RESUMO
Chronic kidney disease (CKD) has emerged as a significant global public health concern. Recent epidemiological studies have highlighted the link between exposure to fine particulate matter (PM2.5) and a decline in renal function. PM2.5 exerts harmful effects on various organs through oxidative stress and inflammation. Acute kidney injury (AKI) resulting from ischaemia-reperfusion injury (IRI) involves biological processes similar to those involved in PM2.5 toxicity and is a known risk factor for CKD. The objective of this study was to investigate the impact of PM2.5 exposure on IRI-induced AKI. Through a unique environmentally controlled setup, mice were exposed to urban PM2.5 or filtered air for 12 weeks before IRI followed by euthanasia 48 h after surgery. Animals exposed to PM2.5 and IRI exhibited reduced glomerular filtration, impaired urine concentration ability, and significant tubular damage. Further, PM2.5 aggravated local innate immune responses and mitochondrial dysfunction, as well as enhancing cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway activation. This increased renal senescence and suppressed the anti-ageing protein klotho, leading to early fibrotic changes. In vitro studies using proximal tubular epithelial cells exposed to PM2.5 and hypoxia/reoxygenation revealed heightened activation of the STING pathway triggered by cytoplasmic mitochondrial DNA, resulting in increased tubular damage and a pro-inflammatory phenotype. In summary, our findings imply a role for PM2.5 in sensitising proximal tubular epithelial cells to IRI-induced damage, suggesting a plausible association between PM2.5 exposure and heightened susceptibility to CKD in individuals experiencing AKI. Strategies aimed at reducing PM2.5 concentrations and implementing preventive measures may improve outcomes for AKI patients and mitigate the progression from AKI to CKD. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Assuntos
Injúria Renal Aguda , Camundongos Endogâmicos C57BL , Material Particulado , Traumatismo por Reperfusão , Animais , Injúria Renal Aguda/patologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Traumatismo por Reperfusão/patologia , Material Particulado/efeitos adversos , Material Particulado/toxicidade , Camundongos , Masculino , Poluição do Ar/efeitos adversos , Modelos Animais de Doenças , Rim/patologia , Rim/metabolismo , Transdução de Sinais , Taxa de Filtração GlomerularRESUMO
BACKGROUND: Immune Checkpoint Inhibitors (ICI) have been widely used in treating different types of cancer. They increase survival in many oncologic patients and enable cancer-specific therapy. Acute Kidney Injury (AKI) is one of the adverse effects associated with using ICI, where knowledge of the prevalence and renal histological findings are still reasons for discussion. OBJECTIVE: Therefore, this meta-analysis evaluates the association between ICI use and AKI. METHODS: The search was performed in PubMed, Lilacs, and Cochrane platforms. Studies published up to December 1, 2022, were included. RESULTS: A total of 16 studies met the established PICOT criteria and were included in this review. Comparing the ICI plus chemotherapy against chemotherapy alone, the relative risk (RR) for AKI's development with ICI use was 2.89 (95%CI 1.37-6.10). In the analyses by class and drug type, programmed cell death 1 monoclonal antibody (anti-PD-1) showed an increased risk of 2.11 (95%CI 1.26-3.52), and pembrolizumab demonstrated a risk of AKI (RR= 2.77, 95%CI 1.46-5.26). Likewise, regarding the severity of AKI, AKI grade 3 or higher was more common in the ICI plus chemotherapy compared to the chemotherapy group: 3.66 (95%CI 1.19-11.30), while the subgroup analyses pooled studies comparing ICI alone versus chemotherapy alone in the control group did not demonstrate an association with AKI. CONCLUSIONS: These findings suggest that ICI use is associated with an increased risk of AKI and that anti-PD-1 use is associated with a higher incidence of renal adverse events than programmed cell death ligand 1 monoclonal antibody (anti-PD-L1). Studies with adequate power and well-defined criteria for acute interstitial nephritis, nowadays taken as a synonym for AKI related to ICI, are necessary.
