P6358Novel biomarkers for prediction of acute cardiorenal syndrome

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Dankova ◽  
Z Minarikova ◽  
J Danko ◽  
J Gergel ◽  
P Pontuch ◽  
...  
Keyword(s):  
Renal Injury ◽  
Diagnostic Yield ◽  
Kidney Injury ◽  
Cardiorenal Syndrome ◽  
Urine Concentration ◽  
Reduced Ejection Fraction ◽  
Frequent Event ◽  
Novel Biomarkers ◽  
New Biomarkers ◽  
Time Of Admission

Abstract Objectives Acute kidney injury (AKI) is frequent event in patients with acute heart failure (AHF) and is associated with poor short and longterm outcome. Aim of the study was to decribe diagnostic yield of selected novel biomarkers in prediction of AKI in patients addmitted for AHF. Methods We performed a prospective cohort study of 72 consecutive patients (46/26 M/F) aged 69±10,3 years admitted for AHF. Renal damage was defined according to KDIGO guidelines. Patients were divided into two groups: AKI- (without renal injury, n=52) and AKI+ (with renal injury, n=20). Urine samples for AKI biomarkers measurements (NGAL, TIMP2, IGFBP7) were collected at admission. The ROC and linear logistic regression of new biomarkers and selected clinical variables was performed for evaluation of the AKI prediction. Results Patients with AKI + were older (median age: 75 vs. 64 years, p=0,01), had lower BMI (median: 28 vs. 29,5 kg/m2, p=0,04), were with higher proportion of patients with HF with reduced ejection fraction (55% vs 23,1%, p=0,01) and higher level of serum NTproBNP. Urinary NGAL at admission was significantly higher in the AKI+ compared to AKI – group (152 vs. 19,5 ng/ml, p <.0001); also median of u-TIMP-2 and u-IGFBP-7 in the AKI+ patients were significantly higher: 194,1 versus 42,5 ng/ml (p<0.0001) and 379 versus 92,4 pg/ml (p<0.0001) resp. Age, u-NGAL, u-TIMP2, u-IGFBP7, s-hemoglobin, NTproBNP and LVEF were associated with the development of AKI. Urine concentration IGFBP-7 performs the best for the prediction AKI (AUC 0,94). Conclusion Urine concentrations of NGAL, TIMP2, IGFBP7 at the time of admission for AHF predict developement of AKI. Age, NTproBNP, LVEF and s-hemoglobin are also associated with AKI in AHF patients. Acknowledgement/Funding Project was supported by Slovak Society of Cardiology research grant 2015-2018.

scholarly journals Renalase and Biomarkers of Contrast-Induced Acute Kidney Injury

2015 ◽  
Vol 6 (1) ◽  
pp. 25-36 ◽  
Author(s):  
Maciej T. Wybraniec ◽  
Katarzyna Mizia-Stec
Keyword(s):  
Acute Kidney Injury ◽  
Renal Injury ◽  
Amine Oxidase ◽  
Kidney Injury ◽  
Cardiorenal Syndrome ◽  
Creatinine Concentration ◽  
Invasive Cardiology ◽  
Proximal Tubular ◽  
Novel Biomarkers

Background: Contrast-induced acute kidney injury (CI-AKI) remains one of the crucial issues related to the development of invasive cardiology. The massive use of contrast media exposes patients to a great risk of contrast-induced nephropathy and chronic kidney disease development, and increases morbidity and mortality rates. The serum creatinine concentration does not allow for a timely and accurate CI-AKI diagnosis; hence numerous other biomarkers of renal injury have been proposed. Renalase, a novel catecholamine-metabolizing amine oxidase, is synthesized mainly in proximal tubular cells and secreted into urine and blood. It is primarily engaged in the degradation of circulating catecholamines. Notwithstanding its key role in blood pressure regulation, renalase remains a potential CI-AKI biomarker, which was shown to be markedly downregulated in the aftermath of renal injury. In this sense, renalase appears to be the first CI-AKI marker revealing an actual loss of renal function and indicating disease severity. Summary: The purpose of this review is to summarize the contemporary knowledge about the application of novel biomarkers of CI-AKI and to highlight the potential role of renalase as a functional marker of contrast-induced renal injury. Key Messages: Renalase may constitute a missing biochemical link in the mutual interplay between kidney and cardiac pathology known as the cardiorenal syndrome.

