RESUMO
OBJECTIVE: To evaluate the predictive performance of urine biomarkers for acute kidney injury (AKI) in neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia. STUDY DESIGN: We performed a multicenter prospective observational study of 64 neonates. Urine specimens were obtained at 12, 24, 48, and 72 hours of life and evaluated for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), cystatin C, interleukin-18 (IL-18), tissue inhibitor of metalloproteinases 2 (TIMP2), and insulin-like growth factor-binding protein 7 (IGFBP7). Logistic regression models with receiver operating characteristics for area under the curve (AUC) were used to assess associations with neonatal modified KDIGO (Kidney Disease: Improving Global Outcomes) AKI criteria. RESULTS: AKI occurred in 16 of 64 infants (25%). Neonates with AKI had more days of vasopressor drug use compared with those without AKI (median [IQR], 2 [0-5] days vs 0 [0-2] days; P = .026). Mortality was greater in neonates with AKI (25% vs 2%; P = .012). Although NGAL, KIM-1, and IL-18 were significantly associated with AKI, the AUCs yielded only a fair prediction. KIM-1 had the best predictive performance across time points, with an AUC (SE) of 0.79 (0.11) at 48 hours of life. NGAL and IL-18 had AUCs (SE) of 0.78 (0.09) and 0.73 (0.10), respectively, at 48 hours of life. CONCLUSIONS: Urine NGAL, KIM-1, and IL-18 levels were elevated in neonates with HIE receiving therapeutic hypothermia who developed AKI. However, wide variability and unclear cutoff levels make their clinical utility unclear.
Assuntos
Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/urina , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/terapia , Biomarcadores/urina , Cistatina C/urina , Feminino , Receptor Celular 1 do Vírus da Hepatite A/análise , Humanos , Recém-Nascido , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/urina , Interleucina-18/urina , Lipocalina-2/urina , Masculino , Estudos Prospectivos , Inibidor Tecidual de Metaloproteinase-2/urina , Vasoconstritores/administração & dosagemRESUMO
Obesity has been firmly established as a major risk factor for common disease states including hypertension, type 2 diabetes mellitus, and chronic kidney disease. Increased body mass index (BMI) contributes to the activation of both the systemic and intra-tubular renin angiotensin systems (RAS), which are in turn associated with increased blood pressure (BP) and kidney damage. In this cross-sectional study, 43 subjects of normal or increased body weight were examined in order to determine the correlation of BMI or body fat mass (BFM) with blood pressure, fasting blood glucose (FBG), and urinary kidney injury markers such as interleukin-18 (IL-18), connective tissue growth factor (CTGF), neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 (KIM-1). Our results showed that: (1) subjects with increased body weight showed significantly higher BP, BFM, total body water and metabolic age; (2) BMI was positively correlated to both systolic (R2 = 0.1384, P = 0.01) and diastolic BP (R2 = 0.2437, P = 0.0008); (3) BFM was positively correlated to DBP (R2 = 0.1232, P = 0.02) and partially correlated to urine protein (R2 = 0.047, P = 0.12) and FBG (R2 = 0.07, P = 0.06); (4) overweight young adults had higher urinary mRNA levels of renin, angiotensinogen, IL-18 and CTGF. These suggest that BMI directly affects BP, kidney injury markers, and the activation of the intra-tubular RAS even in normotensive young adults. Given that BMI measurements and urine analyses are non-invasive, our findings may pave the way to developing a new and simple method of screening for the risk of chronic kidney disease in adults.
Assuntos
Biomarcadores/urina , Rim/lesões , Rim/metabolismo , Sobrepeso/genética , Sobrepeso/urina , Sistema Renina-Angiotensina/genética , Tecido Adiposo , Adiposidade , Adolescente , Angiotensinogênio/metabolismo , Glicemia/metabolismo , Pressão Sanguínea , Índice de Massa Corporal , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/urina , Jejum/sangue , Feminino , Humanos , Interleucina-18/genética , Interleucina-18/urina , Rim/fisiopatologia , Modelos Lineares , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Renina/metabolismo , Adulto JovemRESUMO
Acute kidney injury (AKI) consists of a rapid renal function decline which usually increases serum urea and creatinine levels. Since kidney injury begins by inducing biological and molecular changes which evolve to cellular damage, biomarkers could be used as tools for monitoring early AKI appearance, and predicting its recovery. Among the main AKI biomarkers the neutrophil gelatinase-associated lipocalin, cystatin C, kidney injury molecule-1, monocyte chemotactic peptide-1, N-acetyl-ß-D-glucosaminidase, interleukin-18, liver-type fatty acid-binding protein, netrin-1, cycle arrest markers, endogenous ouabain, selenium-binding protein 1, and BPIFA2 marker, have been described. Even though novel biomarkers seem to be more helpful to early detect AKI and/or predict the need for renal replacement, and mortality compared to serum creatinine, more comprehensive studies are still required to determine their clinical utility.
