Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 311
Filtrar
1.
Ann Hematol ; 100(6): 1401-1409, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33796899

RESUMO

Sickle cell nephropathy (SCN) develops via altered hemodynamics and acute kidney injury, but conventional screening tests remain normal until advanced stages. Early diagnostic biomarkers are needed so that preventive measures can be taken. This study evaluates the role of neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of SCN in steady state and vaso-occlusive crisis (VOC). In this case-control study, 74 sickle cell disease (SCD) patients (37 in steady state and 37 in VOC) and 53 control subjects had hematological and biochemical measurements including plasma and urine NGAL. Univariate and logistic regression analyses were used to find the associations between variables. The receiver operating characteristic (ROC) curve was used to determine the diagnostic performance characteristics of plasma and urine NGAL for detection of VOC. Plasma and urine NGAL, urine microalbumin:creatinine ratio, and urine protein:creatinine ratio were significantly higher in VOC. Microalbuminuria was present in 17.1% steady state and 32.0% VOC patients. Microalbuminuria showed significant correlations with age, plasma NGAL, WBC, and hemolytic parameters. Area under the ROC curve for plasma NGAL was 0.69 (95%CI = 0.567-0.813; p = 0.006) and 0.86 (95%CI = 0.756-0.954; p < 0.001) for urine NGAL. Urine NGAL cut-off value of 12.0 ng/mL had 95% sensitivity and 65% specificity. These results confirm the presence of nephropathy during VOC and suggest that plasma and urine NGAL would be useful in the identification of SCN. Urine NGAL should be used as the screening biomarker, and patients with VOC and urine NGAL > 12.0 ng/mL should be selected for aggressive management to prevent progression of renal damage.


Assuntos
Injúria Renal Aguda/sangue , Anemia Falciforme/sangue , Lipocalina-2/sangue , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/urina , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/urina , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Feminino , Humanos , Lipocalina-2/urina , Masculino , Curva ROC
2.
J Ayub Med Coll Abbottabad ; 33(1): 9-13, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33774946

RESUMO

BACKGROUND: The most common complication of SLE is lupus nephritis (LN) causing high morbidity and mortality. The routine biomarkers used for the diagnosis of LN do not have the ability to predict the worsening in renal disease activity. Thus, there is need of a new biomarker leading to detection of flare in LN. The objective of this study was to assess the role of urinary neutrophil gelatinase associated lipocalin (uNGAL) as a predictor of renal flare in patients with lupus nephritis. METHODS: Including a total of 84 subjects, 42 cases were lupus patients without renal involvement and 42 cases were lupus patients with nephritis (24 active nephritis and 18 inactive nephritis). The diagnosis of lupus nephritis was established on the basis of renal biopsy. uNGAL was estimated in both groups. RESULTS: This study revealed that the nephritis group had increased levels of uNGAL as compared to systemic erythematosus patients without having lupus nephritis (p-value <0.05). Patients with active nephritis had increased uNGAL levels as compared to patients with inactive nephritis. CONCLUSIONS: From the findings in our study, it can be stated that uNGAL can prove to be a noninvasive, reliable and sensitive biomarker to predict flare in cases of lupus nephritis.


Assuntos
Lipocalina-2/urina , Nefrite Lúpica , Biomarcadores/urina , Humanos , Rim/metabolismo , Rim/fisiopatologia , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/metabolismo , Nefrite Lúpica/fisiopatologia , Nefrite Lúpica/urina
3.
Clin Nephrol ; 95(3): 127-135, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33355088

