Green coffee bean extract attenuates gentamicin induced acute nephrotoxicity in rats / El extracto de grano de café verde atenúa la nefrotoxicidad aguda inducida por gentamicina en ratas

Gentamicin induced acute nephrotoxicity (GIAN) is considered as one of the important causes of acute renal failure. In recent years' great effort has been focused on the introduction of herbal medicine as a novel therapeutic agent for prevention of GIAN. Hence, the current study was designed to investigate the effect of green coffee bean extract (GCBE) on GIAN in rats. Results of the present study showed that rat groups that received oral GCBE for 7 days after induction of GIAN(by a daily intraperitoneal injection of gentamicin for 7days), reported a significant improvement in renal functions tests when compared to the GIAN model groups. Moreover, there was significant amelioration in renal oxidative stress markers (renal malondialdehyde, renal superoxide dismutase) and renal histopathological changes in the GCBE-treated groups when compared to GIAN model group. These results indicate that GCBE has a potential role in ameliorating renal damage involved in GIAN.

La nefrotoxicidad aguda inducida por gentamicina (GIAN) se considera una de las causas importantes de insuficiencia renal aguda. En los últimos años, el gran esfuerzo se ha centrado en la introducción de la medicina herbal como un nuevo agente terapéutico para la prevención de GIAN. Por lo tanto, el estudio actual fue diseñado para investigar el efecto del extracto de grano de café verde (GCBE) sobre la GIAN en ratas. Los resultados del presente estudio mostraron que los grupos de ratas que recibieron GCBE oral durante 7 días después de la inducción de GIAN (mediante una inyección intraperitoneal diaria de gentamicina durante 7 días), informaron una mejora significativa en las pruebas de función renal en comparación con los grupos del modelo GIAN. Además, hubo una mejora significativa en los marcadores de estrés oxidativo renal (malondialdehído renal, superóxido dismutasa renal) y cambios histopatológicos renales en los grupos tratados con GCBE en comparación con el grupo del modelo GIAN. Estos resultados indican que GCBE tiene un papel potencial en la mejora del daño renal involucrado en GIAN.

Can paricalcitol increase the effectiveness of n-acetylcysteine in contrast induced acute kidney prophylaxis in rats? A biochemical and histopathological study / ¿Puede el paricalcitol aumentar la eficacia de la n-acetilcisteína en la profilaxis renal aguda inducida por contraste en ratas? Un estudio bioquímico e histopatológico

SUMMARY: N-Acetylcysteine (NAC) is used for contrast induced acut kidney injury (CI-AKI) prophylaxis because of its antioxidant effects. Paricalcitol, which has reno-protective effects, is likely to provide a more effective prophylaxis when added to NAC treatment. The study was designed based on this hypothesis. The study was organised to include 4 groups each consisting of 7 rats. Group 1 was the control group, and Group 2 included rats with CI-AKI. Rats in Group 3 were administered NAC at a dose of 100 mg/kg via oral gavage once a day for 5 days. Rats in group 4 were administered paricalcitol at a dose of 0.4 mcg/kg once a day for 5 days in addition to NAC. CI-AKI was induced after the treatments in both groups. The study was terminated on the sixth day. Samples were collected from the rats' sera and kidney tissues to study oxidant and antioxidant parameters; kidney function tests were also studied. There were significant differences between the contrast nephropathy group (Group 2) and NAC and NAC+paricalcitol groups with respect to serum urea and creatinine levels. When the same groups were compared regarding oxidant (TOS-MDA) and antioxidant (TAC-Paraoxonase) parameters, we observed that the oxidant parameters increased in serum and kidney tissue samples with NAC use, and that effect was strengthened by the addition of paricalcitol to NAC treatment. However, despite increased antioxidant effectiveness, we observed no decrease in urea and creatinine levels when paricalcitol was added for CI-AKI in rats. There was no significant difference between Group 3 and Group 4. Paricalcitol provides a more potent antioxidant effect in both serum and kidney tissue samples when added to NAC treatment in rats with CI-AKI. Despite increased antioxidant parameters, however, paricalcitol does not provide a significant decrease in urea and creatinine levels.

RESUMEN: Debido a sus efectos atioxidantes la N- acetilcisteína (NAC) se usa para la profilaxis de la lesión renal aguda inducida por contraste (CI-AKI). Es probable que el paricalcitol, que tiene efectos renoprotectores, proporcione una profilaxis más eficaz cuando se agrega al tratamiento con NAC. En base a esta hipótesis el estudio fue diseñado para incluir cuatro grupos cada uno compuesto por siete ratas. El grupo 1 fue el grupo control y el grupo 2 incluyó ratas con CI-AKI. A las ratas del Grupo 3 se les administró NAC con una dosis de 100 mg/kg por sonda oral una vez al día, durante 5 días. A las ratas del grupo 4 se les administró paricalcitol a una dosis de 0,4 mcg/kg una vez al día durante 5 días, además de NAC. Se indujo CI-AKI después de los tratamientos en ambos grupos. El estudio finalizó el sexto día. Se recolectaron muestras de suero y tejidos renales de ratas para estudiar los parámetros oxidantes y antioxidantes; También se estudiaron las pruebas de función renal. Hubo diferencias significativas entre el grupo de nefropatía por contraste (Grupo 2) y los grupos NAC y NAC+paricalcitol con respecto a los niveles séricos de urea y creatinina. Cuando se compararon los mismos grupos con respecto a los parámetros oxidantes (TOS-MDA) y antioxidantes (TAC-Paraoxonase), observamos que los parámetros oxidantes aumentaron en muestras de suero y tejido renal con el uso de NAC, y ese efecto se vio reforzado por la adición de paricalcitol a tratamiento NAC. Sin embargo, a pesar de una mayor eficacia antioxidante, no observamos una disminución en los niveles de urea y creatinina cuando se agregó paricalcitol para CI-AKI en ratas. No hubo diferencias significativas entre el Grupo 3 y el Grupo 4. El paricalcitol proporciona un efecto antioxidante más potente tanto en muestras de suero como de tejido renal cuando se agrega al tratamiento con NAC en ratas con CI-AKI. Sin embargo, a pesar del aumento de los parámetros antioxidantes, el paricalcitol no proporciona una disminución sig- nificativa en los niveles de urea y creatinina.

