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

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

[Background] 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.[Methods] 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.[Results] 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%.[Conclusions] 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.FISEVI (Andalusian Public Foundation for the Management of Health Research in Seville) paid the fees for publication.Peer reviewe

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

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