RESUMO

BACKGROUND: Febrile urinary tract infection (fUTI) can be associated with acute kidney injury (AKI). We aimed to study the risk factors for AKI, its pathophysiological categories, and the role of urinary neutrophil gelatinase-associated lipocalin (uNGAL) in differentiating these categories in patients hospitalized with fUTI. MATERIALS AND METHODS: We prospectively studied patients with fUTI admitted to the Department of Medicine of a tertiary care hospital in southern India from January 2017 to December 2018. Clinical evaluation, renal imaging, and estimation of fractional excretion of sodium (FeNa) and uNGAL were done at baseline. AKI was defined as ≥ 0.3 mg/dL rise in serum creatinine (SCr) within 48 hours during hospital stay (KDIGO criterion) or discharge SCr value 0.5 mg/dL or less compared to peak SCr after admission. RESULTS: We studied 100 patients. Their mean age was 52 (± 14) years; 45 were men. In all, 52 had AKI: pre-renal in 11 (21%), intrinsic renal in 24 (47%), post-renal in 16 (31%), and missing data 1 patient. uNGAL levels were significantly higher in the AKI group compared to the no-AKI group (median [IQR] 91.1 [13.2 - 188] vs. 264.9 [115.2 - 355.2] ng/mL; p < 0.001). On multivariable analysis, male sex (adjusted odds ratio, aOR [95% CI] 2.8 [1.09 - 7.14]), hypertension (4.12 [1.24 - 13.7]) and hydroureteronephrosis (7.82 [1.55 - 39.4]) were independently associated with AKI. There was an increasing trend of uNGAL across the three categories of AKI (pre-renal 106.1 [14.6 - 261.7] ng/mL, intrinsic renal 210.8 [8.5 - 353.8] ng/mL, and post-renal 335.5 [269.2 - 692.8] ng/mL; p = 0.001). Patients with pre-renal AKI had significantly lower levels of uNGAL compared to the other two categories combined (106.1 [14.6 - 261.7] vs. 284.6 [179 - 434.4] ng/mL; p = 0.016). CONCLUSION: Hospitalized fUTI patients should be evaluated for AKI, and obstructive uropathy should be ruled out in those with AKI. uNGAL levels may help in differentiating the pre-renal type of AKI from the other two categories.


Assuntos
Injúria Renal Aguda , Infecções Urinárias , Injúria Renal Aguda/complicações , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Adulto , Idoso , Creatinina/sangue , Feminino , Febre , Hospitalização , Humanos , Lipocalina-2/urina , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Urinárias/complicações , Infecções Urinárias/epidemiologia , Infecções Urinárias/terapia
4.
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
Injúria Renal Aguda/veterinária , Doenças do Cão/microbiologia , Leptospirose/veterinária , Injúria Renal Aguda/complicações , Injúria 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
5.
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 , Injúria Renal Aguda/sangue , Injúria Renal Aguda/urina , Obstrução Uretral/sangue , Obstrução Uretral/urina , Biomarcadores/sangue , Biomarcadores/urina , Valores de Referência
6.
Saudi Med J ; 41(7): 690-697, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32601635

RESUMO

OBJECTIVES: To evaluate 2 renal tubular enzymes; urinary neutrophil gelatinase-associated lipocalin (uNGAL), and urinary N-acetyl-beta-D-glucosaminidase (uNAG), and serum Cystatin C as candidate biomarkers for early diagnosis of early stage of diabetic nephropathy (DB) in patients with type 2 diabetes mellitus (T2DM). METHODS: This cross-sectional study was carried out at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia during the period between  May 2017 and May 2018 and was conducted on 86 patients with T2DM. Patients were classified according to their albumin/creatinine ratio (ACR) into 3 groups; a normal albuminuria group with ACR less than 30 mg/g creatinine, a moderately increased albuminuria group with ACR: 30-299 mg/g creatinine, and a severely increased albuminuria group with ACR ≥300 mg/g.  Healthy adults were recruited as a control group. Urine uNGAL, uNAG, and serum Cystatin C were measured in all patients. RESULTS: Compared with healthy control, diabetic patients with normal albuminuria excreted significantly higher levels of uNGAL (p less than 0.001). In addition, significantly elevated uNGAL, uNAG and cystatin C levels were observed in moderately increased albuminuria and severely increased albuminuria groups when compared to the control and normoalbuminuric groups (p less than 0.001). urinary neutrophil gelatinase-associated lipocalin, urinary N-acetyl-beta-D-glucosaminidase and Cystatin C showed a positive correlation with fasting blood glucose (FBG), HbA1c, duration of diabetes, urea, creatinine, and ACR. CONCLUSION: Our results indicated that uNGAL could be a sensitive biomarker for early renal dysfunction in diabetic patients while uNAG and serum Cystatin C might have prognostic value.