Assuntos
Injúria Renal Aguda , Inibidores de Checkpoint Imunológico , Receptor de Morte Celular Programada 1 , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Inibidores de Checkpoint Imunológico/efeitos adversos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêuticoRESUMO
Metformin is a hypoglycemic agent used as the first line for the treatment of non-insulin dependent Diabetes Mellitus. While it is a generally safe drug, it has an infrequent adverse reaction called lactic acidosis. We report a 49 year-old patient with non-insulin-requiring type 2diabetes who developed an acute kidney failure injury along with severe metabolic acidosis secondary to pneumonia during treatment.
La metformina es un agente hipoglucemiante que se ocupa de primera línea para el tratamiento de la Diabetes Mellitus no insulino dependiente. Si bien es un medicamento bien tolerado, tiene una reacción adversa bastante infrecuente que es la acidosis láctica. Reportamos el caso de una paciente de 49 años insulino no dependiente que desarrolló una injuria renal aguda junto con acidosis metabólica severa secundaria a una neumonía en tratamiento.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Acidose Láctica/induzido quimicamente , Acidose Láctica/terapia , Injúria Renal Aguda/induzido quimicamente , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversosRESUMO
INTRODUCTION AND OBJECTIVES: Acute kidney injury (AKI) is prevalent and has deleterious effects on postoperative outcomes following liver transplantation (LT). The impact of nonselective beta-blockers (NSBBs) in patients with liver cirrhosis remains controversial. This study investigated the association between preoperative NSBB use and AKI after living donor LT (LDLT). PATIENTS AND METHODS: We evaluated 2,972 adult LDLT recipients between January 2012 and July 2022. The patients were divided into two groups based on the preoperative NSBB use. Propensity score matched (PSM) and inverse probability of treatment weighting (IPTW) analyses were performed to evaluate the association between preoperative NSBB use and postoperative AKI. Multiple logistic regression analyses were also used to identify the risk factors for AKI. RESULTS: The overall incidence of AKI was 1,721 (57.9%) cases. The NSBB group showed a higher incidence of AKI than the non-NSBB group (62.4% vs. 56.7%; P = 0.011). After PSM and IPTW analyses, no significant difference in the incidence of AKI was found between the two groups (Odds ratio, OR 1.13, 95% confidence interval, CI 0.93-1.37, P = 0.230, PSM analysis; OR 1.20, 95% CI 0.99-1.44, P = 0.059, IPTW analysis). In addition, preoperative NSBB use was not associated with AKI after multivariate logistic regression analysis (OR 1.16, 95% CI 0.96-1.40, P = 0.118). CONCLUSIONS: Preoperative NSBB use was not associated with AKI after LDLT. Further studies are needed to validate our results.
Assuntos
Injúria Renal Aguda , Antagonistas Adrenérgicos beta , Transplante de Fígado , Doadores Vivos , Pontuação de Propensão , Humanos , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Transplante de Fígado/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Incidência , Fatores de Risco , Antagonistas Adrenérgicos beta/uso terapêutico , Antagonistas Adrenérgicos beta/efeitos adversos , Estudos Retrospectivos , Adulto , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Cuidados Pré-Operatórios/métodos , Cirrose Hepática/cirurgia , Cirrose Hepática/complicações , Medição de RiscoRESUMO
BACKGROUND: Piperacillin/tazobactam is one of the most common antibiotics prescribed in the ICU and the combination of piperacillin/tazobactam with vancomycin has been associated with acute kidney injury (AKI) in critically ill patients. However, data on the risk of AKI with piperacillin/tazobactam, despite vancomycin co-exposure, are lacking. OBJECTIVES: To investigate the association of piperacillin/tazobactam with AKI and renal replacement therapy (RRT) among adult ICU patients. METHODS: We analysed data from patients included in two open access databases (MIMIC-IV and eICU). Critically ill patients who received piperacillin/tazobactam or cefepime (a cephalosporin with similar broad-spectrum activity to piperacillin/tazobactam) during their first ICU stay were eligible for the study. Marginal structural Cox models, accounting for time-fixed covariates and time-dependent covariates were performed. The primary outcomes were AKI and need of RRT. RESULTS: A total of 20 107 patients were included, with 11 213 in the piperacillin/tazobactam group and 8894 in the cefepime group. Exposure to piperacillin/tazobactam was associated with AKI (HR 1.77; 95% CI 1.51-2.07; P < 0.001) and with need of RRT (HR 1.31; 95% CI 1.08-1.57; P = 0.005). Tests for interaction were not statistically significant for occurrence of AKI and RRT in the subgroup of patients exposed to vancomycin or not (P = 0.26 and P = 0.6, respectively). CONCLUSIONS: In critically ill patients, exposure to piperacillin/tazobactam was associated with increased risk of AKI and with increased risk of RRT, regardless of combination therapy with vancomycin.
