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Early Biomarkers (early + biomarker)
Selected AbstractsKidney Injury Molecule-1 is an Early Noninvasive Indicator for Donor Brain Death-Induced Injury Prior to Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009W. N. Nijboer With more marginal deceased donors affecting graft viability, there is a need for specific parameters to assess kidney graft quality at the time of organ procurement in the deceased donor. Recently, kidney injury molecule-1 (Kim-1) was described as an early biomarker of renal proximal tubular damage. We assessed Kim-1 in a small animal brain death model as an early and noninvasive marker for donor-derived injury related to brain death and its sequelae, with subsequent confirmation in human donors. In rat kidney, real-time PCR revealed a 46-fold Kim-1 gene upregulation after 4 h of brain death. In situ hybridization showed proximal tubular Kim-1 localization, which was confirmed by immunohistochemistry. Also, Luminex assay showed a 6.6-fold Kim-1 rise in urine after 4 h of brain death. In human donors, 2.5-fold kidney injury molecule-1 (KIM-1) gene upregulation and 2-fold higher urine levels were found in donation after brain death (DBD) donors compared to living kidney donors. Multiple regression analysis showed that urinary KIM-1 at brain death diagnosis was a positive predictor of recipient serum creatinine, 14 days (p < 0.001) and 1 year (p < 0.05) after kidney transplantation. In conclusion, we think that Kim-1 is a promising novel marker for the early, organ specific and noninvasive detection of brain death-induced donor kidney damage. [source] Oxidative stress, defense response, and early biomarkers for lead-contaminated soil in Vicia faba seedlings,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2008Cheng-Run Wang Abstract Chemical analyses and biological measurements were investigated in leaves of Vicia faba seedlings exposed to extraneous lead (Pb) at 0 to 2,000 mg/kg of soil for a month. The results showed that superoxide radical (O,,2) production, increased along with total Pb in leaves and available Pb in soil, resulted in enhancement of malondialdehyde and carbonyl groups. Antioxidant enzymes, including corresponding isoenzymes and heat shock protein 70 (hsp 70), were also enhanced to some extent. Significant changes were detected in the patterns and intensities of guaiacol peroxidase isoenzymes, while superoxide dismutase, catalase, and ascorbate peroxidase isoenzymes only changed intensities. Superoxide dismutase activities increased with the increase of extraneous Pb at 0 to 500 mg/kg of soil and tended to decline thereafter, which might be responsible for the decrease of hydrogen peroxide and accumulation of O,,2. Guaiacol peroxidase and ascorbate peroxidase enzymes were upregulated to become major scavengers of excess hydrogen peroxide on the condition of decreased catalase activities. Levels of hsp 70 were well correlated with Pb contents in leaves (r = 0.777), O,,2 accumulation (r = 0.985, p < 0.01), and carbonyl groups (r = 0.920, p < 0.01) under extraneous Pb at 0 to 250 mg/kg of soil, suggesting that hsp 70 induced by O,,2 was possibly involved in disposal of denatured proteins. The results showed that O,,2, hsp 70, and guaiacol peroxidase isoenzymes had the most sensitive responses in the seedlings and these parameters could be potential early biomarkers of soil Pb contamination. [source] Review: Neutrophil gelatinase-associated lipocalin: A troponin-like biomarker for human acute kidney injuryNEPHROLOGY, Issue 4 2010PRASAD DEVARAJAN ABSTRACT Acute kidney injury (AKI) is a common and serious condition, the diagnosis of which currently depends on functional markers such as serum creatinine measurements. Unfortunately, creatinine is a delayed and unreliable indicator of AKI. The lack of early biomarkers of structural kidney injury (akin to troponin in acute myocardial injury) has hampered our ability to translate promising experimental therapies to human AKI. Fortunately, understanding the early stress response of the kidney to acute injuries has revealed a number of potential biomarkers. The discovery, translation and validation of neutrophil gelatinase-associated lipocalin (NGAL), possibly the most promising novel AKI biomarker, is reviewed. NGAL is emerging as an excellent stand-alone troponin-like structural biomarker in the plasma and urine for the early diagnosis of AKI, and for the prediction of clinical outcomes such as dialysis requirement and mortality in several common clinical scenarios. The approach of using NGAL as a trigger to initiate and monitor therapies for AKI, and as a safety biomarker when using potentially nephrotoxic agents, is also promising. In addition, it is hoped that the use of sensitive and specific biomarkers such as NGAL as endpoints in clinical trials will result in a reduction in required sample sizes, and hence the cost incurred. Furthermore, predictive biomarkers like NGAL may play a critical role in expediting the drug development process. However, given the complexity of AKI, additional biomarkers (perhaps a panel of plasma and urinary biomarkers) may eventually