scholarly journals SAT-LB303 Severe Refractory Volume Overload With Diazoxide in the Treatment of Insulinoma

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Pouneh Pasha ◽  
Graydon S Meneilly ◽  
Jordanna Esther Kapeluto
Keyword(s):  
Surgical Resection ◽  
Myocardial Infarct ◽  
Kidney Injury ◽  
Volume Overload ◽  
Cardiorenal Syndrome ◽  
Intermittent Hemodialysis ◽  
Close Monitoring ◽  
Clinical Pharmacokinetics ◽  
Reduced Ejection Fraction ◽  
Supportive Management

Abstract Background: Insulinoma is the most common neuroendocrine tumor (NET), occurring in 1-4 people per million. Surgical resection remains standard of care for symptomatic control and long-term remission. Where surgery is not feasible medical therapy with diazoxide and somatostatin analogues is used as supportive management. Case: A 88-year-old male with background hypertension, remote myocardial infarct and chronic kidney disease (CKD) (Cr 130-150 umol/L; N 60-115) was diagnosed with insulinoma following a presentation for confusion and CBG of 0.9 mmol/L. Diagnosis was confirmed by 72 hour fast with inappropriate insulin (85 pmol/L; N&lt95) and elevated c-peptide (1875 pmol/L; N 325-1090) with documented hypoglycemia (2.8 mmol/L). CT abdomen localized a 1.2 cm exophytic lesion in the pancreatic tail suggestive of insulinoma. Normal morning cortisol (547 nmol/L) excluded adrenal insufficiency. Initial management included resuscitation with dextrose infusions. Due to advanced age and high cardiac risk profile, the patient was not a candidate for surgical resection of the NET. Endoscopic ultrasound (EUS) ablation was deferred at time of initial hospitalization due to stabilization of hypoglycemia with high glycemic diet. An episode of nocturnal hypoglycemia prompted initiation of diazoxide 100 mg as an outpatient. Subsequent dyspnea (NYHA IV) developed and acute on chronic kidney injury (peak Cr 416 umol/L) with evidence of anasarca secondary to diazoxide use prompted readmission to hospital. With conversion to octreotide, discontinuation of diazoxide and treatment with multiple diuretics, volume overload did not improve. The patient was deemed not a candidate for intermittent hemodialysis and the decision was made to change goals of care. The patient died of complications of volume overload from cardiorenal syndrome 21 days after the initiation of diazoxide. Conclusion: Volume overload has been documented as a complication of diazoxide use in both hypoglycemia and hypertension, occurring in up to 50% of cases, however mortality is not common with supportive management.1, 2 Risk factors for refractory volume overload appear to include reduced ejection fraction, extremes of age and history of CKD3. Possible mechanisms for acute decompensation in CKD include increased unbound diazoxide levels, prerenal effect from hypotension and sodium retention4,5. This case highlights the need for close monitoring with diazoxide use in high risk patients. Clinicians should consider echocardiogram, close monitoring of clinical volume status and renal parameters. References: 1) Goode PN. (1986). World J Surg 10: 586. 2) Komatsu Y. (2016) Endocr J. 63(3): 311. 3) Tarçin O. (2018). Endocrine Abstracts56 EP4. 4) Pearson RM. (1977) Clinical Pharmacokinetics vol 2: 198. 5) Allen WR. (1983). Pharmacology 27: 336.

Activation of hypoxia-sensing pathways promotes renal ischemic preconditioning following myocardial infarction

2021 ◽  
Author(s):  
Andrew S Terker ◽  
Kensuke Sasaki ◽  
Juan Pablo Arroyo ◽  
Aolei Niu ◽  
Suwan Wang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ischemic Preconditioning ◽  
Renal Injury ◽  
Cardiac Injury ◽  
Kidney Injury ◽  
Cardiorenal Syndrome ◽  
Experimental Myocardial Infarction ◽  
Common Mechanism ◽  
Cardiac Damage ◽  
Chronic Kidney Injury

