angiotensinogen and Acute-Disease

A major challenge in early treatment of acute cardiorenal syndrome (CRS) is the lack of predictors for progression of AKI. We aim to investigate the utility of urinary angiotensinogen and other renal injury biomarkers in predicting AKI progression in CRS.. In this prospective, multicenter study, we screened 732 adults who admitted for acute decompensated heart failure from September 2011 to December 2014, and evaluated whether renal injury biomarkers measured at time of AKI diagnosis can predict worsening of AKI. In 213 patients who developed Kidney Disease Improving Global Outcomes stage 1 or 2 AKI, six renal injury biomarkers, including urinary angiotensinogen (uAGT), urinary neutrophil gelatinase-associated lipocalin (uNGAL), plasma neutrophil gelatinase-associated lipocalin, urinary IL-18 (uIL-18), urinary kidney injury molecule-1, and urinary albumin-to-creatinine ratio, were measured at time of AKI diagnosis. The primary outcome was AKI progression defined by worsening of AKI stage (50 patients). The secondary outcome was AKI progression with subsequent death (18 patients).. After multivariable adjustment, the highest tertile of three urinary biomarkers remained associated with AKI progression compared with the lowest tertile: uAGT (odds ratio [OR], 10.8; 95% confidence interval [95% CI], 3.4 to 34.7), uNGAL (OR, 4.7; 95% CI, 1.7 to 13.4), and uIL-18 (OR, 3.6; 95% CI, 1.4 to 9.5). uAGT was the best predictor for both primary and secondary outcomes with area under the receiver operating curve of 0.78 and 0.85. These three biomarkers improved risk reclassification compared with the clinical model alone, with uAGT performing the best (category-free net reclassification improvement for primary and secondary outcomes of 0.76 [95% CI, 0.46 to 1.06] and 0.93 [95% CI, 0.50 to 1.36]; P<0.001). Excellent performance of uAGT was further confirmed with bootstrap internal validation.. uAGT, uNGAL, and uIL-18 measured at time of AKI diagnosis improved risk stratification and identified CRS patients at highest risk of adverse outcomes.

Topics: Acute Disease; Acute Kidney Injury; Aged; Aged, 80 and over; Albuminuria; Angiotensinogen; Biomarkers; Cardio-Renal Syndrome; Creatinine; Disease Progression; Female; Hepatitis A Virus Cellular Receptor 1; Humans; Interleukin-18; Lipocalin-2; Male; Middle Aged; Prospective Studies; Risk Assessment; Time Factors

Although several risk factors for acute kidney injury (AKI) have been identified, early detection of AKI in acute decompensated heart failure patients remains a challenge. The aim of this study was to develop and validate a risk score for early prediction of AKI in acute decompensated heart failure patients.. A total of 676 consecutive acute decompensated heart failure participants were prospectively enrolled from 6 regional central hospitals. Data from 507 participants were analyzed. Participants from 4 of the 6 hospitals (n=321) were used to develop a risk score and conduct internal validation. External validation of the developed risk score was conducted in participants from the other 2 hospitals (n=186). Sequential logistic regression was used to develop and validate the risk score. The c statistic and calibration plot were used to assess the discrimination and calibration of the proposed risk score. The overall occurrence of AKI was 33.1% (168/507). The risk score, ranging from 0 to 55, demonstrated good discriminative power with an optimism-corrected c statistic of 0.859. Similar results were obtained from external validation with c statistic of 0.847 (95% CI 0.819-0.927). The risk score had good calibration with no apparent over- or under-prediction observed from calibration plots.. The novel risk score is a simple and accurate tool that can help clinicians assess the risk of AKI in acute decompensated heart failure patients, which in turn helps them plan and initiate the most appropriate disease management for patients in time.

Topics: Acute Disease; Acute Kidney Injury; Aged; Aged, 80 and over; Angiotensinogen; Cardio-Renal Syndrome; China; Cohort Studies; Female; Heart Failure; Humans; Lipocalin-2; Logistic Models; Male; Middle Aged; Prospective Studies; Renal Insufficiency, Chronic; Reproducibility of Results; Risk Assessment; Risk Factors

Acute (AMS) and chronic (CMS) mountain sicknesses are illnesses that occur among humans visiting or inhabiting high-altitude environments, respectively. Some individuals are genetically less fit than others when stressed by an extreme high-altitude environment. Seven blood physiological parameters and five genetic polymorphisms were studied in Han patients with AMS and Tibetan patients with CMS.. We compared 98 AMS patients with 60 Han controls as well as 50 CMS patients with 36 Tibetan controls. The genetic loci studied are ACE I/D (rs4340), AGT M235T (rs699), AGTR1 A1166C (rs5186), GNB3 A(-350)G (rs2071057) and APOB A/G (rs693).. All physiological parameters (RBC, HCT, Hb, SaO(2), HR, and BPs/d) studied significantly changed in the CMS patients while SaO(2) and HR changed in the AMS Han patients compared to their controls. The ACE D and AGT 235M alleles were found to be significantly associated with AMS and CMS, respectively, while a significantly high incidence of the G-protein (GNB3) (-350)A allele was found in the AMS patients. ACE (I/D) was significantly associated with HR in CMS patients while the AGT M235T was significantly associated with SaO(2) and BPs/d in AMS patients. APOB A/G was significantly associated with BPs/d in AMS and HR in CMS patients.. AMS and CMS share very similar genetic results for the ACE I/D and AGT M235T polymorphisms indicating that these mutations have an effect on both illnesses.

