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1.
J Ren Nutr ; 34(2): 115-124, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37793468

RESUMO

OBJECTIVE: The incidence of acute kidney injury (AKI) is identified more frequently in noncritical compared with intensive care settings. The prognosis of malnourished AKI patients is far worse than those with normal nutritional status. However, a method for estimating the optimal amount of energy required to guide nutritional support among noncritically ill AKI patients is yet to be determined. METHODS: We evaluated the performance of weight-based formulas (20-30 kcal/kg/day) with the reference values of energy expenditure (EE) measured by indirect calorimetry (IC) among noncritically ill AKI patients during hospitalization. The statistics for assessing agreement, including total deviation index and accuracy within 10% represent the percentage of estimations falling within the IC value range of ±10%, were tested. Parameters for predicting the EE equation were also developed using a regression analysis model. RESULTS: A total of 40 noncritically ill AKI patients were recruited. The mean age of participants was 62.5 ± 16.5 years with 50% being male. The average IC-derived EE was 1,124.6 ± 278.9 kcal/day with respiratory quotients 0.8-1.3, indicating good validity of the IC test. Receiving dialysis, protein catabolic rate, and age was not significantly associated with measured EE. Nearly all weight-based formulas overestimated measured EE. The magnitude of total deviation index values was broad with the proportion of patients achieving an accuracy of 10% being as low as 20%. The proposed equation to predict EE derived from this study was EE (kcal/day) = 618.27 + (8.98 x weight in kg) + 137.0 if diabetes - 199.7 if female (r2 = 0.68, P < .001). In the validation study with an independent group of noncritically ill AKI patients, predicted EE using the newly derived equation was also significantly correlated with measured EE by IC (r = 0.69, P = .004). CONCLUSION: Estimation of EE by weight-based formulas usually overestimated measured EE among noncritically ill AKI patients. In the absence of IC, the proposed predictive equation, specifically for noncritically ill AKI patients might be useful, in addition to weight-based formulas, for guiding caloric dosing in clinical practice.


Assuntos
Injúria Renal Aguda , Estado Terminal , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Metabolismo Energético , Estado Nutricional , Apoio Nutricional , Injúria Renal Aguda/metabolismo , Calorimetria Indireta/métodos
2.
Am J Physiol Renal Physiol ; 326(2): F178-F188, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37994409

RESUMO

Chronic kidney disease is increasing at an alarming rate and correlates with the increase in diabetes, obesity, and hypertension that disproportionately impact socioeconomically disadvantaged communities. Iron plays essential roles in many biological processes including oxygen transport, mitochondrial function, cell proliferation, and regeneration. However, excess iron induces the generation and propagation of reactive oxygen species, which lead to oxidative stress, cellular damage, and ferroptosis. Iron homeostasis is regulated in part by the kidney through iron resorption from the glomerular filtrate and exports into the plasma by ferroportin (FPN). Yet, the impact of iron overload in the kidney has not been addressed. To test more directly whether excess iron accumulation is toxic to kidneys, we generated a kidney proximal tubule-specific knockout of FPN. Despite significant intracellular iron accumulation in FPN mutant tubules, basal kidney function was not measurably different from wild type kidneys. However, upon induction of acute kidney injury (AKI), FPN mutant kidneys exhibited significantly more damage and failed recovery, evidence for ferroptosis, and increased fibrosis. Thus, disruption of iron export in proximal tubules, leading to iron overload, can significantly impair recovery from AKI and can contribute to progressive renal damage indicative of chronic kidney disease. Understanding the mechanisms that regulate iron homeostasis in the kidney may provide new therapeutic strategies for progressive kidney disease and other ferroptosis-associated disorders.NEW & NOTEWORTHY Physiological iron homeostasis depends in part on renal resorption and export into the plasma. We show that specific deletion of iron exporters in the proximal tubules sensitizes cells to injury and inhibits recovery. This can promote a chronic kidney disease phenotype. Our paper demonstrates the need for iron balance in the proximal tubules to maintain and promote healthy recovery after acute kidney injury.


Assuntos
Injúria Renal Aguda , Proteínas de Transporte de Cátions , Sobrecarga de Ferro , Insuficiência Renal Crônica , Humanos , Rim/metabolismo , Injúria Renal Aguda/genética , Injúria Renal Aguda/metabolismo , Ferro/metabolismo , Sobrecarga de Ferro/metabolismo , Homeostase/fisiologia , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/metabolismo
3.
Pak J Pharm Sci ; 34(5): 1645-1649, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34802997

RESUMO

Severe acute respiratory viral infections are frequently associated with multiple organ failure, including acute kidney damage. The present study aimed to investigate the associated influence of COVID-19 on renal function in patients admitted to the intensive care unit in Asir region, Saudi Arabia. Thirty patients infected with COVID-19 who were referred to the intensive care unit during November and October 2020 at Asir central hospital, Asir region, Saudi Arabia were recruited. The age of patients ranged between 30 and 90 years old. Renal function tests exhibited dramatic changes in the renal biomarkers in patients with COVID-19. Blood urea levels in COVID-19 patients were significantly higher than in the control group. In addition, significantly lower albumin levels with abnormally decreased total protein levels were found in COVID-19 patients. Among the different electrolytes analyzed, a significantly lower calcium level was observed in COVID-19 patients' groups than in the controls. Renal function tests for COVID-19-infected ICU patients revealed significant changes, indicating the major impact of COVID-19 on kidney function. Monitoring renal function tests may assist in the early prognosis of COVID-19 patients. It is, therefore, crucial to increase the understanding of renal function tests in COVID-19 patients who were admitted to the hospital before their condition deteriorated.


