scholarly journals Plasma Lipopolysaccharide Concentrations in Cardiorenal Syndrome Type 1

2019 ◽  
Vol 9 (5) ◽  
pp. 308-315
Author(s):  
Grazia Maria Virzì ◽  
Andrea Breglia ◽  
Ghada Ankawi ◽  
Chiara Bolin ◽  
Massimo de Cal ◽  
...  

Background: Cardiorenal syndrome (CRS) type 1 is characterized by a rapid worsening of cardiac function that leads to acute kidney injury (AKI). This study evaluated the role of lipopolysaccharide (LPS) in the development of AKI in patients with acute heart failure (AHF) and its relationship with renal parameters, to enable a better comprehension of the pathophysiology of CRS type 1. Methods: We enrolled 32 AHF patients, 15 of whom were classified as having CRS type 1. Eight of these 15 exhibited AKI at the time of admission (caused by AHF) and the other 7 developed AKI during their stay in hospital (in the first 48 h). We evaluated the plasmatic LPS concentrations as well as conventional (serum creatinine [sCr] and urea) and unconventional (neutrophil gelatinase-associated lipocalin [NGAL] and cystatin C) renal markers. Results: LPS levels were significantly higher in the CRS type 1 patients. No significant difference in LPS level was found in patients who were admitted with AKI and those developed AKI in hospital, but there was a tendency towards a higher level of LPS in CRS type 1 patients admitted with AKI. The LPS concentrations at admission were similar in CRS type 1 survivors (n = 12) and nonsurvivors (n = 3) (p = 0.22). We observed a positive correlation between LPS level and NGAL, Scr at admission and peak Scr during hospitalization and urea at admission. Conclusion: CRS type 1 patients present with an increased level of LPS and there is a direct correlation between LPS and renal parameters. This pilot research is the first study to explore the premise of LPS as novel pathophysiological factor in CRS type 1.

2021 ◽  
pp. 1-11
Author(s):  
Katrien Leyssens ◽  
Niels Van Regenmortel ◽  
Ella Roelant ◽  
Khadija Guerti ◽  
Marie Madeleine Couttenye ◽  
...  

<b><i>Introduction:</i></b> Acute kidney injury (AKI) is a frequent complication among patients in the intensive care unit (ICU). The limitations of serum Cr (sCr) in timely detecting AKI are well known. Beta-trace protein (BTP) is emerging as a novel endogenous glomerular filtration rate marker. The aim of this study was to explore the role of BTP as a marker of AKI. <b><i>Methods:</i></b> Patients admitted to the ICU undergoing surgery were included. BTP, sCr, Cystatin C (CysC), and neutrophil gelatinase-associated lipocalin (NGAL) were measured preoperatively, postoperatively (post-op), and at the first (D1) and second (D2) post-op day. AKI was defined as an increase of sCr to ≥1.5-fold from baseline within 2 days after surgery. <b><i>Results:</i></b> Of the 52 patients studied, 10 patients (19%) developed AKI. Patients with AKI were older (69.6 ± 10.7 vs. 58.1 ± 16.7 years, <i>p</i> = 0.043) and had a longer length of ICU stay (13 [IQR 6–49] vs. 6 [IQR 5–8] days, <i>p</i> = 0.032). Between the 2 groups, the evolution of BTP, sCr, CysC, and NGAL over time differed significantly, with overall higher values in the AKI group. ROC analysis for the detection of AKI within 2 days after surgery showed a great accuracy for BTP. The area under the curve (AUC) for BTP post-op; D1; and D2 was, respectively, 0.869 ± 0.049; 0.938 ± 0.035; and 0.943 ± 0.032. The discriminative power of a BTP measurement on D1 was superior in detecting AKI compared to NGAL (adjusted <i>p</i> value = 0.027). We could not detect a significant difference between the AUCs of other biomarkers (NGAL, sCr, and CysC). <b><i>Conclusion:</i></b> Serum BTP is a promising marker for diagnosing AKI in ICU patients undergoing surgery.


2021 ◽  
pp. 1-8
Author(s):  
Grazia Maria Virzì ◽  
Anna Clementi ◽  
Sabrina Milan Manani ◽  
Chiara Castellani ◽  
Giovanni Giorgio Battaglia ◽  
...  

<b><i>Background:</i></b> Recent research highlighted the potential role of circulating cell-free DNA (cfDNA), resulted by apoptosis or cell necrosis, as a prognostic marker in the setting of different clinical conditions. Cardiorenal syndrome type 1 (CRS type 1) is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Apoptosis of renal epithelial cells is proposed as a mechanism involved in CRS type 1. In this study, we investigated cfDNA levels in patients with acute heart failure (AHF) and CRS type 1 and the possible correlation between cfDNA levels and inflammatory and apoptotic parameters. <b><i>Methods:</i></b> We enrolled 17 AHF patients and 15 CRS type 1 who exhibited AKI at the time of admission (caused by AHF) or developed AKI during the first 48 h from admission. cfDNA was extracted from plasma and quantified by real-time polymerase chain reaction. Plasma levels of NGAL, tumor necrosis factor-α, interleukin (IL)-6, IL-18, and caspase-3 were measured. <b><i>Results:</i></b> We observed significantly higher levels of cfDNA in patients with CRS type 1 than patients with AHF. Caspase-3, IL-6, IL-18, and NGAL levels resulted significantly increased in patients with CRS type 1. Moreover, a positive correlation between cfDNA levels and caspase-3 levels was found, as well as between cfDNA levels and IL-6 and renal parameters. <b><i>Conclusion:</i></b> Our study explores the premise of cfDNA as a marker for apoptosis and inflammation in CRS type 1 patients. cfDNA could potentially serve as an index for noninvasive monitoring of tissue damage and apoptosis in patients with AKI induced by AHF.