Suppression of diabetes-induced renal inflammatory cell infiltration by metformin associated with the amelioration of renal injury biomarkers / Supresión de la infiltración de células inflamatorias renales de diabetes-inducida, por metformina asociada con la mejora de los biomarcadores de lesión renal

SUMMARY: Diabetes and hypertension account for the majority of chronic kidney injury cases that can lead to renal failure. The link between the leukocytes common antigen (CD45) and diabetic kidney disease (DKD) with and without metformin incorporation in an animal model has not been investigated before. Therefore, we sought to assess the extent of leukocytes infiltration into kidney tissues 10 weeks following the induction of diabetes in rats treated with metformin. In addition, we monitored blood and urine parameters associated with diabetes. The model group of rats received streptozotocin (STZ; 50 mg/kg) injection after being fed for 14 days on a high-fat diet (HFD) and continuously fed a HFD until they were culled, at week 12. The protective group was treated in the same way except that these animals were put from day 1 on metformin (200 mg/kg) until being culled, on week 12. Kidneys were immunostained with CD45 as a marker of leukocytes infiltration and examined by light microscopy. Urine samples were tested for urine albumin and collected blood was analyzed for sugar, urea, creatinine, and oxidative stress and antioxidants biomarkers. Kidney injury secondary to diabetes was developed as demonstrated by (i) increased blood glucose, urea, and malondialdehyde (MDA) as a marker of lipid peroxidation; and (ii) kidney tissue damage and marked increase in kidney tissues expressing CD45 positive cells. The above markers were inhibited (p0.0006) by metformin. Also, a significant correlation was observed between CD45 score and glycemia, urea, MDA, and the antioxidant superoxide dismutase (SOD). Thus, our data demonstrate an association between the infiltration of CD45+ inflammatory cells into kidney tissues and biomarkers of kidney damage in a rat model of DKD, which was effectively protected by metformin.

RESUMEN: La diabetes y la hipertensión representan la mayoría de los casos de lesión renal crónica que pueden provocar insuficiencia renal. El vínculo entre el antígeno común de los leucocitos (CD45) y la enfermedad renal diabética (DKD) con y sin incorporación de metformina en un modelo animal no se había anteriormente investigado. El objetivo fue evaluar el grado de infiltración de leucocitos en los tejidos renales 10 semanas después de la inducción de diabetes en ratas tratadas con metformina. Además, monitoreamos los parámetros de sangre y orina asociados con la diabetes. El grupo modelo de ratas recibió una inyección de estreptozotocina (STZ; 50 mg/kg) después de ser alimentadas durante 14 días con una dieta alta en grasas (HFD) y continuamente alimentadas con un HFD hasta que fueron sacrificadas, en la semana 12. El grupo protector fue tratado de la misma manera excepto que estos animales fueron recibieron desde el día 1 metformina (200 mg/kg) hasta ser sacrificados, en la semana 12. Los riñones fueron inmunoteñidos con CD45 como marcador de infiltración de leucocitos y examinados por microscopía óptica. Las muestras de orina se analizaron en busca de albúmina y la sangre recolectada se analizó en busca de glucosa, urea, creatinina y biomarcadores de estrés oxidativo y antioxidantes. La lesión renal secundaria a la diabetes se desarrolló como lo demuestra (i) el aumento de la glucosa en sangre, la urea y el malondialdehído (MDA) como marcador de la peroxidación lipídica; y (ii) daño del tejido renal y marcado aumento en los tejidos renales que expresan células positivas para CD45. Los marcadores anteriores fueron inhibidos (p≤0.0006) por metformina. Además, se observó una correlación significativa entre la puntuación de CD45 y la glucemia, la urea, la MDA y la superóxido dismutasa antioxidante (SOD). Por lo tanto, nuestros datos demuestran una asociación entre la infiltración de células inflamatorias CD45+ en los tejidos renales y biomarcadores de daño renal en un modelo de rata con DKD, que fue protegido de manera efectiva por metformina.

Factores de riesgo para el desarrollo de lesión renal aguda en el posoperatorio inmediato / Risk factors for the development of acute renal lesion in the immediate posoperative period

Introducción: La disfunción renal aguda es frecuente en pacientes quirúrgicos. Objetivo: Identificar los factores de riesgo que influyen en el desarrollo de lesión renal aguda durante el postoperatorio inmediato en cuatro años. Métodos: Se realizó un estudio de tipo casos y controles. (750 controles y 230 casos). Fue empleado el Chi Cuadrado (α< 0,05), el OR con IC 95 por ciento y el cálculo de valores predictivos. Resultados: La frecuencia fue de un 23,4 por ciento. Los factores de riesgo en el posoperatorio fueron: mayores de 60 años (OR 4,0 IC 95 por ciento 2,9-5,6) (p=0,00), cirugía de urgencia (OR 2,7 IC 95 por ciento 2,1-3,6) (p=0,00), ASA clase 4 (OR 2,0 IC 95 por ciento 1,4-2,8,) (p=0,00). En el intra y posoperatorio: cirugía de fractura de cadera (OR 4,9 IC 95 por ciento 3,2-7,5), anestesia general (OR 3,0 IC 95 por ciento 2,2-4,2), administración mayor de 2500 mL de cristaloides (OR 186,1 IC 95 por ciento 107,4-321,9) (p=0,00), más de 60 mg de furosemida (OR 3,3 IC 95 por ciento 2,4-4,6) (p=0,00), APACHE II inicial ≥ 15 puntos (OR 46 IC 95 por ciento 28,1-74,8) (p=0,00). El mayor valor predictivo lo obtuvo el APACHE II inicial (sensibilidad 92,0 por cientoy especificidad 80,0 por ciento). Conclusiones: El control de los factores de riesgo en el posoperatorio inmediato disminuiría de forma significativa la incidencia de lesión renal aguda, en especial en aquellos mayores de 60 años, con cirugía de urgencia, anestesia general, fractura de cadera y APACHE II por encima de 15 puntos. Debe garantizarse la normovolemia, individualizar y optimizar dosis-tiempo de exposición de la furosemida, hemoderivados y aminas vasoactivas(AU)