Topics: Acute Disease; Altitude; Altitude Sickness; Angiotensinogen; China; Chronic Disease; Genome-Wide Association Study; Geography; Hematologic Tests; Humans; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Tibet

Maternal spiral artery remodeling is the consequence of controlled trophoblast invasive interaction with the maternal cellular environment and is fundamentally important for successful placentation. In preeclampsia, trophoblast invasion is shallow, remodeling is incomplete, and vessels develop an inflammatory appearance, termed "acute atherosis." We noted that, in our preeclampsia, human renin-human angiotensinogen transgenic rat model, complement component 3 (C3), and tumor necrosis factor-alpha were upregulated and heavily expressed in atherotic uteroplacental vessels. We next used coculture involving human trophoblasts, rat vascular smooth muscle cells (VSMCs), and human VSMCs to observe VSMC-trophoblast regulatory interactions. Tumor necrosis factor-alpha induced complement C3 and interleukin-6 expression in VSMCs. We found that trophoblasts were able to reduce VSMC C3 and interleukin-6 expression after the VSMCs were stimulated with tumor necrosis factor-alpha. However, a direct VSMC-trophoblast cell-cell contact was necessary for this anti-inflammatory response. We also studied double-transgenic VSMCs that express inflammatory components and exhibit accelerated proliferation ("synthetic" phenotype). Trophoblasts could not downregulate C3 in these cells. We then examined uteroplacental tissues from preeclamptic and control patients. In control deciduas, only traces of C3 staining were observed, and vessels were thin walled without thrombus formation. In preeclampsia, the decidual vessels showed atherosis, thrombus formation, and C3 expression. Our data suggest that fetally derived trophoblasts require direct cell-cell contact with maternally derived VSMCs to downregulate VSMC C3 and interleukin-6 expression and to avoid atherosis. The findings also implicate C3 in the placental vasculopathy observed in preeclampsia.

Topics: Acute Disease; Angiotensinogen; Animals; Animals, Genetically Modified; Atherosclerosis; Cell Communication; Cells, Cultured; Chorionic Villi; Coculture Techniques; Complement C3; Decidua; Female; Humans; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Pre-Eclampsia; Pregnancy; Rats; Rats, Sprague-Dawley; Renin; Thrombosis; Trophoblasts

Angiotensin II (Ang II) mediates the up-regulation of fibrogenic factors such as transforming growth factor-beta1 (TGF-beta1) in chronic renal diseases. In addition, it has been proposed that the intrarenal renin-angiotensin system (RAS) is as important as the systemic RAS in kidney disease progression.. We suppressed angiotensinogen (AGT) gene expression in the kidney by transferring recombinant adenoviral vectors carrying a transgene expressing AGT antisense mRNA, and determined the effect of the local inhibition of the RAS on TGF-beta1 synthesis in the kidneys of rats with unilateral ureteral obstruction (UUO). Immediately after UUO, recombinant adenovirus vectors were injected intraparenchymally into the cortex of obstructed kidneys.. beta-galactosidase (beta-gal)-stained kidney sections revealed the efficient transduction of the recombinant adenoviral vectors into tubular epithelial cells. Kidney cortex injected with AGT antisense showed significantly lower native AGT mRNA and protein expressions than control UUO kidneys at 24 hours and 5 days post-UUO. TGF-beta1 was significantly up-regulated in the renal cortex 24 hours and 5 days post-UUO, whereas AGT antisense-injected UUO rats showed significantly reduced TGF-beta1 expression compared to control UUO rats. Both fibronectin and collagen type I expressions were increased 24 hours and 5 days post-UUO, and these augmentations were considerably reduced by AGT antisense RNA treatment.. This study demonstrates that the suppression of intrarenal RAS prevents the formation of renal cortical TGF-beta1, and of related fibrogenic factors, in early UUO.

