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1.
Int J Mol Sci ; 22(6)2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33801801

RESUMO

BACKGROUND: Vancomycin is commonly used as a first line therapy for gram positive organisms such as methicillin resistant Staphylococcusaureus. Vancomycin-induced acute kidney injury (V-AKI) has been reported in up to 43% of patients, especially in those with higher targeted trough concentrations. The precise mechanism of injury in humans remains elusive, with recent evidence directed towards proximal tubule cell apoptosis. In this study, we investigated the protein contents of urinary exosomes in patients with V-AKI to further elucidate biomarkers of mechanisms of injury and potential responses. METHODS: Urine samples from patients with V-AKI who were enrolled in the DIRECT study and matched healthy controls from the UAB-UCSD O'Brien Center Biorepository were included in the analysis. Exosomes were extracted using solvent exclusion principle and polyethylene glycol induced precipitation. Protein identity and quantification was determined by label-free liquid chromatography mass spectrometry (LC/MS). The mean peak serum creatinine was 3.7 ± 1.4 mg/dL and time to kidney injury was 4.0 ± 3.0 days. At discharge, 90% of patients demonstrated partial recovery; 33% experienced full recovery by day 28. Proteomic analyses on five V-AKI and 7 control samples revealed 2009 proteins in all samples and 251 proteins significantly associated with V-AKI (Pi-score > 1). The top discriminatory proteins were complement C3, complement C4, galectin-3-binding protein, fibrinogen, alpha-2 macroglobulin, immunoglobulin heavy constant mu and serotransferrin. CONCLUSION: Urinary exosomes reveal up-regulation of inflammatory proteins after nephrotoxic injury in V-AKI. Further studies are necessary in a large patient sample to confirm these findings for elucidation of pathophysiologic mechanisms and validation of potential injury biomarkers.


Assuntos
Lesão Renal Aguda/metabolismo , Biomarcadores/metabolismo , Exossomos/metabolismo , Inflamação/metabolismo , Proteômica/métodos , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/urina , Adulto , Biomarcadores/urina , Cromatografia Líquida/métodos , Creatinina/urina , Humanos , Inflamação/urina , Masculino , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem/métodos , Vancomicina/efeitos adversos , Adulto Jovem
2.
Diabetes Metab Syndr ; 15(1): 187-191, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33383438

RESUMO

BACKGROUND AND AIMS: Renal involvement in Covid-19 infection is varied and can affect glomeruli, tubules, interstitium and can cause acute kidney injury (AKI). AKI is a strong predictor of mortality. Routine urinalysis gives an insight into the renal pathology of the patient. We studied the incidence of urinary abnormalities in hospitalised Covid-19 patients and analysed their impact on development of AKI and mortality. METHODS: Information on 110 hospitalised patients with confirmed Covid-19 was retrospectively collected and analysed. The demographic data such as age, gender, comorbid conditions such as diabetes mellitus, the need for dialysis and laboratory data such as urine for albumin, glucose, RBC and WBC, and serum creatinine were collected. The diagnosis of AKI was based on the KDIGO criteria. The outcomes studied were development of AKI and hospital mortality. RESULTS: Urine abnormalities were seen in 71% of the patients. Proteinuria in 58.2%, haematuria in 17.3%, pyuria in 8.2% of patients and concurrent proteinuria and haematuria was seen in 13.6% of patients. AKI was seen in 28.2% of patients and hospital mortality was 24.5%. AKI was strongly associated with mortality. Proteinuria and haematuria were good predictors of development of AKI, more strongly when they occurred concurrently (p < 0.01). CONCLUSION: Our results suggest that urine analysis is a simple test, which can be used to predict development of AKI and mortality and may be used for risk stratification of Covid-19 patients, especially in low resource settings.


Assuntos
Lesão Renal Aguda/epidemiologia , Lesão Renal Aguda/urina , /urina , Lesão Renal Aguda/diagnóstico , Adulto , Idoso , Feminino , Hospitalização/tendências , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Proteinúria/diagnóstico , Proteinúria/epidemiologia , Proteinúria/urina , Estudos Retrospectivos , Urinálise/tendências
3.
Vet J ; 266: 105573, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33323170

RESUMO

In humans, leptospiral acute kidney injury (AKI) is characterised by tubulointerstitial involvement and renal electrolyte losses, impacting clinical presentation and case management. The aim of this study was to evaluate urine chemistry findings in dogs with leptospirosis in order to identify characteristic patterns of tubular damage associated with this disease. Dogs with intrinsic AKI caused by leptospirosis and by other aetiologies were prospectively enrolled. Clinical and clinicopathological variables, including serum and urine chemistry, fractional excretion (FE%) of electrolytes, and urinary neutrophil gelatinase-associated lipocalin (NGAL), were evaluated in both groups and compared statistically. Dogs with leptospirosis (n = 38) had significantly higher serum creatinine concentration than dogs with AKI caused by other aetiologies (n = 37). Serum potassium and glucose concentrations were comparable between groups. Dogs with leptospiral AKI had significantly higher FE of potassium (median 100%, range 20-480 vs. median 68%, range 5-300; P = 0.048), as well as higher magnitude of glucosuria (urine glucose to creatinine ratio, median 0.64, range 0-26 vs. median 0.22, range 0-13; P = 0.023) and frequency of positive glucose dipstick reaction (59% vs. 18%; P = 0.002), than dogs with AKI of other aetiologies. Additional markers of tubular damage considered in this study, including FE of other electrolytes and urinary NGAL, did not differ between groups. In conclusion, when compared to other aetiologies of intrinsic AKI, canine leptospirosis was characterised by increased glucosuria and kaliuresis.


