Systematic review and meta-analysis of the efficacy of clinically tested protectants of cisplatin nephrotoxicity.

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.

Quercetin, a Promising Clinical Candidate for The Prevention of Contrast-Induced Nephropathy.

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.

Seroprevalence of SARS-CoV-2 Antibodies and Factors Associated with Seropositivity at the University of Salamanca: The DIANCUSAL Study.

BACKGROUND: Systematic screening for antibodies against SARS-CoV-2 is a crucial tool for surveillance of the COVID-19 pandemic. The University of Salamanca (USAL) in Spain designed a project called "DIANCUSAL" (Diagnosis of New Coronavirus, COVID-19, in University of Salamanca) to measure antibodies against SARS-CoV-2 among its ~34,000 students and academic staff, as the influence of the university community in the spread of the SARS-CoV-2 pandemic in the city of Salamanca and neighboring towns hosting USAL campuses could be substantial. OBJECTIVE: The aim of this study was to estimate the prevalence of SARS-CoV-2 antibodies among USAL students, professors and staff and to evaluate the demographic, academic, clinical and lifestyle and behavioral factors related to seropositivity. METHODOLOGY: The DIANCUSAL study is an ongoing university population-based cross-sectional study, with the work described herein conducted from July-October 2020. All USAL students, professors and staff were invited to complete an anonymized questionnaire. Seroprevalence of anti-SARS-CoV-2 antibodies was detected and quantified by using chemiluminescent assays for IgG and IgM. PRINCIPAL FINDINGS: A total of 8197 (24.71%) participants were included. The mean age was 31.4 (14.5 SD) years, and 66.0% of the participants were female. The seroprevalence was 8.25% overall and was highest for students from the education campus (12.5%) and professors from the biomedical campus (12.6%), with significant differences among faculties (p = 0.006). Based on the questionnaire, loss of smell and fever were the symptoms most strongly associated with seropositivity, and 22.6% of seropositive participants were asymptomatic. Social distancing was the most effective hygiene measure (p = 0.0007). There were significant differences in seroprevalence between participants with and without household exposure to SARS-CoV-2 (p = 0.0000), but not between students who lived in private homes and those who lived in dormitories. IgG antibodies decreased over time in the participants with confirmed self-reported COVID-19 diagnoses. CONCLUSIONS: The analysis revealed an overall 8.25% seroprevalence at the end of October 2020, with a higher seroprevalence in students than in staff. Thus, there is no need for tailored measures for the USAL community as the official average seroprevalence in the area was similar (7.8% at 22 June and 12.4 at 15 November of 2020). Instead, USAL members should comply with public health measures.

Designing new diagnostic systems for the early detection of tobacco-associated chronic renal damage in patients of a primary care centre in Salamanca, Spain: an observational, prospective study protocol.

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.

A systematic meta-analysis on the efficacy of pre-clinically tested nephroprotectants at preventing aminoglycoside nephrotoxicity.

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.

Sub-nephrotoxic cisplatin sensitizes rats to acute renal failure and increases urinary excretion of fumarylacetoacetase.

Nephrotoxicity limits the therapeutic efficacy of the antineoplastic drug cisplatin. Due to dosage adjustment and appropriate monitoring, most therapeutic courses with cisplatin produce no or minimal kidney damage. However, we studied whether even sub-nephrotoxic dosage of cisplatin poses a potential risk for the kidneys by predisposing to acute kidney injury (AKI), specifically by lowering the toxicity threshold for a second nephrotoxin. With this purpose rats were treated with a single sub-nephrotoxic dosage of cisplatin (3mg/kg, i.p.) and after two days, with a sub-nephrotoxic regime of gentamicin (50mg/kg/day, during 6 days, i.p.). Control groups received only one of the drugs or the vehicle. Renal function and renal histology were monitored throughout the experiment. Cisplatin treatment did not cause any relevant functional or histological alterations in the kidneys. Rats treated with cisplatin and gentamicin, but not those under single treatments, developed an overt renal failure characterized by both renal dysfunction and massive tubular necrosis. In addition, the urinary excretion of fumarylacetoacetase was increased in cisplatin-treated animals at subtoxic doses, which might be exploited as a cisplatin-induced predisposition marker. In fact, the urinary level of fumarylacetoacetase prior to the second nephrotoxin correlated with the level of AKI triggered by gentamicin in predisposed animals.

Genotype profiles for the Costa Rican population at 7 PCR-based loci.

Complete electronic DNA profiles of 2006 randomly selected Costa Ricans, typed for 7 PCR-based loci, are presented. Such data may prove valuable for anthropological and forensic studies of the Costa Rican population.

Increased urinary excretion of albumin, hemopexin, transferrin and VDBP correlates with chronic sensitization to gentamicin nephrotoxicity in rats.