Assuntos
COVID-19/fisiopatologia , Rim/fisiopatologia , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/metabolismo , Cálcio/metabolismo , Feminino , Hospitalização , Humanos , Unidades de Terapia Intensiva , Rim/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , SARS-CoV-2/patogenicidade , Arábia Saudita
4.
JAMA Netw Open ; 4(3): e211095, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33688965

RESUMO

Importance: Acute kidney injury (AKI) occurs in up to half of patients hospitalized with coronavirus disease 2019 (COVID-19). The longitudinal effects of COVID-19-associated AKI on kidney function remain unknown. Objective: To compare the rate of change in estimated glomerular filtration rate (eGFR) after hospital discharge between patients with and without COVID-19 who experienced in-hospital AKI. Design, Setting, and Participants: A retrospective cohort study was conducted at 5 hospitals in Connecticut and Rhode Island from March 10 to August 31, 2020. Patients who were tested for COVID-19 and developed AKI were screened, and those who survived past discharge, did not require dialysis within 3 days of discharge, and had at least 1 outpatient creatinine level measurement following discharge were included. Exposures: Diagnosis of COVID-19. Main Outcomes and Measures: Mixed-effects models were used to assess the association between COVID-19-associated AKI and eGFR slope after discharge. The secondary outcome was the time to AKI recovery for the subgroup of patients whose kidney function had not returned to the baseline level by discharge. Results: A total of 182 patients with COVID-19-associated AKI and 1430 patients with AKI not associated with COVID-19 were included. The population included 813 women (50.4%); median age was 69.7 years (interquartile range, 58.9-78.9 years). Patients with COVID-19-associated AKI were more likely to be Black (73 [40.1%] vs 225 [15.7%]) or Hispanic (40 [22%] vs 126 [8.8%]) and had fewer comorbidities than those without COVID-19 but similar rates of preexisting chronic kidney disease and hypertension. Patients with COVID-19-associated AKI had a greater decrease in eGFR in the unadjusted model (-11.3; 95% CI, -22.1 to -0.4 mL/min/1.73 m2/y; P = .04) and after adjusting for baseline comorbidities (-12.4; 95% CI, -23.7 to -1.2 mL/min/1.73 m2/y; P = .03). In the fully adjusted model controlling for comorbidities, peak creatinine level, and in-hospital dialysis requirement, the eGFR slope difference persisted (-14.0; 95% CI, -25.1 to -2.9 mL/min/1.73 m2/y; P = .01). In the subgroup of patients who had not achieved AKI recovery by discharge (n = 319), COVID-19-associated AKI was associated with decreased kidney recovery during outpatient follow-up (adjusted hazard ratio, 0.57; 95% CI, 0.35-0.92). Conclusions and Relevance: In this cohort study of US patients who experienced in-hospital AKI, COVID-19-associated AKI was associated with a greater rate of eGFR decrease after discharge compared with AKI in patients without COVID-19, independent of underlying comorbidities or AKI severity. This eGFR trajectory may reinforce the importance of monitoring kidney function after AKI and studying interventions to limit kidney disease after COVID-19-associated AKI.


Assuntos
Injúria Renal Aguda/metabolismo , COVID-19/metabolismo , Creatinina/metabolismo , Injúria Renal Aguda/complicações , Injúria Renal Aguda/epidemiologia , Negro ou Afro-Americano , Idoso , Idoso de 80 Anos ou mais , COVID-19/complicações , COVID-19/epidemiologia , Estudos de Coortes , Comorbidade , Feminino , Seguimentos , Taxa de Filtração Glomerular , Hispânico ou Latino , Humanos , Hipertensão/epidemiologia , Testes de Função Renal , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , SARS-CoV-2 , Estados Unidos/epidemiologia
5.
Saudi J Kidney Dis Transpl ; 32(5): 1330-1339, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35532702

RESUMO

Platelet (PLT), one of blood cells, plays a major role in physiological and pathological processes such as coagulation, thrombosis, inflammation, and keeping the integrity of vascular endothelium. There are a group of parameters that are used to measure the total amount of PLTs, PLTs morphology, and proliferation. PLT indices are associated with the severity of illness and patients' prognosis. It was reported that mean platelet volume (MPV) was raising synchronously with interleukin (IL)-6 and C-reactive protein in sepsis, and was correlated to the severity of the disease. We aimed to study PLT indices and its changes in sepsis and septic acute kidney injury (AKI) patients to assess the disease and its severity. The present study is a cross-sectional study, had been carried out at Menoufia University hospitals from August 2017 to August 2019. The various platelet indices [MPV, platelet distribution width (PDW) and plateletcrit (PCT)] are considered as outcome variables were compared among controls, cases with sepsis, and cases with sepsis associated AKI. Group I (31) cases with the clinical diagnosis of septic AKI, Group II (33) cases with the diagnosis of sepsis, and Group III (28) consecutive persons marked as negative in the output of the cell counter were taken as controls. Data were tabulated and statistically analyzed. There were 15 men and 15 women for Group I (septic AKI), 17 males and 16 females for Group II (sepsis) and 15 men and 13 women healthy controls as a control group. According to PLT indices MPV, there was a significant statistical difference (P1 <0.01) between Group I and II of patients as it were12.06 ± 1.23, 11.01 ± 1.20, respectively, and PDW also there was a significant statistical difference (P1 <0.01) as it were16.01 ± 2.33, 13.97 ± 2.14, respectively, and PCT there was no significant difference between the two groups. Furthermore, there was a significant statistical difference between Group I and II of patients according to procalcitonin, TNF-α and IL-10. From these results, we conclude that there were a statistical significant difference between the patient groups of critically ill.


