Predictive value of procalcitonin in chronic allograft dysfunction in kidney transplant recipients.

The present study was designed to determine the potential role of circulating procalcitonin (PCT) in predicting chronic allograft dysfunction (CAD) in kidney transplant recipients (KTRs). A total of 87 KTRs were retrospectively analyzed and divided into a CAD and a non-CAD (normal renal function) group. Clinical features and inflammatory markers were compared between the groups, including PCT, white blood cell count, C-reactive protein, neutrophil percentage (N%) and lipoprotein(a) [Lp(a)], and the receiver operating characteristic (ROC) curve for CAD prediction was plotted. Univariate and multivariate logistic regression analyses were used to analyze the relevant risk factors for CAD. The results indicated that i) the values of these indicators in the CAD group, including the male ratio, years after transplantation, PCT, N% and Lp(a), were significantly higher than those in the non-CAD group, while the body mass index, aspartate aminotransferase, high-density lipoprotein and low-density lipoprotein were significantly lower; ii) PCT and Lp(a) were able to predict CAD with an area under the ROC curve of 0.893 and 0.770, respectively; iii) multivariate logistic regression analysis of factors influencing CAD in KTRs suggested that elevated PCT was an independent risk factor. In KTRs, PCT was identified as a potential biomarker for predicting CAD.

LncRNA MALAT1/miR-181a-5p affects the proliferation and adhesion of myeloma cells via regulation of Hippo-YAP signaling pathway.

Multiple myeloma (MM) is a plasma cells malignant proliferative disease, especially in aged people. LncRNAs have been considered as important regulators in MM. This research was to study the effect of LncRNA MALAT1 on the proliferation and adhesion of myeloma cells and whether Long non-coding RNAs MALAT1(LncRNA MALAT1) plays its regulative role through Hippo-YAP signaling pathway by targeting miR-181a-5p. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was used to detect the LncRNA MALAT1/miR-181a-5p expression and improve the transfection efficiency. Western blot analysis was used to analyze the expression of proliferation and apoptosis related proteins and Hippo-Yes-associated protein (YAP) signaling pathway related proteins. Cell proliferative ability and cell apoptosis were respectively determined by Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis. ELISA assay was for the determination of adherence factors. Immunohistochemistry was to detect the expression of proliferation and adhesion related proteins. LncRNA MALAT1 targeting gene was determined by Dual-luciferase reporter assay. LncRNA MALAT1 was increased in MM cells and LncRNA MALAT1 interference could inhibit cell proliferation and promote cell apoptosis with the changes in the related proteins. Also, LncRNA MALAT1 interference could inhibit cell adhesion through Hippo-YAP signaling pathway. MiR-181a-5p was demonstrated to be a target of LncRNA MALAT1 and miR-181a-5p overexpression could also regulate the changes in cellular behavior in accordance with the LncRNA MALAT1 interference. In addition, LncRNA MALAT1 interference could decrease the expression of miR-181a-5p and inhibit the growth of tumor. In conclusion, this study showed that LncRNA MALAT1 interference inhibited the proliferation and adhesion of myeloma cells by the up-regulation of miR-181a-5p through activating the Hippo-YAP signaling pathway.

The profibrotic effects of MK-8617 on tubulointerstitial fibrosis mediated by the KLF5 regulating pathway.

The discovery of hypoxia-inducible factor (HIF)-prolyl hydroxylase inhibitor (PHI) has revolutionized the treatment strategy for renal anemia. However, the presence of multiple transcription targets of HIF raises safety concerns regarding HIF-PHI. Here, we explored the dose-dependent effect of MK-8617 (MK), a kind of HIF-PHI, on renal fibrosis. MK was administered by oral gavage to mice for 12 wk at doses of 1.5, 5, and 12.5 mg/kg. In vitro, the human proximal tubule epithelial cell line HK-2 was treated with increasing doses of MK administration. Transcriptome profiling was performed, and fibrogenesis was evaluated. The dose-dependent biphasic effects of MK on tubulointerstitial fibrosis (TIF) were observed in chronic kidney disease mice. Accordingly, high-dose MK treatment could significantly enhance TIF. Using RNA-sequencing, combined with in vivo and in vitro experiments, we found that Krüppel-like factor 5 (KLF5) expression level was significantly increased in the proximal tubular cells, which could be transcriptionally regulated by HIF-1α with high-dose MK treatment but not low-dose MK. Furthermore, our study clarified that HIF-1α-KLF5-TGF-ß1 signaling activation is the potential mechanism of high-dose MK-induced TIF, as knockdown of KLF5 reduced TIF in vivo. Collectively, our study demonstrates that high-dose MK treatment initiates TIF by activating HIF-1α-KLF5-TGF-ß1 signaling. These findings provide novel insights into TIF induction by high-dose MK (HIF-PHI), suggesting that the safety dosage window needs to be emphasized in future clinical applications.-Li, Z.-L., Lv, L.-L., Wang, B., Tang, T.-T., Feng, Y., Cao, J.-Y., Jiang, L.-Q., Sun, Y.-B., Liu, H., Zhang, X.-L., Ma, K.-L., Tang, R.-N., Liu, B.-C. The profibrotic effects of MK-8617 on tubulointerstitial fibrosis mediated by the KLF5 regulating pathway.

