Urinary biomarkers augment the diagnosis of acute kidney injury (AKI), with AKI after cardiovascular surgeries being a prototype of prognosis scenario. Glutathione S-transferases (GST) were evaluated as biomarkers of AKI. Urine samples were collected in 141 cardiovascular surgical patients and analyzed for urinary alpha-(α-) and pi-(π-) GSTs. The outcomes of advanced AKI (KDIGO stage 2, 3) and allcause in-patient mortality, as composite outcome, were recorded. Areas under the receiver operator characteristic (ROC) curves and multivariate generalized additive model (GAM) were applied to predict outcomes. Thirty-eight (26.9%) patients had AKI, while 12 (8.5%) were with advanced AKI. Urinary π-GST differentiated patients with/without advanced AKI or composite outcome after surgery (p < 0.05 by generalized estimating equation). Urinary π-GST predicted advanced AKI at 3 hrs post-surgery (p = 0.033) and composite outcome (p = 0.009), while the corresponding ROC curve had AUC of 0.784 and 0.783. Using GAM, the cutoff value of 14.7 μg/L for π-GST showed the best performance to predict composite outcome. The addition of π-GST to the SOFA score improved risk stratification (total net reclassification index = 0.47). Thus, urinary π-GST levels predict advanced AKI or hospital mortality after cardiovascular surgery and improve in SOFA outcome assessment specific to AKI.In a physician's daily clinical practice, the evaluation of kidney function is certainly part of the comprehensive care for patients, with collection of numerous data points for association of acute kidney injury (AKI) and adverse clinical outcome 1 . Creatinine is certainly a useful tool for evaluation of kidney excretory function. However, it tells little about whether structural damage coexists or precedes the functional change. Urinary biomarkers have been proposed to predict and/or augment the diagnosis of AKI in order to overcome the limitations inherent to creatinine and urine output criteria, i.e., inadequate sensitivity and delayed response. A variety of serum and urinary biomarkers have been under extensive investigation and validation 2 since the pioneer study series of neutrophil gelatinase-associated lipocalin (NGAL) more than a decade ago 3,4 . Biomarkers of AKI could be used to evaluate the severity of AKI at an earlier time point in the course of the disease, defining those with high risk of progression to more advanced kidney injury. Moreover, there is urgent need to use novel biomarkers as a guide for clinical decision-making, and augmenting selection of effective management strategies for advanced AKI, e.g. dialysis. The list of candidate biomarkers is ever-growing 5 , including but not limited to neutrophil gelatinase-associated lipocalin (NGAL), liver fatty acid-binding protein (L-FABP), kidney injury molecule 1 (KIM1), interleukin-18 (IL-18), cystatin C, and the combination of tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7), either serum or urine concentration. However, the predic...
BackgroundAccumulating evidence indicates that persistent human cytomegalovirus (HCMV) infection is associated with several health-related adverse outcomes including atherosclerosis and premature mortality in individuals with normal renal function. Patients with end-stage renal disease (ESRD) exhibit impaired immune function and thus may face higher risk of HCMV-related adverse outcomes. Whether the level of anti-HCMV immune response may be associated with the prognosis of hemodialysis patients is unknown.ResultsAmong 412 of the immunity in ESRD study (iESRD study) participants, 408 were HCMV seropositive and were analyzed. Compared to 57 healthy individuals, ESRD patients had higher levels of anti-HCMV IgG. In a multivariate-adjusted logistic regression model, the log level of anti-HCMV IgG was independently associated with prevalent coronary artery disease (OR = 1.93, 95% CI = 1.2~ 3.2, p = 0.01) after adjusting for age, sex, hemoglobin, diabetes, calcium phosphate product and high sensitivity C-reactive protein. Levels of anti-HCMV IgG also positively correlated with both the percentage and absolute number of terminally differentiated CD8+ and CD4+ CD45RA+ CCR7- TEMRA cells, indicating that immunosenescence may participate in the development of coronary artery disease.ConclusionThis is the first study showing that the magnitude of anti-HCMV humoral immune response positively correlates with T cell immunosenescence and coronary artery disease in ESRD patients. The impact of persistent HCMV infection should be further investigated in this special patient population.Electronic supplementary materialThe online version of this article (10.1186/s12979-018-0120-0) contains supplementary material, which is available to authorized users.
plasma leucine-Rich α-2-glycoprotein 1 (LRG1) is an innovative biomarker for inflammation and angiogenesis. Many adverse pathophysiological changes including inflammation, atherosclerosis, and premature mortality is associated with End-stage renal disease (ESRD). However, whether levels of plasma LRG1 correlate with the co-morbidities of ESRD patients is unknown. Plasma LRG1 and high-sensitivity C-reactive protein (hsCRP) were analyzed by ELISA in 169 hemodialysis patients from the Immunity in ESRD (iESRD) study. Patient demographics and comorbidities at the time of enrollment were recorded. Peripheral blood monocyte and T cell subsets were assessed by multicolor flow cytometry. In the univariate analysis, a higher level of LRG1 was associated with the presence of cardiovascular disease (CVD) and peripheral arterial occlusive disease (PAOD). In multivariate logistic regression models, higher LRG1 tertile was significantly associated with PAOD (odds ratio = 3.49) and CVD (odds ratio = 1.65), but not with coronary artery disease, history of myocardial infarction, or stroke after adjusting for gender, diabetes, hemoglobin, albumin, calcium-phosphate product, and level of hsCRP. In addition, the level of LRG1 had a positive correlation with IL-6, hsCRP, and also more advanced T cell differentiation. The association suggests that LRG1 participates in the progression of atherosclerosis by inducing inflammation. Therefore, the role of LRG1 in coexisting inflammatory response should be further investigated in the pathogenesis of cardiovascular morbidity and mortality in patients with ESRD. Cardiovascular mortality in patients with end-stage renal disease (ESRD) remains the leading cause of death 1,2. These patients exhibit a strikingly higher risk (20-400 folds) of cardiovascular mortality compared to age-matched health subjects without any kidney disease 3. Traditional risk factors as well as non-traditional risk factors, such as inflammation, are believed to contribute to the excessively heavy burden of cardiovascular disease in chronic kidney disease (CKD) and ESRD patients 3. The pro-inflammatory microenvironment is collectively caused by uremic milieu, infection, and tissue ischemia even before the initiation of dialysis 4. Innate immunity is the evolutionarily conserved host response mediated by pattern recognition receptors (PRRs), which bind endogenous or exogenous ligands and initiate downstream signaling pathways to establish an immediate responses as the first line of defense. Two types of PRRs, Toll-like receptors (TLRs) over the cell surface and inflammasomes in the cytoplasm can interact with endogenous ligands. They are involved in the development of pro-inflammatory microenvironment in renal failure. Activation of these innate immune pathways is
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