Blockade of interleukin-6 as a possible therapeutic target for AA amyloidosis

Introducción La amiloidosis secundaria (AA) es una complicación grave asociada a enfermedades inflamatorias. Se caracteriza por el depósito sistémico de proteína fibrilar AA, con especial repercusión renal. La participación de la interleucina 6 en su mecanismo patogénico ha supuesto que tocilizumab (TCZ) sea considerado una opción terapéutica en estos pacientes. Varias series publicadas muestran su eficacia en el tratamiento de la amiloidosis AA, permitiendo incluso la regresión de depósitos renales ya presentes. Material y método Revisión retrospectiva que incluyó pacientes con diagnóstico histológico de amiloidosis renal AA en tratamiento con TCZ durante los años 2018-2019 en nuestro centro. Registramos variables clínicas y demográficas; evaluamos la función renal mediante filtrado glomerular (FG) calculado por CKD-EPI e índice proteína/creatinina a los 3, 6 y 12 meses de seguimiento. Definimos «respuesta renal» como la disminución > 30% de la proteinuria y/o estabilización o mejoría del FG. Consideramos «respuesta antiinflamatoria» la disminución > 50% de las cifras de proteína sérica amiloide (PSA) y/o proteína C reactiva (PCR). Resultados Presentamos una serie de 3 pacientes (2 varones y una mujer; 55, 74 y 75 años, respectivamente), con un tiempo de seguimiento de 13, 14 y 75 meses, respectivamente. Con la terapia con TCZ, el FG se estabilizó en 2 pacientes; el tercero permaneció en hemodiálisis durante el seguimiento, aunque con excelente control de su enfermedad inflamatoria de base; a los 12 meses recibió un trasplante renal. En los 3 casos se objetivó reducción de proteína PSA y PCR. No se han producido eventos adversos. Conclusiones El TCZ es una opción terapéutica eficaz y segura para los pacientes con amiloidosis AA y afectación renal. Nuestros resultados lo posicionan como una opción terapéutica a considerar en estos casos, aunque sería necesario la realización de estudios prospectivos en los que se evalúe el papel global de TCZ en la amiloidosis AA.Introduction AA (secondary) amyloidosis is a severe complication of chronic inflammatory disorders. It is characterized by the systemic deposition of an abnormal protein called amyloid, affecting mainly renal function. IL-6 is a cytokine with a relevant role in this disease development. Interleukin-receptor antagonists, like Tocilizumab (TCZ), have become possible treatment choice for AA amyloidosis. In published reports, TCZ has shown good efficacy for AA amyloidosis, being associated with regression of renal amyloid deposits. Methods Retrospective review that included patients with histological diagnosis of AA renal amyloidosis under treatment with TCZ during the years 2018-2019 in our center. We have registered clinical and demographic variables. Renal function was measured by means of CKD-EPI equation to estimate the glomerular filtration rate (FG) and protein/creatinine ratio (IPC) at 3, 6 and 12 months. We define renal response as a decrease by at least 30% of proteinuria and/or stabilization or improvement of FG. We consider that an anti-inflammatory response is a decrease of more than 50% in serum amyloid protein (PSA) and/or C-reactive protein (CRP). Results We collected 3 cases of patients with histologically proven AA amyloidosis treated with TCZ (2 men; 1 woman; aged 55, 74 and 75 years). The follow-up was 13, 14 and 75 months. FG was stabilized in two patients. The third patient remained on hemodialysis during follow-up, although with excellent control of her underlying inflammatory disease. In all three cases, reduced PSA and CRP were observed. There have been no adverse events. Conclusions The TCZ may be an effective and safe option in treatment of AA amyloidosis with renal involvement. Our results position it as an interesting therapeutic option to consider in these cases, although prospective studies would be necessary to evaluate the global role of TCZ in AA amyloidosis

Nefritis intersicial aguda por rabeprazol

Acute interstitial nephritis is an increasingly common cause of acute kidney damage. The incidence is variable according to the series and challenging to quantify with precision due to the long-time interval between taking the drug and detecting kidney damage. Proton pump inhibitors are currently selected as one of the main drugs responsible for this entity after antibiotics. Early diagnosis and drug withdrawal are essential to treatment. Increased awareness might facilitate more rapid diagnosis and management of this potentially reversible kidney injury and avoid chronic kidney disease.La nefritis tubulointersticial aguda (NTIA) asociada a fármacos es una causa cada vez más frecuente de daño renal agudo. Su incidencia es variable y difícil de cuantificar con precisión por el intervalo de tiempo entre la toma del fármaco y la detección de la lesión renal. Los inhibidores de la bomba de protones (IBP) se consideran uno de los principales fármacos responsables de esta entidad tras los antibióticos. Una mayor conciencia acerca de la NTIA por IBP podría facilitar un diagnóstico y manejo más rápidos de esta lesión renal potencialmente reversible y evitar así la progresión a enfermedad renal crónica