Assuntos
Injúria Renal Aguda , Vancomicina , Adulto , Humanos , Cefepima/efeitos adversos , Vancomicina/efeitos adversos , Estudos de Coortes , Estado Terminal , Estudos Retrospectivos , Combinação Piperacilina e Tazobactam/efeitos adversos , Injúria Renal Aguda/induzido quimicamenteRESUMO
INTRODUCTION: Contrast-associated acute kidney injury (CA-AKI) is a deterioration of kidney function that occurs after the administration of a iodinated contrast medium (ICM). Most studies that defined this phenomenon used older ICMs that were more prone of causing CA-AKI. In the past decade, several articles questioned the true incidence of CA-AKI. However, there is still a paucity of a data about the safety of newer ICM. OBJECTIVE: To assess the incidence of CA-AKI in hospitalized patients that were exposed to computed tomography (CT) with and without ICM. METHODS: Prospective cohort study with 1003 patients who underwent CT in a tertiary hospital from December 2020 through March 2021. All inpatients aged > 18 years who had a CT scan during this period were screened for the study. CA-AKI was defined as a relative increase of serum creatinine of ≥ 50% from baseline or an absolute increase of ≥ 0.3 mg/dL within 18 to 48 hours after the CT. Chi-squared test, Kruskal-Wallis test, and linear regression model with restricted cubic splines were used for statistical analyses. RESULTS: The incidence of CA-AKI was 10.1% in the ICM-exposed group and 12.4% in the control group when using the absolute increase criterion. The creatinine variation from baseline was not significantly different between groups. After adjusting for baseline factors, contrast use did not correlate with worse renal function. CONCLUSION: The rate of CA-AKI is very low, if present at all, with newer ICMs, and excessive caution regarding contrast use is probably unwarranted.
Assuntos
Injúria Renal Aguda , Meios de Contraste , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Incidência , Meios de Contraste/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Creatinina , Fatores de RiscoRESUMO
BACKGROUND AND OBJECTIVES: Acute kidney injury (AKI) has emerged as an important toxicity among patients with advanced cancer treated with immune checkpoint inhibitors. The aim of this study was to describe the incidence, risk factors and mortality of AKI in patients receiving immune checkpoint inhibitors alone or in combination with another form of immunotherapy or chemotherapy. DESIGN, SETTING AND PARTICIPANTS: We included all patients who received immune checkpoint inhibitors alone or in combination with another form of immunotherapy or chemotherapy at AC Camargo Cancer Center from January 2015 to December 2019. AKI was defined as a ≥ 1.5 fold increase in creatinine from baseline within 12 months of immune checkpoint inhibitor initiation. We assessed the association between baseline demographics, comorbidities, medications and risk of AKI using a competing risk model, considering death as a competing event. RESULTS: We included 614 patients in the analysis. The mean age was 58.4 ± 13.5 years, and the mean baseline creatinine was 0.8 ± 0.18 mg/dL. AKI occurred in 144 (23.5%) of the patients. The most frequent AKI etiologies were multifactorial (10.1%), hemodynamic (8.8%) and possibly immunotherapy-related (3.6%). The likelihood of AKI was greater in patients with genitourinary cancer (sHR 2.47 95% CI 1.34-4.55 p < 0.01), with a prior AKI history (sHR 2.1 95% CI 1.30-3.39 p < 0.01) and taking antibiotics (sHR 2.85 95% CI 1.54-5.27 p < 0.01). CONCLUSIONS: In this study, genitourinary cancer, previous AKI and antibiotics use were associated with a higher likelihood of developing AKI.