Assuntos
Lesão Renal Aguda/veterinária , Doenças do Cão/microbiologia , Leptospirose/veterinária , Lesão Renal Aguda/complicações , Lesão Renal Aguda/urina , Animais , Creatinina/sangue , Doenças do Cão/sangue , Doenças do Cão/urina , Cães , Feminino , Glicosúria/veterinária , Túbulos Renais/fisiopatologia , Leptospira , Leptospirose/complicações , Leptospirose/urina , Lipocalina-2/urina , Masculino , Potássio/urina
4.
BMJ Case Rep ; 13(12)2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33334751

RESUMO

A 55-year-old male presented to our emergency department with haematuria and abdominal pain. Investigations including a computed tomography (CT) scan revealed an intraluminal filling defect within the left collecting system, consistent in appearance with blood clot. With an initial working diagnosis of upper tract urothelial cell carcinoma, he was discharged with plans for an urgent cystoscopy and ureteroscopy. He subsequently represented with ongoing frank haematuria, anasarca, dropping haemoglobin and new right collecting system blood clot. Subsequent investigations showed that the patient had acquired haemophilia A resulting in the episodes of haematuria, highlighted after an elevated activated partial thromboplastic time prompted a thrombophilia screen. The patient was subsequently treated with factor eight inhibitor bypass activity, corticosteroids and cyclophosphamide.


Assuntos
Dor Abdominal/etiologia , Lesão Renal Aguda/diagnóstico , Hematúria/etiologia , Hemofilia A/diagnóstico , Dor Abdominal/sangue , Dor Abdominal/urina , Lesão Renal Aguda/sangue , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/urina , Fatores de Coagulação Sanguínea/uso terapêutico , Cistoscopia , Fator VIIa/uso terapêutico , Hematúria/sangue , Hematúria/urina , Hemofilia A/sangue , Hemofilia A/complicações , Hemofilia A/tratamento farmacológico , Humanos , Túbulos Renais Coletores/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tempo de Tromboplastina Parcial , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento , Ureteroscopia , Urografia
5.
Toxicol Lett ; 334: 21-26, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32910981

RESUMO

MicroRNAs are key regulators of the normal kidney function and development, and altered in acute kidney injury (AKI). However, there is a lack of studies comparing serum and urine miRNA expression in toxic AKI in humans. We aimed to compare the global signature of urinary and serum microRNAs, with and without kidney injury, after human oxalic acid poisoning. We profiled urinary microRNAs in patients who ingested oxalic acid and developed no injury (No AKI n = 3), moderate injury (AKIN2 n = 3) or severe injury (AKIN3 n = 3) and healthy controls (n = 3). We validated a signature of 30 urinary microRNAs identified in the discovery profiling, in a second cohort of individuals exposed to oxalic acid (No AKI n = 15, AKIN2 n=11 & AKIN3 n= 18) and healthy controls (n=-27) and we compared the results with previously published serum data. Global profiling in toxic AKI patients showed a higher expression of urinary microRNAs and lower expression of serum microRNAs. Most urine microRNA in the validation cohort were significantly upregulated (25/30, fold change >2.8 and p < 0.05) in AKIN2/3 patients compared to No AKI. Four urinary microRNAs (miR-191, miR-19b, miR-20a and miR-30b) had good diagnostic performance (AUC greater than 0.8) to predict AKIN2/3 between 4-8 hours post ingestion. Poisoning irrespective of AKI led to significantly lower expression of many microRNAs in serum but relatively few changes in urinary miRNA expression. In conclusion, urinary microRNA signature provides a stronger measure of AKI in oxalic acid poisoning compared to serum microRNA. Kidney injury has the greatest impact on urinary microRNA, while poisoning itself was better reflected in serum miRNA. Plasma and urinary microRNAs signatures provide complementary information in toxic kidney injury.