Ischemic heart disease is the leading cause of death worldwide and is frequently comorbid with chronic kidney disease. Physiological communication is known to occur between the heart and the kidney and primary dysfunction in either organ can induce dysfunction in the other, a clinical entity known as cardiorenal syndrome, but mechanistic details are lacking. Here, we used a model of experimental myocardial infarction (MI) to test effects of chronic cardiac ischemia on acute and chronic kidney injury. Surprisingly, chronic cardiac damage protected animals from subsequent acute ischemic renal injury, an effect that was accompanied by evidence of chronic kidney hypoxia. The protection observed post-MI was similar to protection observed in a separate group of healthy animals housed in ambient hypoxic conditions prior to kidney injury, suggesting a common mechanism. There was evidence that chronic cardiac injury activates renal hypoxia-sensing pathways. Increased renal abundance of several glycolytic enzymes following MI suggested a shift towards anaerobic glycolysis may confer renal ischemic preconditioning. In contrast, effects on chronic renal injury followed a different pattern with post-MI animals displaying worsened chronic renal injury and fibrosis. These data show that while chronic cardiac injury following MI protected against acute kidney injury via activation of hypoxia-sensing pathways, it worsened chronic kidney injury. The results further our understanding of cardiorenal signaling mechanisms and have implications for the treatment of heart failure patients with associated renal disease.

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 ◽  
...  
Keyword(s):  
Kidney Injury ◽  
Cardiorenal Syndrome ◽  
Syndrome Type ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Significant Difference ◽  
Renal Markers ◽  
Neutrophil Gelatinase ◽  
Time Of Admission

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.

Pro-Apoptotic Effects of Plasma from Patients with Cardiorenal Syndrome on Human Tubular Cells

2015 ◽  
Vol 41 (6) ◽  
pp. 474-484 ◽  
Author(s):  
Grazia Maria Virzì ◽  
Massimo de Cal ◽  
Sonya Day ◽  
Alessandra Brocca ◽  
Dinna N. Cruz ◽  
...  
Keyword(s):  
Kidney Injury ◽  
Cardiorenal Syndrome ◽  
Tubular Damage ◽  
Protein Levels ◽  
Proinflammatory Mediators ◽  
Apoptotic Activity ◽  
Renal Tubular ◽  
Apoptotic Effects ◽  
Time Of Admission

Background: The pathophysiology of Cardiorenal Syndrome Type 1 (CRS1) is widely studied, although the mechanisms by which renal tubular epithelial cells (TECs) cease to proliferate and embark upon terminal differentiation, following the initial insult of heart failure (HF), remain a key target. This study seeks to provide insight into the pathophysiological pathways in CRS1; we evaluated in vitro the effects of CRS1 plasma on TECs. Methods: We enrolled 40 acute HF patients and 15 controls (CTR) without HF or acute kidney injury (AKI). Ten out of 40 HF patients exhibited AKI at the time of admission for HF or developed AKI during hospitalization and were classified as CRS1. In vitro, cell viability, DNA fragmentation and caspase-3 levels were investigated in TECs incubated with HF, CRS1, and CTR plasma. We assessed inflammatory cytokines and NGAL expression at the gene and protein levels. Results: We observed a marked pro-apoptotic activity and a significantly increased in vitro level of apoptosis in TECs incubated with plasma from CRS1 patients compared to HF and CTR (p < 0.01). In the CRS1 group, the mRNA expression of IL-6, IL-18 and NGAL resulted significantly higher in TECs incubated with CRS1 plasma compared with those incubated with plasma from HF and CTR (p < 0.01). IL-6, IL-18, NGAL, and RANTES levels were significantly higher in TECs supernatant incubated with CRS1 plasma compared with HF patients and CTR plasma (p < 0.01). Conclusion: In vitro exposure to plasma from CRS1 patients altered the expression profile of TECs characterized by increases in proinflammatory mediators, release of tubular damage markers, and apoptosis.

scholarly journals A Review of Specific Biomarkers of Chronic Renal Injury and Their Potential Application in Nonclinical Safety Assessment Studies

2021 ◽  
pp. 019262332098504
Author(s):  
Leslie A. Obert ◽  
Susan A. Elmore ◽  
Daniela Ennulat ◽  
Kendall S. Frazier
Keyword(s):  
Renal Disease ◽  
Renal Injury ◽  
Chronic Renal Disease ◽  
Kidney Injury ◽  
Drug Induced ◽  
Clinical Biomarkers ◽  
Safety Studies ◽  
Novel Biomarkers ◽  
Underlying Mechanisms ◽  
Dimethyl Arginine