Assuntos
Injúria Renal Aguda , Neoplasias Urogenitais , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Creatinina , Inibidores de Checkpoint Imunológico/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Fatores de Risco , Imunoterapia/efeitos adversos , Neoplasias Urogenitais/complicações , Antibacterianos , Estudos RetrospectivosRESUMO
We report the observations of two patients, having voluntarily ingested lethal doses of paraquat with suicidal intent, with an unfavorable prognostic score. The treatment consisted of gastric lavage, administration of activated charcoal, n-acetylcysteine and cyclophosphamide + methylprednisolone + dexamethasone. The installation of acute renal failure motivated the initiation of daily conventional hemodialysis (HD) over 10 to 14 days, with a favorable evolution. The following complications were recorded: anemia, bacteremia and deep vein thrombosis. These observations raise three questions in the treatment of paraquat intoxication: the effectiveness of HD, the interest of its association with the above therapies in the prevention of pulmonary fibrosis, and the need for infectious prevention and thromboembolism. Furthermore, the absence of a paraquatemia assay cannot constitute a limitation for management, and hemoperfusion on an inaccessible charcoal column can be replaced by an HD usually available.
Nous rapportons les observations de deux patients ayant ingéré volontairement des doses létales du paraquat à but suicidaire, avec un score pronostic défavorable. Le traitement a consisté en un lavage gastrique, une administration du charbon activé, du n-acétylcystéine et du cyclophosphamide + méthylprednisolone + dexaméthasone. L'installation d'une insuffisance rénale aiguë a motivé l'initiation d'une hémodialyse conventionnelle quotidienne (HD) sur 10 à 14 jours, avec une évolution favorable. Les complications suivantes ont été enregistrées : anémie, bactériémie et thrombose veineuse profonde. Ces observations soulèvent trois questions dans le traitement d'une intoxication au paraquat : l'efficacité de l'HD, l'intérêt de son association avec les thérapeutiques supra dans la prévention de la fibrose pulmonaire, et la nécessité d'une prévention infectieuse et thrombo-embolique. Par ailleurs, l'absence d'un dosage de la paraquatémie ne peut constituer une limite pour la prise en charge, et l'hémoperfusion sur colonne de charbon non accessible peut être remplacée par une HD habituellement disponible.
Assuntos
Injúria Renal Aguda , Paraquat , Intoxicação , Humanos , Corticosteroides/uso terapêutico , Carvão Vegetal/uso terapêutico , Ciclofosfamida/uso terapêutico , Dexametasona/uso terapêutico , Guiana Francesa , Lavagem Gástrica , Hospitais , Paraquat/intoxicação , Intoxicação/terapia , Diálise Renal , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/terapiaRESUMO
ABSTRACT: Background: Approximately 50% of patients with sepsis develop acute kidney injury (AKI), which is predictive of poor outcomes, with mortality rates of up to 70%. The endothelium is a major target for treatments aimed at preventing the complications of sepsis. We hypothesized that human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) could attenuate tubular and endothelial injury in a porcine model of sepsis-induced AKI. Methods: Anesthetized pigs were induced to fecal peritonitis, resulting in septic shock, and were randomized to treatment with fluids, vasopressors, and antibiotics (sepsis group; n = 11) or to that same treatment plus infusion of 1 × 10 6 cells/kg of hUC-MSCs (sepsis+MSC group; n = 11). Results: At 24 h after sepsis induction, changes in serum creatinine and mean arterial pressure were comparable between the two groups, as was mortality. However, the sepsis+MSC group showed some significant differences in comparison with the sepsis group: lower fractional excretions of sodium and potassium; greater epithelial sodium channel protein expression; and lower protein expression of the Na-K-2Cl cotransporter and aquaporin 2 in the renal medulla. Expression of P-selectin, thrombomodulin, and vascular endothelial growth factor was significantly lower in the sepsis+MSC group than in the sepsis group, whereas that of Toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) was lower in the former. Conclusion: Treatment with hUC-MSCs seems to protect endothelial and tubular cells in sepsis-induced AKI, possibly via the TLR4/NF-κB signaling pathway. Therefore, it might be an effective treatment for sepsis-induced AKI.