Drug nephrotoxicity is a serious health and economic problem worldwide. Rats can be acutely sensitized to acute kidney injury (AKI) by subnephrotoxic treatments with potentially nephrotoxic drugs. Acquired sensitization to AKI poses a silent risk impossible to diagnose pre-emptively with the technology available at the clinical level. Herein, we hypothesized whether a chronic, subnephrotoxic insult to the kidneys might result in chronically acquired sensitization to AKI, and whether chronic sensitization might be detected through specific urinary markers. To this end, rats were treated with a subtoxic dosage of the experimental nephrotoxin uranyl nitrate (UN) in the drinking water for 21 weeks, or plain water (as control), and then with low-dose gentamicin for 7 days. Renal function and renal tissue damage were evaluated through the experiment. The mild renal damage caused by gentamicin was markedly magnified in rats having received UN chronically, which was evident both at the functional and histological level. Four proteins, namely albumin, hemopexin, transferrin and vitamin D binding protein were increased in the urine in temporal association with the appearance of chronic predisposition. Although further studies are necessary, our results suggest that these proteins might be potentially used as markers of hidden, chronic predisposition to gentamicin nephrotoxicity, in order to appropriately and pre-emptively stratify and handle individuals according to their specific risk in the long term, and to conveniently optimize their life conditions or additional clinical procedures or treatments that might trigger the disease. This might reduce AKI incidence and severity and the associated costs.

Aplicación del índice biótico de familias de macroinvertebrados para la caracterización del agua del río teusacá, afluente del río bogotá / Application of the family biotic index of macroinvertebrates for water characterization of the teusaca river, tributary of the bogota river

RESUMEN La subcuenca del Río Teusacá presenta alta actividad urbanística e industrial en, aproximadamente, el 50% de su superficie, lo cual, ha generado vertimientos de aguas residuales al ambiente acuático. El objetivo de este estudio fue caracterizar la calidad del agua, con base en el Índice Biótico de Familias (IBF), en dos sectores (alto y bajo) del río, en dos temporadas (seca y lluviosa) y analizar la correlación del IBF con: COT, fosfatos, sulfatos, nitratos, nitritos e índices de diversidad. Los muestreos, se realizaron con una red Surber (malla 500 micras y 0,09m2 de área), en 10 sitios, distribuidos en el curso principal: en octubre de 2016, al finalizar una temporada seca y en julio de 2017, al terminar una temporada lluviosa. En total, se registraron 35 taxones y los órdenes con más familias fueron: Diptera (28%), Coleoptera (17%) y Hemiptera (11%). El IBF presentó correlación positiva (>76%) con los contaminantes químicos y se observó que los principales contaminantes del río fueron los fosfatos y el COT, mientras que el IBF con los índices de diversidad, no mostró correlación. La calidad del agua en el sector alto del río estuvo entre buena y regular en ambas temporadas, mientras que en el sector bajo estuvo entre malsana y muy nociva. Estos resultados sugieren que en IBF es un buen indicador de la calidad de agua en los ríos.

ABSTRACT The Teusacá River subbasin presents high industrial and urbanization activities in approximately 50% of its surface, which has generated discharges of waste water and pollutants into the aquatic environment. The aim of this study was to characterize the quality of water based on the insect family biotic index (FBI) in two river sectors (low and high) in two seasons (dry and rainy) and to analyze the FBI correlation with: TOC, phosphates sulphates, nitrates, nitrites and diversity indices. Sampling was carried out in October 2016 and in July 2017 at the end of the dry season and the rainy season, repectively, using a Surber net (500 microns and 0.09m2) at 10 sites, distributed along in the main course of the river. A total of 35 taxa were recorded, the groups with more families were: Diptera (28%), Coleoptera (17%) and Hemiptera (11%). The IBF was significantly and positively correlated with chemical pollutants (>76%) and the main pollutants of the River observed were phosphates and the TOC; while the IBF was not correlated with the diversity indices. The water quality in the high river sector was between good and regular in both seasons; while in the lower river sector it was very harmful and unhealthy. The results obtained suggest that the FBI is an appropriate indicator for determining the water quality of the river.

Nephrotoxicity of uranium: pathophysiological, diagnostic and therapeutic perspectives.

As in the case of other heavy metals, a considerable body of evidence suggests that overexposure to uranium may cause pathological alterations to the kidneys in both humans and animals. In the present work, our aim was to analyze the available data from a critical perspective that should provide a view of the real danger of the nephrotoxicity of this metal for human beings. A further aim was to elaborate a comparative compilation of the renal pathophysiological data obtained in humans and experimental animals with a view to gaining more insight into our knowledge of the mechanisms of action and renal damage. Finally, we address the existing perspectives for the improvement of diagnostic methods and the treatment of intoxications by uranium, performing an integrated analysis of all these aspects.

