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NEAT1 functions as a key mediator of BMP2 to promote osteogenic differentiation of renal interstitial fibroblasts.
Zhu, Z, Zhang, X, Jiang, Y, Ruan, S, Huang, F, Zeng, H, Liu, M, Xia, W, Zeng, F, Chen, J, et al
Epigenomics. 2021;(15):1171-1186
Abstract
Aim: To clarify the mechanism of NEAT1, an aberrantly upregulated lncRNA in Randall's plaques (RP) similar to biomineralization, in mediating osteogenic differentiation of human renal interstitial fibroblasts. Materials & methods: A comprehensive strategy of bioinformatic analysis and experimental verification was performed. Results:BMP2 silence abolished the osteogenic differentiation of human renal interstitial fibroblasts promoted by NEAT1. Mechanically, NEAT1 not only induced the nucleolar translocation of EGR1 binding to BMP2 promotor, but also functioned as a sponge of miR-129-5p in the cytoplasm to promote BMP2 expression. Moreover, there was a positive correlation between NEAT1 and BMP2 expression in RP instead of normal renal papilla. Conclusion:NEAT1 acted as a key mediator of BMP2 to promote human renal interstitial fibroblast osteogenic differentiation, through which NEAT1 might be involved in RP formation.
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Prognostic of different glomerular filtration rate formulas in patients receiving percutaneous coronary intervention: insights from a multicenter observational cohort.
Chen, W, Chen, P, Ni, Z, Liu, Y, Guo, W, Jiang, L, Wei, X, Chen, J, Tan, N, He, P, et al
BMC cardiovascular disorders. 2020;(1):341
Abstract
BACKGROUND The relationships of renal dysfunction (RD) and chronic kidney disease (CKD) with prognosis have been well established among non-ST elevation acute coronary syndrome (NSTE-ACS) patients who receive percutaneous coronary intervention (PCI), but the efficacy of different estimated glomerular filtration rate (eGFR) formulas for predicting the prognosis is unknown. METHODS The cohort originated from a retrospective data, which consecutively enrolled 8197 patients. The eGFR was calculated by the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), CKD Epidemiology Collaboration-creatinine, CKD Epidemiology Collaboration-Cys-C, CKD Epidemiology Collaboration-Cys-C-creatinine and a modified abbreviated MDRD (c-aGFR) equations in Chinese CKD patients. Patients were excluded if the eGFR could not be obtained by one of the formulas. Patients were categorized as having normal renal function, mild RD, moderate RD, severe RD, or kidney failure to compare prognosis. The primary outcome was the in-hospital net adverse clinical events (NACE). The secondary outcomes were NACE and all-cause death during follow-up. RESULTS In total, 2159 NSTE-ACS patients (age: 64.23 ± 10.25 years; males: 73.7%) were enrolled. 39 (1.8%) patients with in-hospital NACE were observed. During the 3.23 ± 1.55-year follow-up, 1.7% death and 4.2% NACE were observed in 1 year. The percentage of severe RD patients ranged from 15.4 to 39.2% according to different calculation formulas. A high prevalence of in-hospital NACE was observed in the severe RD groups (ranging from 8 to 14.3% for different formulas). Multiple regression analysis showed that a high eGFR is a protect factor against NACE and all-cause death regardless of the formula use. Receiver operating characteristic curves showed similar predictive performance of the c-aGFR when compared to other formulas (in-hospital NACE AUC = 0.612, follow-up NACE AUC = 0.622, and follow-up death: AUC = 0.711). CONCLUSIONS Severe RD results in a high prevalence of in-hospital NACE in NSTE-ACS patients after PCI regardless of the formulas use. Different formulas have a similar ability to predict in-hospital and long-term prognosis in NSTE-ACS patients. The c-aGFR formula is the simplest and a more convenient formula for use in practice.
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Serum Metabolomic Alterations Associated with Proteinuria in CKD.
