NLRP3 inflammasome: A therapeutic option for kidney disease? / El inflamasoma NLRP3: ¿Es realmente una opción terapéutica para la enfermedad renal?

ABSTRACT Objective To determine if considering inflammasome NLRP3 as a treatment option for kidney disease is possible. Methods Literature review related to NLRP3 inflammasome structure, biological function and relationship with renal disease and others (hypertension, diabetes, gout, atherosclerosis, amyloidosis, Alzheimer's disease); the systematic review was made searching in the databases PubMed and SciELO for the following terms: "The NLRP3 inflammasome therapeutic for kidney disease", "NLRP3 nflammasome in kidney disease" in PubMed, and "Inflammasome" for Scielo. Results 146 documents were found, althoughonly 34 matched the working hypothesis concerning the NLRP3 inflammasome as a central component of various diseases in humans, with potential therapeutic use. The NLRP3 inflammasome is responsible for the maturation of inflammatory pro-interleukin IL-1 β and IL-18, which can be triggered by aggregated or crystalline materials (particles), and by various microorganisms and toxins derived from these; however, the way how activation mechanisms work is not completely clear. Conclusions Research on new therapies that focus on removing or inhibiting inflammasome components, both individually and together, is proposed.(AU)

RESUMEN Objetivo Determinar si el inflamasoma NLRP3 puede considerarse como opción de tratamiento para la enfermedad renal. Métodos Con el fin de encontrar bibliografía relacionada con la estructura del inflamasoma NLRP3, su función biológica y su relación con la enfermedad renal y otras (hipertensión, diabetes, gota, aterosclerosis, amiloidosis, enfermedad de Alzheimer), se realizó una revisión sistemática en dos bases de datos (PubMed y SciELO) con los términos: "NLRP3 inflammasome therapeutic for kidney disease" y "NLRP3 inflammasome in kidney disease" en PubMed, e "Iinflammasome" en SciELO. Resultados Se encontró un total de 146 documentos, de los cuales solo 34 concuerdan con la hipótesis de trabajo desarrollada con relación al inflamasoma NLRP3 como componente central de diversas enfermedades en seres humanos y con potencial uso terapéutico. El inflamasoma NLRP3 es responsable de la maduración de la interleucina inflamatoria pro-IL-1 β y IL-18, l cual puede darse por causa de materiales agregados o cristalinos (partículas), y por diversos microorganismos y toxinas derivadas de los mismos; sin embargo, los mecanismos de activación de este proceso siguen sin ser claros en la actualidad. Conclusiones Se propone estudiar nuevas terapias que se centren en la eliminación o inhibición de los componentes inflamasoma, de manera individual y conjunta.(AU)

Relationship between disease stage and renal function in bisphosphonate-related osteonecrosis of the jaw

OBJECTIVES: Bisphosphonate is the primary cause of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Bisphosphonates are eliminated from the human body by the kidneys. It is anticipated that bisphosphonate levels in the body will increase if the kidney is in a weak state or if there is systemic disease that affects kidney function. The aim of this study was to analyze the relevance of renal function in the severity of BRONJ. MATERIALS AND METHODS: Ninety-three patients diagnosed with BRONJ in Pusan National University Dental Hospital from January 2012 to December 2014 were included in this study. All patients underwent a clinical exam, radiographs, and serologic lab test, including urine analysis. The patient's medical history was also taken, including the type of bisphosphonate drug, the duration of administration and drug holiday, route of administration, and other systemic diseases. In accordance with the guidelines of the 2009 position paper of American Association of Oral and Maxillofacial Surgeons, the BRONJ stage was divided into 4 groups, from stage 0 to 3, according to the severity of disease. IBM SPSS Statistics version 21.0 (IBM Co., USA) was used to perform regression analysis with a 0.05% significance level. RESULTS: BRONJ stage and renal factor (estimated glomerular filtration rate) showed a moderate statistically significant correlation. In the group with higher BRONJ stage, the creatinine level was higher, but the increase was not statistically significant. Other factors showed no significant correlation with BRONJ stage. There was a high statistically significant correlation between BRONJ stage and ‘responder group’ and ‘non-responder group,’ but there was no significant difference with the ‘worsened group.’ In addition, the age of the patients was a relative factor with BRONJ stage. CONCLUSION: With older age and lower renal function, BRONJ is more severe, and there may be a decrease in patient response to treatment.

Factores de progresión de disfunción renal en diabéticos ingresados en Medicina Interna / Renal disease´s progression factors in diabetic people admitted in Internal Medicine

Introducción: la nefropatía diabética es un factor de riesgo para desarrollar eventos cardiovasculares. Debido a que si su presencia se establece se reduce el filtrado glomerular y se acelera la aterosclerosis. Existen muchos factores de progresión que comprometen aun más sus aspectos fisiopatológicos y el pronóstico. Objetivo: caracterizar factores de progresión de disfunción renal en diabéticos ingresados en el Servicio de Medicina Interna, período 2012 a 2013. Materiales y Métodos: se realizó un estudio descriptivo, transversal y observacional en diabéticos ingresados en Servicio de Medicina Interna, Hospital Militar de Matanzas, con menos de diez años de evolución, en el período de 2012 a 2013; con consentimiento informado de pacientes y Jefe del Servicio. Se caracterizó la función renal para detectar precozmente factores de progresión de nefropatía diabética, en cada uno, en cuanto a filtrado glomerular y microalbuminuria. Para ello se revisaron historias clínicas. Las variables de afectación renal con factores de riesgo de progresión, tanto clínicos como paraclínicos fueron: edad, microalbuminuria, alteraciones del filtrado glomerular, hiperuricemia, dislipidemia, hiperglucemia, nivel de tensión arterial, sedentarismo, dieta y hábitos tóxicos. Usando la planilla de recolección de datos y la representación mediante tablas, números y por ciento. Resultados: la hipertrigliceridemia, hiperuricemia e hiperglucemia constituyeron los más asociados a descenso del filtrado glomerular y microalbuminuria positiva con 94,44 %, 80,33 % y 48,24 % respectivamente; en tan solo diez años de evolución de la diabetes. Conclusiones: evidente presencia de factores de progresión de enfermedad renal crónica en pacientes diabéticos.

Introduction: Diabetic Nephropathy is a very important risk factor for the development of cardiovascular disorders. It´s related with glomerular filtrate reduction and atherosclerosis. Then also many renal disease´s progression factors affect their physiophatological aspects and the prognosis. Objective: To caracterize renal disease´s progression factors in diabetic people admitted in Internal Medicine period of 2012 to2013. Materials and Methods: A retrospective descriptive longitudinal study was carried out. The sample was formed by 496 patients entered in the Internal Medicine Service, Military Hospital of Matanzas, and they haved less than ten years of evolution of their illness, in the understood period of 2012 at 2013. The used variables of chronic renal disease´s progression factors were: age, microalbuminuria, glomerular filtrate, toxic habits, diet, sedentarism, blood pressure level, serum uric acid and lipid levels. For organizing the obtained indicators authors applied the descriptive statistic method, analyzing the information through distribution tables. The results were represented in numbers and percent. Results: The most associated renal disease´s progression factors were hypertrygliceridemia, hyperuricemia and hyperglucemia. They respectively showed about 94,44 %, 80,33 % and 48,24 %. They were also associated with the worst affectation on glomerular filtrate and microalbuminuria in less than ten years old of diabetes evolution. Conclusions: there is a high presence of chronic renal disease´s progression factors in diabetic people.