scholarly journals Novel Biomarkers, Oxidative Stress, and the Role of Labile Iron Toxicity in Cardiopulmonary Bypass-Associated Acute Kidney Injury

2010 ◽  
Vol 55 (19) ◽  
pp. 2024-2033 ◽  
Author(s):  
Michael Haase ◽  
Rinaldo Bellomo ◽  
Anja Haase-Fielitz
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Cardiopulmonary Bypass ◽  
Kidney Injury ◽  
Iron Toxicity ◽  
Novel Biomarkers ◽  
Labile Iron

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.

Acute kidney injury, stroke and death after cardiopulmonary bypass surgery: the role of perfusion flow and pressure

Perfusion ◽  
2020 ◽  
Vol 36 (1) ◽  
pp. 78-86
Author(s):  
Laura Turner ◽  
Ashutosh Hardikar ◽  
Matthew D Jose ◽  
Keshav Bhattarai ◽  
Carmel Fenton ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Cardiopulmonary Bypass ◽  
Bypass Surgery ◽  
Perfusion Pressure ◽  
Kidney Injury ◽  
Hospital Death ◽  
Perfusion Flow ◽  
Cardiopulmonary Bypass Surgery ◽  
Secondary Outcomes

Introduction: Acute kidney injury after cardiopulmonary bypass surgery is associated with morbidity and mortality. This study aims to evaluate the role of low perfusion flow and pressure in the development of cardiopulmonary bypass–associated acute kidney injury, stroke and death, using multicentre registry data. Methods: We identified patients from the Australian and New Zealand Collaborative Perfusion Registry who underwent coronary artery bypass grafting and/or valvular surgery between 2008 and 2018. Primary predictor variables were the length of time the perfusion flow was <1.6 L/min/m2 and the length of time perfusion pressure was < 50mmHg. The primary outcome was new postoperative acute kidney injury defined by the risk-injury-failure-loss-end stage criteria. Secondary outcomes were stroke and in-hospital death. The influence of perfusion flow and pressure during cardiopulmonary bypass on the primary and secondary outcomes was estimated using separate multivariate models. Results: A total of 16,356 patients were included. The mean age was 66 years and 75% were male. Acute kidney injury was observed in 1,844 patients (11%), stroke in 204 (1.3%) and in-hospital death in 286 (1.8%). Neither the duration of the time spent for perfusion flow (<1.6 L/minute/m2) nor the duration of the time spent for perfusion pressure (<50 mmHg) was associated with postoperative acute kidney injury, stroke or death in adjusted models. Conclusions: Neither low perfusion pressure nor low perfusion flow during cardiopulmonary bypass were predictive of postoperative acute kidney injury, stroke or death.

scholarly journals Catalytic iron and acute kidney injury

2016 ◽  
Vol 311 (5) ◽  
pp. F871-F876 ◽  
Author(s):  
David E. Leaf ◽  
Dorine W. Swinkels
Keyword(s):  
Acute Kidney Injury ◽  
Animal Models ◽  
Length Of Stay ◽  
Kidney Injury ◽  
Redox Cycling ◽  
Hospital Length ◽  
Hospital Length Of Stay ◽  
Translational Studies ◽  
Labile Iron

Acute kidney injury (AKI) is a common and often devastating condition among hospitalized patients and is associated with markedly increased hospital length of stay, mortality, and cost. The pathogenesis of AKI is complex, but animal models support an important role for catalytic iron in causing AKI. Catalytic iron, also known as labile iron, is a transitional pool of non-transferrin-bound iron that is readily available to participate in redox cycling. Initial findings related to catalytic iron and animal models of kidney injury have only recently been extended to human AKI. In this review, we discuss the role of catalytic iron in human AKI, focusing on recent translational studies in humans, assay considerations, and potential therapeutic targets for future interventional studies.

scholarly journals SUN-182 THE ROLE OF PERFUSION PRESSURE AND FLOW IN CARDIOPULMONARY BYPASS ASSOCIATED ACUTE KIDNEY INJURY

2019 ◽  
Vol 4 (7) ◽  
pp. S234
Author(s):  
L. TURNER ◽  
A. Hardikar ◽  
M. Jose ◽  
K. Bhattarai ◽  
C. Fenton ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Cardiopulmonary Bypass ◽  
Perfusion Pressure ◽  
Kidney Injury