Assuntos
Injúria Renal Aguda , Sepse , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Plaquetas , Estudos Transversais , Feminino , Humanos , Masculino , Volume Plaquetário Médio , Contagem de Plaquetas , Estudos Retrospectivos , Sepse/complicações , Sepse/diagnóstico
6.
Kidney Int ; 95(3): 590-610, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30709662

RESUMO

Acute kidney injury (AKI) is a systemic disease associated with widespread effects on distant organs, including the heart. Normal cardiac function is dependent on constant ATP generation, and the preferred method of energy production is via oxidative phosphorylation. Following direct ischemic cardiac injury, the cardiac metabolome is characterized by inadequate oxidative phosphorylation, increased oxidative stress, and increased alternate energy utilization. We assessed the impact of ischemic AKI on the metabolomics profile in the heart. Ischemic AKI was induced by 22 minutes of renal pedicle clamping, and 124 metabolites were measured in the heart at 4 hours, 24 hours, and 7 days post-procedure. Forty-one percent of measured metabolites were affected, with the most prominent changes observed 24 hours post-AKI. The post-AKI cardiac metabolome was characterized by amino acid depletion, increased oxidative stress, and evidence of alternative energy production, including a shift to anaerobic forms of energy production. These metabolomic effects were associated with significant cardiac ATP depletion and with echocardiographic evidence of diastolic dysfunction. In the kidney, metabolomics analysis revealed shifts suggestive of energy depletion and oxidative stress, which were reflected systemically in the plasma. This is the first study to examine the cardiac metabolome after AKI, and demonstrates that effects of ischemic AKI on the heart are akin to the effects of direct ischemic cardiac injury.


Assuntos
Injúria Renal Aguda/metabolismo , Síndrome Cardiorrenal/etiologia , Insuficiência Cardíaca Diastólica/etiologia , Isquemia/metabolismo , Estresse Oxidativo , Injúria Renal Aguda/complicações , Injúria Renal Aguda/etiologia , Animais , Síndrome Cardiorrenal/diagnóstico , Síndrome Cardiorrenal/metabolismo , Modelos Animais de Doenças , Ecocardiografia , Metabolismo Energético , Coração/diagnóstico por imagem , Insuficiência Cardíaca Diastólica/diagnóstico , Insuficiência Cardíaca Diastólica/metabolismo , Humanos , Isquemia/complicações , Isquemia/etiologia , Rim/irrigação sanguínea , Rim/patologia , Masculino , Metaboloma , Metabolômica , Camundongos , Miocárdio/metabolismo , Miocárdio/patologia
7.
Methods Mol Biol ; 1857: 135-144, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30136237

RESUMO

The kidney has been studied as an organ to investigate cell death in vivo for a number of reasons. The unique vasculature that does not contain collateral vessels favors the kidney over other organs for the investigation of ischemia-reperfusion injury. Unilateral uretic obstruction has become the most prominently studied model for fibrosis with impact far beyond postrenal kidney injury. In addition, the tubular elimination mechanisms render the kidney susceptible to toxicity models, such as cisplatin-induced acute kidney injury. During trauma of skeletal muscles, myoglobulin deposition causes tubular cell death in the model of rhabdomyolysis-induced acute kidney injury. Here, we introduce these clinically relevant in vivo models of acute kidney injury (AKI) and critically review the protocols we use to effectively induce them.


Assuntos
Injúria Renal Aguda/patologia , Biomarcadores/metabolismo , Morte Celular , Cisplatino/toxicidade , Traumatismo por Reperfusão/complicações , Rabdomiólise/complicações , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Animais , Antineoplásicos/toxicidade , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL
8.
Mol Biol Rep ; 45(5): 839-847, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29978383

RESUMO

Critically ill patients revealed significant adverse outcomes (sepsis, septic shock, organ dysfunction/failure, and mortality) despite variable effort. AIM: this study evaluated the association of TNF-a-238 (rs 361525) with adverse outcomes in critically ill patients. TNF-α-238 (rs 361525) SNP was performed by RT-PCR on 200 critically-ill patients (112 had severe sepsis and septic shock and 88 were septic), 127 of them had AKI. Urinary N-acetyl-ß-(D)-glucosaminidase and serum creatinine were assessed by modified Jaffé and ELISA respectively. These results revealed that heterozygous genotype GA of TNF-α-238 (rs 361525) SNP significantly increased the risk of adverse-outcome (mortality rate) (P = 0.0001; OR 8.9), regardless of organ dysfunction (P = 0.09) or severity of sepsis (P = 0.6). Moreover, heterozygous genotype GA of TNF-α-238 (rs 361525) SNP was significantly associated with inflammatory marker (sTNF-α) (P = 0.014) and tubular injury marker (uNAG) (P = 0.001) that displayed a significant association with severity of sepsis (0.001, 0.035) and organ dysfunction (0.012, 0.0001) respectively. In critically ill patients with sepsis induced AKI, serum TNF-α and uNAG measured at admission can predict severity of sepsis and AKI (defined by REFILE) occurrence along with pre-existing CKD and DM. However, TNF-238 yielded additional prognostic information on ICU mortality irrelevant to AKI in septic patients.