Luo, S, Coresh, J, Tin, A, Rebholz, CM, Appel, LJ, Chen, J, Vasan, RS, Anderson, AH, Feldman, HI, Kimmel, PL, et al
Clinical journal of the American Society of Nephrology : CJASN. 2019;(3):342-353
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Abstract
BACKGROUND AND OBJECTIVES Data are scarce on blood metabolite associations with proteinuria, a strong risk factor for adverse kidney outcomes. We sought to investigate associations of proteinuria with serum metabolites identified using untargeted profiling in populations with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Using stored serum samples from the African American Study of Kidney Disease and Hypertension (AASK; n=962) and the Modification of Diet in Renal Disease (MDRD) study (n=620), two rigorously conducted clinical trials with per-protocol measures of 24-hour proteinuria and GFR, we evaluated cross-sectional associations between urine protein-to-creatinine ratio and 637 known, nondrug metabolites, adjusting for key clinical covariables. Metabolites significantly associated with proteinuria were tested for associations with CKD progression. RESULTS In the AASK and the MDRD study, respectively, the median urine protein-to-creatinine ratio was 80 (interquartile range [IQR], 28-359) and 188 (IQR, 54-894) mg/g, mean age was 56 and 52 years, 39% and 38% were women, 100% and 7% were black, and median measured GFR was 48 (IQR, 35-57) and 28 (IQR, 18-39) ml/min per 1.73 m2. Linear regression identified 66 serum metabolites associated with proteinuria in one or both studies after Bonferroni correction (P<7.8×10-5), 58 of which were statistically significant in a meta-analysis (P<7.8×10-4). The metabolites with the lowest P values (P<10-27) were 4-hydroxychlorthalonil and 1,5-anhydroglucitol; all six quantified metabolites in the phosphatidylethanolamine pathway were also significant. Of the 58 metabolites associated with proteinuria, four were associated with ESKD in both the AASK and the MDRD study. CONCLUSIONS We identified 58 serum metabolites with cross-sectional associations with proteinuria, some of which were also associated with CKD progression. PODCAST This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_02_07_CJASNPodcast_19_03_.mp3.
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Potential effects of aggressive decongestion during the treatment of decompensated heart failure on renal function and survival.
Testani, JM, Chen, J, McCauley, BD, Kimmel, SE, Shannon, RP
Circulation. 2010;(3):265-72
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Abstract
BACKGROUND Overly aggressive diuresis leading to intravascular volume depletion has been proposed as a cause for worsening renal function during the treatment of decompensated heart failure. If diuresis occurs at a rate greater than extravascular fluid can refill the intravascular space, the concentration of such intravascular substances as hemoglobin and plasma proteins increases. We hypothesized that hemoconcentration would be associated with worsening renal function and possibly would provide insight into the relationship between aggressive decongestion and outcomes. METHODS AND RESULTS Subjects in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial limited data set with a baseline/discharge pair of hematocrit, albumin, or total protein values were included (336 patients). Baseline-to-discharge increases in these parameters were evaluated, and patients with >or=2 in the top tertile were considered to have evidence of hemoconcentration. The group experiencing hemoconcentration received higher doses of loop diuretics, lost more weight/fluid, and had greater reductions in filling pressures (P<0.05 for all). Hemoconcentration was strongly associated with worsening renal function (odds ratio, 5.3; P<0.001), whereas changes in right atrial pressure (P=0.36) and pulmonary capillary wedge pressure (P=0.53) were not. Patients with hemoconcentration had significantly lower 180-day mortality (hazard ratio, 0.31; P=0.013). This relationship persisted after adjustment for baseline characteristics (hazard ratio, 0.16; P=0.001). CONCLUSIONS Hemoconcentration is significantly associated with measures of aggressive fluid removal and deterioration in renal function. Despite this relationship, hemoconcentration is associated with substantially improved survival. These observations raise the question of whether aggressive decongestion, even in the setting of worsening renal function, can positively affect survival.