renal failure. This disorderhas been traditionally considered to be different entities: Autosomal DominantAlport syndrome, Familial Benign Hematuria, Autosomal Recessive Alport Syndromecarriers. But the increased knowledge of the molecular basis of this clinicaldiversity prompted us to agglutinate these entities under the name of «collagentype IV nephropathy». This fact has relevant implications in diagnosis, prognosisand management

Enfermedades renales hereditarias. Papel de la asistencia primaria / No disponible

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Tratamiento de la glomerulopatía membranosa / No disponible

La glomerulopatía membranosa (GNM) es una de las causas más frecuentes de síndrome nefrótico en el adulto. Dos tercios de los sujetos afectos desarrollan una insuficiencia renal o mantienen una proteinuria de rango nefrótico durante los 10 primeros años después de la biopsia renal, el otro tercio remite espontáneamente. Es difícil individualizar en el momento del diagnóstico los pacientes que van a evolucionar hacia la insuficiencia renal terminal. Sólo algunos datos bioquímicos son claros factores de pronóstico: una proteinuria inferior a 3g/24h durante más de 6 meses se asocia a un buen pronóstico, una insuficiencia renal en el momento de la BR o aparecida durante el seguimiento es factor de mal pronóstico. Un modelo matemático que utiliza el factor tiempo y la proteinuria permite calcular el riesgo de evolución de un paciente hacia la insuficiencia renal. Frente a estos datos, los nefrólogos han propuesto alternativas terapéuticas opuestas adoptar una actitud conservadora intentando evitar a pacientes que hubieran presentado una remisión espontánea los riesgos de un tratamiento agresivo o administrar corticoides e inmmunosupresores para evitar a dos tercios de los pacientes la evolución hacia una insuficiencia renal o las complicaciones de un síndrome nefrótico persistente (AU)

Idiopathic membranous nephropathy is a common cause of nephrotic syndrome in adults and is characterized by great variability of the evolution. Studies on its natural history show that up to 40% of the untreated patients progress to end stage renal disease, up to 30% experience spontaneous remission and another one third of patients have a slow progression and remain proteinuric. Its treatment is a controversial issue. Some nephrologist recommend and immunosupresive therapy and others prone toward a more conservative approach. The first group have proposed several protocols: steroids and chlorambucil for six months, oral or intravenous cyclophosphamide and steroids for one to two years, low-dose oral azathioprine plus steroids for very prolonged periods. Several risk factors that do predict a worse outcome (sex, age, massive proteinuria, elevation of serum creatinine, histologic changes such as tubular intersticial damage and glomeruloesclerosis) have been proposed to select individuals worth treating. Cattran et al. have suggested that time must be added to the pronostic factors to improve prediction. Their algorithm, which uses only the presenting creatinine level, the quantity of proteinuria and change in renal function over the initial 6 month of observation improve the ability to separate patients with poor from those with good prognosis (AU)