Assuntos
Injúria Renal Aguda/complicações , Polimorfismo de Nucleotídeo Único , Sepse/genética , Fator de Necrose Tumoral alfa/genética , Acetilglucosaminidase/urina , Injúria Renal Aguda/genética , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/mortalidade , Adulto , Idoso , Creatinina/sangue , Estado Terminal , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sepse/metabolismo , Sepse/mortalidade , Fator de Necrose Tumoral alfa/metabolismo
9.
PLoS One ; 13(5): e0197833, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29791495

RESUMO

Contrast-induced acute kidney injury (CI-AKI) is a serious complication during percutaneous coronary interventions (PCI). Currently, the diagnosis of CI-AKI relies on serum creatinine (SCr) that is however affected by several limitations potentially leading to delayed or missed diagnoses. In this study we examined the diagnostic accuracy of a "bedside" measurement of plasma Neutrophil Gelatinase-Associated Lipocalin (NGAL) in the early detection of CI-AKI in 97 patients undergoing elective PCI. The overall incidence of CI-AKI was 3%. A significant positive correlation was observed between 6-hours NGAL and post-PCI SCr (r = 0.339, p = 0.004) and a significant negative correlation between 6-hours NGAL and post-PCI CrCl (r = -0.303, p = 0.010). In patients with post-PCI SCr increase > 0.24 mg/dl (median SCr absolute increase), delta NGAL 0-6 hours and 6-hours NGAL values were higher compared with patients with SCr elevation below the defined threshold (p = 0.049 and p = 0.056). The ROC analysis showed that a 6 hours NGAL value > 96 ng/ml significantly predicted an absolute SCr increase > 0.24 mg/dl after contrast exposure with sensitivity of 53% and specificity of 74% (AUC 0.819, 95% CI: 0.656 to 0.983, p = 0.005). The use of bedside NGAL assessment may significantly hasten diagnosis and treatment of CI-AKI, with remarkable clinical prognostic consequences.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Meios de Contraste/efeitos adversos , Procedimentos Cirúrgicos Eletivos , Lipocalina-2/metabolismo , Intervenção Coronária Percutânea , Injúria Renal Aguda/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
10.
Biomaterials ; 155: 41-53, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29169037

RESUMO

In this study, we developed a multilayer microfluidic device to simulate nephron, which was formed by "glomerulus", "Bowman's capsule", "proximal tubular lumen" and "peritubular capillary". In this microdevice, artificial renal blood flow was circulating and glomerular filtrate flow was single passing through, mimicking the behavior of a nephron. In this dynamic artificial nephron, we observed typical renal physiology, including the glomerular size-selective barrier, glomerular basement membrane charge-selective barrier, glucose reabsorption and para-aminohippuric acid secretion. To demonstrate the capability of our microdevice, we used it to investigate the pathophysiology of drug-induced acute kidney injury (AKI) and give assessment of drug-induced nephrotoxicity, with cisplatin and doxorubicin as model drugs. In the experiment, we loaded the doxorubicin or cisplatin in the "renal blood flow", recorded the injury of primary glomerular endothelial cells, podocytes, tubular epithelial cells and peritubular endothelial cells by fluorescence imaging, and identified the time-dependence, dose-dependence and the death order of four types of renal cells. Then by measuring multiple biomarkers, including E-cadherin, VEGF, VCAM-1, Nephrin, and ZO-1, we studied the mechanism of cell injuries caused by doxorubicin or cisplatin. Also, we investigated the effect of BSA in the "renal blood flow" on doxorubicin-or-cisplatin-induced nephrotoxicity, and found that BSA enhanced the tight junctions between cells and eased cisplatin-induced nephrotoxicity. In addition, we compared the nephron model and traditional tubule models for assessment of drug-induced nephrotoxicity. And it can be inferred that our biomimetic microdevice simulated the complex, dynamic microenvironment of nephron, yielded abundant information about drug-induced-AKI at the preclinical stage, boosted the drug safety evaluation, and provided a reliable reference for clinical therapy.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/metabolismo , Animais , Transporte Biológico , Caderinas/metabolismo , Bovinos , Cisplatino/uso terapêutico , Doxorrubicina/uso terapêutico , Rim/efeitos dos fármacos , Rim/metabolismo , Glomérulos Renais/citologia , Glomérulos Renais/metabolismo , Túbulos Renais Proximais/citologia , Túbulos Renais Proximais/metabolismo , Proteínas de Membrana/metabolismo , Microfluídica , Néfrons/efeitos dos fármacos , Néfrons/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
11.
Sci Rep ; 7(1): 15397, 2017 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-29133918

RESUMO

Simultaneous assessment of excretory liver and kidney function is still an unmet need in experimental stress models as well as in critical care. The aim of the study was to characterize two polymethine-dyes potentially suitable for this purpose in vivo. Plasma disappearance rate and elimination measurements of simultaneously injected fluorescent dyes DY-780 (hepato-biliary elimination) and DY-654(renal elimination) were conducted using catheter techniques and intravital microscopy in animals subjected to different organ injuries, i.e. polymicrobial sepsis by peritoneal contamination and infection, ischemia-reperfusion-injury and glycerol-induced acute kidney-injury. DY-780 and DY-654 showed organ specific and determined elimination routes in both healthy and diseased animals. They can be measured simultaneously using near-infrared imaging and spectrophotometry. Plasma-disappearance rates of DY-780 and DY-654 are superior to conventional biomarkers in indicating hepatic or kidney dysfunction in different animal models. Greatest impact on liver function was found in animals with polymicrobial sepsis whereas glomerular damage due to glycerol-induced kidney-injury had strongest impact on DY-654 elimination. We therefore conclude that hepatic elimination and renal filtration can be assessed in rodents measuring plasma-disappearance rates of both dyes. Further, assessment of organ dysfunction by polymethine dyes correlates with, but outperforms conventional biomarkers regarding sensitivity and the option of spatial resolution if biophotonic strategies are applied. Polymethine-dye clearance thereby allows sensitive point-of-care assessment of both organ functions simultaneously.