Assuntos
Lesão Renal Aguda/sangue , Lesão Renal Aguda/urina , MicroRNAs , Ácido Oxálico/envenenamento , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/genética , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Coortes , Humanos , Rim/efeitos dos fármacos , Testes de Função Renal , MicroRNAs/sangue , MicroRNAs/urina
7.
Arch. esp. urol. (Ed. impr.) ; 73(6): 554-560, jul.-ago. 2020. tab, ilus, graf
Artigo em Inglês | IBECS | ID: ibc-195931

RESUMO

OBJECTIVES: To compare the urinary NGAL levels with serum creatinine levels as an early biomarker for renal injury in rats with bladder outlet obstruction (BOO). METHODS: Twenty male Wistar Albino rats divided into 4 groups. In each group basal serum creatinine and urinary NGAL levels were evaluated. In Group 1 (Sham/Control group) only laparotomy was performed. In Group 2 (14th day partial BOO) and Group 3 (28th day partial BOO) partial obstruction and in Group 4 (Complete BOO) complete obstruction was performed. Serum creatinine levels and urinary NGAL levels were evaluated in Group 4 on the third day of the study, in Group 2 on the 14th day and in Group 3 and Group 1 on the 28th day. Urethra, ureters and kidneys were excracted by laparotomy and evaluated for histopathologic examination. RESULTS: The increase in plasma creatinine levels after obstruction was statistically significant in Group 4 (p < 0.05). There was significant difference between the groups in urinary NGAL levels after obstruction (p < 0.05). Post-obstruction urinary NGAL levels was highest in Group 4 and it was statistically significant when compared to beginning levels (p < 0.05). In Group 3, increase in urinary NGAL levels were higher (p < 0.05) with no increase in plasma creatinine levels after obstruction. CONCLUSIONS: It can be concluded that urinary NGAL levels might be an early biomarker for renal dysfunction in partial bladder outlet obstruction which may cause renal impairment through upper urinary tract injury. Therefore, urinary NGAL may play role during the treatment choice and follow-up in BOO patients


OBJETIVOS: Comparar los niveles urinarios de NGAL con la creatinina sérica como marcador precoz de daño renal en ratas con obstrucción del tracto urinario inferior. MÉTODOS: 20 ratas Wistar Albino masculinas fueron divididas en 4 grupos. En cada grupo se midió el nivel basal de creatinina en suero así como los niveles urinarios de NGAL. En el grupo 1 (Sham/Grupo Control) solo se realizó laparotomía. En el grupo 2 (14 días después de una obstrucción tracto urinario inferior parcial) y el grupo 3 (28 días después de una obstrucción tracto urinario inferior parcial) se realizó una obstrucción parcial y en el grupo 4 (obstrucción completa) una obstrucción completa. Los niveles de creatinina sérica y NGAL urinario fueron evaluados en el grupo 4 en el 3er día del estudio; en el grupo 2 en el día 14 del estudio y en el grupo 1 en el día 28. Uretra, uréteres y riñones se quitaron por laparotomía y se hizo un análisis histológico. RESULTADOS: El incremento en la creatinina sérica después de la obstrucción fue estadísticamente significativo en el grupo 4 (p < 0,05). Hubo suficiente diferecia entre los grupos en términos de NGAL urinario después de la obstrucción (p < 0,005). Los niveles de NGA post-obstructivos fueron superiores en el grupo 4 y fue estadísticamente significativo en comparación con los niveles iniciales. En el grupo 3, el incremento en los niveles de NGAL urinario fue superior (p < 0,005) sin incrementeo en los niveles de creatinina en plasma después de la obstrucción. CONCLUSIONES: Se puede concluir que los niveles de NGAL urinarios podrían ser un marcador de lesión renal en caso de obstrucción parcial del tracto urinario inferior. Por tanto, NGAL urinario debe jugar un papel durante la elección de tratamiento y seguimiento de pacientes con obstrucción del tracto urinario inferior


Assuntos
Animais , Masculino , Ratos , Lipocalina-2/urina , Creatinina/sangue , Obstrução do Colo da Bexiga Urinária/sangue , Obstrução do Colo da Bexiga Urinária/urina , Ratos Wistar , Lesão Renal Aguda/sangue , Lesão Renal Aguda/urina , Obstrução Uretral/sangue , Obstrução Uretral/urina , Biomarcadores/sangue , Biomarcadores/urina , Valores de Referência
9.
Crit Care ; 24(1): 356, 2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32552872

RESUMO

BACKGROUND: The aim of this study is to assess the prevalence of abnormal urine analysis and kidney dysfunction in COVID-19 patients and to determine the association of acute kidney injury (AKI) with the severity and prognosis of COVID-19 patients. METHODS: The electronic database of Embase and PubMed were searched for relevant studies. A meta-analysis of eligible studies that reported the prevalence of abnormal urine analysis and kidney dysfunction in COVID-19 was performed. The incidences of AKI were compared between severe versus non-severe patients and survivors versus non-survivors. RESULTS: A total of 24 studies involving 4963 confirmed COVID-19 patients were included. The proportions of patients with elevation of sCr and BUN levels were 9.6% (95% CI 5.7-13.5%) and 13.7% (95% CI 5.5-21.9%), respectively. Of all patients, 57.2% (95% CI 40.6-73.8%) had proteinuria, 38.8% (95% CI 26.3-51.3%) had proteinuria +, and 10.6% (95% CI 7.9-13.3%) had proteinuria ++ or +++. The overall incidence of AKI in all COVID-19 patients was 4.5% (95% CI 3.0-6.0%), while the incidence of AKI was 1.3% (95% CI 0.2-2.4%), 2.8% (95% CI 1.4-4.2%), and 36.4% (95% CI 14.6-58.3%) in mild or moderate cases, severe cases, and critical cases, respectively. Meanwhile, the incidence of AKI was 52.9%(95% CI 34.5-71.4%), 0.7% (95% CI - 0.3-1.8%) in non-survivors and survivors, respectively. Continuous renal replacement therapy (CRRT) was required in 5.6% (95% CI 2.6-8.6%) severe patients, 0.1% (95% CI - 0.1-0.2%) non-severe patients and 15.6% (95% CI 10.8-20.5%) non-survivors and 0.4% (95% CI - 0.2-1.0%) survivors, respectively. CONCLUSION: The incidence of abnormal urine analysis and kidney dysfunction in COVID-19 was high and AKI is closely associated with the severity and prognosis of COVID-19 patients. Therefore, it is important to increase awareness of kidney dysfunction in COVID-19 patients.