Assuntos
Cistatina C/sangue , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Lipocalina-2/urina , Biomarcadores/sangue , Biomarcadores/urina , Estudos Transversais , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
7.
PLoS One ; 15(7): e0234921, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32673348

RESUMO

BACKGROUND: Subjects with chronic kidney disease are at increased risk for contrast-induced acute kidney injury (CI-AKI). Risk stratification is traditionally based on glomerular filtration rate (GFR) and proteinuria. The present trial examines, whether tubular and inflammatory biomarkers are able to identify subjects at increased risk as well. METHODS: We performed a prospective study in 490 patients undergoing coronary angiography. An increase of serum creatinine concentration ≥ 0.3 mg/dl from baseline to day 2-3 was defined as primary endpoint (CI-AKI). Urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and calprotectin were assessed < 24h before coronary angiography. Prognostic accuracy was assessed by receiver operating characteristics (ROC) calculations. RESULTS: 30 (6.1%) patients suffered from CI-AKI (27 AKIN stage I, 3 AKIN stage II, 0 AKIN stage III). Those subjects who developed CI-AKI had 3.1 fold higher baseline urinary NGAL/creatinine ratios than those without CI-AKI (60.8 [IQR 18.7-93.1] µg/mg vs. 19.9 [IQR 12.3-38.9] µg/mg, p = 0.001). In those subjects without clinically overt CKD (eGFR > 60 ml/min, urinary albumin creatinine ratio <30 mg/g), the NGAL/creatinine ratio was 2.6 higher in CI-AKI vs. no CI-AKI (47.8 [IQR 11.8-75.3] vs. 18.6 [IQR 11.7-36.3] µg/mg). No significant differences were obtained for KIM-1 and calprotectin (p>0.05 each). ROC analyses revealed an area under the curve (AUC) of 0.68 (95% CI 0.60-0.81) for NGAL/creatinine. An NGAL/creatinine ratio < 56.4 µg/mg has a negative predictive value of 96.5%. CONCLUSIONS: The present study is the largest investigation on the use of urinary biomarkers for CI-AKI risk stratification so far. It shows that NGAL provides prognostic information beyond the glomerular biomarkers eGFR and proteinuria.


Assuntos
Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Meios de Contraste/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Idoso , Área Sob a Curva , Biomarcadores/sangue , Angiografia Coronária/efeitos adversos , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Receptor Celular 1 do Vírus da Hepatite A/análise , Humanos , Complexo Antígeno L1 Leucocitário/urina , Lipocalina-2/urina , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Proteinúria , Curva ROC , Insuficiência Renal Crônica/complicações
8.
Nutr. hosp ; 37(3): 436-442, mayo-jun. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-193849

RESUMO

Aim and background: the incidence of obesity has increased among children, and obesity has been considered an independent risk factor for chronic kidney disease. We aimed to determine the degree of kidney function impairment by evaluating urine neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) levels. MATERIALS AND METHODS: in total, 15 obese, 26 overweight, and 26 control adolescents aged 10 to 16 years were enrolled into the study. Urine samples were evaluated for NGAL and KIM-1 levels using enzyme-linked immunosorbent assay kits. We investigated the association between obesity and related comorbidities with urinary NGAL and KIM-1 excretion. RESULTS: no significant differences were noted between the obese, overweight, and control groups in urinary NGAL and KIM-1 excretion (p = 0.327 and p = 0.917, respectively). In the obese and overweight groups urinary NGAL levels were 50.39 [30.88-74.22] in females and 26.67 [23.24-45.59] in males (p = 0.013). Also, urinary NGAL levels were increased in obese and overweight adolescents with LDL dyslipidemia at 64.12 [30.98-114.32] as compared to those without LDL dyslipidemia: 39.51 [25.59.56.37] (p = 0.024). Furthermore, a correlation was observed between insulin and homeostasis model assessment of insulin resistance levels with the NGAL/creatinine ratio in the overweight group (r = 0.515; p = 0.008, and r = 0.483; p = 0.014, respectively). Such correlation was not found in the obese group. CONCLUSION: the effect of obesity on renal function could not be determined in children. A longer exposure may be required for obesity-induced disruption of renal function in children. Renal function may be disrupted by dyslipidemia in obese adolescents. Furthermore, obesity impaired renal function in female adolescents. The normalization of these urinary markers as related to urine creatinine should be discussed


