Renal ischemia/reperfusion induces prominent progressive kidney disease in diabetic mice.

Acute kidney injury (AKI) is a public health concern associated with high rates of mortality, even in milder cases. One of the reasons for the difficulty in managing AKI in patients is due to its association with pre-existing comorbidities, such as diabetes. In fact, diabetes increases the susceptibility to develop more severe AKI after renal ischemia. However, the long-term effects of this association are not known. Thus, an experimental model was designed to evaluate the chronic effects of renal ischemia/reperfusion (IR) in streptozotocin (STZ)-treated mice. We focused on the glomerular and tubulointerstitial damage, as well as kidney function and metabolic profile. It was found that pre-existing diabetes may potentiate progressive kidney disease after AKI, mainly by exacerbating proinflammatory and sustaining fibrotic responses and altering renal glucose metabolism. To our knowledge, this is the first report that highlights the long-term effects of renal IR on diabetes. The findings of this study can support the management of AKI in clinical practice.NEW & NOTEWORTHY This study demonstrated that early diabetes potentiates progressive kidney disease after ischemia/reperfusion (IR)-induced acute kidney injury, mainly by exacerbating pro-inflammatory and sustaining fibrotic responses and altering renal glucose metabolism. Thus, these findings will contribute to the therapeutic support of patients with type 1 diabetes with eventual renal IR intervention in clinical practice.

Usefulness of vancomycin treatment individualization via Bayesian algorithms: a 5-year study in critical patients.

Aim: Compare two vancomycin dosing strategies in critical patients with methicillin-resistant Staphylococcus aureus (MRSA) infections, considering the heterogeneity of the dosing regimens administered and their implications for toxicity and efficacy. Materials & methods: Longitudinal retrospective observational study in two patient cohorts (standard dosing vs dosing via Bayesian algorithms). Results: The group of Bayesian algorithms received substantially higher and significantly heterogeneous doses, with an absence of nephrotoxicity. The speed of decrease observed in CRP and PCT was greater for the Bayesian strategy (p = 0.045 and 0.0009, respectively). Conclusion: Applying Bayesian algorithms to vancomycin dosage individualization allows for administering much higher doses than with standard regimens, facilitating a quicker clinical response in the absence of nephrotoxicity.

[Box: see text].

Associations among environmental exposure to trace elements and biomarkers of early kidney damage in the pediatric population.

BACKGROUND: In kidney damage, molecular changes can be used as early damage kidney biomarkers, such as Kidney Injury Molecule-1 and Neutrophil gelatinase-associated lipocalin. These biomarkers are associated with toxic metal exposure or disturbed homeostasis of trace elements, which might lead to serious health hazards. This study aimed to evaluate the relationship between exposure to trace elements and early damage kidney biomarkers in a pediatric population. METHODS: In Tlaxcala, a cross-sectional study was conducted on 914 healthy individuals. The participants underwent a medical review and a socio-environmental questionnaire. Five early damage kidney biomarkers were determined in the urine with Luminex, and molybdenum, copper, selenium, nickel, and iodine were measured with ICP-Mass. RESULTS: The eGFR showed a median of 103.75 mL/min/1.73 m2. The median levels for molybdenum, copper, selenium, nickel, and iodine were 24.73 ng/mL, 73.35 ng/mL, 4.78 ng/mL, 83.68 ng/mL, and 361.83 ng/mL, respectively. Except for molybdenum and nickel, the other trace elements had significant associations with the eGFR and the early kidney damage biomarkers. Additionally, we report the association of different exposure scenarios with renal parameters. DISCUSSION: and Conclusions. Among the explored metals, exposure to Cu and iodine impairs renal function. In contrast, Se may manifest as a beneficial metal. Interactions of Mo-Se and Mo-Iodine seem to alter the expression of NGAL; Mo-Cu for CLU; Mo-Cu, Mo-Se, and Mo-iodine for Cys-C and a-1MG; and Mo-Cu and Mo-iodine for KIM-1; were noticed. Our study could suggest that trace element interactions were associated with early kidney damage biomarkers.

Liver and kidney damage in quail embryos hatched from eggs sprayed once with chlorpyrifos during artificial incubation.