Topics: Acute Disease; Angiotensinogen; Animals; Base Sequence; Collagen Type I; Fibronectins; Kidney; Male; Molecular Sequence Data; Rats; Rats, Wistar; Renin-Angiotensin System; RNA, Antisense; Transforming Growth Factor beta; Transforming Growth Factor beta1; Ureteral Obstruction

Our previous studies have provided evidence for the existence of an intrinsic renin-angiotensin system (RAS) in the rat pancreas, which may play a role in the regulation of pancreatic microcirculation and ductal secretion. Such a pancreatic RAS has recently shown to be activated by chronic hypoxia. The activation of a local RAS in the pancreas by chronic hypoxia and its significance of changes may be important for the physiological and pathophysiological aspects of the pancreas. In the present study, the regulation of experimentally induced acute pancreatitis on the expression of local RAS in the pancreas was investigated using Western blot, semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical approaches. Results from Western blot demonstrated that experimentally induced pancreatitis caused significantly increased expression of the pancreatic RAS component proteins. In keeping with the protein level, RT-PCR analysis also revealed the enhanced expression of pancreatic RAS genes, notably the angiotensinogen in experimental pancreatitis. Immunohistochemical results further demonstrated that increased immunoreactivity for RAS in experimental pancreatitis was predominantly localized to the endothelia and epithelia of pancreatic vasculature and ductal system respectively. The data indicate that experimental pancreatitis may elicit activation of a local RAS in the pancreas. Such an activation of pancreatic RAS and its significance of differential changes in individual RAS components could play a role in the pathophysiology of acute pancreatitis

Topics: Acute Disease; Angiotensinogen; Animals; Blotting, Western; Gene Expression Regulation; Immunohistochemistry; Pancreas; Pancreatitis; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptors, Angiotensin; Renin-Angiotensin System; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Plasma concentration and urine excretion of the renin-angiotensin system proteins are altered in rats with nephrotic syndrome (NS). In this work the messenger ribonucleic acid (mRNA) levels of angiotensinogen (Ao) were analyzed with the slot-blot hybridization technique in liver and other extrahepatic tissues: kidney, heart, brain, and adrenal gland from control, nephrotic, and pair-fed (PF) rats. NS was induced by a single injection of puromycin amino-nucleoside (PAN). Although a great urinary excretion and half-normal plasma levels of Ao were observed on day 6 after PAN injection, when NS was clearly established, hepatic Ao mRNA levels did not change. Furthermore, the Ao mRNA levels did not change in any of the extrahepatic tissues studied on day 6, nor did its hepatic levels at days 1, 3, 5, or 7 after PAN injection. These data suggest that the hepatic and extrahepatic Ao mRNA levels are unaltered during the development of the acute NS induced by PAN.

Topics: Acute Disease; Adrenal Glands; Angiotensinogen; Animals; Brain; Gene Expression; Kidney; Liver; Male; Myocardium; Nephrotic Syndrome; Nucleic Acid Hybridization; Puromycin Aminonucleoside; Rats; Rats, Wistar; RNA, Messenger; Tissue Distribution

Angiotensinogen is the precursor of biologically active peptide angiotensin II and its hepatic synthesis is increased by the induction of acute inflammation. Studies were carried out to know whether the rise in plasma angiotensinogen is actually involved in the activity of the renin-angiotensin system during acute inflammation. The plasma level of angiotensinogen in rats was increased to 2.5 times the normal level 16 h after the induction of acute inflammation by administration of lipopolysaccharide (LPS). The plasma renin concentration (PRC) was decreased to about 40% of the normal level concomitantly with a reduction of plasma renin activity (PRA) at 4 h after LPS administration. In contrast, 16 h after LPS injection, when plasma angiotensinogen showed a high level and PRC had recovered to the normal range, PRA was increased to 1.7 times the normal level. These results indicate that acute inflammation induced by LPS causes a biphasic change in the generation of angiotensin I, i.e., an early decrease depending upon the reduction of PRC and later increase depending upon elevation of the angiotensinogen concentration.

Topics: Acute Disease; Angiotensin I; Angiotensinogen; Animals; Inflammation; Lipopolysaccharides; Male; Rats; Rats, Inbred F344; Renin; Renin-Angiotensin System

Accumulating information concerning the structure of angiotensinogen suggests a resemblance of this component of the renin-angiotensin system to the acute-phase protein alpha 1-antitrypsin. Compared to a group of age- and sex-matched controls without signs of infection, markedly elevated levels of angiotensinogen (increase in median value: 70%), alpha 1-antitrypsin (102%), caeruloplasmin (76%), haptoglobin (261%), and orosomucoid (162%) were found in plasma from 14 patients with acute inflammatory disease. This finding indicates that angiotensinogen should be included in the list of acute-phase proteins in man, and raises the question whether angiotensinogen is involved in the regulation of the renin-angiotensin system during inflammation and tissue injury.

Topics: Acute Disease; Adolescent; Adult; Aged; alpha 1-Antitrypsin; Angiotensinogen; Female; Humans; Inflammation; Male; Middle Aged