INTRODUCCIÓN: la incidencia de la obesidad en la edad infantil ha aumentado. Se considera la obesidad como un factor de riesgo independiente para el desarrollo de la enfermedad renal crónica. El objetivo de este estudio fue valorar el grado de alteración de la función renal evaluando los niveles urinarios de NGAL y KIM-1. MATERIAL Y MÉTODOS: el estudio incluyó a 15 adolescentes con obesidad, 26 con sobrepeso y 26 controles sanos. Las edades de los participantes estaban entre los 10 y los 16 años. Los niveles de NGAL y KIM-1 en orina se determinaron mediante un kit ELISA. Se investigó la asociación entre la obesidad y su comorbilidad con la excreción urinaria de NGAL y KIM-1. RESULTADOS: no se encontraron diferencias significativas en la excreción urinaria de NGAL y KIM-1 entre los sujetos con obesidad, los sujetos con sobrepeso y los controles sanos (p = 0,327 y 0,917, respectivamente). En el grupo con sobrepeso y obesidad, los niveles de NGAL en las niñas fueron de 50,39 (30,88-74,22), mientras que en los niños fueron de 26,67 (23,24-45,59) (p = 0,013). Para los sujetos con dislipemia de LDL, el nivel de NGAL fue de 64,12 (30,98-114,32) frente a 39,5 (25,59-56,37) entre los que no la tenían (p = 0,024). Se encontró correlación entre los nivles de insulina, el HOMA-IR y la ratio NGAL/creatinina en el grupo con sobrepeso (r = 0,515; p = 0,008, y r = 0,483; p = 0,014, respectivamente). En el grupo con obesidad no se encontró dicha correlación. CONCLUSIONES: se precisa una duración más prolongada para encontrar alterada la función renal en los niños con exceso de peso. La función renal puede alterase por la dislipemia en el caso de los adolescentes con obesidad. La función renal se afecta más en las adolescentes femeninas. En el artículo se discute la normalización de estos marcadores urinarios con la creatinina en orina


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Lipocalina-2/análise , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Lipocalina-2/urina , Creatinina/urina , Sobrepeso/diagnóstico , Obesidade/diagnóstico , Ensaio de Imunoadsorção Enzimática/métodos
9.
Artigo em Chinês | MEDLINE | ID: mdl-32306679

RESUMO

Objective: To explore the evaluate of neutrophil gelatinase-associated lipocalin (NGAL) , combined with neutrophil/lymphocyte ratio (NLR) in the early prognosis of patients with acute paraquat poisoning (APP) . Methods: In March 2019, 108 APP patients admitted to Emergency Medicine Department of Hebei Medical University from January 2017 to December 2018 were selected as the observation group, 60 healthy people in the same period were see as the control group according to the results of diagnosis and 28-day survival, the observation group was divided into 51 death group and 57 survival group. The correlation between NGAL, NLR and the death of APP patients was analyzed, to explore the value of NGAL and NLR in predicting the death of APP patients. Results: Compared with the Control group, the NGAL and NLR in the observation group were significantly higher (P<0.01) , and the NGAL and NLR in the death group were significantly higher (P<0.05) . The results showed that NGAL and NLR were positively correlated with the death of APP patients on 28th day, and the Correlation Coefficient was 0.456 and 0.638 at 2nd Day (P<0.01) The area under the ROC curve of NGAL, NLR and their combination were 0.764, 0.869 and 0.905, respectively. Conclusion: The combined detection of NGAL and NLR has important clinical significance in the early prediction of 28-day mortality in APP patients.