Assuntos
Lesão Renal Aguda/epidemiologia , Lesão Renal Aguda/virologia , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Lesão Renal Aguda/urina , Infecções por Coronavirus/urina , Humanos , Pandemias , Pneumonia Viral/urina , Prevalência
10.
Crit Care Resusc ; 22(2): 142-151, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32389106

RESUMO

BACKGROUND: Frequent assessment of urine output (UO), serum creatinine (sCr) and urinary cell cycle arrest biomarkers (CCAB) may improve acute kidney injury (AKI) prediction. OBJECTIVE: To study the performance of UO, short term sCr changes and urinary CCAB to predict severe AKI. METHODS: We measured 6 hours of UO, 6-hourly sCr changes, and urinary CCABs in all critically ill patients with cardiovascular or respiratory failure or early signs of renal stress between February and October 2018. We studied the association of such measurements, and their combination, with the development of AKI Stage 2 or 3 of the Kidney Disease: Improving Global Outcomes (KDIGO) definition at 12 hours. We evaluated predictive performance with logistic regression, area under the receiver operating characteristic (AUROC) curve, and net reclassification indices. We computed an optimal cut-off value for each biomarker. RESULTS: We assessed 622 patients and, as per the exclusion criteria, we enrolled 105 critically ill patients. After 12 hours of enrolment, AKI occurred in 32 patients (30%). UO, sCr change over 6 hours and CCABs were significantly associated with severe AKI at 12 hours, with all variables achieving an AUROC > 0.7 after adjustment. Combination of any of the two or three variables achieved an AUROC > 0.7 for subsequent severe AKI at 12 hours. The optimal predictive high specificity cut-off values were ≤ 0.4 mL/kg/h for UO, variation of +15 µmol/L over 6 hours in sCr, and ≥ 1.5 (ng/mL)2/1000 for CCABs. CONCLUSION: In this prospective study, an integrative approach using UO, short term sCr change and/or urinary CCABs showed a satisfactory performance for the prediction of severe AKI development at 12 hours.


Assuntos
Lesão Renal Aguda , Biomarcadores/urina , Pontos de Checagem do Ciclo Celular/fisiologia , Urina , Lesão Renal Aguda/sangue , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/urina , Creatinina/sangue , Estado Terminal , Taxa de Filtração Glomerular , Humanos , Unidades de Terapia Intensiva , Testes de Função Renal , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Micção
11.
Toxicology ; 439: 152462, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32348786

RESUMO

Drug-induced kidney injury (DIKI) is a frequent occurrence in nonclinical drug development. It is well established that novel urine kidney safety biomarkers will outperform urea nitrogen (BUN) and serum creatinine (sCr) for monitoring direct drug injury to the kidney across numerous compounds spanning diverse mechanisms and efforts are underway for a formal regulatory clinical qualification. However, it remains unclear how these novel biomarkers will perform under prerenal azotemia when BUN and sCr are elevated but no intra-renal injury is suspected. This lack of knowledge is largely due to the dearth of such nonclinical animal models. We report here that treatment of dogs with a potent antihypertensive compound MK-5478 at a suprapharmacologic dose for up to 9 days results in the development of prerenal azotemia and, in some dogs, kidney toxicity through the dual sustained effects of MK-5478 as a nitric oxide donor and an angiotensin II receptor blocker (ARB). While conventional serum biomarkers BUN, and often sCr as well, were highly elevated in these dogs with or without kidney damage, urine kidney biomarkers clusterin (CLU) and neutrophil gelatinase-associated lipocalin (NGAL) showed increases only in dogs with kidney histopathologic changes following the sustained period of prerenal azotemia. Urine albumin (ALB) and total protein also tracked with kidney lesions but with less sensitivity. Thus, we present evidence for the first time that urine kidney safety biomarkers used together with BUN and sCr can distinguish intra-renal injury among dogs with prerenal azotemia while the conventional serum biomarkers alone are ambiguous, either being interpreted as false positives of kidney injury, or dismissed under circumstances as benign without appreciation for a threshold of impending injury.