Birds have enough conditions to be used as bioindicators for the presence of environmental contaminants. Notably, chlorpyrifos (CPF) remains extensively employed in Argentina, particularly in fruit plantations and livestock settings This study aimed to assess the potential impacts of CPF on common quail (Coturnix coturnix) embryos through external eggshell application during key embryonic stages (days 1, 4, and 14). Concentrations equivalent to those used in fruit applications, 5× and 10 × (38.4, 192, and 384 µg/egg), were employed. A 48% commercial formulation of CPF (Pirfos - Icona®) was utilized. An increase in embryonic deaths, as well as a statistical association between the degree of liver or kidney lesions and CPF concentrations was observed. The results suggest that CPF can induce embryotoxic effects with a single exposure to quail embryos and compromise the viability of the organisms. The study suggests a potential exposure risk for embryos through contact with the insecticide on the eggshell's exterior.

Acute renal failure, COVID-19 and deaths, worrying rates in intensive care units: a cross-sectional study

ABSTRACT BACKGROUND: Acute kidney failure is a serious consequence of coronavirus disease 2019 (COVID-19). OBJECTIVES: To identify the prevalence of COVID-19, kidney failure, frequency of death, and associated factors in patients receiving intensive care. DESIGN AND SETTING: Analytical cross-sectional study conducted in the intensive care unit (ICU) of a medium-sized philanthropic general hospital in center-west Minas Gerais. METHODS: Adults and older individuals who underwent real-time polymerase chain reaction testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were evaluated by the nephrology team. RESULTS: Among the 176 patients, the prevalence of COVID-19 and acute kidney injury (AKI) were 103 (58.5%) and 132 (75%), respectively, and 44 (25%) had chronic kidney disease (CKD) and 16 (15,5%) were positive for SARS-CoV-2. In the Charlson index classification, which estimates the risk of death, a statistically significant difference was identified in the percentages of groups with and without COVID-19 for indices 0, 1, and 2. There was a significant association between kidney disease and ICU mortality (P < 0.05). Patients with CKD had fewer fatal outcomes (13/97, 13.4%) than those with AKI (85/97, 87.6%). CONCLUSIONS: COVID-19 rates remained high long after diagnosis and prevention of SARS-CoV-2 infection. In addition, a higher death rate among patients who developed AKI, whose prevalence was also greater than that in the national literature, regardless of the presence of COVID-19, revealed a worrying scenario and corroborated the need for early and judicious approaches to preserve the lives of patients with AKI admitted to intensive care units.

Relationship between urinary biomarkers of early kidney damage and exposure to inorganic toxins in a pediatric population of Apizaco, Tlaxcala, Mexico.

BACKGROUND: In recent years, chronic kidney disease has increased in the pediatric population and has been related to environmental factors. In the diagnosis of kidney damage, in addition to the traditional parameters, early kidney damage biomarkers, such as kidney injury molecule 1, cystatin C, and osteopontin, among others, have been implemented as predictors of early pathological processes. OBJECTIVE: This study aimed to evaluate the relationship between exposure to environmental pollutants and early kidney damage biomarkers. METHODS: A cross-sectional pilot study was conducted in February 2016 and involved 115 apparently healthy children aged 6-15 residing in Apizaco, Tlaxcala. Participant selection was carried out randomly from among 16,472 children from the municipality of Apizaco. A socio-demographic questionnaire included  age, sex, education, duration of residence in the area, occupation, water consumption and dietary habits, pathological history, and some non-specific symptoms. Physical examination included blood pressure, weight, and height. The urine concentrations of urinary aluminum, total arsenic, boron, calcium, chromium, copper, mercury, potassium, sodium, magnesium, manganese, molybdenum, lead, selenium, silicon, thallium, vanadium, uranium, and zinc, were measured. Four of the 115 participants selected for the study were excluded due to an incomplete questionnaire or lack of a medical examination, leaving a final sample population of 111 participants. RESULTS: The results showed a mean estimated glomerular filtration rate of 89.1 ± 9.98 mL/min/1.73m2 and a mean albumin/creatinine ratio of 12.9 ± 16.7 mg/g urinary creatinine. We observed a positive and significant correlation between estimated glomerular filtration rate with fluoride, total arsenic and lead, and a correlation of albumin/creatinine ratio with fluoride, vanadium, and total arsenic. There was also a significant correlation between the early kidney damage biomarkers and fluoride, vanadium, and total arsenic, except for cystatin C. CONCLUSION: In conclusion, our results show that four urinary biomarkers: α1-microglobulin, cystatin C, kidney injury molecule 1, and neutrophil gelatinase-associated lipocalin are related to environmental exposure to urinary fluoride, vanadium, and total arsenic in our pediatric population.