Assuntos
Lipocalina-2/urina , Linfócitos/citologia , Neutrófilos/citologia , Paraquat/envenenamento , Biomarcadores/urina , Estudos de Casos e Controles , Humanos , Mortalidade , Prognóstico , Curva ROC
10.
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
Injúria 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
11.
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
Injúria 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
12.
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
Injúria 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 , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/diagnóstico , Injúria 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
13.
Clin Lab ; 66(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32013365

RESUMO

BACKGROUND: Glomerular and tubulointerstitial damage plays a role in renal function failure in diabetic patients. While both serum and urine levels of neutrophil gelatinase-associated lipocalin (NGAL) show significantly increased levels in acute renal pathologies, the NGAL increase in active phase indicates a reversible condition in chronic cases. MATERIALS AND METHODS: 52 type 1 diabetic patients and 30 healthy volunteers participated in the study. The diabetic participants were separated into two groups as follows: a normoalbuminuria group consisting of those with an albumin/creatinine ratio less than 30 mg/g and an albuminuria group consisting of those with an albumin/ creatinine ratio equal or greater than 30 mg/g. Albumin, creatinine and NGAL were measured in all participants. RESULTS: Urinary NGAL median level was 21.1 ng/mL for diabetic patients and 11.9 ng/mL for healthy controls, and the difference between the two groups was statistically significant. When diabetic patients were compared as those with and without albuminuria, the median urinary NGAL levels of normoalbuminuria and albuminuria were 24.7 and 16.1 ng/mL, respectively, but the difference was not statistically significant. Statistically similar results were obtained through evaluation of the ratio of urinary NGAL excretion to creatinine excretion. The NGAL/Cr ratio was significantly higher in diabetic patients than in healthy controls, but no statistically significant difference was found between the diabetic patients with and without albuminuria. CONCLUSIONS: Urinary NGAL excretion in type 1 diabetic patients is found to be increased over a wide range, but it does not correlate with urinary albumin excretion. In this regard, urinary NGAL excretion should not be used as an alternative to microalbuminuria in detecting diabetic nephropathy. The greater amount of NGAL excretion among diabetic patients may be due to diabetic nephropathy with possible tubulointerstitial damage pathologies.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Nefropatias Diabéticas , Lipocalina-2/urina , Adulto , Biomarcadores/urina , Estudos de Casos e Controles , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Adulto Jovem
14.
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
Injúria Renal Aguda/induzido quimicamente , Lipocalina-2 , Receptores de Lipopolissacarídeos/sangue , Paraquat/envenenamento , Fragmentos de Peptídeos/sangue , APACHE , Injúria Renal Aguda/sangue , Injúria 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
15.
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
Injúria Renal Aguda/veterinária , Biomarcadores/urina , Doenças do Cão/induzido quimicamente , Lipocalina-2/urina , Injúria Renal Aguda/induzido quimicamente , Injúria 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
16.
Vet J ; 255: 105420, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31982083

RESUMO

Pathophysiological cardiac and renal interactions are termed cardiovascular-renal disorder (CvRD). Cardiovascular disease/dysfunction secondary to kidney disease (CvRDK), is a leading cause of death in human chronic kidney disease (CKD) patients. The presence and clinical impact of CvRDK in dogs with CKD is unknown. We hypothesized that echocardiographic measurements, and cardiac and renal biomarkers, will be altered in dogs with CKD and associated with survival. Eleven dogs with CKD (n = 6 IRIS stage 2, n = 5 IRIS stage 3) and without primary cardiac disease, plus 12 healthy age-matched control dogs, were recruited to this prospective observational study. Dogs underwent standard echocardiography, glomerular filtration rate (GFR) estimation by iohexol clearance, and measurement of plasma cardiac troponin I and N-terminal pro-B-type natriuretic peptide (NT-proBNP), plasma and urinary cystatin B, and urinary clusterin and neutrophil gelatinase-associated lipocalin (NGAL). Values were compared between groups, and their association with all-cause mortality explored. Dogs with CKD had significantly lower GFR and higher NT-proBNP, urinary cystatin B, clusterin, and NGAL, compared to controls (P < 0.05). Echocardiographic measurements were similar between dogs with CKD and controls. Median follow-up time was 666 days, during which six dogs with CKD died. Risk of death was associated with increasing age, serum total protein, and normalized left ventricular posterior wall thickness (LVPWDN) and decreasing bodyweight and packed cell volume. Although baseline differences in echocardiographic measurements were not evident between dogs with moderate CKD and controls, the presence of CvRDK was suggested by the association between LVPWDN and survival.