Conciliación de la medicación en farmacia comunitaria / Reconciliation of the medication in community pharmacy

Introducción: La conciliación del tratamiento farmacológico consiste en revisar y registrar de forma completa y precisa la medicación habitual de un paciente, con objeto de conseguir la seguridad del mismo en cuanto al uso de los medicamentos. El objetivo principal de este estudio es cuantificar las discrepancias de conciliación producidas como consecuencia de la transición sanitaria del paciente entre los distintos niveles asistenciales. Métodos: Estudio piloto descriptivo multicéntrico desarrollado con 29 pacientes en seis farmacias comunitarias onubenses durante tres meses. Se estudia el tratamiento farmacológico del paciente comparando su tratamiento habitual con el nuevo tratamiento instaurado. Para la toma de decisiones se emplean la Base de Datos de Medicamentos y Productos Sanitarios, el método Dáder en seguimiento farmacoterapéutico y los criterios Stopp-Start en pacientes mayores de 65 años. Resultados: En un 37,9% de los pacientes estudiados se encontraron discrepancias en la medicación, principalmente en pacientes que proceden del hospital (36,4% tras alta hospitalaria y 45,5% tras visita al especialista). Las discrepancias mayoritarias tras la conciliación se detectan en la patología cardiovascular, seguida en menor medida por la patología renal. En un 36,4% de los casos el tipo de error observado ha sido la duplicidad de tratamiento farmacológico para una misma patología y en un 27,3% de los pacientes se detectaron enfermedades que no estaban siendo tratadas. Asimismo, se observaron pautas erróneas en el tratamiento (18,2%) y dosis erróneas de administración (9,1%). Un 81,8 % de los pacientes fue derivado al médico. Conclusión: Las discrepancias en el tratamiento farmacológico de un paciente tras el cambio de nivel asistencial son muy elevadas. Dado que el farmacéutico comunitario es el último profesional sanitario en contacto con el paciente antes de la administración del medicamento, su intervención permite detectar estas discrepancias, disminuyendo la morbilidad asociada a las mismas y contribuyendo a garantizar la continuidad asistencial (AU)

Introduction: Proper usage of medicines is the main objective of the medication reconciliation. It consists of a method to review systematically the patient medicine intakes to guarantee their safety. Objectives: This paper aims to demonstrate the correlation between failure in treatment reconciliation and patient changes in the different care levels. Methods: A multisite descriptive pilot study was developed in six pharmacies from Huelva for three months. Twenty nine patients’ ordinary pharmacological treatments were compared to new prescribed treatments. BOT PLUS medicine database, Dader method and Stopp-Start criteria were used in the decision making process to analyze data. Results: A 37.9% patients show discrepancies in their pharmacological treatments, mainly those who come from a hospital discharge (36.4%) and those who come from specialists (45.5%). Heart disease patients showed the highest discrepancies, followed by kidney disease patients. Discrepancies were due to double prescription for the same pathology (36.4%) and non treatment diseases detection (27.3%). Additionally, mistakes in treatment (18.2%) and mistakes in dosage prescription (9.1%) were observed. As a consequence, 81.8% were sent back to receive medical attention. Discussion: As a summary, discrepancies in pharmacological treatments are found to be very high when patients change care levels. Pharmacist role to avoid these discrepancies is key, since they are the last sanitary professional in contact with the patient before medicines intake (AU)

Acute renal toxic effect of amiodarone in rats.

Amiodarone is an antiarrhythmic drug now more frequently used after a number of years in which the use had been on the decline due to a number of studies which reported side effects such as chronic toxicity, primarily in the lungs, liver and thyroid glands. Additionally, in some patients an increase in serum creatinine was noted, however the effect of amiodarone on renal function had never been closely examined. Thus, the aim of our study was to analyse the effects of amiodarone on renal function in rats. Experiments were carried out in male Wistar rats divided in two experimental groups: 1) a control group, (n=8), 2) a group that received a daily intraperitoneal injection of amiodarone (50 mg/kg body weight) for 6 days (n=5). At the end of the treatment, renal function was measured by clearance creatinine and acute clearance studies. Renal toxicity was evaluated by urinary N-acetyl-glucosamine and alkaline phosphatase. At the end of the experiment, histology studies were done. Rats treated with amiodarone had a higher serum creatinine (182%) and a lower glomerular filtration rate (53%), renal plasma flow (68%) and filtration fraction (62%) than controls. Rats treated with amiodarone also showed an increase in urinary N-acetyl-glucosamine (221%) and alkaline phosphatase (4.151%) excretion which corresponds with tubular alterations showed on electron microscopy. In conclusion our data confirm that amiodarone induces acute renal damage in the rat.

La implementación forense de la tecnología del ADN en Costa Rica: un análisis retrospectivo: [revisión] / Forensic implementation of DNA technology in Costa Rica: a retrospective analysis: [review]

La reciente utilización de la tecnología del ADN para la identificación individual a traído consigo una revolución en las ciencias forenses, que ha alcanzado también a la America Latina. El análisis histórico muestra que en Costa Rica sehan logrado importantes avances y en la actualidad se encuentra consolidado el trabajo con los STRs, y se están en proceso de implementación los marcadores de ADNmt y del cromosoma Y. Sin embargo, la incorporación delas innovaciones de la genética forense se ha venido realizando, cíclicamente, de 5 a 10 años tarde respecto a lospaises desarrollados en este campo. Se espera un cambio de actitud en el futuro, al estar disponibles nuevas generacionesde marcadores de ADN, que permitan explotar a corto plazo todo el potencial de esta útil herramienta al servicio de la justicia.