2015 ◽  
Vol 6 (1) ◽  
pp. 61-72 ◽  
Author(s):  
Annalisa Angelini ◽  
Chiara Castellani ◽  
Grazia Maria Virzì ◽  
Marny Fedrigo ◽  
Gaetano Thiene ◽  
...  

Background: In cardiorenal syndrome type 2 (CRS2), the role of systemic congestion in heart failure (HF) is still obscure. We studied a model of CRS2 [monocrotaline (MCT)-treated rats] secondary to pulmonary hypertension and right ventricular (RV) failure in order to evaluate the contribution of prevalent congestion to the development of kidney injury. Methods: Ten animals were treated with MCT for 4 weeks until they developed HF. Eleven animals were taken as controls. Signs of hypertrophy and dilatation of the right ventricle demonstrated the occurrence of HF. Brain natriuretic peptide (BNP), serum creatinine (sCreatinine), both kidney and heart neutrophil gelatinase-associated lipocalin (NGAL), matrix metallopeptidase 9 (MMP9), serum cytokines as well as kidney and heart cell death, as assessed by TUNEL, were studied. Results: Rats with HF showed higher BNP levels [chronic HF (CHF) 4.8 ± 0.5 ng/ml; controls 1.5 ± 0.2 ng/ml; p < 0.0001], marked RV hypertrophy and dilatation (RV mass/RV volume: CHF 1.46 ± 0.31, controls 2.41 ± 0.81; p < 0.01) as well as pleural and peritoneal effusions. A significant increase in proinflammatory cytokines and sCreatinine was observed (CHF 3.06 ± 1.3 pg/ml vs. controls 0.54 ± 0.23 pg/ml; p = 0.04). Serum (CHF 562.7 ± 93.34 ng/ml vs. controls 245.3 ± 58.19 ng/ml; p = 0.02) as well as renal and heart tissue NGAL levels [CHF 70,680 ± 4,337 arbitrary units (AU) vs. controls 32,120 ± 4,961 AU; p = 0.001] rose significantly, and they were found to be complexed with MMP9 in CHF rats. A higher number of kidney TUNEL-positive tubular cells was also detected (CHF 114.01 ± 45.93 vs. controls 16.36 ± 11.60 cells/mm2; p = 0.0004). Conclusion: In this model of CHF with prevalent congestion, kidney injury is characterized by tubular damage and systemic inflammation. The upregulated NGAL complexed with MMP9 perpetuates the vicious circle of kidney/heart damage by enhancing the enzymatic activity of MMP9 with extracellular matrix degradation, worsening heart remodeling.


2019 ◽  
Vol 4 (1) ◽  
pp. 208-214
Author(s):  
Adem Atici ◽  
Samim Emet ◽  
Ilkim Deniz Toprak ◽  
Ramazan Cakmak ◽  
Murat Akarsu ◽  
...  

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Hao T Phan

Introduction: The presence of acute kidney injury in the setting of acute heart failure is very common occurrence and was termed cardiorenal syndrome 1 (CRS1). In CRS1 the diagnosis of acute kidney damage is often delayed by creatinine and urine output following KDIGO standards (Kidney Disease Improving Global Outcomes). Neutrophil gelatinase-associated lipocalin (NGAL) in the blood and urine is one of the earliest markers of acute kidney damage due to anemia or nephrotoxicity. Hypothesis: Plasma NGAL has good value in the diagnosis of cardiorenal syndrome type 1. Methods: There were 139 patients with acute heart failure or acute decompensated heart failure (ADHF) in the Department of cardiovascular resuscitation and Interventional cardiology at our hospital from September 2018 to June 2019. This is a prospective cohort study Results: There were 48 cases (rate 34.5%) with CRS1, medium age 66.12 ± 15.77, men accounted for 50.4%. The optimal cut-off for diagnosing NGAL CRS1 is > 353.23 ng/ml, AUC is 0.732 (95% CI 0.65-0.80, p <0.001), sensitivity 74.47%, specificity 68.48%, positive predictive value 54.7%, negative predictive value 84%. Building the optimal regression model by the BMA (Bayesian Model Average) method with 2 variables NGAL and creatinin day 1: Odds Ratio= e^y while y = - 2.39 + 0.0037 x NGAL + 0.17 x CreatininD1. Moreover, a nomogram with 2 variables NGAL and creatinin day 1 was designed to predict the likelihood of CRS1 with AUC 0.79 and validated on a testing set (consiting of 40 % of the data) by 10-cross-validation method with accuracy 79.82%. Ultimately, a confusion matrix was constructed to determine model accuracy 75.93%, sensitivity 76.74%, specificity 72.73%, positive predictive value 91.67%, negative predictive value 44.44%. Conclusions: Plasma NGAL is quite good value in the diagnosis of CRS1 in patients with acute heart failure or ADHF. A predictive model based on NGAL may help early diagnose CRS1 in patients with acute heart failure or ADHF.