¿Debemos manejar la hiperuricemia asintomática para proteger al riñón?

Contexto: el ácido úrico es el producto final de la degradación de las purinas en los primates, en condiciones normales es un agente antioxidante endógeno y participa en varias vías fisiológicas, sin embargo, cuando los niveles séricos de urato se incrementan, estos participan en el desarrollo de diversas enfermedades. Desde el siglo XIX se conoce de la asociación entre hiperuricemia y daño renal, aunque ninguna guía de manejo recomienda el uso de fármacos hipouricemiantes en pacientes asintomáticos, en algunos casos especiales, el manejo farmacológico beneficiará a pacientes con hiperuricemia, brindando protección al riñón y disminuyendo el riesgo de desarrollar enfermedad renal terminal. Objetivo: describir la relación entre hiperuricemia y daño renal, y analizar los casos en los que el manejo de esta condición con medicamentos resultará en un beneficio para el riñón de los pacientes. Metodología: revisión de la literatura sobre la participación de la hiperuricemia en el daño renal y análisis de los artículos revisados. Resultados: el manejo de la hiperuricemia asintomática puede proteger el riñón en algunas situaciones específicas. Conclusiones: hay situaciones específicas para la disminución de los niveles séricos de ácido úrico.

Background: Uric acid is the end product of purine degradation in primates, under normal conditions it is an endogenous antioxidant agent and participates in several physiological pathways. However, when serum urate levels are increased, they participate in the development of various diseases. Since the nineteenth century, the association between hyperuricemia and kidney damage has been known. Although no management guideline recommends the use of hypouricemic drugs in asymptomatic patients, in some special cases pharmacological management will benefit patients with hyperuricemia, providing protection to the kidney and decreasing the risk of developing end-stage renal disease. Purpose: To describe the relationship between hyperuricemia and kidney damage, and to analyze the cases in which the management of this condition with medications will result in a benefit for the kidney of patients. Methodology: Review of the literature on the involvement of hyperuricemia in kidney damage, analysis of the reviewed articles. Results: Management of asymptomatic hyperuricemia may protect the kidney in some specific situations. Conclusions: There are specific situations for the decrease of serum uric acid levels.

Naringin prevents diabetic nephropathy in rats through blockage of oxidative stress and attenuation of the mitochondrial dysfunction.

We have studied the effects of naringin (NAR), a flavonoid from citric fruits, on morphology, ultrastructure and function of the kidney in streptozotocin (STZ)-induced diabetic rats. Two groups of animals were used: (1) control rats and (2) STZ rats (60 mg STZ/kg b.w.). At 3 days after induction, one group of STZ-treated rats received 40 mg NAR/kg b.w. daily. NAR blocked completely alterations in the biochemical renal markers in STZ rats except the increase in serum urea that was partially avoided by the flavonoid. NAR ameliorated the kidney morphological lesions from STZ rats. STZ treatment induced round and smaller mitochondria, which was avoided by NAR. Citrate synthase, isocitrate and malate dehydrogenases, enzyme activities of the Krebs cycle, were decreased in STZ rats. NAR abolished this decrease in the latter proteins. NAR also prevented a decrease in the ATP synthase activity of the mitochondria from renal cortex by about 49% in STZ rats, returning the enzyme activity to control values. The nephroprotection caused by NAR is mediated through counteraction of oxidative stress in mitochondria of proximal tubules. NAR might be a therapeutic strategy to reduce the complication of diabetic nephropathy in type 1 diabetic patients.

Protective Effects of Kefir Against Unpredictable Chronic Stress Alterations in Mice Central Nervous System, Heart, and Kidney.