Assuntos
Injúria Renal Aguda , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Sepse , Humanos , Injúria Renal Aguda/terapia , Injúria Renal Aguda/induzido quimicamente , Células Endoteliais/metabolismo , Rim/metabolismo , Células-Tronco Mesenquimais/metabolismo , NF-kappa B/metabolismo , Sepse/complicações , Sepse/terapia , Sepse/metabolismo , Receptor 4 Toll-Like/metabolismo , Cordão Umbilical/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , SuínosRESUMO
SUMMARY: The toxic effects of thioacetamide (TAA) and carbon tetrachloride on the human body are well recognized. In this study, we examined whether TAA intoxication can induce kidney leukocyte infiltration (measured as leukocyte common antigen CD45) associated with the augmentation of the reactive oxygen species (ROS)/tumor necrosis factor-alpha (TNF-α) axis, as well as biomarkers of kidney injury with and without metformin treatment. Rats were either injected with TAA (200 mg/kg; twice a week for 8 weeks) before being sacrificed after 10 weeks (experimental group) or were pre-treated with metformin (200 mg/kg) daily for two weeks prior to TAA injections and continued receiving both agents until the end of the experiment, at week 10 (protective group). Using basic histology staining, immunohistochemistry methods, and blood chemistry analysis, we observed profound kidney tissue injury such as glomerular and tubular damage in the experimental group, which were substantially ameliorated by metformin. Metformin also significantly (p0.05) increase in kidney expression of CD45 positive immunostaining cells. In conclusion, we found that TAA induces kidney injury in association with the augmentation of ROS/TNF-α axis, independent of leukocyte infiltration, which is protected by metformin.
Son bien conocidosos los efectos tóxicos de la tioacetamida (TAA) y el tetracloruro de carbono en el cuerpo humano. En este estudio, examinamos si la intoxicación por TAA puede inducir la infiltración de leucocitos renales (medida como antígeno leucocitario común CD45) asociada con el aumento de las especies reactivas de oxígeno (ROS)/factor de necrosis tumoral-alfa (TNF-α), así como biomarcadores de daño renal con y sin tratamiento con metformina. A las ratas se les inyectó TAA (200 mg/kg; dos veces por semana durante 8 semanas) antes de sacrificarlas a las 10 semanas (grupo experimental) o se les pretrató con metformina (200 mg/kg) diariamente durante dos semanas antes de las inyecciones de TAA y continuaron recibiendo ambos agentes hasta el final del experimento, en la semana 10 (grupo protector). Usando tinción histológica básica, métodos de inmunohistoquímica y análisis químico de la sangre, observamos una lesión profunda del tejido renal, como daño glomerular y tubular en el grupo experimental, que mejoraron sustancialmente con la metformina. La metformina también inhibió significativamente (p0,05) en la expresión renal de células de inmunotinción positivas para CD45. En conclusión, encontramos que el TAA induce la lesión renal en asociación con el aumento del eje ROS/TNF-α, independientemente de la infiltración de leucocitos, que está protegida por metformina.