RESUMEN
INTRODUCTION: Tobacco causes kidney damage that can progress to chronic kidney disease. However, the diagnostic parameters used in clinics are not effective in identifying smokers at risk. Our first objective is to more effectively detect subclinical renal damage in smokers. In addition, we hypothesise that tobacco consumption can predispose smokers to renal damage on exposure to other potentially nephrotoxic events (drugs, diagnostic procedures and so on). We will test this hypothesis in our second objective by investigating whether certain predisposition markers (GM2 ganglioside activator protein (GM2AP), transferrin and t-gelsolin) are able to detect smokers who are predisposed to kidney damage. Finally, in our third objective, we will study whether smoking cessation reduces subclinical and/or predisposition to renal damage. METHODS AND ANALYSIS: For our first objective, a prospective cross-sectional study will be carried out with patients from a primary healthcare centre. The influence of tobacco on renal damage, in patients both with and without additional risk factors, will be studied using a panel of early biomarkers (albuminuria, N-acetyl-beta-D-glucosaminidase, kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin). For our second objective, a prospective longitudinal study will be carried out with patients recruited for our first objective. We will study whether certain predisposition biomarkers (GM2AP, transferrin and t-gelsolin) are able to detect smokers predisposed to renal damage. For our third objective, a prospective longitudinal study will be carried out with patients from a smoking cessation unit. We will study the evolution of the markers described above following smoking cessation. ETHICS AND DISSEMINATION: The study has been approved by the Clinical Research Ethics Committee of the Healthcare Area of Salamanca. All study participants will sign an informed consent form in compliance with the Declaration of Helsinki and the WHO standards for observational studies. Results will be presented at conferences and submitted to peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03850756.
Asunto(s)
Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/etiología , Uso de Tabaco/efectos adversos , Albuminuria/sangre , Biomarcadores , Estudios Transversales , Proteína Activadora de G (M2)/sangre , Gelsolina/sangre , Humanos , Pruebas de Función Renal , Estudios Longitudinales , Atención Primaria de Salud , Estudios Prospectivos , Proyectos de Investigación , Factores de Riesgo , Índice de Severidad de la Enfermedad , España , Transferrina/análisisRESUMEN
INTRODUCTION: Cisplatin is a potent antineoplastic drug that has been widely used to treat a number of solid tumors. However, a high incidence of renal damage observed in patients has led researchers to search for alternate strategies that prevent or at least reduce the cisplatin-induced nephrotoxicity. The objective of the present study was to conduct a systematic review and a subsequent meta-analysis to evaluate and identify compounds with effective antitumor activity and lesser side effects that could provide protection against cisplatin-induced nephrotoxicity. METHODS: The study included all placebo-controlled trials published up to December 2017 that met the inclusion criteria. A total of 22 articles were finally included to extract the following information: number of patients, doses of cisplatin and protectant, qualitative (acute kidney injury incidence) and quantitative (plasma creatinine, blood urea nitrogen, and creatinine clearance) indicators of renal function. The odds ratio or the mean difference (95% confidence interval) of each parameter was calculated for each study and group of studies. RESULTS: The results of this meta-analysis show that there is great variability in the nephroprotective capacity of a variety of products evaluated. Of all the compounds tested, only magnesium sulfate and cystone were found to exert protective effects. However, more studies need to be conducted to confirm these results. CONCLUSIONS: The administration of 1 g of Mg i.v. seems to be the best strategy for the prevention of cisplatin nephrotoxicity.
Asunto(s)
Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiología , Cisplatino/efectos adversos , Cisplatino/farmacología , Neoplasias/tratamiento farmacológico , Creatinina/sangre , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Riñón/efectos de los fármacosRESUMEN
Iodinated contrast media (CM) are the leading cause of acute renal failure of toxic origin. Between 21% and 50% of patients that receive them develop contrast-induced nephropathy (CIN). All prophylactic measures used so far have failed to provide effective prevention. Since oxidative stress is involved in the damage, a possible preventive strategy could be the administration of antioxidant substances, such as quercetin. This compound has shown renoprotective effects in experimental studies. The aim of this study was to evaluate whether quercetin may be helpful in preventing CIN in patients undergoing coronary catheterization. A clinical phase II study was conducted. Patients were distributed in two groups, namely, CM (patients who only received contrast media) and CM+Q (patients who were pretreated with quercetin orally for 3-5 days). Results showed less incidence of CIN in the CM+Q group, possibly due to glomerular protection, evidenced by a lower increase in serum creatinine and albuminuria; and a lower decrease in the glomerular filtration rate (GFR). Furthermore, in this group, the relative risk of developing CIN observed in patients that received a high dose of contrast media was inferior. In conclusion, this is the first study that demonstrates that quercetin is a promising safe candidate in preventing CIN.