Assuntos
Doenças Cardiovasculares/veterinária , Doenças do Cão/urina , Insuficiência Renal Crônica/veterinária , Animais , Biomarcadores/sangue , Biomarcadores/urina , Doenças Cardiovasculares/diagnóstico por imagem , Estudos de Casos e Controles , Clusterina/urina , Cistatina B/sangue , Cistatina B/urina , Doenças do Cão/sangue , Doenças do Cão/diagnóstico por imagem , Cães , Ecocardiografia/veterinária , Feminino , Taxa de Filtração Glomerular/veterinária , Lipocalina-2/urina , Masculino , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Estudos Prospectivos , Insuficiência Renal Crônica/complicações , Troponina I/sangue
17.
Am J Physiol Renal Physiol ; 318(3): F689-F701, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31928224

RESUMO

Acute kidney injury (AKI) is a highly prevalent medical syndrome associated with high mortality and morbidity. Several types of cells, including epithelial cells, vascular endothelial cells, pericytes, and macrophages, participate in the development of AKI. Recently, renal fibroblasts were found to play an important role in the regulation of tubular injury, repair, and recovery after AKI. However, the mechanisms underlying fibroblast activation and proliferation during the progression of AKI remain unclear. In the present study, we found many activated myofibroblasts located in the renal interstitium with an abundance of extracellular matrix deposition following folic acid-induced AKI. The proliferative pattern of tubular epithelial cells and interstitial cells following acute injury was different, indicating that the proliferation of fibroblasts followed the proliferation of tubular epithelial cells. Furthermore, we observed that proliferative tubular epithelial cells preferred aerobic glycolysis as the dominating metabolic pathway in the progression of AKI. Lactate generated from injured tubules was taken up by interstitial fibroblasts in the later stages of AKI, which induced fibroblast activation and proliferation in vitro. Early inhibition of lactate production in tubules by glycolytic inhibitors suppressed fibroblast activation after folic acid-induced injury. Collectively, these results support the important role of fibroblasts in the development of AKI and suggest that lactate produced by glycolysis in tubular epithelial cells is a novel regulator of fibroblast activation and proliferation.


Assuntos
Injúria Renal Aguda/metabolismo , Fibroblastos/fisiologia , Túbulos Renais/metabolismo , Lactatos/metabolismo , Animais , Apoptose , Nitrogênio da Ureia Sanguínea , Linhagem Celular , Creatinina/sangue , Hepatócitos , Lactatos/sangue , Lipocalina-2/urina , Masculino , Camundongos
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
Injúria Renal Aguda/urina , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/urina , DNA Mitocondrial/urina , Injúria Renal Aguda/diagnóstico , Injúria 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: 109684, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31810121

RESUMO

Nephrotoxicity is an important limitation to the clinical use of many drugs and contrast media. Drug nephrotoxicity occurs in acute, subacute and chronic manifestations ranging from glomerular, tubular, vascular and immunological phenotypes to acute kidney injury. Pre-emptive risk assessment of drug nephrotoxicity poses an urgent need of precision medicine to optimize pharmacological therapies and interventional procedures involving nephrotoxic products in a preventive and personalized manner. Biomarkers of risk have been identified in animal models, and risk scores have been proposed, whose clinical use is abated by their reduced applicability to specific etiological models or clinical circumstances. However, our present data suggest that the urinary level of transferrin may be indicative of risk of renal damage, where risk is induced by subclinical tubular alterations regardless of etiology. In fact, urinary transferrin pre-emptively correlates with the subsequent renal damage in animal models in which risk has been induced by drugs and toxins affecting the renal tubules (i.e. cisplatin, gentamicin and uranyl nitrate); whereas transferrin shows no relation with the risk posed by a drug affecting renal hemodynamics (i.e. cyclosporine A). Our experiments also show that transferrin increases in the urine in the risk state (i.e. prior to the damage) precisely as a consequence of reduced tubular reabsorption. Finally, urinary transferrin pre-emptively identifies subpopulations of oncological and cardiac patients at risk of nephrotoxicity. In perspective, urinary transferrin might be further explored as a wider biomarker of an important mechanism of predisposition to renal damage induced by insults causing subclinical tubular alterations.