Assuntos
Corantes Fluorescentes , Indóis , Rim , Hepatopatias , Fígado , Insuficiência Renal Crônica , Doença Aguda , Injúria Renal Aguda/diagnóstico por imagem , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/fisiopatologia , Animais , Doença Crônica , Corantes Fluorescentes/farmacocinética , Corantes Fluorescentes/farmacologia , Indóis/farmacocinética , Indóis/farmacologia , Rim/diagnóstico por imagem , Rim/metabolismo , Rim/fisiopatologia , Testes de Função Renal , Fígado/diagnóstico por imagem , Fígado/metabolismo , Fígado/fisiopatologia , Hepatopatias/diagnóstico por imagem , Hepatopatias/metabolismo , Hepatopatias/fisiopatologia , Camundongos , Insuficiência Renal Crônica/diagnóstico por imagem , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/fisiopatologia
12.
Nephrol Dial Transplant ; 32(7): 1167-1175, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28340139

RESUMO

BACKGROUND: Early and accurate assessment of renal function is required for the successful detection and treatment of acute kidney injury (AKI). However, only retention parameters such as plasma urea and creatinine, and the indirect estimation of glomerular filtration rate are commonly available. METHODS: Here, we measured the kinetics of plasma fluorescein isothiocyanate (FITC)-sinistrin excretion to detect alterations of renal function over time in a murine model of rhabdomyolysis-induced AKI. The half-life of FITC-sinistrin was evaluated using a transcutaneous device at different time points in conscious mice, from 4 days before renal damage up to 30 days after. Retention markers were also evaluated, in parallel. RESULTS: Evaluation of the FITC-sinistrin half-life revealed early reduction of renal filtration, observed as early as 6 h after renal damage, and maintained up to 12 h following AKI. Plasma creatinine and urea levels correlated with the transcutaneous measurements of sinistrin excretion. Evaluation of sinistrin excretion also demonstrated that glycerol-treated animals did not develop AKI. Finally, histological analysis showed the presence of renal parenchymal lesions, which developed following the reduced renal filtration and persisted over time, highlighting the causative role of vascular dysfunction and myoglobin toxicity on the subsequent induction of tissue damage. CONCLUSIONS: Taken together, the results of this study provide important insights into the pathophysiology of kidney injury in rhabdomyolytic mice, and indicate that the transcutaneous measurement of FITC-sinistrin is an efficient and simple method to assess renal function precisely. This method also allows reduction of the required number of experimental animals by monitoring the same mouse over time.


Assuntos
Injúria Renal Aguda/diagnóstico , Oligossacarídeos/metabolismo , Rabdomiólise/complicações , Pele/metabolismo , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Animais , Estado de Consciência , Creatinina/metabolismo , Fluoresceínas/metabolismo , Taxa de Filtração Glomerular , Testes de Função Renal , Cinética , Masculino , Camundongos , Modelos Teóricos
13.
J Bras Nefrol ; 39(1): 15-22, 2017 Mar.
Artigo em Português, Inglês | MEDLINE | ID: mdl-28355404

RESUMO

INTRODUCTION: It is needed for nutrition prescription correct estimate of resting energy expenditure (REE), which is a challenge given the possible daily variation in critically ill patients with acute kidney injury (AKI). OBJECTIVE: To evaluate the daily variability of REE measured by indirect calorimetry (IC) in patients with AKI and dialysis indication and identify clinical variables associated with REE. METHODS: The REE was measured on the time of dialysis indication and the subsequent four days. We also evaluated parameters that can influence the REE. The daily differences were analyzed by generalized linear model for repeated measures. We also used Spearman correlation and multiple linear regression. RESULTS: There were 301 IC measurements in 114 patients, mean age of 60.65 ± 16.9 years and 68.4% were male. The average REE was 2081 ± 645 kcal, rising on day 5 (2270 ± 556 kcal) compared to the days 2 and 3 (2022 ± 754; 2022 ± 660 kcal, respectively, p = 0,04). When normalized to weight, there was no significant difference in REE (kcal/kg/day) during follow-up. REE was positively correlated with total leukocyte count, C-reactive protein, minute volume (MV), fraction of inspired oxygen (FiO2) urea nitrogen appearance (UNA), weight and height and inversely with age. After multiple regression, MV, FiO2, weight and age are correlated independently with REE. CONCLUSION: Patients with AKI have REE stable. The REE was associated independently with FiO2, MV, body weight and age. Thus, ventilatory parameters should be evaluated each day for the necessary dietary changes may be made.