Introduction: Acute renal dysfunction is frequent in surgical patients. Objective: To identify the risk factors that influence the development of acute kidney injury during the immediate postoperative period in four years. Methods: A case-control study was carried out, with 750 controls and 230 cases. Chi-square (α<0.05), odds ratio [OR] (95 percent confidence interval [95 percent CI]) and calculation of predictive values ​​were used. Results: The frequency was 23.4 percent. The postoperative risk factors were age over 60 years (OR: 4.0; 95 percent CI: 2.9-5.6) (P=0.00), emergency surgery (OR: 2.7; 95 percent CI: 2.1-3.6) (P=0.00), and American Society of Anesthesiologists (ASA) class IV (OR: 2.0; 95 percent CI: 1.4-2.8) (P=0.00). In the intraoperative and postoperative periods, the risk factors were hip fracture surgery (OR: 4.9; 95 percent CI: 3.2-7.5), general anesthesia (OR: 3.0; 95 percent CI 2.2-4.2), administration of more than 2500 mL of crystalloids (OR: 186.1; 95 percent CI: 107.4-321.9) (P=0.00), more than 60 mg of furosemide (OR: 3.3; 95 percent CI: 2.4-4.6) (p=0.00), initial acute physiology and chronic health evaluation (APACHE) II score ≥ 15 points (OR: 46; 95 percent CI: 28.1-74.8) (p=0.00). The highest predictive value was obtained by the initial APACHE II (sensitivity of 92.0 percent and specificity of 80.0 percent). Conclusions: The control of risk factors in the immediate postoperative period would reduce the incidence of acute renal injury significantly, especially in patients aged over 60 years, who underwent emergency surgery, received general anesthesia, with hip fracture and APACHE II above 15 points. Normovolemia must be guaranteed, as well as individualizing and optimizing the relationship dose-time of exposure of furosemide, blood products and vasoactive amines(AU)

Shen-fu injection alleviates acute renal injury by reducing cytokine levels and modulating apoptosis in a porcine hemorrhagic shock model

ABSTRACT Purpose Shen-fu injection (SFI) was used to intervene in the resuscitation of porcine hemorrhagic shock (HS) model to study its protective effects on acute kidney injury. Methods After 60 min of HS, 28 animals were randomly assigned into four groups. The groups were as follows: hemorrhagic shock group (HS); HS resuscitation with shed-blood group (HSR); HS resuscitation with shed-blood and SFI (1 mL·kg-1) group (HSR-SFI); and the sham operation group (Sham). The bloods were analyzed for serum creatinine (sCr), cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL). BAX, Bcl-2, and caspase-3 protein expressions by Western blot analysis and immunohistochemical staining. The renal tissues were removed and pathologic changes were observed. Results Mean aortic pressure (MAP) in HSR-SFI groups were higher than that in HSR groups after shock. At the 6th hour after shock, the urine volume per hour in the HSR-SFI groups was more than that in the HSR groups. The sCr, NGAL, CysC and cytokine levels of HSR-SFI groups were lower. The Bcl-2 expression was increased in the HSR-SFI groups. The BAX and caspase-3 expressions were reduced. The histopathologic score in the HSR-SFI was lower. Conclusions SFI may reduce the risk of acute kidney injury (AKI) following hemorrhagic shock by attenuating systemic inflammatory responses, and regulating the expression of apoptosis-related proteins.

The renoprotective effects of Heme Oxygenase-1 during contrast-induced acute kidney injury in preclinical diabetic models

OBJECTIVES: Contrast-induced acute kidney injury (CI-AKI) is an important clinical problem that can be aggravated by diabetes mellitus, a major risk factor. However, heme oxygenase-1 (HO-1), a promising therapeutic target, can exert antioxidant effects against CI-AKI. Thus, we investigated the role of HO-1 in CI-AKI in the presence of diabetes mellitus. METHODS: Twenty-eight male Wistar rats weighing 250-300g were subjected to left uninephrectomy, and concomitantly, diabetes induced by streptozotocin (65 mg/kg). After 12 weeks, iodinated contrast (meglumine ioxithalamate, 6 mL/kg) and hemin (HO-1 inducer-10 mg/k) were administered 60 min before iodinated contrast treatment. The rats were randomly divided into four groups: control, diabetes mellitus (DM), DM iodinated contrast (DMIC), and DMIC hemin (DMICH). Kidney function, albuminuria, oxidative profile, and histology were assessed. All experimental data were subjected to statistical analyses. RESULTS: CI-AKI in preclinical diabetic models decreased creatinine clearance and increased urinary neutrophil gelatinase-associated lipocalin (NGAL) levels and the degree of albuminuria. Additionally, the levels of oxidative and nitrosative stress metabolites (urinary peroxides, thiobarbituric acid-reactive substances, and NO) were elevated, while thiol levels in kidney tissue were reduced. Kidney histology showed tubular cell vacuolization and edema. HO-1 inducer treatment improved kidney function and reduced urinary the NGAL levels. The oxidative profile showed an increase in the endogenous thiol-based antioxidant levels. Additionally, the tubular injury score was reduced following HO-1 treatment. CONCLUSIONS: Our findings highlight the renoprotective effects of HO-1 in CI-AKI and preclinical diabetic models. Therefore, HO-1 ameliorates kidney dysfunction, reduces oxidative stress, and prevents cell necrosis.