Kefir is a probiotic mixture with anxiolytic and antioxidant properties. Chronic stress can lead to anxiety disorders and increase oxidative damage in organs such as the heart and kidney. In this study, we examined whether kefir ameliorates the anxiety-like behavior of mice submitted to chronic unpredictable stress (CUS) by modulating brain-derived neurotrophic factor (BDNF) and corticosterone levels and whether kefir modifies the oxidative parameters in the heart and kidney of mice. Male Swiss mice received kefir (0.3 mL/100 g/day) or milk for 30 days (gavage). On the 10th day, the mice were submitted to CUS. Behavioral analysis was performed using the elevated plus maze and forced swimming tests. BDNF levels were analyzed in brain tissues. Heart and kidney superoxide dismutase (SOD), catalase, glutathione (GSH), thiobarbituric acid reactive substances (TBARS), 3-nitrotyrosine, metalloproteinase-2 (MMP-2), and plasma corticosterone were evaluated. Kefir reverted the CUS-induced decrease in the time spent in the open arms, the increase in grooming frequency, and decrease in the head dipping frequency, but not the reduced immobility time. CUS decreased the cerebellum BDNF levels and increased corticosterone levels, which were restored by Kefir. Neither catalase and SOD activities nor GSH, TBARS, 3-nitrotyrosine, and MMP-2 were modified by CUS in the heart. In the kidney, CUS increased 3-nitrotyrosine and MMP-2. Kefir increased the antioxidant defense in the heart and kidney of control and CUS mice. These results suggest that kefir ameliorated CUS-induced anxiety-like behavior by modulating brain BDNF and corticosterone levels. Kefir also increased the antioxidant defense of mice heart and kidney.

Factor reumatoide en vasculitis ANCA asociadas / Rheumatoid factor in ANCA associated vasculitis

Introducción: las pruebas de factor reumatoide (FR) se utilizan principalmente para el diagnóstico de artritis reumatoidea (AR), sin embargo, también pueden estar presentes en otras enfermedades. Su significado clínico en contexto de vasculitis ANCA asociadas (VAA) todavía es incierto. El objetivo de este estudio fue establecer el significado clínico y pronóstico del FR en pacientes con VAA. Materiales y métodos: se realizó un estudio observacional, retrospectivo. Se evaluaron pacientes con diagnóstico de VAA (granulomatosis con poliangitis -GPA-, poliangitis microscópica -PAM- y granulomatosis eosinofílica con poliangitis -GEPA-), mayores de 18 años, con FR solicitado antes del inicio del tratamiento. Se recolectaron los siguientes datos: edad, sexo, tipo de VAA, duración de la enfermedad, tratamiento, órganos afectados, Birmingham Vasculitis Activity Score (BVAS), Five Factor Score (FFS), eritrosedimentación, proteína C reactiva, requerimiento de diálisis, asistencia respiratoria mecánica, mortalidad y causa de muerte. Se calculó el odds ratio (OR) y su intervalo de confianza del 95% (IC 95%) para determinar la fuerza de asociación entre las variables. Resultados: incluimos 32 pacientes en los que encontramos 31,2% de FR positivo. Comparados con aquellos con FR negativo, no hubo diferencias significativas con respecto a manifestaciones clínicas, ni actividad de la enfermedad medida por el BVAS y reactantes de fase aguda. La presencia de factor reumatoide se asoció a menor ingreso a diálisis (OR 0.14 IC 0,02-0,8; p=0,02) y mortalidad (p=0,04). No hubo diferencias significativas con respecto al FFS. Conclusiones: en nuestro estudio la presencia de FR en pacientes con vasculitis ANCA se asoció a menor requerimiento de diálisis y menor mortalidad. Estos hallazgos no se correlacionaron estadísticamente con el FFS. No se encontró asociación entre la presencia de FR y el compromiso de órgano, actividad de la enfermedad, ni requerimiento de asistencia respiratoria mecánica.

Introduction: rheumatoid factor tests are mainly used for the diagnosis of rheumatoid arthritis (RA); however, it may also be present in other diseases. Its clinical significance in the context of ANCA associated vasculitis (AAV) is still uncertain. The objective was to establish the clinical and prognostic significance of RF in patients with AAV. Materials and methods: a retrospective observational study was carried out. Patients with a diagnosis of AAV (GPA, MAP and AGEP) over 18 years of age with RF requested before the start of treatment were evaluated. The following data were collected: age, sex, type of AAV, disease duration, treatment, affected organs, Birmingham Vasculitis Activity Score (BVAS), Five Factor Score (FFS), erythrocyte sedimentation rate, C-reactive protein, dialysis requirement, attendance mechanical ventilation, mortality and cause of death. The odds ratio (OR) and its 95% confidence interval (95%CI) were calculated to determine the strength of association between variables. Results: we included 32 patients in whom we found 31.2% positive RF. Compared to those with negative RF, there were no significant differences with respect to clinical manifestations, nor disease activity measured by BVAS and acute phase reactants. The presence of the rheumatoid factor was associated with lower admission to dialysis (OR 0.14 CI 0.02-0.8 p=0.02) and mortality (p=0.04). There were no significant differences with respect to FFS. Conclusions: in our study, the presence of RF in patients with ANCA vasculitis was associated with a lower requirement for dialysis and lower mortality. These findings were not statistically correlated with the FFS. No association was found between the presence of RF and organ involvement, disease activity, or mechanical ventilation requirement.