Assuntos
Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/terapia , Metabolismo Energético , Diálise Renal , Ritmo Circadiano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo
14.
J. bras. nefrol ; 39(1): 15-22, Jan.-Mar. 2017. tab
Artigo em Inglês | LILACS | ID: biblio-841199

RESUMO

Abstract Introduction: It is needed for nutrition prescription correct estimate of resting energy expenditure (REE), which is a challenge given the possible daily variation in critically ill patients with acute kidney injury (AKI). Objective: To evaluate the daily variability of REE measured by indirect calorimetry (IC) in patients with AKI and dialysis indication and identify clinical variables associated with REE. Methods: The REE was measured on the time of dialysis indication and the subsequent four days. We also evaluated parameters that can influence the REE. The daily differences were analyzed by generalized linear model for repeated measures. We also used Spearman correlation and multiple linear regression. Results: There were 301 IC measurements in 114 patients, mean age of 60.65 ± 16.9 years and 68.4% were male. The average REE was 2081 ± 645 kcal, rising on day 5 (2270 ± 556 kcal) compared to the days 2 and 3 (2022 ± 754; 2022 ± 660 kcal, respectively, p = 0,04). When normalized to weight, there was no significant difference in REE (kcal/kg/day) during follow-up. REE was positively correlated with total leukocyte count, C-reactive protein, minute volume (MV), fraction of inspired oxygen (FiO2) urea nitrogen appearance (UNA), weight and height and inversely with age. After multiple regression, MV, FiO2, weight and age are correlated independently with REE. Conclusion: Patients with AKI have REE stable. The REE was associated independently with FiO2, MV, body weight and age. Thus, ventilatory parameters should be evaluated each day for the necessary dietary changes may be made.


Resumo Introdução: É imprescindível a correta estimativa do gasto energético de repouso (GER), que pode apresentar considerável variação diária no paciente crítico com lesão renal aguda (LRA). Objetivo: Avaliar a variabilidade diária do GER medido por calorimetria indireta (CI) em pacientes com LRA e indicação dialítica e identificar as variáveis clínicas associadas ao GER. Métodos: O GER foi medido no dia da indicação do procedimento dialítico e nos quatro dias subsequentes. Também foram avaliados parâmetros que podem influenciar o GER. As diferenças diárias foram analisadas pelo modelo linear generalizado para medidas repetidas, com distribuição gama, além da correlação de Spearman e regressão linear múltipla. Resultados: Foram 301 medidas de CI realizadas em 114 pacientes, com idade de 60,65 ± 16,9 anos e 68,4% do sexo masculino. O GER médio foi de 2081 ± 645 Kcal, com aumento no dia 5 (2270 ± 556 Kcal), quando comparado aos dias 2 e 3 (2022 ± 754; 2022 ± 660 kcal, respectivamente, p = 0,04); quando normalizado para peso, não houve diferença significante no GER (kcal/kg/dia) durante o acompanhamento. GER correlacionou-se positivamente com temperatura corporal, contagem total de leucócitos, proteína C reativa, volume minuto (VM), fração inspirada de oxigênio (FiO2), aparecimento de nitrogênio ureico (UNA), peso corporal e estatura e inversamente com idade. Após a regressão linear múltipla, somente VM, FiO2 e peso corporal e idade se correlacionaram independentemente. Conclusão: Pacientes com LRA dialíticos apresentam GER estável. O GER foi associado independentemente com FiO2, VM, peso e idade. Assim, requisitos ventilatórios precisam ser avaliados diariamente para que alterações necessárias na prescrição dietética sejam feitas.


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Diálise Renal , Metabolismo Energético , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/terapia , Fatores de Tempo , Estudos Prospectivos , Ritmo Circadiano
15.
Am J Kidney Dis ; 69(5): 647-657, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28117208

RESUMO

BACKGROUND: This study aimed to describe the burden of community-acquired acute kidney injury (AKI) in China based on a nationwide survey about AKI. STUDY DESIGN: Cross-sectional and retrospective study. SETTING & PARTICIPANTS: A national sample of 2,223,230 hospitalized adult patients from 44 academic/local hospitals in Mainland China was used. AKI was defined according to the 2012 KDIGO AKI creatinine criteria or an increase or decrease in serum creatinine level of 50% during the hospital stay. Community-acquired AKI was identified when a patient had AKI that could be defined at hospital admission. PREDICTORS: The rate, cause, recognition, and treatment of community-acquired AKI were stratified according to hospital type, latitude, and economic development of the regions in which the patients were admitted. OUTCOMES: All-cause in-hospital mortality and recovery of kidney function at hospital discharge. RESULTS: 4,136 patients with community-acquired AKI were identified during the 2 single-month snapshots (January 2013 and July 2013). Of these, 2,020 (48.8%) had cases related to decreased kidney perfusion; 1,111 (26.9%), to intrinsic kidney disease; and 499 (12.1%), to urinary tract obstruction. In the north versus the south, more patients were exposed to nephrotoxins or had urinary tract obstructions. 536 (13.0%) patients with community-acquired AKI had indications for renal replacement therapy (RRT), but only 347 (64.7%) of them received RRT. Rates of timely diagnosis and appropriate use of RRT were higher in regions with higher per capita gross domestic product. All-cause in-hospital mortality was 7.3% (295 of 4,068). Delayed AKI recognition and being located in northern China were independent risk factors for in-hospital mortality, and referral to nephrology providers was an independent protective factor. LIMITATIONS: Possible misclassification of AKI and community-acquired AKI due to nonstandard definitions and missing data for serum creatinine. CONCLUSIONS: The features of community-acquired AKI varied substantially in different regions of China and were closely linked to the environment, economy, and medical resources.