Renoprotective effect of N-acetylcysteine depends upon the severity of the ischemia reperfusion injury

Acute kidney injury (AKI) is a common complication in seriously ill patients, while renal ischemia-reperfusion (I/R) injury is the most frequent event in this oxidative renal injury. N-acetylcysteine (NAC) is a small molecule containing a thiol group that has antioxidant properties, promoting detoxification and acting directly as a free radical scavenger. In this study, the protective effect of NAC was investigated in short-term (30 min) and long-term (45 min) ischemic AKI. This was achieved via clamping of the renal artery for 30 or 45 min in Wistar rats to induce I/R injury. AKI worsened with a longer period of ischemia (45 compared to 30 min) due to probable irreversible damage. Preconditioning with NAC in short-term ischemia improved renal blood flow and increased creatinine clearance by reducing oxidative metabolites and increasing antioxidant capacity. Otherwise, NAC did not change these parameters in the long-term ischemia. Therefore, this study demonstrated that the period of ischemia determines the severity of the AKI, and NAC presented antioxidant effects in short-term ischemia but not in long-term ischemia, confirming that there is a possible therapeutic window for its renoprotective effect.

Clinical efficacy of Danhong injection in preventing contrast-induced acute kidney injury based on propensity score matching method / 中南大学学报(医学版)

OBJECTIVES@#Contrast-induced acute kidney injury (CI-AKI) is the third cause of hospital-acquired AKI, and existing clinical prevention and treatment measures such as hydration therapy and/or administration of antioxidants N-acetylcysteine treatment and other treatments still show little effect on the prevention and treatment of CI-AKI. This study aims to explore the effect of Danhong injection on prevention of CI-AKI.@*METHODS@#A total of 12 867 patients, who received coronary angiography, percutaneous coronary intervention, enhanced CT or vascular intervention in a tertiary hospital, were enrolled for this study. Among them, 423 in the treatment group received intravenous drip of Danhong injection, and 12 444 in the control group received routine medicine. Propensity score matching was conducted to balance confounding factors between the 2 groups and then the prevention effect of Danhong injection on CI-AKI was compared between them.@*RESULTS@#A total of 423 pairs of patients were matched successfully. The incidence of CI-AKI in the non-Danhong control group was higher than that in the Danhong treatment group (5.7% vs 2.4%). The difference between the 2 groups was statistically significant (@*CONCLUSIONS@#The results of this study support the use of Danhong injection in the prevention of the Stage 1 of CI-AKI.

Conhecimento dos enfermeiros da atenção primária à saúde sobre fatores de risco para Lesão Renal Aguda / Conocimiento de las enfermeras de atención primaria de salud sobre los factores de riesgo de lesión renal aguda / Knowledge of primary health care nurses about risk factors of acute kidney injury

RESUMO Objetivo Descrever o conhecimento dos enfermeiros sobre a identificação, medidas de prevenção e de autocuidado direcionadas à lesão renal aguda (LRA) em hipertensos e/ou diabéticos na atenção primária à saúde (APS). Método Estudo transversal e quantitativo. Amostra constituída de 57 enfermeiros atuantes na APS. Adotou-se questionário semiestruturado para coleta de dados. Realizou-se análise descritiva e inferencial. Considerou-se significativo resultado com p≤0,05. Resultados O perfil dos enfermeiros era jovem (idade 42± 9 anos) e tempo de exercício profissional de 9±6 anos. O conhecimento sobre aspectos gerais relacionados a LRA mostrou-se abaixo da média (48±19 pontos), embora, uma maioria, tenha descrito o conceito corretamente 41 (71,9%). Os fatores de risco relacionados à LRA foram majoritariamente: exposição às drogas 56 (98,2%) e diabetes mellitus 49 (86%). O tempo de atuação na APS aliado ao conhecimento insuficiente sobre alteração do valor da creatinina sérica implicou na decisão sobre a necessidade de encaminhamento ao nefrologista (p=0,004). Conclusões e implicações para a prática O conhecimento dos enfermeiros mostrou-se insuficiente para reconhecimento dos fatores de risco, prevenção e autocuidado da doença renal. Evidencia-se, portanto, a necessidade de capacitação dos enfermeiros da APS para otimizar a identificação precoce da LRA, evitando progressão e cronificação dessa doença.

RESUMEN Objetivo Describir el conocimiento de las enfermeras en materia de medidas de identificación, prevención y autocuidado, dirigidas a la lesión renal aguda (LRA) en pacientes hipertensos y / o diabéticos en atención primaria de salud (APS). Método estudio transversal y cuantitativo. Muestra compuesta por 57 enfermeras que trabajan en atención primaria de salud (APS). Se adoptó un cuestionario semiestructurado para la recopilación de datos. Se realizó un análisis descriptivo e inferencial. El resultado con p≤0.05 se consideró significativo. Resultados El perfil de las enfermeras se circunscribió a personas jóvenes (edad 42 ± 9 años) con tiempo de práctica profesional de 9 ± 6 años. Sin embargo, el conocimiento sobre los aspectos generales vinculados con la LRA se consideró por debajo del promedio (48±19 puntos), aunque el concepto se describió de manera adecuada por la mayoría (41, equivalente a 71.9%). Los factores de riesgo reconocidos como determinantes para la LRA fueron principalmente la exposición a medicamentos (56, equivalente a 98.2%) y la diabetes mellitus 49 (86%). La duración de la práctica en APS se asoció con un conocimiento reducido sobre la necesidad de derivación al nefrólogo basado en el valor de creatinina sérica (p=0,004). Conclusiones e implicaciones para la práctica El conocimiento de las enfermeras era insuficiente para el reconocimiento de los factores de riesgo, prevención y autocuidado de la enfermedad renal. Por lo tanto, se advierte la necesidad de capacitación permanente de enfermeras en APS para optimizar la identificación temprana de LRA, y evitar la progresión, la cronificación y las complicaciones de la enfermedad.

