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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.

Urothelial cancer (UC) is a common kidney cancer in Taiwan and patients with chronic kidney disease (CKD) are more at risk for UC than the general population. The diagnostic value of urine analysis and urine cytology is limited, especially in CKD patients. The aim of the study is to develop a nomogram to predict the risk of UC in CKD patients. We enrolled 169 UC patients and 1383 CKD patients from 9 hospitals in Taiwan between 2012 and 2015. CA125, HE4, clinical characteristics, and medical history were analyzed using multivariable logistic regression for its association with UC. A nomogram was developed to predict the risk of UC and was validated using Bootstrap. CA125 was associated with UC in CKD patients (OR: 5.91, 95% CI: 3.24-10.77) but HE4 was not (OR: 1.29, 95% CI: 0.67-2.35). A nomogram based on patients' age, estimated glomerular filtration rate, CA125 (log transformed), smoking, exposure of environmental toxin, use of nonsteroid anti-inflammatory drugs, and use of traditional Chinese medicine was conducted. The AUC of the nomogram was 0.90 (95% CI: 0.86-0.92, p < 0.01). Serum CA125 may identify UC patients from CKD patients but has limited diagnostic value due to low sensitivity. The diagnostic value of serum CA125 level can be improved by the combination with clinical characteristics including age, renal function, and medical history.

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 all-cause 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.

Data regarding the risk of various liver diseases among different hepatitis viruses in kidney transplantation have not yet been identified.We selected individuals with kidney transplantation (ICD-9-CM V420 or 996.81) from 2000-2009 from the catastrophic illness registry of National Health Insurance Research Database (NHIRD)as the study cohort. The two end-points in the study included overall death, and post-transplant occurrence of hepatic disease. After adjustment for other risk factors, the risk of mortality was increased in patients with HBV infection (N = 352) and with HCV infection (N = 275) compared to those with neither HBV nor HCV infection (N = 3485). In addition,renal transplant recipients with HBV alone,HCV alone, and both with HBV and HCVinfectionrespectively had an approximately 10-fold hazard ratio (HR) = 9.84, 95% confidence interval (CI): 4.61-21.0, 4-fold increased risk (HR = 4.40, 95% CI: 1.85-10.5)and 5-fold increased risk (HR = 4.63, 95% CI: 1.06-20.2)of hepatocellular carcinoma (HCC)compared to those with neither HBV nor HCV infection. Our findings showed a significant risk of de novo liver disease in recipients with hepatitis virus infection. Based on our findings, we reinforce the importance and impact of hepatitis virus in renal transplantation.

RANTES (Regulated on activation, normal T-cell expressed and secreted), recruits circulating leukocytes and augments inflammatory responses in many clinical conditions. Inflammatory responses in ischemia-reperfusion injury (IRI) significantly affect the unfavorable outcomes of acute kidney injury (AKI), and that infiltrating immune cells are important mediators of AKI. However, the significance of RANTES in AKI and whether hypoxia-induced LncRNAs are involved in the regulatory process of AKI are not known. Here we show that, in the kidney IRI mice model, significant RANTES expression was observed in renal tubular cells of wild type mice. RANTES deficient (RANTES(-/-)) mice showed better renal function by reducing the acute tubular necrosis, serum creatinine levels, infiltration of inflammatory cells and cytokine expressions compared to wild type. In vitro, we found that RANTES expression was regulated by NF-κB. Further, renal tubular cells showed deregulated LncRNA expression under hypoxia. Among HIF-1α dependent LncRNAs, PRINS (Psoriasis susceptibility-related RNA Gene Induced by Stress) was significantly up regulated in hypoxic conditions and had specific interaction with RANTES as confirmed through reporter assay. These observations show first evidence for RANTES produced by renal tubular cells act as a key chemokine in AKI and HIF-1α regulated LncRNA-PRINS might be involved in RANTES production.

Decoy receptor 3 (DcR3) expression in kidneys has been shown to predict progression of chronic kidney disease. We prospectively investigated a cohort comprising 96 renal transplant recipients (RTRs) undergoing graft kidney biopsies. Computer-assisted quantitative immunohistochemical staining value of DcR3 in renal tubular epithelial cells (RTECs) was used to determine the predictive role of DcR3 in kidney disease progression. The primary end point was doubling of serum creatinine and/or graft failure. A multivariate Cox proportional hazards model was used to assess the risk of DcR3 expression in rejected kidney grafts toward the renal end point. In total, RTRs with kidney allograft rejection were evaluated and the median follow-up was 30.9 months. The greater expression of DcR3 immunoreactivity in RTECs was correlated with a higher rate of the histopathological concordance of acute T cell-mediated rejection. Compared with 65 non-progressors, 31 progressors had higher DcR3 expression (HDE) regardless of the traditional risk factors. Cox regression analysis showed HDE was significantly associated with the risk of renal end point with a hazard ratio of 3.19 (95% confidence interval, 1.40 to 7.27; P = 0.006) after adjusting for other variables. In repetitive biopsies, HDE in tissue showed rapid kidney disease progression due to persistent inflammation.