Assessment of biomarkers of early kidney damage and exposure to pollutants in artisanal mercury mining workers from Mexico.

Artisanal mercury mining (AMM) is an informal economic activity that employs low technology and limited protection, and poses a risk to workers and their families; due to the extraction process, these scenarios involve exposure to complex mixtures of pollutants that synergistically aggravate the health of miners and people living near the site. Although mercury is the predominant pollutant, there are others such as polycyclic aromatic hydrocarbons (PAHs), toluene, arsenic, and lead which have been classified as nephrotoxic pollutants. Therefore, the purpose of this research was to evaluate the association between exposure to a complex mixture of pollutants (mercury, lead, arsenic, PAHs, and toluene) and kidney damage in artisanal Hg mining workers through early kidney damage proteins (KIM-1, OPN, RBP-4, NGAL, and Cys-C). The results demonstrate the presence of OH-PAHs at concentrations of 9.21 (6.57-80.63) µg/L, hippuric acid as a biomarker of exposure to toluene, As and Pb (655. 1 (203.8-1231) mg/L, 24.05 (1.24-42.98) g/g creatinine, and 4.74 (2.71-8.14) g/dL, respectively), and urinary Hg (503.4 (177.9-878.7) g/g creatinine) in the study population. As well as biomarkers of kidney damage, NGAL and RPB-4 were found in 100% of the samples, KIM-1 and Cys-C in 44.1%, and OPN in 41% of the miners. Significant correlations were found between several of the evaluated pollutants and early kidney damage proteins. Our results demonstrate the application of the early kidney damage biomarkers for the assessment of damage caused by the exposure to mixtures of pollutants and, therefore, the urgent need for monitoring in AMM areas.

Wistar rat as an animal model to study high-fat induced kidney damage: a systematic review.

The effects of high-fat-associated kidney damage in humans are not completely elucidated. Animal experiments are essential to understanding the mechanisms underlying human diseases. This systematic review aimed to compile evidence of the role of a high-fat diet during the development of renal lipotoxicity and fibrosis of Wistar rats to understand whether this is a satisfactory model for the study of high fat-induced kidney damage. We conducted systematic searches in PUBMED, EMBASE, Lilacs, and Web of Science databases from inception until May 2021. The risk of bias was assessed using SYRCLE toll. Two reviewers independently screened abstracts and reviewed full-text articles. A total of 11 studies were included. The damage varied depending on the age and sex of the animals, time of protocol, and amount of fat in the diet. In conclusion, the Wistar rat is an adequate animal model to assess the effects of a high-fat diet on the kidneys.HighlightsA high-fat diet may promote kidney damage in Wistar rats.Wistar rat is efficient as an animal model to study high-fat-induced kidney damage.The effect of the diet depends on the fat amount, consumption time, and animal age.

Green Tea Extract Increases Soluble RAGE and Improves Renal Function in Patients with Diabetic Nephropathy.

One of the proposed mechanisms for the development of diabetic nephropathy (DN) is the increase of end products of advanced glycosylation (AGEs), which bind to its receptor (RAGE), favoring nephron cellular damage. An isoform of this receptor is soluble RAGE (sRAGE), which can antagonize AGE-altered intracellular signaling. It has known that green tea extract (GTE) increases the expression of sRAGE, but it is unknown whether this could improve kidney function. The objective of this study was to evaluate the effect of the administration of GTE on the concentrations of sRAGE, renal function, and metabolic profile in patients with type 2 diabetes mellitus (T2DM) and DN. A randomized, double-blinded, placebo-controlled clinical trial was carried out in 39 patients who received GTE (400 mg every 12 h) or placebo for 3 months. sRAGE levels, renal function, and metabolic parameters were determined before and after the intervention. In the GTE group, there were statistically significant increase on sRAGE (320.55 ± 157.63 pg/mL vs. 357.59 ± 144.99 pg/mL; P = .04) and glomerular filtration rate (GFR; 66.44 ± 15.17 mL/min/1.73 m2 vs. 71.70 ± 19.33 mL/min/1.73 m2; P = .04), and a statistically significant decrease in fasting serum glucose (7.62 ± 3.00 mmol/L vs. 5.86 ± 1.36 mmol/L; P ≤ .01) and triacylglycerols (1.91 ± 0.76 mmol/L vs. 1.58 ± 0.69; P = .02). Administration of GTE increases the serum concentration of sRAGE and the GFR and decreases the concentration of fasting serum glucose and triacylglycerols. The study was registered in ClinicalTrials.gov with the identifier NCT03622762.