Assuntos
Lesão Renal Aguda/urina , Azotemia/induzido quimicamente , Azotemia/urina , Biomarcadores/urina , Albuminúria/urina , Bloqueadores do Receptor Tipo 1 de Angiotensina II/toxicidade , Animais , Anti-Hipertensivos/toxicidade , Nitrogênio da Ureia Sanguínea , Clusterina/urina , Creatinina/sangue , Cães , Feminino , Lipocalina-2/urina , Masculino , Doadores de Óxido Nítrico/toxicidade
12.
Sci Rep ; 10(1): 4057, 2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-32132597

RESUMO

The immature preterm kidney is likely to be vulnerable to acute kidney injury (AKI). However, the biomarkers currently used for AKI are not sensitive or specific and are also inadequate for the timely detection of AKI in preterm infants. The objectives of this study were to identify novel urinary biomarkers of AKI using proteomic techniques, and to verify and validate that the candidates can serve as early predictive biomarkers for AKI. In total, 1,810 proteins were identified in the discovery phase. Among those proteins, 174 were selected as the 1st targeted proteins. A total of 168 proteins were quantified, and the levels of 6 were significantly increased in the AKI group in the verification phase. Using a clinical assay, the results were confirmed and validated using samples of the first urine after birth from the biorepository. Finally, enzyme-linked immunosorbent assays revealed that the levels of annexin A5, neutrophil gelatinase-associated lipocalin (NGAL), and protein S100-P were significantly higher in the samples of the first urine from patients with AKI than in those from patients without AKI. In conclusion, urinary annexin A5, NGAL and protein S100-P levels are promising biomarkers for early, accurate prediction of AKI in preterm infants.


Assuntos
Lesão Renal Aguda/urina , Anexina A5/urina , Doenças do Recém-Nascido/urina , Recém-Nascido Prematuro/urina , Lipocalina-2/urina , Proteômica , Proteínas S100/urina , Biomarcadores/urina , Feminino , Humanos , Lactente , Recém-Nascido , Masculino
13.
PLoS One ; 15(3): e0229616, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130237

RESUMO

BACKGROUND: The aim of this study was to characterize the time-resolved progression of clinical laboratory disturbances days-following an exertional heat stroke (EHS). Currently, normalization of organ injury clinical biomarker values is the primary indicator of EHS recovery. However, an archetypical biochemical recovery profile following EHS has not been established. METHODS: We performed a retrospective analysis of EHS patient records in US military personnel from 2008-2014 using the Military Health System Data Repository (MDR). We focused on commonly reported clinical laboratory analytes measured on the day of injury and all proceeding follow-up visits. RESULTS: Over the prescribed period, there were 2,529 EHS episodes treated at 250 unique treatment locations. Laboratory results, including a standardized set of blood, serum and urine assays, were analyzed from 0-340 days following the initial injury. Indicators of acute kidney injury, including serum electrolyte disturbances and abnormal urinalysis findings, were most prevalent on the day of the injury but normalized within 24-48hours (creatinine, blood urea nitrogen, and blood and protein in urine). Muscle damage and liver function-associated markers peaked 0-4 days after injury and persisted outside their respective reference ranges for 2-16 days (alanine aminotransferase, aspartate aminotransferase, creatine phosphokinase, myoglobin, prothrombin time). CONCLUSION: Biochemical recovery from EHS spans a 16-day time course, and markers of end-organ damage exhibit distinct patterns over this period. This analysis underscores the prognostic value of each clinical laboratory analyte and will assist in evaluating EHS patient presentation, injury severity and physiological recovery.


Assuntos
Golpe de Calor/sangue , Golpe de Calor/urina , Esforço Físico/fisiologia , Lesão Renal Aguda/sangue , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/urina , Adulto , Biomarcadores/sangue , Biomarcadores/urina , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/etiologia , Feminino , Insuficiência Hepática/sangue , Insuficiência Hepática/etiologia , Insuficiência Hepática/urina , Humanos , Masculino , Saúde Militar , Militares , Músculos/lesões , Mioglobina/sangue , Estudos Retrospectivos , Fatores de Tempo , Estados Unidos , Adulto Jovem
14.
JACC Cardiovasc Interv ; 13(7): 833-842, 2020 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-32171721