need to be developed and validated for optimal progress to occur. [source] Proteomic analysis of acute myeloid leukemia: Identification of potential early biomarkers and therapeutic targetsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue S1 2006Chary López-Pedrera Dr. Abstract The main goal of this study was to analyze, using proteomic techniques, changes in protein expression of acute myeloid leukemia (AML) cells that could give insights into a better early prognosis for tumor pathophysiology. Proteomic analysis of different subtypes of AML cells was carried out using 2-DE and MALDI-TOF,PMF analysis. Proteins identified as more significantly altered between the different AMLs belonged to the group of suppressor genes, metabolic enzymes, antioxidants, structural proteins and signal transduction mediators. Among them, seven identified proteins were found significantly altered in almost all the AML blast cells analyzed in relation to normal mononuclear blood cells: alpha-enolase, RhoGDI2, annexin,A10, catalase, peroxiredoxin,2, tromomyosin,3, and lipocortin,1 (annexin,1). These differentially expressed proteins are known to play important roles in cellular functions such as glycolysis, tumor suppression, apoptosis, angiogenesis and metastasis, and they might contribute to the adverse evolution of the disease. Proteomic analysis has identified for the first time novel proteins that may either help to form a differential prognosis or be used as markers for disease outcome, thus providing potential new targets for rational pathogenesis-based therapies of AML. [source] Urine NGAL and IL-18 are Predictive Biomarkers for Delayed Graft Function Following Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2006C. R. Parikh Delayed graft function (DGF) due to tubule cell injury frequently complicates deceased donor kidney transplants. We tested whether urinary neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) represent early biomarkers for DGF (defined as dialysis requirement within the first week after transplantation). Urine samples collected on day 0 from recipients of living donor kidneys (n = 23), deceased donor kidneys with prompt graft function (n = 20) and deceased donor kidneys with DGF (n = 10) were analyzed in a double blind fashion by ELISA for NGAL and IL-18. In patients with DGF, peak postoperative serum creatinine requiring dialysis typically occurred 2,4 days after transplant. Urine NGAL and IL-18 values were significantly different in the three groups on day 0, with maximally elevated levels noted in the DGF group (p < 0.0001). The receiver,operating characteristic curve for prediction of DGF based on urine NGAL or IL-18 at day 0 showed an area under the curve of 0.9 for both biomarkers. By multivariate analysis, both urine NGAL and IL-18 on day 0 predicted the trend in serum creatinine in the posttransplant period after adjusting for effects of age, gender, race, urine output and cold ischemia time (p < 0.01). Our results indicate that urine NGAL and IL-18 represent early, predictive biomarkers of DGF. [source] Urinary lipocalin-2 is associated with renal disease activity in human lupus nephritisARTHRITIS & RHEUMATISM, Issue 6 2007Milena Pitashny Objective Pathogenic monoclonal anti,double-stranded DNA (anti-dsDNA) antibodies up-regulate the expression of lipocalin-2 in glomerular mesangial cells. This study was undertaken to investigate whether polyclonal anti-dsDNA antibodies promote the local secretion of lipocalin-2 in the kidneys of patients with systemic lupus erythematosus (SLE), and whether urinary lipocalin-2 represents a marker of kidney involvement in SLE. Methods Hispanic, African American, and white patients with SLE and normal healthy control subjects from affiliated hospitals of the Albert Einstein College of Medicine were recruited for this cross-sectional study. Patients were classified based on the presence of active renal disease according to the SLE Disease Activity Index (SLEDAI). Correlations of clinical and laboratory data with urinary and serum levels of lipocalin-2 were assessed. Results Among SLE patients, urinary lipocalin-2 levels were significantly higher in those with lupus nephritis (LN) (median 17.1 ng/mg creatinine, interquartile range [IQR] 10.3,45.4; n = 32) than in those without LN (median 11.2 ng/mg creatinine, IQR 3.1,20.3; n = 38) (P = 0.023). Compared with the values in normal controls (median 4 ng/ml, IQR 0,11.1; n = 14), urinary levels of lipocalin-2 in SLE patients were significantly higher (non-normalized median 19.3 ng/ml, IQR 8,34.2) (P = 0.004). The presence of lipocalin-2 in the urine of patients with LN correlated significantly with the renal SLEDAI score (r = 0.452, P = 0.009), but not with extrarenal disease activity. Conclusion The high prevalence of LN in SLE patients and the prognostic significance of kidney disease support the need for identifying early biomarkers to assess the risk of nephritis development and for following up patients with established disease. These findings indicate that urinary lipocalin-2 is a potential marker of the presence and severity of renal involvement in adult patients with SLE. [source] | ||||||||||