Predictive value of procalcitonin for infection of patients with type-2 diabetes mellitus.

The aim of the present study was to investigate the predictive value of procalcitonin (PCT) for infection in patients with type 2 diabetes mellitus (T2DM). A retrospective analysis of 178 patients with T2DM who were divided into non-infection, local infection and sepsis groups was conducted; in conjunction with 33 healthy control patients. Clinicopathological characteristics and inflammatory indicators were compared between the four groups. Patients in the non-infection group exhibited significantly higher PCT levels compared with healthy controls (P=0.002). In addition, PCT, C-reactive protein (CRP), white blood cell count and neutrophil percent were significantly different amongst patients with T2MD across different infection groups (all P<0.001) with the following rank order: Sepsis group > local infection group > non-infection group (all P<0.05). In addition, the following observations were made: i) PCT and CRP demonstrated larger areas under the curve (AUC) for predicting local infection (0.804 and 0.741, respectively); ii) PCT displayed lower sensitivity of only 21.8% at its classical cutoff value (0.500 ng/ml) whereas CRP exhibited higher sensitivity and specificity at 64.1 and 76.1%, respectively, at its classical cutoff value (10.0 mg/l); and iii) PCT exhibited the largest AUC (0.914) for predicting sepsis with high sensitivity and specificity (86.4 and 84.5%, respectively) at its cutoff value (0.990 ng/ml). Patients with T2DM without infection demonstrated higher baseline PCT levels. The present study clarified the value of PCT in predicting infection of T2DM patients. The application of PCT to predict local infection in patients with T2DM was identified to be inferior to CRP, but its ability to predict sepsis was concluded to be the best when compared with CRP, white blood cell count and neutrophil percent.

Biomarkers and risk factors for sepsis in stage 5 chronic kidney disease: a retrospective case-control study.

PURPOSE: To assess the predictive value of procalcitonin (PCT) in the risk of sepsis in patients with stage 5 chronic kidney disease (CKD). METHODS: A total of 373 inpatients with stage 5 CKD were retrospectively analyzed. The patients were divided into non-infection group, local infection group, and sepsis group. The clinical characteristics and inflammatory parameters including PCT, C-reactive protein (CRP), white blood cell count (WBC), and neutrophil percentage (NEU%) were compared and the receiver operating characteristic (ROC) curves to predict sepsis were plotted. Related risk factors of sepsis were analyzed by logistic regression analysis. RESULTS: (1) The hemodialysis ratio of sepsis group was the highest at 92.3%. PCT, CRP, and NEU% were significantly different among the three subgroups (P < 0.05 for all). Total cholesterol and low density lipoprotein (LDL) levels in sepsis group were significantly lower than that in local infection group (P < 0.05 for both). (2) CRP and WBC were unable to predict sepsis (P > 0.05 for all), while PCT and NEU% could predict sepsis with areas under the curve (AUC) of 0.838 and 0.691, respectively (P < 0.05 for all). (3) Multivariate logistic regression analysis showed that PCT > 1.650 ng/mL was a risk factor (OR = 6.926, P = 0.002) while LDL was probably a protective factor (OR = 0.336, P = 0.040) of sepsis in patients with stage 5 CKD. CONCLUSIONS: At stage 5 CKD, the predictive value of PCT for sepsis is best among inflammatory markers, and PCT and LDL levels are independent factors of sepsis.

Assessing the influence of acute kidney injury on the mortality in patients with acute myocardial infarction: a clinical trail.

OBJECTIVES: Acute kidney injury (AKI) increases the risk of death following acute myocardial infarction (AMI). In this current study, we tried to understand the role of newly KDIGO defined AKI in AMI-induced early and late mortality. METHODS: We retrospectively analyzed the clinical data of AMI patients (totaling 1371 cases) from the hospital's computer database. And AKI was defined based on the KDIGO criteria but GFR or urinary output assessment was not used. Subsequently, we compared the association of AKI with 30-day and 30-day to 5-year all-cause mortality, using multivariate COX regression analysis with two models. RESULTS: We observed the development of AKI in 410 (29.9%) patients during the hospital stay. The 30-day and 30-day to 5-year mortality rates were 5.6% and 11.3%, respectively, in 1371 AMI patients. Further, adjusted Cox regression analysis based on model 1 revealed that AKI severity was an independent risk factor of 30-day mortality, while AKI Stage 3 was an independent predictor of 30-day to 5-year mortality. Adjusted Cox regression analysis based on model 2 revealed that normal baseline renal function with AKI and impaired renal function with AKI were independent risk factors of 30-day mortality, while normal baseline renal function with AKI and impaired renal function with AKI were identified to be independent predictors of 30-day to 5-year mortality. CONCLUSIONS: Whether the baseline renal function decreased or not, AKI strongly correlated with short- and long-term all-cause mortality in patients with AMI. Specifically, the short-term mortality of AMI patients increased with more severe AKI.