ABSTRACT Objective To describe nurses' knowledge about the identification, prevention and self-care measures directed to Acute Kidney Injury (AKI) in hypertensive and / or diabetic patients in Primary Health Care (PHC). Method Cross-sectional and quantitative study. Sample consisting of 57 nurses working in primary health care (PHC). The semi-structured questionnaire was adopted for data collection. A descriptive and inferential analysis was performed. The result with p≤0.05 was considered significant. Results The nurses' profile was young (age 42 ± 9 years old) and professional practice time being 9 ± 6 years. Knowledge about general aspects related to AKI was identified as below average (48±19 points), however, although the concept was correctly described by a majority 41 (71.9%). Risk factors recognized as determinant for AKI were mostly drug exposure 56 (98.2%) and diabetes mellitus 49 (86%). The length of practice in PHC was associated with reduced knowledge about the need for referral to the nephrologist based on serum creatinine value (p=0.004). Conclusion and implications for the practice Nurses' knowledge was insufficient for recognition of risk factors, prevention and self-care activities of kidney disease. Thus, there is a need for permanent training of nurses in PHC to optimize the early identification of AKI, avoiding progression, and chronification and complications of this disease.

Enfermedad renal crónica de causa desconocida: investigaciones en Guatemala y oportunidades para su prevención / Chronic kidney disease of unknown cause: investigations in Guatemala and opportunities for its prevention

El Centro para la Salud, el Trabajo y el Ambiente (CHWE por sus siglas en inglés) inició un proyecto de colaboración con Pantaleon, una empresa agrícola de caña de azúcar en Guatemala, para hacer frente a una epidemia de enfermedad renal crónica (ERC) de causa no tradicional (ERCnT) que afecta a las comunidades agrícolas en Centroamérica y otros lugares. Este artículo describe el conocimiento actual de la epidemia en Centroamérica, las manifestaciones clínicas, el tratamiento y el manejo; las hipótesis actuales de su etiología, la colaboración y el enfoque de CHWE-Pantaleon. Nuestro enfoque de Total Worker Health® (TWH) para abordar la salud renal en Guatemala incluye múltiples estudios de investigación con trabajadores de caña de azúcar, para evaluar la prevalencia, incidencia y factores de riesgo de la lesión renal aguda y la ERC; se incluye también el desarrollo e implementación de medidas de prevención mejoradas e intervenciones para proteger a los trabajadores abordando los factores de riesgo ya conocidos. Se examinan también las necesidades futuras de investigación y las implicaciones globales de la ERCnT, al igual que la producción de bienes y la economía, así como las recomendaciones actuales para las estrategias de prevención ocupacional y comunitaria.

The Center for Health, Work and Environment (CHWE) began a collaborative project with Pantaleon, a Guatemalan sugarcane agribusiness, to address an epidemic of chronic kidney disease of unknown cause (CKDu) that affects agricultural communities in Central America and elsewhere. This paper describes the current knowledge of the epidemic in Central America including clinical manifestations, course, and management, current etiology hypotheses, and the CHWE-Pantaleon collaboration and approach. Our Total Worker Health® (TWH) approach to addressing kidney health in Guatemala has included multiple research studies with sugarcane workers to assess prevalence, incidence and risk factors for acute kidney injury and chronic kidney disease, as well as development and implementation of enhanced prevention measures and interventions to protect workers by addressing known risk factors. Future research needs and the global implications of CKDu including for economy and commodity production are discussed, as well as current recommendations for occupational and community prevention strategies.

Impacto do controle glicêmico intensivo na lesão renal aguda: ensaio clínico randomizado / Impacto del control glucémico intensivo en la lesión renal aguda: ensayo clínico aleatorizado / Impact of intensive glycemic control on acute renal injury: a randomized clinical trial

Resumo Objetivo Avaliar o impacto do controle glicêmico intensivo na redução da incidência de lesão renal aguda em pacientes adultos submetidos à cirurgia cardíaca. Métodos Ensaio clínico randomizado que avaliou 95 pacientes submetidos a duas estratégias de controle glicêmico. Os pacientes foram randomizados para o grupo intervenção (GI), com a meta de manutenção da glicemia pós-operatória entre 90 e 110 mg/dl. Nos pacientes alocados no grupo convencional (GC) o objetivo era a manutenção da glicemia entre 140 e 180 mg/dl. O ajuste da dose de insulina foi baseado em medições de glicose no sangue arterial não diluído, em intervalos de uma hora por meio de um sistema de monitoramento de glicose e beta-cetona no sangue. Resultados A incidência de LRA foi de 53,7% (KDIGO estágios 1, 2 ou 3). Não houve diferença significante entre os grupos quanto ao desfecho primário (p=0,294). Entretanto, observou-se maior frequência de recuperação da função renal (p=0,010), na alta da UTI (p=0,028) e alta hospitalar (p=0,048) entre os pacientes submetidos ao controle glicêmico convencional. A utilização do controle glicêmico intensivo esteve associada com maior tempo de permanência na UTI (p=0,031). O número de episódios de hipoglicemia foi semelhante nos dois grupos (1,6 ± 0,9 vs. 1,3 ± 0,6, p=0,731), demonstrando a segurança das estratégias utilizadas. Conclusão Não se observou o impacto do controle glicêmico intensivo na redução da incidência de lesão renal aguda. Em contrapartida, os pacientes tratados no GC apresentaram maior frequência de recuperação da função renal.

Resumen Objetivo Evaluar el impacto del control glucémico intensivo en la reducción de la incidencia de lesión renal aguda en pacientes adultos sometidos a cirugía cardíaca. Métodos Ensayo clínico aleatorizado que analizó 95 pacientes sometidos a dos estrategias de control glucémico. Los pacientes fueron colocados de forma aleatoria en el grupo experimental (GE), con el objetivo de mantener la glucemia posoperatoria entre 90 y 110 mg/dl. El objetivo para los pacientes ubicados en el grupo convencional (GC) era mantener la glucemia entre 140 y 180 mg/dl. El ajuste de la dosis de insulina se basó en mediciones de glucosa en sangre arterial no diluida, en intervalos de una hora mediante un sistema de monitoreo de glucosa y beta-cetona en sangre. Resultados: La incidencia de LRA fue de 53,7% (KDIGO nivel 1, 2 o 3). No hubo diferencia significativa entre los grupos con relación al criterio principal de valoración (p=0,294). Sin embargo, se observó mayor frecuencia de recuperación de la función renal (p=0,010), en el alta de la UCI (p=0,028) y alta hospitalaria (p=0,048) en pacientes sometidos al control glucémico convencional. La utilización del control glucémico intensivo estuvo relacionada con mayor tiempo de permanencia en la UCI (p=0,031). El número de episodios de hipoglucemia fue parecido en los dos grupos (1,6 ± 0,9 vs. 1,3 ± 0,6, p=0,731), lo que demuestra la seguridad de las estrategias utilizadas. Conclusión No se observó el impacto del control glucémico intensivo en la reducción de la incidencia de lesión renal aguda. Por otro lado, los pacientes tratados en el GC presentaron mayor frecuencia de recuperación de la función renal.