Assuntos
Injúria Renal Aguda/sangue , Injúria Renal Aguda/urina , Cistatina C , Proteínas de Ligação a Ácido Graxo , Receptor Celular 1 do Vírus da Hepatite A , Lipocalina-2 , Acetilglucosaminidase/urina , Injúria Renal Aguda/diagnóstico , Biomarcadores/sangue , Biomarcadores/urina , Quimiocina CCL2/sangue , Quimiocina CCL2/urina , Cistatina C/sangue , Cistatina C/urina , Proteínas de Ligação a Ácido Graxo/urina , Receptor Celular 1 do Vírus da Hepatite A/análise , Humanos , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/urina , Interleucina-18/urina , Lipocalina-2/sangue , Lipocalina-2/urina , Inibidor Tecidual de Metaloproteinase-2/urinaRESUMO
AIM: To evaluate the performance of urinary neutrophil gelatinase-associated lipocalin (uNGAL), kidney injury molecule, interleukin-18 and heat shock protein 72 for differential diagnosis between causes of acute kidney injury in kidney transplant recipients, especially immunological rejection. PATIENTS AND METHODS: We measured these biomarkers in 67 kidney transplant recipients with acute kidney injury according to the RIFLE criteria. RESULTS: There were no statistical differences in biomarkers between kidney transplant recipients with immunological rejection (n = 20), pre-renal causes (n = 20) and other AKI causes (n = 27). Only the uNGAL level relative to urinary creatinine (uNGAL/uCr) for immunological rejection was different in comparison with others (P < 0.001); a cut-off of 59 µg/g of uNGAL/uCr had a sensitivity and specificity of 60% and 58% respectively (area under the curve in receiver-operating characteristic curve, 0.65). The other biomarkers were not useful in differentiating the causes of acute kidney injury. CONCLUSION: The biomarkers tested are not useful in identifying immunological rejection as cause of acute kidney injury in kidney transplant recipients.
Assuntos
Injúria Renal Aguda , Rejeição de Enxerto , Transplante de Rim/efeitos adversos , Túbulos Renais/metabolismo , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/urina , Proteínas de Fase Aguda/urina , Adulto , Biomarcadores/urina , Diagnóstico Diferencial , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/urina , Proteínas de Choque Térmico HSP72/urina , Receptor Celular 1 do Vírus da Hepatite A , Humanos , Interleucina-18/urina , Lipocalina-2 , Lipocalinas/urina , Masculino , Glicoproteínas de Membrana/urina , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas/urina , Curva ROC , Receptores Virais , Sensibilidade e Especificidade , Adulto JovemRESUMO
Over the past few years and with the use of innovative genomic and proteomic tools, several molecules that their urinary concentration is modified during acute kidney injury have been identified and proposed as biomarkers. Among the most studied biomarkers are neutrophil gelatinase-associated lipocalin-2, kidney injury molecule-1, interleukin-18, cystatin C, N-acetyl-ß-D-glucosaminidase, liver fatty-acid binding protein, and heat shock protein 72. Here, we reviewed and compared the sensitivity and specificity of each biomarker for the appropriate diagnosis of acute kidney injury, as well as its ability to stratify renal injury and to monitor a renoprotective pharmacologic strategy.
Assuntos
Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/urina , Biomarcadores/urina , Acetilglucosaminidase/urina , Proteínas de Fase Aguda/urina , Cistatina C/urina , Proteínas de Ligação a Ácido Graxo/urina , Proteínas de Choque Térmico HSP72/urina , Receptor Celular 1 do Vírus da Hepatite A , Humanos , Interleucina-18/urina , Lipocalina-2 , Lipocalinas/urina , Glicoproteínas de Membrana/urina , Proteínas Proto-Oncogênicas/urina , Receptores Virais , Sensibilidade e EspecificidadeRESUMO
This study was designed to assess whether heat shock protein Hsp72 is an early and sensitive biomarker of acute kidney injury (AKI) as well as to monitor a renoprotective strategy. Seventy-two Wistar rats were divided into six groups: sham-operated and rats subjected to 10, 20, 30, 45 and 60 min of bilateral ischemia (I) and 24 h of reperfusion (R). Different times of reperfusion (3, 6, 9, 12, 18, 24, 48, 72, 96 and 120 h) were also evaluated in 30 other rats subjected to 30 min of ischemia. Hsp72 messenger RNA (mRNA) and protein levels were determined in both kidney and urine. Hsp72-specificity as a biomarker to assess the success of a renoprotective intervention was evaluated in rats treated with different doses of spironolactone before I/R. Renal Hsp72 mRNA and protein, as well as urinary Hsp72 levels, gradually increased relative to the extent of renal injury induced by different periods of ischemia quantified by histomorphometry as a benchmark of kidney damage. Urinary Hsp72 increased significantly after 3 h and continued rising until 18 h, followed by restoration after 120 h of reperfusion in accord with histopathological findings. Spironolactone renoprotection was associated with normalization of urinary Hsp72 levels. Accordingly, urinary Hsp72 was significantly increased in patients with clinical AKI before serum creatinine elevation. Our results show that urinary Hsp72 is a useful biomarker for early detection and stratification of AKI. In addition, urinary Hsp72 levels are sensitive enough to monitor therapeutic interventions and the degree of tubular recovery following an I/R insult.