Assuntos
Túbulos Renais/patologia , Transferrina/urina , Acetilglucosaminidase/urina , Animais , Biomarcadores/urina , Meios de Contraste/efeitos adversos , Creatinina/sangue , Suscetibilidade a Doenças , Feminino , Humanos , Nefropatias/induzido quimicamente , Nefropatias/urina , Lipocalina-2/urina , Masculino , Pessoa de Meia-Idade , Platina/efeitos adversos , Ratos Wistar , Fatores de Risco , Ureia/sangue
20.
Eur J Drug Metab Pharmacokinet ; 45(1): 71-80, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31605364

RESUMO

BACKGROUND AND OBJECTIVES: Renal elimination of amikacin and other aminoglycosides is slowed down in sepsis-induced acute kidney injury increasing the risk of adverse effects. Since neutrophil gelatinase-associated lipocalin (NGAL) and aminoglycosides share the mechanisms for renal excretion, the predictive power of NGAL was examined towards the changes in amikacin pharmacokinetics during early endotoxemia in anesthetized Wistar rats. METHODS: Endogenous biomarkers of inflammation and acute kidney injury were assessed including NGAL in saline-injected controls and two groups of rats challenged with an intravenous injection of bacterial lipopolysaccharide (5 mg/kg)-a fluid-resuscitated group (LPS) and a fluid-resuscitated group infused intravenously with 8 µg/kg/h terlipressin (LPS-T). Sinistrin and amikacin were infused to measure glomerular filtration rate (GFR) and amikacin clearance (CLam). The investigations included blood gas analysis, chemistry and hematology tests and assessment of urine output, creatinine clearance (CLcr) and sinistrin clearance (CLsini). RESULTS: Within 3 h of injection, systemic and renal inflammatory responses were induced by lipopolysaccharide. Gene and protein expression of NGAL was increased in the kidneys and the concentrations of NGAL in the plasma (pNGAL) and urine rose 4- to 38-fold (P < 0.01). The decreases in CLam and the GFR markers (CLcr, CLsini) were proportional, reflecting the extent to which endotoxemia impaired the major elimination mechanism for the drug. Terlipressin attenuated lipopolysaccharide-induced renal dysfunction (urine output, CLcr, CLsini) and accelerated CLam. The pNGAL showed a strong association with the CLsini (rs = - 0.77, P < 0.0005). Concerning prediction of CLam, pNGAL was comparable to CLcr (mean error - 24%) and inferior to CLsini (mean error - 6.4%), while the measurement of NGAL in urine gave unsatisfactory results. CONCLUSIONS: During early endotoxemia in the rat, pNGAL has a moderate predictive ability towards CLam. Clinical studies should verify whether pNGAL can support individualized dosing of aminoglycosides to septic patients.


Assuntos
Amicacina/farmacocinética , Biomarcadores/sangue , Lipocalina-2/metabolismo , Ratos Wistar , Sepse/metabolismo , Injúria Renal Aguda/sangue , Amicacina/sangue , Amicacina/metabolismo , Animais , Citocinas , Endotoxemia/induzido quimicamente , Taxa de Filtração Glomerular/fisiologia , Inflamação , Rim/fisiopatologia , Lipocalina-2/sangue , Lipocalina-2/urina , Lipopolissacarídeos/farmacologia , Masculino , Taxa de Depuração Metabólica , Modelos Animais , Oligossacarídeos/farmacocinética , Valor Preditivo dos Testes , Ratos , Sepse/tratamento farmacológico , Urina
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...