Abstract Objective To evaluate the impact of intensive glycemic control on the reduction of the incidence of acute renal injury in adult patients undergoing cardiac surgery. Methods Randomized clinical trial, evaluating 95 patients undergoing two glycemic control strategies. Patients were randomized to the intervention n group (IG), with the goal of maintaining postoperative glycemia between 90 and 110 mg/dl. For patients allocated into the conventional group (CG) the goal was to maintain glycaemia between 140 and 180 mg/dl. The insulin dose adjustment was based on undiluted arterial blood glucose measurements at one hour intervals, by means of a blood glucose and beta-ketone monitoring system. Results The incidence of acute kidney injury was 53.7% (KDIGO stages 1, 2 or 3). There was no significant difference between the groups regarding the primary outcome (p=0.294). However, a greater frequency of complete renal function recovery (p = 0.010), ICU discharge (p = 0.028), and hospital discharge (p = 0.048) was found among patients undergoing conventional glycemic control. The use of intensive glycemic control was associated with longer ICU stay (p=0.031). The number of episodes of hypoglycemia was similar in both groups (1.6±0.9 vs. 1.3±0.6, p=0.731), demonstrating the safety of the strategies used. Conclusion The impact of intensive glycemic control on reducing the incidence of acute kidney injury was not observed. In contrast, patients treated in the CG had a higher frequency of complete renal function recovery.

2019 World Kidney Day Editorial - burden, access, and disparities in kidney disease / Editorial do Dia Mundial do Rim 2019 - impacto, acesso e disparidades na doença renal

Abstract Kidney disease is a global public health problem, affecting over 750 million persons worldwide. The burden of kidney disease varies substantially across the world, as does its detection and treatment. In many settings, rates of kidney disease and the provision of its care are defined by socio-economic, cultural, and political factors leading to significant disparities. World Kidney Day 2019 offers an opportunity to raise awareness of kidney disease and highlight disparities in its burden and current state of global capacity for prevention and management. Here, we highlight that many countries still lack access to basic diagnostics, a trained nephrology workforce, universal access to primary health care, and renal replacement therapies. We point to the need for strengthening basic infrastructure for kidney care services for early detection and management of acute kidney injury and chronic kidney disease across all countries and advocate for more pragmatic approaches to providing renal replacement therapies. Achieving universal health coverage worldwide by 2030 is one of the World Health Organization's Sustainable Development Goals. While universal health coverage may not include all elements of kidney care in all countries, understanding what is feasible and important for a country or region with a focus on reducing the burden and consequences of kidney disease would be an important step towards achieving kidney health equity.

Resumo A doença renal é um problema de saúde pública global, afetando mais de 750 milhões de pessoas em todo o mundo. O ônus da doença renal varia substancialmente em todo o mundo, assim como sua detecção e tratamento. Em muitos contextos, as taxas de doença renal e a provisão de seus cuidados são definidas por fatores socioeconômicos, culturais e políticos que levam a disparidades significativas. O Dia Mundial do Rim 2019 oferece uma oportunidade para aumentar a conscientização sobre doenças renais e destacar as disparidades em seu impacto e estado atual da capacidade global de prevenção e tratamento. Aqui, destacamos que muitos países ainda carecem de acesso a diagnósticos básicos, uma força de trabalho treinada em nefrologia, acesso universal à atenção primária à saúde e terapias de substituição renal. Apontamos para a necessidade de fortalecer a infra-estrutura básica para serviços de cuidados renais para detecção e tratamento precoce de lesão renal aguda e doença renal crônica em todos os países e defender abordagens mais pragmáticas para o fornecimento de terapias de substituição renal. Alcançar a cobertura universal de saúde em todo o mundo até 2030 é um dos Objetivos de Desenvolvimento Sustentável da Organização Mundial da Saúde. Embora a cobertura universal de saúde não inclua todos os elementos do tratamento renal em todos os países, entender o que é viável e importante para um país ou região com foco na redução do impacto e das consequências da doença renal seria um passo importante para alcançar a equidade na saúde renal.

Milk fat globule-epidermal growth factor 8 (MFG-E8) attenuates sepsis-induced acute kidney injury by inhibiting NF-κB signaling pathway1

Abstract Purpose: To explore the effect of milk fat globule-epidermal growth factor 8 (MFG-E8) on sepsis-induced acute kidney injury (SAKI). Methods: Male C57BL/6 mice were randomized to control, sham, CLP, CLP+PBS, and CLP+rmMFG-E8 groups. SAKI was induced by cecal ligation and puncture (CLP). Recombinant mouse MFG-E8 (rmMFG-E8) (20 μg/kg) or PBS (vehicle) was administered intraperitoneally. Blood, urine and renal tissue were collected at 24 h after CLP. Blood samples were tested for serum kidney injury biomarker and cytokines. Urine samples were collected to detect KIM-1, and NGAL. Real-time PCR was tested for Bax and Bcl-2. TUNEL staining was used to determine renal apoptosis. Western blot was used to detect the expression of Bax, Bcl-2, and proteins in the NF-κB pathway. Results: MFG-E8 alleviated SAKI by decreasing serum Cre, BUN, urine KIM-1 and NGAL and by mitigating renal pathological changes significant (p < 0.05). IL-1β, IL-6, TNF-α were significantly inhibited by MFG-E8 (p < 0.05). Apoptosis induced by SAKI was markedly suppressed by MFG-E8. Finally, MFG-E8 attenuated the activation of the NF-��B signaling pathway in SAKI. Conclusion: MFG-E8 has beneficial effects on SAKI, which may be achieved by inhibiting the NF-κB pathway.