Evaluation of hydroxylated metabolites of polycyclic aromatic hydrocarbons and biomarkers of early kidney damage in indigenous children from Ticul, Yucatán, Mexico.

Polycyclic aromatic hydrocarbons (PAHs) are environmental persistent chemicals, produced by the incomplete combustion of solid fuels, found in smoke. PAHs are considered carcinogenic, teratogenic, and genotoxic. Children are susceptible to environmental pollutants, particularly those living in high-exposure settings. Therefore, the main objective of this study was to evaluate the exposure to PAHs through hydroxylated metabolites of PAHs (OH-PAHs), 1-hydroxynaphtalene (1-OH-NAP), and 2-hydroxynaphtalene (2-OH-NAP); 2-,3-, and 9-hydroxyfluorene (2-OH-FLU, 3-OH-FLU, 9-OH-FLU); 1-,2-,3-, and 4-hydroxyphenanthrene (1-OH-PHE, 2-OH-PHE, 3-OH-PHE, 4-OH-PHE); and 1-hydroxypyrene (1-OH-PYR), as well as kidney health through biomarkers of early kidney damage (osteopontin (OPN), neutrophil gelatinase-associated lipocalin (NGAL), α1-microglobulin (α1-MG), and cystatin C (Cys-C)) in children from an indigenous community dedicated to footwear manufacturing and pottery in Ticul, Yucatán, Mexico. The results show a high exposure to PAHs from the found concentrations of OH-PAHs in urine in 80.5% of the children in median concentrations of 18.4 (5.1-71.0) µg/L of total OH-PAHs, as well as concentrations of kidney damage proteins in 100% of the study population in concentrations of 4.8 (3-12.2) and 7.9 (6.5-13.7) µg/g creatinine of NGAL and Cys-C respectively, and 97.5% of the population with concentrations of OPN and α1-MG at mean concentrations of 207.3 (119.8-399.8) and 92.2 (68.5-165.5) µg/g creatinine. The information provided should be considered and addressed by the health authorities to establish continuous biomonitoring and programs to reduce para-occupational exposure in the vulnerable population, particularly children, based on their fundamental human right to health.

Kidney Injury Molecule-1 in the detection of early kidney injury in dogs with leptospirosis.

Renal damage, a common feature in canine leptospirosis, ranges from a subclinical affection to kidney dysfunction and death. Chances of recovery can be improved by early intervention. However, traditional biomarkers (serum urea and creatinine) have limited relevance for precocity. Kidney Injury Molecule-1 (KIM-1) is a transmembrane protein upregulated in early stages of tubular injury. This study evaluated the use of urinary KIM-1 to detect early renal injury in naturally occurring canine leptospirosis. This exploratory research included 30 dogs divided into two groups: (1) dogs with leptospirosis (n = 25) and (2) healthy dogs (n = 5). Leptospira sp. infection was diagnosed through urine PCR and/or direct bacteriologic culture and/or serology (single MAT titters ≥800). Additionally, stage of infection was further characterized in acute and subacute phases based on the onset of clinical symptoms from 3 to 7 days. Urinary KIM-1 (uKIM-1) concentrations were measured in both groups with a commercial canine ELISA kit. uKIM-1 levels were statistically different (P < 0.01) between the studied groups, especially in non-azotemic dogs (P = 0.0042). The biomarker showed 88 % sensibility to diagnosis of kidney injury at> 1.49 ng/mL cut-off. Urine KIM-1 was negatively correlated with urine specific gravity (USG) but accompanied histopathological evidence of renal degeneration, necrosis and regeneration processes, extending information on kidney health. Measurement of KIM-1 in the urine of canine patients was able to detect naturally occurring acute and subacute leptospirosis accompanied by tubular injury in early non-azotemic infections.