Assuntos
Injúria Renal Aguda/epidemiologia , Mortalidade Hospitalar , Recuperação de Função Fisiológica , Injúria Renal Aguda/classificação , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , China/epidemiologia , Creatinina/metabolismo , Estudos Transversais , Diagnóstico Tardio , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Terapia de Substituição Renal/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco
16.
Clin Nutr ; 36(4): 1170-1174, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27595381

RESUMO

BACKGROUND: Currently, the execution of indirect calorimetry, which is considered the gold standard for measuring energy expenditure, is not indicate during dialysis, and it may interfere on nutritional therapy of these patients. This study aimed to evaluate the resting energy expenditure (REE) in patients with severe acute kidney injury treated by different modalities of dialysis and to identify whether dialysis influences on REE. METHODS: This was a prospective cohort study that evaluated patients admitted in intensive care units with diagnosis of acute kidney injury AKIN-3, mechanically ventilated, and submitted to conventional hemodialysis (CHD), extended hemodialysis (EHD) or high volume peritoneal dialysis (HVPD). Indirect calorimetry was performed at pre dialysis time and during the dialysis procedure. Parameters that could change REE were also evaluated. RESULTS: One-hundred patients undergoing 290 dialysis sessions were evaluated, with mean age 60.3 ± 17 years, 69% were male and 74% have died. There was no significant difference between REE of predialysis time and during dialysis time (2156 ± 659 kcal vs. 2100 ± 634 kcal, respectively, p = 0.15). No difference was observed in the REE before and during dialysis of different modalities. There were no differences between parameters pre and during dialysis of each modality. There was only a difference in norepinephrine dose, which was higher in pre dialysis time in HVPD and EHD modalities, compared with CHD modality. Moreover, during dialysis time, EHD modality had significantly higher VAD compared to other dialysis modalities. CONCLUSION: The three evaluated modalities did not change REE. Indirect calorimetry can be performed during dialysis procedures and there was no difference between ventilation parameters, sedatives use, body temperature and VAD in both moments.


Assuntos
Injúria Renal Aguda/terapia , Metabolismo Basal , Diálise Peritoneal , Diálise Renal , Injúria Renal Aguda/complicações , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/fisiopatologia , Idoso , Metabolismo Basal/efeitos dos fármacos , Temperatura Corporal , Brasil , Calorimetria Indireta , Estudos de Coortes , Estado Terminal/terapia , Feminino , Humanos , Hipnóticos e Sedativos/uso terapêutico , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Norepinefrina/uso terapêutico , Diálise Peritoneal/efeitos adversos , Estudos Prospectivos , Diálise Renal/efeitos adversos , Respiração Artificial , Índice de Gravidade de Doença , Fatores de Tempo , Vasoconstritores/uso terapêutico
17.
Rev Assoc Med Bras (1992) ; 62(7): 672-679, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27925048

RESUMO

Patients on intensive care present systemic, metabolic, and hormonal alterations that may adversely affect their nutritional condition and lead to fast and important depletion of lean mass and malnutrition. Several factors and medical conditions can influence the energy expenditure (EE) of critically ill patients, such as age, gender, surgery, serious infections, medications, ventilation modality, and organ dysfunction. Clinical conditions that can present with EE change include acute kidney injury, a complex disorder commonly seen in critically ill patients with manifestations that can range from minimum elevations in serum creatinine to renal failure requiring dialysis. The nutritional needs of this population are therefore complex, and determining the resting energy expenditure is essential to adjust the nutritional supply and to plan a proper diet, ensuring that energy requirements are met and avoiding complications associated with overfeeding and underfeeding. Several evaluation methods of EE in this population have been described, but all of them have limitations. Such methods include direct calorimetry, doubly labeled water, indirect calorimetry (IC), various predictive equations, and, more recently, the rule of thumb (kcal/kg of body weight). Currently, IC is considered the gold standard.


Assuntos
Calorimetria/métodos , Estado Terminal , Metabolismo Energético/fisiologia , Descanso/fisiologia , Injúria Renal Aguda/metabolismo , Algoritmos , Feminino , Humanos , Masculino , Necessidades Nutricionais , Valor Preditivo dos Testes
18.
Rev. Assoc. Med. Bras. (1992) ; 62(7): 672-679, Oct. 2016. tab
Artigo em Inglês | LILACS | ID: biblio-829513

RESUMO

Summary Patients on intensive care present systemic, metabolic, and hormonal alterations that may adversely affect their nutritional condition and lead to fast and important depletion of lean mass and malnutrition. Several factors and medical conditions can influence the energy expenditure (EE) of critically ill patients, such as age, gender, surgery, serious infections, medications, ventilation modality, and organ dysfunction. Clinical conditions that can present with EE change include acute kidney injury, a complex disorder commonly seen in critically ill patients with manifestations that can range from minimum elevations in serum creatinine to renal failure requiring dialysis. The nutritional needs of this population are therefore complex, and determining the resting energy expenditure is essential to adjust the nutritional supply and to plan a proper diet, ensuring that energy requirements are met and avoiding complications associated with overfeeding and underfeeding. Several evaluation methods of EE in this population have been described, but all of them have limitations. Such methods include direct calorimetry, doubly labeled water, indirect calorimetry (IC), various predictive equations, and, more recently, the rule of thumb (kcal/kg of body weight). Currently, IC is considered the gold standard.