Inflammation and kidney injury attenuated by prior intake of Brazil nuts in the process of ischemia and reperfusion / Inflamação e lesão renal atenuadas pela ingestão prévia de castanha-do-Brasil no processo de isquemia e reperfusão

ABSTRACT Introduction: Ischemia and reperfusion (IR) is a process inherent to the procedures involved in the transplantation of organs that causes inflammation, cell death and cell injury, and may lead to rejection of the graft. It is possible that the anti-inflammatory properties of the Brazil nuts (BN) can mitigate the renal injury caused by IR. Objective: To investigate whether the previous intake of BN reduces the expression of markers of inflammation, injury, and cell death after renal IR. Methods: Male Wistar rats were distributed into six groups (N = 6/group): SHAM (control), SHAM treated with 75 or 150 mg of BN, IR, and IR treated with 75 or 150 mg of BN. The IR procedure consisted of right nephrectomy and occlusion of the left renal artery with a non-traumatic vascular clamp for 30 min. BN was given daily from day 1 to 7 before surgery (SHAM or IR), and maintained until sacrifice (48 h after surgery). Inflammation was evaluated by renal expression of COX-2 and TGF-β, injury by the expression of vimentin, and cell death by apoptosis through caspase-3 expression (immunohistochemistry). Results: Pretreatment with 75 mg of BN reduced renal expression of the COX-2, TGF-β, vimentin, and caspase-3. The dose of 150 mg caused increased expression of COX-2. Conclusion: In experimental IR, the damage can be minimized with a prior low-dose intake of BN, improving inflammation, injury, and cell death.

RESUMO Introdução: Isquemia e reperfusão (IR) é um processo inerente aos procedimentos envolvidos no transplante de órgãos, que causa inflamação, morte celular e lesão, podendo levar à rejeição do enxerto. É possível que a castanha-do-brasil (CB), por suas propriedades anti-inflamatórias, possa atenuar a lesão renal causada pela IR. Objetivo: Investigar se a ingestão prévia de CB reduz a expressão de marcadores renais de inflamação, lesão e morte celular após a IR. Métodos: Ratos Wistar machos foram distribuídos em seis grupos (N = 6/grupo): SHAM (controle), SHAM tratado com 75 ou 150 mg de CB, IR, e IR tratado com 75 ou 150 mg de CB. O procedimento de IR consistiu na nefrectomia à direita e oclusão da artéria renal esquerda por 30 minutos. A castanha foi administrada diariamente por sete dias antes da cirurgia (SHAM ou IR), e mantida até o sacrifício (48 horas pós-cirurgia). A inflamação foi avaliada pela expressão renal de COX-2 e TGF-β; a lesão pela expressão de vimentina, e a morte celular por apoptose pela expressão de caspase-3, por imuno-histoquímica. Resultados: O pré-tratamento com 75 mg de CB reduziu a expressão renal de COX-2, de TGF-β, de vimentina e de caspase-3. A dose de 150 mg causou elevação da expressão de COX-2. Conclusão: No modelo experimental de IR renal, os danos podem ser minimizados com a ingestão prévia de baixas doses de CB, melhorando a inflamação, a lesão e a morte celular.

Sepsis-induced acute kidney injury: kidney protection effects by antioxidants / Lesión renal aguda inducida por sepsis: efecto de protección renal de los antioxidantes / Lesão renal aguda induzida pela sepse: efeito de proteção renal dos antioxidantes

ABSTRACT Objective: To evaluate the antioxidant action of N-acetylcysteine and diosmin-hesperidin in an experimental model of sepsis-induced acute kidney injury in rats. Methods: The study used 20 Wistar adult male rats divided into the following groups: control (laparotomy with no induction of abdominal sepsis), sepsis (experimental model of sepsis with cecal ligation and puncture), N-acetylcysteine + sepsis and diosmin-hesperidin + sepsis. The evaluation contemplated physiological parameters (temperature, glycemia, and average blood pressure), kidney function (creatinine clearance), oxidative stress (urinary peroxides) and kidney histology. Results: The animals submitted to cecal ligation and puncture (sepsis) presented lower body temperature, lower average blood pressure, reduced creatinine clearance and increased urinary hydrogen peroxide levels. Treatment with diosmin-hesperidin improved kidney function and led to a reduction in the excretion of oxidative metabolites. Conclusion: The present study highlighted the protective antioxidant action of diosmin-hesperidin in the experimental model of sepsis-induced acute kidney injury.

RESUMEN Objetivo: Evaluar la acción antioxidante de agentes como la N-acetilcisteína y Diosmina-Hesperidina en modelo experimental de lesión renal aguda inducida por sepsis en ratones. Método: Fueron utilizados veinte ratones Wistar, adultos y machos, divididos en los grupos: Control (laparotomía sin inducción de sepsis abdominal), Sepsis (modelo experimental de sepsis con ligadura y punción de ciego-LPC), N-acelsisteína+Sepsis y Diosmina Hesperidina+Sepsis. Se evaluaron parámetros fisiológicos (temperatura, glucemia y presión arterial promedio), la función renal (clearance de creatinina), el estrés oxidativo (peróxidos urinarios) e histología renal. Resultados: Los animales sometidos a LPC (sepsis) presentaron reducción de la temperatura corporal, de la presión arterial promedio, del clearance de creatinina e incremento de niveles de peróxidos de hidrógeno urinarios. El tratamiento con Diosmina-Hesperidina mejoró la función renal, reduciendo la excreción de metabolitos oxidativos. Conclusión: Este estudio destacó la acción renoprotectora antioxidante de la Diosmina-Hesperidina en el modelo experimental de lesión renal aguda inducida por sepsis.