RESUMO

OBJECTIVES: This study sought to determine the efficacy profile and safety of recombinant human C1 esterase inhibitor (rhC1INH) in the prevention of contrast-associated acute kidney injury after elective coronary angiography. BACKGROUND: Contrast-associated acute kidney injury is caused by tubular cytotoxicity and ischemia/reperfusion injury. rhC1INH is effective in reducing renal ischemia/reperfusion injury in experimental models. METHODS: In this placebo-controlled, double-blind, single-center trial 77 patients with chronic kidney disease were randomized to receive 50 IU/kg rhC1INH before and 4 h after elective coronary angiography or placebo. The primary outcome was the peak change of urinary neutrophil gelatinase-associated lipocalin within 48 h, a surrogate marker of kidney injury. RESULTS: Median peak change of urinary neutrophil gelatinase-associated lipocalin was lower in the rhC1INH group (4.7 ng/ml vs. 22.5 ng/ml; p = 0.038) in the per-protocol population but not in the modified intention-to-treat analysis, and in patients with percutaneous coronary interventions (median, 1.8 ng/ml vs. 26.2 ng/ml; p = 0.039 corresponding to a median proportion peak change of 11% vs. 205%; p = 0.002). The incidence of a cystatin C increase ≥10% within 24 h was lower in the rhC1INH group (16% vs. 33%; p = 0.045), whereas the frequency of contrast-associated acute kidney injury was comparable. Adverse events during a 3-month follow-up were similarly distributed. CONCLUSIONS: Administration of rhC1INH before coronary angiography may attenuate renal injury as reflected by urinary neutrophil gelatinase-associated lipocalin and cystatin C. The safety profile of rhC1INH was favorable in a patient population with multiple comorbidities. (Recombinant Human C1 Esterase Inhibitor in the Prevention of Contrast-induced Nephropathy in High-risk Subjects [PROTECT]; NCT02869347).


Assuntos
Lesão Renal Aguda/prevenção & controle , Proteína Inibidora do Complemento C1/uso terapêutico , Meios de Contraste/efeitos adversos , Angiografia Coronária/efeitos adversos , Doença da Artéria Coronariana/diagnóstico por imagem , Insuficiência Renal Crônica/complicações , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/urina , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/urina , Proteína Inibidora do Complemento C1/efeitos adversos , Meios de Contraste/administração & dosagem , Doença da Artéria Coronariana/complicações , Método Duplo-Cego , Feminino , Humanos , Lipocalina-2/urina , Masculino , Proteínas Recombinantes/uso terapêutico , Insuficiência Renal Crônica/diagnóstico , Fatores de Risco , Suíça , Fatores de Tempo , Resultado do Tratamento
15.
Int J Mol Sci ; 21(4)2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32054020

RESUMO

Acute kidney injury (AKI) in critically ill children and adults is associated with significant short- and long-term morbidity and mortality. As serum creatinine- and urine output-based definitions of AKI have relevant limitations, there is a persistent need for better diagnostics of AKI. Nuclear magnetic resonance (NMR) spectroscopy allows for analysis of metabolic profiles without extensive sample manipulations. In the study reported here, we examined the diagnostic accuracy of NMR urine metabolite patterns for the diagnosis of neonatal and pediatric AKI according to the Kidney Disease: Improving Global Outcomes (KDIGO) definition. A cohort of 65 neonatal and pediatric patients (0-18 years) with established AKI of heterogeneous etiology was compared to both a group of apparently healthy children (n = 53) and a group of critically ill children without AKI (n = 31). Multivariate analysis identified a panel of four metabolites that allowed diagnosis of AKI with an area under the receiver operating characteristics curve (AUC-ROC) of 0.95 (95% confidence interval 0.86-1.00). Especially urinary citrate levels were significantly reduced whereas leucine and valine levels were elevated. Metabolomic differentiation of AKI causes appeared promising but these results need to be validated in larger studies. In conclusion, this study shows that NMR spectroscopy yields high diagnostic accuracy for AKI in pediatric patients.


Assuntos
Lesão Renal Aguda/urina , Lesão Renal Aguda/diagnóstico , Adolescente , Biomarcadores/urina , Criança , Pré-Escolar , Ácido Cítrico/urina , Feminino , Humanos , Lactente , Recém-Nascido , Leucina/urina , Espectroscopia de Ressonância Magnética , Masculino , Metabolômica , Projetos Piloto , Urinálise , Valina/urina
16.
Hum Exp Toxicol ; 39(4): 402-410, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31957486

RESUMO

OBJECTIVE: The objective of this article is to study the correlation between neutrophil gelatinase-associated lipocalin (NGAL) and soluble CD14 subtype (presepsin) on the severity and prognosis evaluation of acute paraquat poisoning (APP) patients. MATERIALS AND METHODS: We studied 120 APP patients who were divided into three groups: light (28 cases), moderate (52 cases), and heavy poisoning (40 cases) groups. Twenty healthy volunteers were enrolled as controls. RESULTS: Acute kidney injury (AKI) occurred in 86 APP patients (71.7%, 86 of 120). In AKI group, urine NGAL was elevated 3 h after treatment, serum NGAL was elevated 24 h after treatment, and serum creatine (SCr) was elevated 2 days after treatment, which were all significantly higher than non-AKI group. Compared with control group, there were significant differences in presepsin and acute physiology and chronic health status (APACHE) II score of different poisoning groups. There were significant differences in detection indices 24 h, 3 days, and 7 days after treatment among different poisoning groups. There was a positive correlation between urine NGAL and serum paraquat concentration, urine NGAL, and AKI morbidity (r 1 = 0.974, r 2 = 0.766, p < 0.001), suggesting higher urine NGAL level indicated higher AKI morbidity. Receiver operating characteristic curves analysis suggested serum presepsin level and urine NGAL level had higher sensitivity and specificity than APACHE II score when predicting 28-day mortality of APP patients. CONCLUSION: Serum and urine NGAL level is elevated earlier than SCr, which is important for the early diagnosis of APP. Serum presepsin and urine NGAL levels can be used as markers to diagnose the severity of AKI and predict the mortality of APP patients.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Lipocalina-2 , Receptores de Lipopolissacarídeos/sangue , Paraquat/envenenamento , Fragmentos de Peptídeos/sangue , APACHE , Lesão Renal Aguda/sangue , Lesão Renal Aguda/urina , Adolescente , Adulto , Estudos de Casos e Controles , Creatina/sangue , Relação Dose-Resposta a Droga , Humanos , Lipocalina-2/sangue , Lipocalina-2/urina , Pessoa de Meia-Idade , Paraquat/sangue , Prognóstico , Fatores de Tempo , Adulto Jovem
17.
Vet J ; 255: 105423, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31982082