Resumo Os pacientes em cuidados intensivos apresentam alterações sistêmicas, metabólicas e hormonais, que podem afetar adversamente a condição nutricional e levar à rápida e importante depleção da massa magra e desnutrição. Vários fatores e situações clínicas podem exercer influência sobre o gasto energético (GE) de pacientes críticos, como idade, sexo, cirurgias, infecções graves, medicamentos, modalidade ventilatória e disfunção de órgãos. Dentre as condições clínicas que podem cursar com alteração do GE, encontra-se a lesão renal aguda (LRA), distúrbio complexo comumente observado em pacientes críticos, com manifestações que podem variar de mínimas elevações na creatinina sérica até insuficiência renal com necessidade dialítica. Dessa forma, essa população crítica apresenta necessidades nutricionais complexas e a determinação do gasto energético de repouso (GER) torna-se essencial para o ajuste da oferta nutricional e para o planejamento de uma nutrição adequada, assegurando que as necessidades energéticas sejam atingidas e evitando as complicações associadas à hiper ou hipoalimentação. Diversos métodos de avaliação do GE nessa população foram descritos, mas todos apresentam limitações. Dentre eles, destacam-se a calorimetria direta, a água duplamente marcada, a calorimetria indireta (CI), diversas equações preditivas e, mais atualmente, a regra de bolso (kcal/kg de peso). Atualmente, a CI é eleita o método padrão-ouro.


Assuntos
Humanos , Masculino , Feminino , Descanso/fisiologia , Calorimetria/métodos , Estado Terminal , Metabolismo Energético/fisiologia , Algoritmos , Valor Preditivo dos Testes , Injúria Renal Aguda/metabolismo , Necessidades Nutricionais
19.
Regul Toxicol Pharmacol ; 81: 341-352, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27667768

RESUMO

Cisplatin (Cis-diaminedichloroplatinum II) is a chemotherapeutic agent having well documented adverse effect as nephrotoxicity. This study was designed to evaluate the nephroprotective role of Boerhaavia diffusa in cisplatin-induced acute kidney injury. Wistar rats (n = 6) were allocated into six groups constituting normal control, cisplatin-induced, Boerhaavia diffusa root extract in doses 50, 100 and 200 mg/kg and Boerhaavia diffusa per se group, administered orally for a period of ten days. Intraperitoneal injection of cisplatin was administered on day 7, to all groups except normal control and Boerhaavia diffusa per se group. On day 10, cisplatin resulted in substantial nephrotoxicity in Wistar rats with significant (p < 0.001) elevation in serum creatinine and blood urea nitrogen, decline in the concentrations of reduced glutathione and superoxide dismutase, elevation in TNF-α level in renal tissues. Boerhaavia diffusa at a dose of 200 mg/kg body weight significantly (p < 0.001) ameliorates increased in serum creatinine, blood urea nitrogen, oxidative stress and inflammatory markers. In parallel to this, it also exhibits antiapoptotic activity through the reduction of active caspase-3 expression in kidneys. Findings indicate that Boerhaavia diffusa is effective in mitigating cisplatin-induced nephrotoxicity and thus, for this the acute and sub-acute toxicity studies conducted to evaluate the safety profile of Boerhaavia diffusa. The no-observed adverse effect level (NOAEL) of tuberous roots of Boerhaavia diffusa root extract was 1000 mg/kg.


Assuntos
Injúria Renal Aguda/metabolismo , Antineoplásicos/toxicidade , Cisplatino/antagonistas & inibidores , Cisplatino/toxicidade , Nyctaginaceae/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Administração Oral , Animais , Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Relação Dose-Resposta a Droga , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Injeções Intraperitoneais , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Ratos , Ratos Wistar
20.
Magn Reson Med ; 76(5): 1524-1530, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27548739

RESUMO

PURPOSE: The aim of this work was to investigate whether hyperpolarized 13 C,15 N2 -urea can be used as an imaging marker of renal injury in renal unilateral ischemic reperfusion injury (IRI), given that urea is correlated with the renal osmotic gradient, which describes the renal function. METHODS: Hyperpolarized three-dimensional balanced steady-state 13 C magnetic resonance imaging (MRI) experiments alongside kidney function parameters and quantitative polymerase chain reaction measurements were performed in rats subjected to unilateral renal ischemia for 60-minute and 24-hour reperfusion. RESULTS: We revealed a significant reduction in the intrarenal gradient in the ischemic kidney in agreement with cortical injury markers neutrophil gelatinase-associated lipocalin and kidney injury molecule 1, as well as functional kidney parameters. CONCLUSION: Hyperpolarized functional 13 C,15 N2 urea MRI can be used to successfully detect changes in the intrarenal urea gradient post-IRI, thereby enabling in vivo monitoring of the intrarenal functional status in the rat kidney. Magn Reson Med 76:1524-1530, 2016. © 2016 International Society for Magnetic Resonance in Medicine.


Assuntos
Injúria Renal Aguda/diagnóstico por imagem , Injúria Renal Aguda/metabolismo , Biomarcadores , Imageamento por Ressonância Magnética/métodos , Traumatismo por Reperfusão/diagnóstico por imagem , Traumatismo por Reperfusão/metabolismo , Ureia/metabolismo , Animais , Biomarcadores/metabolismo , Isótopos de Carbono/farmacocinética , Simulação por Computador , Feminino , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Modelos Biológicos , Imagem Molecular/métodos , Isótopos de Nitrogênio/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Ratos Wistar , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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