RESUMO Objetivo: Avaliar a ação antioxidante de agentes como a N-acetilcisteína e diosmina-hesperidina em modelo experimental de lesão renal aguda induzida pela sepse em ratos. Método: Foram utilizados vinte ratos Wistar, adultos e machos, divididos nos seguintes grupos: Controle (laparotomia sem indução de sepse abdominal), Sepse (modelo experimental de sepse com ligadura e punção do cécum- LPC), N-acetilcisteína+Sepse e Diosmina Hesperidina+Sepse. Foram avaliados parâmetros fisiológicos (temperatura, glicemia e pressão arterial média), função renal (clearance de creatinina), estresse oxidativo (peróxidos urinários) e histologia renal. Resultados: Os animais submetidos à LPC (sepse) apresentaram redução da temperatura corporal, da pressão arterial média, do clearance de creatinina e elevação nos níveis de peróxidos de hidrogênio urinários. O tratamento com a Diosmina-Hesperidina melhorou a função renal com redução na excreção dos metabólitos oxidativos. Conclusão: Este estudo destacou a ação renoprotetora antioxidante da Diosmina-Hesperidina no modelo experimental de lesão renal aguda induzida pela sepse.

Selenium, vitamin c and n-acetylcysteine do not reduce the risk of acute kidney injury after off-pump cabg: a randomized clinical trial

Abstract Objective: The aim of this study was to investigate the impact of perioperative administration of N-acetylcysteine, selenium and vitamin C on the incidence and outcomes of acute kidney injury after off-pump coronary bypass graft surgery. Methods: 291 patients requiring elective off-pump coronary bypass graft surgery were randomized to receive either N-acetylcysteine, vitamin C and selenium 600 mg, 1500 mg, 0.5 mg, and nothing orally twice a day, respectively, from the day before to 2 days after surgery. They were assessed for the development of acute kidney injury using Acute Kidney Injury Network criteria, time of onset, its severity and duration, duration of mechanical ventilation, intensive care unit and hospital length of stay, and in-hospital mortality. Results: 272 patients completed the study. The total incidence of acute kidney injury was 22.1% (n=60) with 14 (20.9%), 15 (22.1%), 21 (31.8%), and 10 (14.1%) patients in the vitamin C, NAC, selenium, and control groups, respectively (P=0.096). We did not register significant differences in the incidence, the time of occurrence, the severity and the duration of acute kidney injury, as well as the duration of mechanical ventilation, the intensive care unit and hospital length of stay, and the in-hospital mortality among the four groups. Conclusion: We found that perioperative administration of N-acetylcysteine, vitamin C and selenium were not effective in preventing acute kidney injury and associated morbidity and mortality after off-pump coronary bypass graft surgery.

Propofol attenuates sepsis-induced acute kidney injury by regulating miR-290-5p/CCL-2 signaling pathway

Previous studies have indicated that propofol has immunomodulatory and antioxidative properties. However, the renoprotection effect and the precise mechanisms of propofol in sepsis-induced renal injury remain unclear. The purpose of the present study was to investigate the role of miR-290-5p/CCL-2 signaling in septic mice treatment with propofol. Mice were treated with propofol (50 mg/kg) twice within 24 h. Survival outcome was monitored within 48 h. The mRNA and protein levels were assayed by qRT-PCR and western blotting, respectively. Mouse podocytes (MPC5) were treated with lipopolysaccharide (LPS) to establish the cell model in vitro. The proliferation of MPC5 was monitored using the MTS assay. Cell apoptosis was analyzed by flow cytometry. Propofol improved survival outcome and alleviated acute kidney injury in cecal ligation and puncture-operated mice. Propofol increased miR-290-5p expression and decreased CCL-2 and inflammatory cytokines levels in the kidney for septic mice. We found that miR-290-5p was a direct regulator of CCL-2 in MPC5. Propofol could abrogate LPS-induced growth inhibition and apoptosis in MPC5. Meanwhile, propofol inhibited CCL-2 expression in LPS-treated MPC5, however, knockdown of miR-290-5p abrogated the inhibitory effect propofol on the mRNA and protein expressions of CCL-2. Propofol could serve as an effective therapeutic medication to suppress sepsis-induced renal injury in vivo and in vitro by regulating the miR-290-5p/CCL-2 signaling pathway.

Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats

Cyclosporin-A (CsA) is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF) and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1) receptor blockade with bosentan (BOS) and macitentan (MAC) antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR) were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg) for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg) or MAC (25 mg/kg) by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP), RBF and renal vascular resistance (RVR), and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects.

Attenuation of partial unilateral ureteral obstruction - induced renal damage with hyperbaric oxygen therapy in a rat model

ABSTRACT Objective: The objective of the present study was to evaluate the effectiveness of HBO therapy on biochemical parameters, renal morphology and renal scintigraphy in rats undergoing chronic unilateral partial ureteral obstruction (UPUO). Material and methods: Thirty-five rats were divided into five equal groups: Control group; Sham group; HBO group; UPUO group and UPUO/HBO group. The effects of HBO therapy were examined using biochemical parameters and histopathological changes. After calculating the score for each histopathological change, the total histopathological score was obtained by adding all the scores. In addition, dynamic renal scintigraphy findings were evaluated. Results: Serum parameters indicating inflammation, serum tumor necrosis factor- alpha, ischemia modified-albumin, IMA/albumin ratio and Pentraxin-3 levels, were observed to be high in the UPUO group and low in the UPUO/HBO treatment group. Similarly, in the treatment group, the reduction in malondialdehyde, total oxidant status and oxidative stress index levels and increase in total antioxidant capacity values were observed to be statistically significant compared to the UPUO group (p<0.001, p=0.007, p<0.001, p=0.001, respectively). The total score and apoptosis index significantly decreased after administration of HBO treatment. Dynamic 99mTc-MAG3 renal scintigraphy also showed convincing evidence regarding the protective nature of HBO against kidney injury. In the UPUO/HBO therapy group, the percentage contribution of each operated kidney increased significantly compared to the UPUO group (41.73% versus 32.72%). Conclusion: The findings of this study indicate that HBO therapy had a reno-protective effect by reducing inflammation and oxidative stress, and preserving renal function after renal tissue damage due to induction of UPUO.