Predictive value of procalcitonin for diagnosis of infections in patients with chronic kidney disease: a comparison with traditional inflammatory markers C-reactive protein, white blood cell count, and neutrophil percentage.

PURPOSE: To investigate the predictive value of procalcitonin (PCT) in patients with stage 1-4 and stage 5 chronic kidney disease (CKD). METHODS: Five hundred and forty-one CKD inpatients were retrospectively analyzed and divided into CKD stage 1-4 (CKD1-4) and CKD stage 5 (CKD5) groups. Each group was further divided into non-infection, local infection, and sepsis subgroups. The clinical characteristics and inflammatory indexes of each subgroup including PCT, C-reactive protein (CRP), white blood cell count (WBC), and neutrophil percentage (N%) were compared, and the receiver operating characteristic curves to predict local infection and sepsis were plotted. RESULTS: Our research showed that the incidence and severity of infection in CKD5 group were significantly higher than those of CKD1-4 group; the baseline PCT level in CKD patients increased as renal function decreased and strongly correlated with CKD staging (r = 0.749); for CKD1-4 group, PCT, WBC, and N% could predict sepsis with the area under the curve (AUC) of 0.956, 0.854, and 0.917, respectively, but only CRP could predict local infection with AUC of 0.729, and for CKD5 group, only PCT and CRP could predict local infection with AUC of 0.715 and 0.780, respectively, and only PCT and N% could predict sepsis with AUC of 0.823 and 0.683, respectively. CONCLUSIONS: The baseline PCT level of CKD patients is negatively correlated with renal function. In both CKD1-4 and CKD5 patients, the predictive value of PCT for local infection is not as good as that of CRP, while it has a significant advantage in predicting sepsis.

Risk factors of acute kidney injury after acute myocardial infarction.

OBJECTIVES: To study the risk factors for acute kidney injury (AKI) in-patients with acute myocardial infarction (AMI). METHODS: A total of 1371 cases of adult in-patients with AMI in the First People's Hospital of Changzhou from January 2008 to December 2012 were retrospectively analyzed. Based on the occurrence of AKI diagnosed according to the 2012 KDIGO AKI criteria, they were divided into AKI group and non-AKI group and further into conservative treatment groups, coronary angiography (CAG) groups, and coronary artery bypass grafting (CABG) groups based on the timing of AKI occurrence, respectively. Related risk factors of AKI were analyzed by univariate and multivariate logistic regressions. RESULTS: 410 (29.9%) developed AKI. Patients with AKI had significantly increased in-hospital mortality than patients without AKI. Multivariate logistic regression analysis showed that decreased baseline eGFR, increased fasting plasma glucose (FPG), use of diuretics and Killip grade IV were independent risk factors of AKI, while increased DBP on admission was a protective factor for patients in conservative treatment group. Decreased baseline eGFR, increased FPG, use of diuretics, intraoperative hypotension and acute infection were independent risk factors of AKI for patients in the CAG group. Decreased baseline eGFR, increased FPG, use of diuretics and low cardiac output syndrome after operation were independent risk factors of AKI for patients in the CABG group. CONCLUSIONS: AKI is a common complication and associated with increased mortality after AMI. Decreased baseline renal function, increased FPG and use of diuretics were common independent risk factors of AKI after AMI.

Quality of life in peritoneal and hemodialysis patients in China.

BACKGROUND: Much attention has been paid to the quality of life (QOL) in dialysis patients worldwide. However, differences in QOL between peritoneal dialysis (PD) and hemodialysis (HD) patients have not been clearly identified. The objectives of this study were to compare the differences of QOL between PD and HD patients, and to investigate factors contributing to QOL in the Chinese population. METHODS: All patients who received PD or HD more than 3 months were enrolled in the study. The demographic and clinical data were also obtained. SF-36 was used to assess QOL. RESULTS: A total of 190 (91.8%) of 207 dialysis patients were enrolled in the study. PD patients had markedly lower scores on role-physical (RP) and bodily pain (BP) domains than HD patients, but had remarkably higher scores on role-emotional (RE) domain (p < 0.05). While the scores of physical component summary (PCS) and mental component summary (MCS) showed no differences between the two groups (p > 0.05). The results of the multiple linear regression analysis indicated that age and cerebrovascular disease had negative correlations with PCS (p < 0.01), whereas the serum prealbumin level had positive correlation with PCS (p < 0.05). The married status was negatively associated with MCS (p < 0.01). But the higher education level was positively associated with MCS (p < 0.01). CONCLUSIONS: There were no significant differences on QOL between the two dialysis modalities. The possible factors related to QOL were age, cerebrovascular disease, marital status, education, and serum prealbumin levels.