Exposure to polycyclic aromatic hydrocarbon mixtures and early kidney damage in Mexican indigenous population.

The traditions and habits of indigenous communities in México include the use of wood and biomass burning to cook their food, which generates large amounts of smoke and therefore pollution inside the households. This smoke is composed of a complex mixture of polycyclic aromatic hydrocarbons (PAHs) which at high levels of exposure cause carcinogenic, genotoxic effects and some chronic pulmonary and cardiovascular diseases; however, few studies relate kidney health with exposure to PAHs. Thus, the aim of this study was the evaluation of 10 hydroxylated metabolites of PAHs (OH-PAHs), and their correlation with biomarkers of early kidney damage renal (cystatin-C (Cys-C)), osteopontin (OPN), retinol-binding protein-4 (RPB-4), and neutrophil gelatinase-associated lipocalin (NGAL) in the indigenous population of the Huasteca Potosina in Mexico. The results demonstrate the presence of the OH-PAHs and kidney damage biomarkers in 100% of the study population. The OH-PAHs were shown in the following order of frequency, 1-OH-PYR > 4-OH-PHE > 2-OH-NAP > 1-OH-NAP > 9-OH-FLU > 3-OH-FLU > 2-OH-FLU > 3-OH-PHE and with the following percentages of detection 97.6, 87.8, 78, 73.2, 68.3, 31.7, 14.6, and 12.2%, respectively. NGAL and RBP-4 were present in above 85% of the population, with mean concentrations of 78.5 ± 143.9 and 139.4 ± 131.7 ng/g creatinine, respectively, OPN (64%) with a mean concentration of 642.6 ± 723.3 ng/g g creatinine, and Cys-C with a mean concentration of 33.72 ± 44.96 ng/g creatinine. Correlations were found between 1-OH-NAP, 2-OH-NAP, 9-OH-FLU, and 4-OH-PHE and the four biomarkers of early kidney damage. 3-OH-FLU with OPN and 1-OH-PYR correlated significantly with NGAL, OPN, and RPB-4.

Aqueous extract of Paullinia cupana attenuates renal and hematological effects associated with ketoprofen.

This study aimed to evaluate the effect of aqueous extract of Paullinia cupana (AEG) against ketoprofen side effects, through biochemical, hematological, and histological parameters. AEG showed antioxidant activity in the DPPH• scavenging (IC50  = 17.00 ± 1.00 µg/ml) and HPLC analysis revealed that this extract is constituted by antioxidants (caffeine, catechins, theobromine, and polyphenols). In vivo experiments in female Wistar rats demonstrated that alterations in urea, creatinine, and uric acid levels promoted (p < .05) by ketoprofen were reversed when AEG was co-administered. Ketoprofen significantly decreased the catalase levels of animal tissues (p < .05), which were restored when AEG was co-administered with the mentioned drug. Histological analysis showed that AEG protected tissues from damages caused by ketoprofen. Moreover, AEG reestablished the number of white blood cells, which had decreased when ketoprofen was administered. In conclusion, this study suggested that the association between ketoprofen and AEG may be an alternative to reduce health damages caused by this drug. PRACTICAL APPLICATIONS: Paullinia cupana, popularly known as guaraná, is commonly consumed as a beverage in Brazil and exhibits pharmacological and beneficial effects to humans. Ketoprofen is an efficacious drug employed in the treatment of inflammatory processes. However, this drug can cause several side effects in humans. Thus, the usage of natural products and plant extracts that can reduce such undesirable effects consists in a valuable strategy to be applied in therapeutic interventions.

Renal Damage During Continuous Versus Intermittent Treatment with Lithium.

The aim of this study was to evaluate renal damage in animals treated with lithium continuously versus intermittently. Rats were randomized into three groups: control group fed ad libitum powered standard diet for 3 months and two experimental groups, one of them fed ad libitum the same diet or the same diet supplemented with 60 mmol of lithium/kg diet every alternate week, for 3 months and the other fed ad libitum powered standard diet for one and a half month and the same diet supplemented with 60 mmol of lithium/kg diet for the last month and a half. Lithemias in experimental groups were within therapeutic range used in humans. At the end of the protocol, diuresis was higher in experimental groups compared to control group. There was no difference in serum creatinine and creatinine clearance. Both experimental groups showed hypertrophy, hyperplasia, and dilatation of cortical collecting tubules although dilatation was greater in continuous group. Longer studies are necessary to clarify the evolution of renal damage. Our preliminary study shows that histopathological damage associated with the use of lithium occurs during both continuous and intermittent treatment, but it seems to be somewhat greater in the continuous group.

