Monoallelic Mutations to DNAJB11 Cause Atypical Autosomal-Dominant Polycystic Kidney Disease.

Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by the progressive development of kidney cysts, often resulting in end-stage renal disease (ESRD). This disorder is genetically heterogeneous with ∼7% of families genetically unresolved. We performed whole-exome sequencing (WES) in two multiplex ADPKD-like pedigrees, and we analyzed a further 591 genetically unresolved, phenotypically similar families by targeted next-generation sequencing of 65 candidate genes. WES identified a DNAJB11 missense variant (p.Pro54Arg) in two family members presenting with non-enlarged polycystic kidneys and a frameshifting change (c.166_167insTT) in a second family with small renal and liver cysts. DNAJB11 is a co-factor of BiP, a key chaperone in the endoplasmic reticulum controlling folding, trafficking, and degradation of secreted and membrane proteins. Five additional multigenerational families carrying DNAJB11 mutations were identified by the targeted analysis. The clinical phenotype was consistent in the 23 affected members, with non-enlarged cystic kidneys that often evolved to kidney atrophy; 7 subjects reached ESRD from 59 to 89 years. The lack of kidney enlargement, histologically evident interstitial fibrosis in non-cystic parenchyma, and recurring episodes of gout (one family) suggested partial phenotypic overlap with autosomal-dominant tubulointerstitial diseases (ADTKD). Characterization of DNAJB11-null cells and kidney samples from affected individuals revealed a pathogenesis associated with maturation and trafficking defects involving the ADPKD protein, PC1, and ADTKD proteins, such as UMOD. DNAJB11-associated disease is a phenotypic hybrid of ADPKD and ADTKD, characterized by normal-sized cystic kidneys and progressive interstitial fibrosis resulting in late-onset ESRD.

Tratamiento con adalimumab en la amiloidosis secundaria a artritis reumatoide: a propósito de dos casos / Treatment with adalimumab in amyloidosis secondary to rheumatoid arthritis: two case reports

Las patologías reumatológicas, y en primer lugar la artritis reumatoidea (AR), siguen siendo unas de las principales causas de amiloidosis secundaria. La aparición de agentes biológicos como el adalimumab en el tratamiento precoz de la AR puede ser una alternativa eficaz para frenar el desarrollo y la progresión de la amiloidosis secundaria. No todos los pacientes responderán igual al tratamiento; debemos considerar la comorbilidad asociada, los factores de mal pronóstico para predecir la repuesta terapéutica y los posibles efectos adversos. Dentro de los efectos adversos de las terapias biológicas, hay que destacar el aumento de la tasa de infecciones letales y cuadros de insuficiencia cardíaca. Presentamos dos casos clínicos con amiloidosis renal secundaria a AR que han seguido un curso clínico diferente: nuestro primer caso tuvo una buena repuesta al adalimumab, mientras que el segundo caso evolucionó desfavorablemente después del inicio del tratamiento, falleciendo por complicaciones cardiovasculares (AU)

Rheumatological diseases and, firstly, rheumatoid arthritis (RA) remain a major cause of secondary amyloidosis. The emergence of biological agents such as adalimumab in the early treatment of RA can be an effective alternative to stop the development and progression of secondary amyloidosis. Not all patients will respond the same way to treatment; we must consider associated comorbidity, the poor prognosis factors for predicting therapeutic response and possible adverse effects. In the adverse effects of biological therapies, there has been an increase in the rate of lethal infections and congestive heart failure. We present two cases with renal amyloidosis secondary to RA who had a different clinical course: our 1st case had a good response to Adalimumab while the 2nd case evolved unfavourably after treatment, and died from cardiovascular complications (AU)

Treatment with adalimumab in amyloidosis secondary to rheumatoid arthritis: two case reports.

Rheumatological diseases and, firstly, rheumatoid arthritis (RA) remain a major cause of secondary amyloidosis. The emergence of biological agents such as adalimumab in the early treatment of RA can be an effective alternative to stop the development and progression of secondary amyloidosis. Not all patients will respond the same way to treatment; we must consider associated comorbidity, the poor prognosis factors for predicting therapeutic response and possible adverse effects. In the adverse effects of biological therapies, there has been an increase in the rate of lethal infections and congestive heart failure. We present two cases with renal amyloidosis secondary to RA who had a different clinical course: our 1st case had a good response to Adalimumab while the 2nd case evolved unfavourably after treatment, and died from cardiovascular complications.

Utilidad de la monitorización ambulatoria de la presión arterial en la toma de decisiones clínicas / Usefulness of ambulatory blood pressure monitoring for clinical decisions making

La monitorización ambulatoria de la presión arterial (MAPA) es una herramienta de gran utilidad en el diagnóstico y tratamiento de la hipertensión arterial. La MAPA es una técnica en la que se realizan numerosas lecturas de la presión arterial (PA) durante períodos de 24 o 48h, que proporcionan un registro continuo de la PA durante la actividad diaria del paciente. La MAPA ha demostrado relacionarse más estrechamente que la medida de PA en consulta con el pronóstico cardiovascular y la lesión de órganos diana. El uso de la MAPA permite una evaluación más precisa y un mejor tratamiento del paciente con hipertensión. Además, la PA ambulatoria mide con mayor exactitud los cambios en la PA inducidos por el tratamiento farmacológico, de forma que un mayor número de pacientes pueden alcanzar los objetivos terapéuticos con el tratamiento adecuado. Por tanto, la información que suministra la MAPA puede ser de gran utilidad a la hora de tomar decisiones en la práctica clínica habitual. El presente artículo ofrece una visión actualizada sobre el valor pronóstico de la MAPA y el potencial interés de esta herramienta a la hora de tomar decisiones clínicas (AU)

Ambulatory blood pressure monitoring (ABPM) is a useful diagnostic and therapeutic tool in hypertensive patients. ABMP is a technique in which multiple blood pressure (BP) measurements are taken over a 24–48-hour period, providing a continuous BP record during the patient's normal daily activities. By more reliably measuring BP, ABPM has been shown to be a better predictor of end-organ damage and cardiovascular outcome than BP measured in the clinic setting. The use of ABPM enables a more accurate assessment and an improved management of hypertensive patients. Moreover, ABPM is more closely related to treatment-induced changes in BP, so that treatment can be optimized more efficiently and more patients can achieve BP targets with appropriate therapy. Therefore, information provided by ABMP may be very useful for clinical decision making. The present article offers an updated and comprehensive view of the prognostic value of ABMP and the potential interest of this technique for treatment decision making (AU)

[Usefulness of ambulatory blood pressure monitoring for clinical decisions making]. / Utilidad de la monitorización ambulatoria de la presión arterial en la toma de decisiones clínicas.

Ambulatory blood pressure monitoring (ABPM) is a useful diagnostic and therapeutic tool in hypertensive patients. ABMP is a technique in which multiple blood pressure (BP) measurements are taken over a 24-48-hour period, providing a continuous BP record during the patient's normal daily activities. By more reliably measuring BP, ABPM has been shown to be a better predictor of end-organ damage and cardiovascular outcome than BP measured in the clinic setting. The use of ABPM enables a more accurate assessment and an improved management of hypertensive patients. Moreover, ABPM is more closely related to treatment-induced changes in BP, so that treatment can be optimized more efficiently and more patients can achieve BP targets with appropriate therapy. Therefore, information provided by ABMP may be very useful for clinical decision making. The present article offers an updated and comprehensive view of the prognostic value of ABMP and the potential interest of this technique for treatment decision making.