Asunto(s)
Medios de Contraste/efectos adversos , Enfermedades Renales/etiología , Enfermedades Renales/prevención & control , Sustancias Protectoras/farmacología , Quercetina/farmacología , Anciano , Biomarcadores , Medios de Contraste/administración & dosificación , Medios de Contraste/clasificación , Creatinina/metabolismo , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Enfermedades Renales/diagnóstico , Enfermedades Renales/metabolismo , Masculino , Sustancias Protectoras/uso terapéutico , Quercetina/uso terapéuticoRESUMEN
The clinical utility of aminoglycoside antibiotics is partly limited by their nephrotoxicity. Co-administration of a variety of candidate nephroprotectants has been tested at the preclinical level. According to a recent meta-analytic study, antioxidants are the only family of compounds with enough preclinical documentation to draw solid conclusions on their class nephroprotective capacity in animal models. In this study a systematic analysis of the relation between the level of antioxidation and the level of nephroprotection was performed. A regression model is presented which crosses the y-axis (i.e. the axis representing the level of nephroprotection) very nearly the zero value, meaning that maximal prevention of the oxidative stress induced by aminoglycosides results in almost maximal nephroprotection. This indicates that oxidative stress plays a central role in the hierarchy of pathophysiological mechanisms underlying aminoglycoside nephrotoxicity. In addition, this model may potentially serve: i) as a standard to evaluate the role of the antioxidant effect of candidate nephroprotectants; ii) to reveal additional, antioxidant-independent effects among those compounds providing more nephroprotection than that expected from its antioxidant activity; and thus iii) to discriminate and focus most effective nephroprotectants on clinical usage.
Asunto(s)
Lesión Renal Aguda/metabolismo , Antibacterianos , Gentamicinas , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/farmacología , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Animales , Catalasa/metabolismo , Modelos Animales de Enfermedad , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Malondialdehído/metabolismo , Ratones , Sustancias Protectoras/uso terapéutico , Ratas , Superóxido Dismutasa/metabolismoRESUMEN
Nephrotoxicity limits the use of aminoglycoside antibiotics. Kidney damage is produced mainly in the renal tubule due to an inflammatory and oxidative process. At preclinical level, many drugs and natural products have been tested as prospective protectors of aminoglycoside nephrotoxicity. The main objective of this work was to make a systematic literature review of preclinical studies about aminoglycoside nephrotoxicity protection and a statistical analysis based on the meta-analysis methodology. Studies published up to January 2016 were identified. After applying inclusion criteria, 54 studies were chosen. The size of the experimental groups, means and standard deviations of data on renal function (i.e. plasma creatinine and blood urea nitrogen [BUN] concentrations) were extracted and registered in a database. The studies were grouped according to the mechanism of nephroprotection and their route of administration. The Mean Difference (95% confidence interval) was calculated for each study and group. 40 of 54 products tested produced an amelioration of aminoglycoside nephrotoxicity based on creatinine results. Also a dose dependent protective effect was observed (both in creatinine and BUN). Products orally administered were more effective than via i.p. Products with attributed antioxidant activity were the most used and those which proved statistically significant nephroprotection as a class effect. Aminoglycoside tubular reuptake inhibitors, excretion inducers and calcium channel blockers also showed a promising and rather homogeneous class tendency towards nephroprotection, although more research is necessary to obtain solid and conclusive results, based on a larger number of studies.
Asunto(s)
Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/prevención & control , Aminoglicósidos/toxicidad , Extractos Vegetales/uso terapéutico , Sustancias Protectoras/uso terapéutico , Lesión Renal Aguda/sangre , Animales , Evaluación Preclínica de Medicamentos/métodos , Resultado del TratamientoRESUMEN
Registra un total de 323 libros impresos en los siglos XVI, XVII y XVIII, relacionados con la medicina y que se encuentran en la biblioteca histórico-médica Doctor Nicolás León de la Facultad de Medicina de la Universidad Nacional Autónoma de México. Contiene quatro secciones: catálogo bibliográfico, índice temático, índice de autores y índice cronológico.
Asunto(s)
Historia del Siglo XVI , Historia del Siglo XVII , Historia del Siglo XVIII , Bibliografía de Medicina , Almacenamiento y Recuperación de la Información , MéxicoRESUMEN
Registra un total de 323 libros impresos en los siglos XVI, XVII y XVIII, relacionados con la medicina y que se encuentran en la biblioteca histórico-médica Doctor Nicolás León de la Facultad de Medicina de la Universidad Nacional Autónoma de México. Contiene quatro secciones: catálogo bibliográfico, índice temático, índice de autores y índice cronológico.(AU)