2021 ◽  
Vol 10 (11) ◽  
pp. 2353
Author(s):  
Joanna Bagińska ◽  
Agata Korzeniecka-Kozerska

The lack of early biomarkers of renal damage in children with neurogenic bladder (NB) prompts us to investigate the role of promising proteins: neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). This prospective analysis was conducted on 58 children with NB and 25 healthy children. We assessed urinary levels of NGAL and KIM-1 in both groups. Age, sex, anthropometric measurements, activity assessment, renal function, and urodynamics parameters were analyzed. The differences between the median uNGAL and uKIM-1 in the NB group compared to control were recorded. However, only uNGAL levels were statistically significantly higher. Statistically significant correlation was found between gender, recurrent urinary tract infections, bladder trabeculation, its compliance, activity assessment, and uNGAL. To conclude, elevated levels of uNGAL may be considered a biomarker of tubular injury in children with NB due to MMC in contrast to uKIM-1.


Critical Care ◽  
2014 ◽  
Vol 18 (Suppl 1) ◽  
pp. P364
Author(s):  
W Vandenberghe ◽  
S Gevaert ◽  
H Peperstraete ◽  
I Herck ◽  
J Decruyenaere ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Grazia Maria Virzì ◽  
Anna Clementi ◽  
Massimo de Cal ◽  
Alessandra Brocca ◽  
Sonya Day ◽  
...  

Cardiorenal Syndrome Type 1 (Type 1) is a specific condition which is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Even though its pathophysiology is complex and not still completely understood, oxidative stress seems to play a pivotal role. In this study, we examined the putative role of oxidative stress in the pathogenesis of CRS Type 1. Twenty-three patients with acute heart failure (AHF) were included in the study. Subsequently, 11 patients who developed AKI due to AHF were classified as CRS Type 1. Quantitative determinations for IL-6, myeloperoxidase (MPO), nitric oxide (NO), copper/zinc superoxide dismutase (Cu/ZnSOD), and endogenous peroxidase activity (EPA) were performed. CRS Type 1 patients displayed significant augmentation in circulating ROS and RNS, as well as expression of IL-6. Quantitative analysis of all oxidative stress markers showed significantly lower oxidative stress levels in controls and AHF compared to CRS Type 1 patients (P<0.05). This pilot study demonstrates the significantly heightened presence of dual oxidative stress pathway induction in CRS Type 1 compared to AHF patients. Our findings indicate that oxidative stress is a potential therapeutic target, as it promotes inflammation by ROS/RNS-linked pathogenesis.


2018 ◽  
Vol 8 (3) ◽  
pp. 208-216 ◽  
Author(s):  
Andrea Breglia ◽  
Grazia Maria Virzì ◽  
Silvia Pastori ◽  
Alessandra Brocca ◽  
Massimo de Cal ◽  
...  

Background: Cardiorenal syndrome type 1 (CRS type 1) is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Its pathophysiology is complex and not completely understood. In this study, we examined the role of apoptosis and the caspase pathways involved. Material and Methods: We enrolled 40 acute heart failure (AHF) patients, 11 of whom developed AKI characterizing CRS type 1. We exposed the human cell line U937 to plasma from the CRS type 1 and AHF groups and then we evaluated apoptotic activity by annexin-V evaluation, determination of caspase-3, -8 and -9 levels, and BAX, BAD, and FAS gene expression. Results: We observed significant upregulation of apoptosis in monocytes exposed to CRS type 1 plasma compared to AHF, with increased levels of caspase-3 (p < 0.01), caspase-9 (p < 0.01), and caspase-8 (p < 0.03) showing activation of both intrinsic and extrinsic pathways. Furthermore, monocytes exposed to CRS type 1 plasma had increased gene expression of BAX and BAD (intrinsic pathways) (p = 0.010 for both). Furthermore, strong significant correlations between the caspase-9 levels and BAD and BAX gene expression were observed (Spearman ρ = – 0.76, p = 0.011, and ρ = – 0.72, p = 0.011). Conclusion: CRS type 1 induces dual apoptotic pathway activation in monocytes; the two pathways converged on caspase-3. Many factors may induce activation of both intrinsic and extrinsic apoptotic pathways in CRS type 1 patients, such as upregulation of proinflammatory cytokines and hypoxia/ischemia. Further investigations are necessary to corroborate the present findings, and to better understand the pathophysiological mechanism and consequent therapeutic and prognostic implications for CRS type 1.


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