RESUMO

Neutrophil gelatinase-associated lipocalin (NGAL) is used as an early biomarker of renal injury in people. In dogs, increases in urinary NGAL (uNGAL) precede increases in serum creatinine (sCr) in experimental and clinical evaluations of acute kidney injury (AKI) and chronic kidney disease. This study compared uNGAL in two subsets of dogs with AKI and their respective controls. One set included dogs with snake-envenomation at risk for or presenting with International Renal Interest Society (IRIS) grade I AKI; the other group included dogs with AKI, where renal injury was the result of various causes, and IRIS grade was ≥II. Additionally, this study evaluated haemoglobin (Hb) interference during NGAL analysis in Hb spiked urine and plasma from healthy dogs. In both AKI groups, uNGAL was significantly higher than in matched healthy control dogs (P<0.01). Moreover, uNGAL was significantly higher in dogs with IRIS grade ≥II AKI than in dogs at risk of IRIS grade I AKI (P=0.04). In dogs at risk of IRIS grade I AKI, there were no significant differences in uNGAL and uNGAL/uCr between dogs bitten by cytotoxic or neurotoxic snakes (P=0.44). Additionally, Hb did not interfere with the canine NGAL immunoassay. In conclusion, this study confirms the value of uNGAL as a biomarker for early renal damage: uNGAL was significantly increased in dogs with snake-envenomation at risk for or presenting with IRIS grade I AKI, which could be left undiagnosed if evaluated with the traditional renal biomarker sCr. In addition, Hb did not interfere with NGAL measurement in dogs.


Assuntos
Lesão Renal Aguda/veterinária , Biomarcadores/urina , Doenças do Cão/induzido quimicamente , Lipocalina-2/urina , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/urina , Animais , Doenças do Cão/urina , Cães , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/veterinária , Hemoglobinas/química , Imunoensaio/veterinária , Lipocalina-2/sangue , Mordeduras de Serpentes/veterinária
18.
Clin Chim Acta ; 502: 263-268, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31758933

RESUMO

BACKGROUND: The value of urinary mitochondrial DNA (mtDNA) for assessing kidney injury of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) was investigated. METHODS: Thirty-nine kidney biopsy-proved myeloperoxidase (MPO)-ANCA associated AAV patients were enrolled and analyzed. RESULTS: The average urinary mtDNA of patients was significantly higher than that of normal controls (3372.74 ± 1859.72 vs. 474.90 ± 123.59 copy/nmol creatinine, p < 0.001). The patients who needed dialysis at disease onset had the highest levels of urinary mtDNA (5072.23 ± 1302.87 copy/nmol creatinine). Urinary mtDNA positively correlated with urinary neutrophil gelatinase-associated lipocalin (R = 0.661, P < 0.001) and negatively correlated with estimated glomerular filtration rate (R = -0.515, P = 0.001). The urinary mtDNA level of crescentic class (4703.08 ± 1744.31 copy/nmol creatinine) was higher than that of mixed class (3258.14 ± 1158.99 copy/nmol creatinine) and focal class (2268.15 ± 1897.63 copy/nmol creatinine). Univariate correlation analysis showed urinary mtDNA positively correlated with interstitial neutrophils (R = 0.471, P = 0.048) and glomerular neutrophils (R = 0.673, P = 0.002) in kidney biopsy. Among 13 patients who needed hemodialysis at disease onset, 10 patients who got renal recovery had higher urinary mtDNA than 3 patients who remained dialysis dependent (5455.20 ± 1174.64 vs. 3795.67 ± 893.34 copy/nmol creatinine, p = 0.047). CONCLUSIONS: Urinary mtDNA increases in AAV with kidney injury, and its levels correlate with the severity of kidney injury and neutrophils infiltration in pathology.