A host of novel renal biomarkers have been developed over the past few decades which have enhanced monitoring of renal disease and drug-induced kidney injury in both preclinical studies and in humans. Since chronic kidney disease (CKD) and acute kidney injury (AKI) share similar underlying mechanisms and the tubulointerstitial compartment has a functional role in the progression of CKD, urinary biomarkers of AKI may provide predictive information in chronic renal disease. Numerous studies have explored whether the recent AKI biomarkers could improve upon the standard clinical biomarkers, estimated glomerular filtration rate (eGFR), and urinary albumin to creatinine ratio, for predicting outcomes in CKD patients. This review is an introduction to alternative assays that can be utilized in chronic (>3 months duration) nonclinical safety studies to provide information on renal dysfunction and to demonstrate specific situations where these assays could be utilized in nonclinical drug development. Novel biomarkers such as symmetrical dimethyl arginine, dickkopf homolog 3, and cystatin C predict chronic renal injury in animals, act as surrogates for GFR, and may predict changes in GFR in patients over time, ultimately providing a bridge from preclinical to clinical renal monitoring.

scholarly journals Current Status of Novel Biomarkers for the Diagnosis of Acute Kidney Injury: A Historical Perspective

2019 ◽  
Vol 35 (5) ◽  
pp. 415-424 ◽  
Author(s):  
Benjamin R. Griffin ◽  
Katja M. Gist ◽  
Sarah Faubel
Keyword(s):  
Acute Kidney Injury ◽  
Serum Creatinine ◽  
Structural Damage ◽  
Medical Condition ◽  
Kidney Injury ◽  
Cost Of Care ◽  
Current Status ◽  
Short Period ◽  
Novel Biomarkers ◽  
New Biomarkers

Acute kidney injury (AKI) is a common and serious medical condition associated with significant increases in morbidity, mortality, and cost of care. Because of the high incidence and poor outcomes associated with AKI, there has been significant interest in the development of new therapies for the prevention and treatment of the disease. A lack of efficacy in drug trials led to the concern that AKI was not being diagnosed early enough for an effective intervention and that a rise in serum creatinine itself is not a sensitive-enough marker. Researchers have been searching for novel biomarkers that can not only assess a decline in kidney function but also demonstrate structural damage to the kidney and at time points earlier than increases in serum creatinine measurements allow. Over the past 10 years, there have been 3300 new publications and hundreds of new biomarkers investigated, yet concern still remains regarding AKI biomarker performance. The AKI biomarkers are yet to be widely utilized in clinical practice, leading some to question whether AKI biomarkers will ever reach their initial promise. However, we believe that biomarkers are an important part of current and future AKI research and clinical management. In this review, we compare the historical contexts of acute myocardial ischemia and AKI biomarker development to illustrate the progress that has been made within AKI biomarker research in a relatively short period of time and also to point out key differences between the disease processes that have been barriers to widespread AKI biomarker adoption. Finally, we discuss potential paths by which biomarkers can lead to appropriate AKI treatment responses that lower morbidity and mortality.

scholarly journals Cardiorenal Syndrome - A Review Article

2015 ◽  
Vol 16 (1) ◽  
pp. 39-45
Author(s):  
NS Neki
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Acute Coronary Syndromes ◽  
Kidney Injury ◽  
Cardiorenal Syndrome ◽  
Review Article ◽  
Different Types ◽  
Coronary Syndromes ◽  
Novel Biomarkers