The protective effect of lycopene against oxidative kidney damage associated with combined use of isoniazid and rifampicin in rats

It is known that the combined use of antibiotics, such as isoniazid and rifampicin, in the treatment of tuberculosis causes oxidative kidney damage. The aim of this study was to biochemically and histopathologically investigate the effect of lycopene on oxidative kidney damage due to the administration of isoniazid and rifampicin in albino Wistar male rats. Lycopene at a dose of 5 mg/kg was orally administered to lycopene+isoniazid+rifampicin (LIR) rats, and normal sunflower oil (0.5 mL) was orally administered to isoniazid+rifampicin (IR) and healthy control (HG) rats as vehicle by gavage. One hour after the administration of lycopene and vehicle, 50 mg/kg isoniazid and rifampicin were given orally to the LIR and IR groups. This procedure was performed once a day for 28 days. Rats were sacrificed by a high dose of anesthesia at the end of this period, and oxidant-antioxidant parameters were measured in the removed kidney tissues. Creatinine and blood urea nitrogen (BUN) levels were measured in blood samples, and kidney tissues were also evaluated histopathologically. The combined administration of isoniazid and rifampicin changed the oxidant-antioxidant balance in favor of oxidants, and it increased blood urea nitrogen and creatinine levels, which are indicators of kidney function. Co-administration of isoniazid and rifampicin also caused oxidative kidney damage. Lycopene biochemically and histopathologically decreased oxidative kidney damage induced by isoniazid and rifampicin administration. These results suggested that lycopene may be beneficial in the treatment of nephrotoxicity due to isoniazid and rifampicin administration.

Iso-Oncotic Albumin Mitigates Brain and Kidney Injury in Experimental Focal Ischemic Stroke.

Background: There is widespread debate regarding the use of albumin in ischemic stroke. We tested the hypothesis that an iso-oncotic solution of albumin (5%), administered earlier after acute ischemic stroke (3 h), could provide neuroprotection without causing kidney damage, compared to a hyper-oncotic albumin (20%) and saline. Objective: To compare the effects of saline, iso-oncotic albumin, and hyper-oncotic albumin, all titrated to similar hemodynamic targets, on the brain and kidney. Methods: Ischemic stroke was induced in anesthetized male Wistar rats (n = 30; weight 437 ± 68 g) by thermocoagulation of pial blood vessels of the primary somatosensory, motor, and sensorimotor cortices. After 3 h, animals were anesthetized and randomly assigned (n = 8) to receive 0.9% NaCl (Saline), iso-oncotic albumin (5% ALB), and hyper-oncotic albumin (20% ALB), aiming to maintain hemodynamic stability (defined as distensibility index of inferior vena cava <25%, mean arterial pressure >80 mmHg). Rats were then ventilated using protective strategies for 2 h. Of these 30 animals, 6 were used as controls (focal ischemic stroke/no fluid). Results: The total fluid volume infused was higher in the Saline group than in the 5% ALB and 20% ALB groups (mean ± SD, 4.3 ± 1.6 vs. 2.7 ± 0.6 and 2.6 ± 0.5 mL, p = 0.03 and p = 0.02, respectively). The total albumin volume infused (g/kg) was higher in the 20% ALB group than in the 5% ALB group (1.4 ± 0.6 vs. 0.4 ± 0.2, p < 0.001). Saline increased neurodegeneration (Fluoro-Jade C staining), brain inflammation in the penumbra (higher tumor necrosis factor-alpha expression), and blood-brain barrier damage (lower gene expressions of claudin-1 and zona occludens-1) compared to both iso-oncotic and hyper-oncotic albumins, whereas it reduced the expression of brain-derived neurotrophic factor (a marker of neuroregeneration) compared only to iso-oncotic albumin. In the kidney, hyper-oncotic albumin led to greater damage as well as higher gene expressions of kidney injury molecule-1 and interleukin-6 than 5% ALB (p < 0.001). Conclusions: In this model of focal ischemic stroke, only iso-oncotic albumin had a protective effect against brain and kidney damage. Fluid therapy thus requires careful analysis of impact not only on the brain but also on the kidney.