Assuntos
Lesão Renal Aguda/urina , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/urina , DNA Mitocondrial/urina , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/metabolismo , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/metabolismo , Biomarcadores/metabolismo , Biomarcadores/urina , DNA Mitocondrial/metabolismo , Feminino , Taxa de Filtração Glomerular , Humanos , Lipocalina-2/metabolismo , Lipocalina-2/urina , Masculino , Pessoa de Meia-Idade , Peroxidase/metabolismo , Peroxidase/urina
19.
Biomed Pharmacother ; 121: 109662, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31810124

RESUMO

Currently, there is no effective method to prevent renal interstitial fibrosis after acute kidney injury (AKI). In this study, we established and screened a new renal interstitial fibrosis rat model after cisplatin-induced AKI. Our results indicated that rats injected with 4 mg/kg cisplatin once a week for two weeks after firstly administrated with 6.5 mg/kg loading dose of cisplatin could set up a more accurate model reflecting AKI progression to renal interstitial fibrosis. Then, we investigated the effects and possible mechanisms of human umbilical cord blood mononuclear cells (hUCBMNCs) on renal tubular interstitial fibrosis after cisplatin-induced AKI. In rats injected with hUCBMNCs for four times, level of matrix metalloproteinase 7 (MMP-7) in serum and urine, urinary albumin/creatinine ratio, tubular pathological scores, the relative collagen area of the tubulointerstitial region, endoplasmic reticulum dilation and the mitochondrial ultrastructural damage were significantly improved. The level of reactive oxygen species, α-smooth muscle actin (α-SMA), [NOD]-like pyrin domain containing protein 3 and cleaved-Caspase 3 in renal tissue decreased significantly. However, in rats injected with hUCBMNCs for two times, no significant difference was discovered in MMP-7 levels and urinary albumin/creatinine ratio. Although expression of α-SMA and the percentage areas of collagen staining in tubulointerstitial tissues were ameliorated in rats injected with hUCBMNCs for two times, the effects were significantly weaker than those in rats injected with hUCBMNCs for four times. Taken together, our study constructed a highly efficient, duplicable novel rat model of renal fibrosis after cisplatin-induced AKI. Multiple injections of hUCBMNCs may prevent renal interstitial fibrosis after cisplatin-induced AKI.


Assuntos
Cisplatino/efeitos adversos , Sangue Fetal/citologia , Túbulos Renais/patologia , Leucócitos Mononucleares/citologia , Substâncias Protetoras/metabolismo , Cordão Umbilical/citologia , Actinas/metabolismo , Lesão Renal Aguda/sangue , Lesão Renal Aguda/complicações , Lesão Renal Aguda/urina , Animais , Peso Corporal , Caspase 3/metabolismo , Creatinina/sangue , Modelos Animais de Doenças , Progressão da Doença , Fibrose , Humanos , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/ultraestrutura , Masculino , Metaloproteinase 7 da Matriz/sangue , Metaloproteinase 7 da Matriz/metabolismo , Metaloproteinase 7 da Matriz/urina , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
20.
Transplantation ; 104(6): 1272-1279, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31568213

RESUMO

BACKGROUND: Kidneys transplanted from deceased donors with serum creatinine-defined acute kidney injury (AKI) have similar allograft survival as non-AKI kidneys but are discarded at a higher rate. Urine injury biomarkers are sensitive markers of structural kidney damage and may more accurately predict graft outcomes. METHODS: In the 2010-2013 multicenter Deceased Donor Study of 2430 kidney transplant recipients from 1298 donors, we assessed the association of donor urine injury biomarkers microalbumin, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, IL-18, and liver-type fatty acid binding protein with graft failure (GF) and death-censored GF (dcGF) using Cox proportional hazard models (median follow-up 4 y). We examined if serum creatinine-defined donor AKI modified this association to assess the relationship between subclinical donor AKI (elevated biomarkers without creatinine-defined AKI) and GF. Through chart review of a subcohort (1137 recipients), we determined associations between donor injury biomarkers and a 3-year composite outcome of GF, mortality, or estimated glomerular filtration rate ≤ 20mL/min/1.73m. RESULTS: Risk of GF, dcGF, and 3-year composite outcome did not vary with donor injury biomarker concentrations after adjusting for donor, transplant, and recipient characteristics (adjusted hazard ratio ranged from 0.96 to 1.01 per log-2 increase in biomarker). Subclinical injury in transplanted kidneys without AKI was not associated with GF. CONCLUSIONS: AKI measured using injury biomarkers was not associated with posttransplant graft outcomes (at median 4 y posttransplant). When assessing posttransplant graft viability, clinicians can prioritize other donor and recipient factors over donor kidney injury, measured by either serum creatinine or urine injury biomarkers.


Assuntos
Lesão Renal Aguda/diagnóstico , Rejeição de Enxerto/epidemiologia , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Lesão Renal Aguda/fisiopatologia , Lesão Renal Aguda/urina , Adulto , Idoso , Aloenxertos/fisiopatologia , Biomarcadores/urina , Creatinina/urina , Feminino , Seguimentos , Taxa de Filtração Glomerular/fisiologia , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/fisiopatologia , Humanos , Rim/fisiopatologia , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Doadores de Tecidos , Resultado do Tratamento
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