Consensus document for ultrasound training in the specialty of Nephrology

Grupo de Trabajo en Nefrología Diagnóstica e Intervencionista (GNDI) de la Sociedad Española de Nefrología (SEN).[ES] La ecografía es una herramienta esencial en el manejo del paciente nefrológico que permite el diagnóstico, el seguimiento y la realización de intervencionismo sobre el riñón. La utilidad de los ultrasonidos en Nefrología no se circunscribe exclusivamente al estudio ecográfico del riñón. Mediante ecografía el nefrólogo puede, además, optimizar el manejo de la fístula arteriovenosa para hemodiálisis, medir el riesgo cardiovascular (grosor íntima-media), implantar catéteres centrales para hemodiálisis ecoguiados y ayudar en la colocación de los peritoneales, así como calcular la volemia del paciente mediante ecografía cardiaca básica, ecografía de la vena cava inferior y pulmonar. Desde el Grupo de Trabajo en Nefrología Diagnóstica e Intervencionista (GNDI) de la Sociedad Española de Nefrología (SEN) hemos elaborado este documento de consenso en el que se resumen las principales aplicaciones de la ecografía en Nefrología, incluyendo los requisitos técnicos básicos necesarios, el marco normativo y el nivel de capacitación de los nefrólogos en esta materia. El objetivo de este trabajo es promover la inclusión de la ecografía, tanto diagnóstica como intervencionista, en la práctica clínica habitual del nefrólogo y en la cartera de servicios de Nefrología con la finalidad de ofrecer un manejo diligente, eficiente e integral al paciente nefrológico.[EN] Ultrasound is an essential tool in the management of the nephrological patient allowing the diagnosis, monitoring and performance of kidney intervention. However, the usefulness of ultrasound in the hands of the nephrologist is not limited exclusively to the ultrasound study of the kidney. By ultrasound, the nephrologist can also optimize the management of arteriovenous fistula for hemodialysis, measure cardiovascular risk (mean intimate thickness), implant central catheters for ultrasound-guided HD, as well as the patient's volemia using basic cardiac ultrasound, ultrasound of the cava inferior vein and lungs. From the Working Group on Interventional Nephrology (GNDI) of the Spanish Society of Nephrology (SEN) we have prepared this consensus document that summarizes the main applications of ultrasound to Nephrology, including the necessary basic technical requirements, the framework normative and the level of training of nephrologists in this area. The objective of this work is to promote the inclusion of ultrasound, both diagnostic and interventional, in the usual clinical practice of the nephrologist and in the Nephrology Services portfolio with the final objective of offering diligent, efficient and comprehensive management to the nephrological patient

Consensus document for lipid profile determination and reporting in Spanish clinical laboratories

Las enfermedades cardiovasculares (ECV) siguen siendo la principal causa de muerte en nuestro país. El control adecuado de las alteraciones del metabolismo lipídico es un reto clave en prevención cardiovascular que está lejos de alcanzarse en la práctica clínica real. Existe una gran heterogeneidad en los informes del metabolismo lipídico de los laboratorios clínicos españoles, lo que puede contribuir al mal control del mismo. Por ello, un grupo de trabajo de las principales sociedades científicas implicadas en la atención de los pacientes de riesgo vascular hemos elaborado este documento con una propuesta básica de consenso sobre la determinación del perfil lipídico básico en prevención cardiovascular, recomendaciones para su realización y unificación de criterios para incorporar los objetivos de control lipídico adecuados al riesgo vascular de los pacientes en los informes de laboratorio.Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports

Association of Candidate Gene Polymorphisms With Chronic Kidney Disease: Results of a Case-Control Analysis in the Nefrona Cohort

Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2, 445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD

Reflections on the need for Nephropathology Reference Units

RESUMEN1. La ERC tiene una elevada incidencia y prevalencia con unalto impacto sobre la calidad de vida y mortalidad de lospacientes, lo que supone un importante consumo de recur-sos sanitarios.2. En un porcentaje relevante de pacientes no se dispone deun diagnóstico etiológico de la ERC, lo que limita sus posi-bilidades de tratamiento y curación.3. Las acciones dirigidas a mejorar el diagnóstico permitiránfavorecer un mejor conocimiento de las causas de la ERC yoptimizar el tratamiento.4. La biopsia renal, constituye el procedimiento necesa-rio para el estudio histopatológico del tejido renal quepermitirá establecer el diagnóstico, las posibilidades de tra-tamiento y el pronóstico del da˜no renal.5. El trasplante renal constituye la mejor opción de TRS. Lacausa más frecuente de pérdida del injerto renal es elrechazo. La biopsia renal es el único método para establecerel tipo de rechazo e iniciar el tratamiento más adecuado.6. La planificación del tratamiento de la enfermedad renalse establece con base en un diagnóstico preciso y este sebasa en el diagnóstico histológico. La falta de una ade-cuada interpretación diagnóstica, bien por inexperienciadel patólogo, bien por falta de medios diagnósticos (micro-scopia electrónica), condiciona y limita las opciones detratamiento en perjuicio del enfermo

Taurolidina como tratamiento adyuvante en casos de peritonitis recidivante en pacientes en diálisis peritoneal.