Cardiorenal syndromes (CRS) describe the dynamic inter-relationship between heart and kidney malfunction. Recent studies have clearly defined its various types and pathophysiology. Improved survival, cardiovascular risk factors (diabetes, hypertension, dyslipidemia), diagnostic and therapeutic intervention are some contributors in its causation. Types 1 and 2 CRS involve acute and chronic cardiovascular disease (CVD) scenarios leading to acute kidney injury or accelerated chronic kidney disease. Types 3 and 4 CRS describe acute and chronic kidney disease leading primarily to heart failure, although it is possible that acute coronary syndromes, stroke, and arrhythmias could be CVD outcomes in these forms of CRS. Finally, CRS type 5 describes a simultaneous insult to both heart and kidneys, such as sepsis, where both organs are injured simultaneously. This article focuses on different types, pathophysiology, novel biomarkers, preventive and treatment aspects of cardiorenal syndromes.DOI: http://dx.doi.org/10.3329/jom.v16i1.22400 J MEDICINE 2015; 16 : 39-45

scholarly journals Acute kidney injury in patients with chronic heart failure

2021 ◽  
Vol 2 (3) ◽  
pp. 6-17
Author(s):  
A. G. Arutyunov ◽  
R. A. Bashkinov ◽  
T. I. Batluk ◽  
E. S. Melnikov ◽  
A. N. Ermilova
Keyword(s):  
Heart Failure ◽  
Acute Kidney Injury ◽  
Chronic Heart Failure ◽  
Negative Impact ◽  
Kidney Injury ◽  
Cardiorenal Syndrome ◽  
Pathological Process ◽  
Reduced Ejection Fraction ◽  
Coronavirus Infection

The problem of chronic heart failure (CHF) and especially CHF with reduced ejection fraction is one of the most significant for modern healthcare systems. This is due to the high mortality rate, reduced quality of life, frequent hospitalizations and marked comorbidity of patients with this pathology. Involvement of the kidneys in the pathological process is one of the most common comorbid conditions in cardiovascular disease. There are a large number of pathogenetic mechanisms of mutually negative impact of heart failure and renal dysfunction, reflected in the concept of «Cardiorenal syndrome». Moreover, drug therapy of CHF can be one of the causes of kidney damage. Episodes of acute circulatory decompensation as well as a new coronavirus infection (COVID-19) are particularly threatening conditions. The aim of this review is to consolidate the international literature on the problem of acute kidney injury in patients with CHF.

scholarly journals Cardiorenal Syndrome Type 1: Definition, Etiopathogenesis, Diagnostics and Treatment

2018 ◽  
Vol 19 (1) ◽  
pp. 73-80
Author(s):  
Tomislav Nikolic ◽  
Milan Radovanovic ◽  
Miodrag Sreckovic ◽  
Marina Markovic ◽  
Dejan Petrovic
Keyword(s):  
Renal Injury ◽  
Positive Impact ◽  
Heart Function ◽  
Diuretic Therapy ◽  
Kidney Injury ◽  
Cardiorenal Syndrome ◽  
Syndrome Type ◽  
Acute Renal Injury ◽  
Fatty Acid Binding

Abstract Cardiorenal Syndrome Type 1 (CRS-1) is defined as an acute worsening of heart function leading to acute kidney injury and/or dysfunction. It is an important cause of hospitalization which affects the diagnosis as well as the prognosis and treatment of patients. The purpose of this paper is to analyze causes that lead to the development of cardiorenal syndrome type 1 and its clinical consequences, as well as to emphasize the clinical importance of its early detection. The clinical studies and professional papers dealing with etiopathogenesis, diagnosis and treatment of cardiorenal syndrome type 1, have been analyzed. The most important role in the occurrence of cardio renal syndrome type 1 is played by hemodynamic mechanisms, activation of neurohumoral systems, inflammation and imbalance between the production of reactive oxygen species (ROS) and nitric oxide (NO). Diagnosis of cardiorenal syndrome type 1 involves biomarkers of acute renal injury among which the most important are: neutrophil gelatinaseassociated lipocalin (NGAL), cystatin C, kidney injury molecule 1 (KIM-1), liver-type fatty acid binding protein (L-FABP), IL-18 and the values of nitrogen compounds in serum. In addition to a pharmacological therapy, various modalities of extracorporeal ultrafiltration are applied in treatment of CRS-1, particularly if there is resistance to the use of diuretic therapy. As opposed to the experimental models, in clinical practice acute renal injury is often diagnosed late so that the measures taken do not give the expected results and the protective role shown in experimental conditions do not give the same results. For all these reasons, it is necessary to analyze the pathophysiology of renal impairment in cardiorenal syndrome as well as detect early indicators of kidney injury that could have clinical benefit and positive impact on reducing the cost of treatment.

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