Relapsing peritonitis in peritoneal dialysis patients is one of the complications that jeopardizes the continuity of the technique. It is often associated with the formation of biofilm in the lumen of the catheter. To date, its removal remains the only recommended attitude. Due to its antimicrobial and antifungal properties, taurolidine has been previously used for the sealing of central line catheters and hemodialysis. Despite the good results obtained, there is no evidence available regarding its utility in peritoneal dialysis. This case report describes the use of taurolidine (TauroLock™HEP500) in 5 patients with relapsing peritonitis after antibiotic treatment completion. Mean follow-up for the detection of recurrences was 13.4 months. In 4 patients with infections caused by Staphylococcus epidermidis, eradication was achieved. In the remaining case, caused by Staphylococcus aureus, the taurolidine seal was ineffective and the removal of the catheter was required

La inhibición de la interleucina-6 como posible diana terapéutica en la amiloidosis AA.

AA (secondary) amyloidosis is a severe complication of chronic inflammatory disorders. It is characterized by the systemic deposition of an abnormal protein called amyloid, affecting mainly renal function. IL-6 is a cytokine with a relevant role in this disease development. Interleukin-receptor antagonists, like Tocilizumab (TCZ), have become possible treatment choice for AA amyloidosis. In published reports, TCZ has shown good efficacy for AA amyloidosis, being associated with regression of renal amyloid deposits. Retrospective review that included patients with histological diagnosis of AA renal amyloidosis under treatment with TCZ during the years 2018-2019 in our center. We have registered clinical and demographic variables. Renal function was measured by means of CKD-EPI equation to estimate the glomerular filtration rate (FG) and protein/creatinine ratio (IPC) at 3, 6 and 12 months. We define renal response as a decrease by at least 30% of proteinuria and/or stabilization or improvement of FG. We consider that an anti-inflammatory response is a decrease of more than 50% in serum amyloid protein (PSA) and/or C-reactive protein (CRP). We collected 3 cases of patients with histologically proven AA amyloidosis treated with TCZ (2 men; 1 woman; aged 55, 74 and 75 years). The follow-up was 13, 14 and 75 months. FG was stabilized in two patients. The third patient remained on hemodialysis during follow-up, although with excellent control of her underlying inflammatory disease. In all three cases, reduced PSA and CRP were observed. There have been no adverse events. The TCZ may be an effective and safe option in treatment of AA amyloidosis with renal involvement. Our results position it as an interesting therapeutic option to consider in these cases, although prospective studies would be necessary to evaluate the global role of TCZ in AA amyloidosis

Desinfección térmica en hemodiálisis usando el concepto A0 como dosificador.

Patients with chronic kidney disease in the hemodialysis program are exposed to large amounts of water, as this constitutes about 96% of the dialysis fluid. It is known that the use of better quality water decreases the state of chronic inflammation in dialysis patients. Disinfection as part of water treatment plays an important role in meeting the established quality standards; currently, heat disinfection is highly recommended, however its dose is not clearly established in the literature. The objective of this review is to know what is available in the literature on the dose of heat disinfection that should be used in hemodialysis and to present our experience with this method at a set dose of 12.000 A0

Tunneled catheter-related bacteremia in hemodialysis patients: incidence, risk factors and outcomes. A 14-year observational study.

Tunneled catheter-related bacteremia represents one of the major complications in patients on hemodialysis, and is associated with increased morbidity and mortality. This study aimed to evaluate the incidence of tunneled catheter-related bacteremia and, secondly, to identify possible factors involved in the first episode of bacteremia. This is a retrospective study of all tunneled catheters inserted between 1 January, 2005 and 31 December, 2019. Data on patients with a tunneled catheter were analyzed for comorbidities, catheter characteristics, microbiological culture results and variables related to the first episode of bacteremia. Patient outcomes were also assessed. In the 14-year period under study, 406 tunneled catheters were implanted in 325 patients. A total of 85 cases of tunneled catheter-related bacteremia were diagnosed, resulting in an incidence of 0.40 per 1000 catheter days (81.1% after 6 months of implantation). The predominant microorganisms isolated were Gram-positive organisms: Staphylococcus epidermidis (48.4%); Staphylococcus aureus (28.0%). We found no significant differences in time to catheter removal for infections or non-infection-related reasons. The jugular vein, the Palindrome® catheter, and being the first vascular access were protective factors for the first episode of bacteremia. The 30-day mortality rate from the first tunneled catheter-related bacteremia was 8.7%. The incidence of bacteremia in our study was low and did not seem to have a relevant impact on catheter survival. S. epidermidis was the most frequently isolated microorganism, followed by S. aureus. We identified Palindrome® catheter, jugular vein, and being the first vascular access as significant protective factors against tunneled catheter-related bacteremia