P0525ROLE OF NADPH OXIDASE 4 IN ACUTE KIDNEY INJURY ASSOCIATED TO MASSIVE INTRAVASCULAR HEMOLYSIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Cristina García Caballero ◽  
Melania Guerrero Hue ◽  
Alejandra Palomino Antolín ◽  
Matilde Cabanillas ◽  
Cristina Vazquez Carballo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Renal Function ◽  
Renal Damage ◽  
Kidney Injury ◽  
Tubular Injury ◽  
Wild Type ◽  
Intravascular Hemolysis ◽  
Nadph Oxidase 4

Abstract Background and Aims Massive intravascular hemolysis is a common condition of several pathologies. It is associated with acute kidney injury (AKI) and progressive impairment of renal function. In this context, free hemoglobin (Hb) can exert harmful effects by accumulating in the kidney, where induces oxidative stress and it becomes cytotoxic. NADPH oxidase 4 (Nox4) is the principal source of reactive oxygen species (ROS) in the kidney. Nox4 is mostly expressed in proximal tubular cells with lower levels in glomerulus. The role of Nox4 in renal damage is not clear, with studies reporting beneficial or deleterious actions depending of the environmental conditions. For that reason we aimed to investigate the role of Nox4 in massive intravascular hemolysis-associated AKI. Method To study the role of Nox4 in AKI caused by massive intravascular hemolysis, we performed an experimental model of intravascular hemolysis by intraperitoneal injection of phenylhydrazine (200 mg/kg) in wild type (Nox4+/+) and Nox4 knockout mice (Nox4-/-). Mice were sacrificed 24 and 72 hours after intravascular hemolysis induction. We collected serum, urine and tissues sample. We analyzed renal function, oxidative stress, cell death and inflammation in these samples. In other experiments, wild type mice were treated with GKT137831 (10mg/kg/day), a potent Nox4 and Nox1 inhibitor, and mice were sacrificed 72h after induction of hemolysis. We also performed in vitro experiments in murine tubular epithelial cells (MCT) and murine podocytes cells to investigate the regulation of Nox4 in Hb-stimulated cells treated or not with GKT137831. Results Induction of intravascular hemolysis in Nox4+/+ mice increased creatinine and BUN levels and enhanced the expression of tubular injury markers, such as NGAL. These pathological effects were reduced in Nox4 knockout mice. Then, we analyzed oxidative stress in our experimental model thought determination of HO-1, ferritin, GSH and lipid peroxidation levels. All of these oxidative markers were reduced in Nox4-/- mice with intravascular hemolysis as compared with Nox4+/+ mice. We also observed that inflammatory markers such as IL-6, cell death and podocytes injury markers were reduced in Nox4-/- mice than in wild type mice, specially 72 hours after phenylhydrazine injection. In line with these results, GKT137831 administration ameliorated intravascular hemolysis-associated renal function impairment. Moreover, oxidative stress, tubular injury markers and podocyte injury were reduced in hemolytic mice treated with GKT137831. GKT137831 also reduced Hb- and heme-mediated oxidative stress in MCT and podocytes. Conclusion Our results show the important role of Nox4 in renal injury associated to massive intravascular hemolysis. Moreover, the inhibition of Nox4 may be a potential therapeutic target to prevent renal damage associated to Hb accumulation. These findings provide new insights into novel aspects of Hb-toxicity and may have important pathogenic and therapeutic implications for intravascular hemolysis related diseases

scholarly journals Acute Kidney Injury and Organ Dysfunction: What Is the Role of Uremic Toxins?

Toxins ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 551
Author(s):  
Jesús Iván Lara-Prado ◽  
Fabiola Pazos-Pérez ◽  
Carlos Enrique Méndez-Landa ◽  
Dulce Paola Grajales-García ◽  
José Alfredo Feria-Ramírez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Organ Dysfunction ◽  
Kidney Injury ◽  
Uremic Toxins ◽  
Oxygen Species ◽  
Capillary Leakage ◽  
Abrupt Increase ◽  
Epithelial Injury

Acute kidney injury (AKI), defined as an abrupt increase in serum creatinine, a reduced urinary output, or both, is experiencing considerable evolution in terms of our understanding of the pathophysiological mechanisms and its impact on other organs. Oxidative stress and reactive oxygen species (ROS) are main contributors to organ dysfunction in AKI, but they are not alone. The precise mechanisms behind multi-organ dysfunction are not yet fully accounted for. The building up of uremic toxins specific to AKI might be a plausible explanation for these disturbances. However, controversies have arisen around their effects in organs other than the kidney, because animal models usually depict AKI as a kidney-specific injury. Meanwhile, humans present AKI frequently in association with multi-organ failure (MOF). Until now, medium-molecular-weight molecules, such as inflammatory cytokines, have been proven to play a role in endothelial and epithelial injury, leading to increased permeability and capillary leakage, mainly in pulmonary and intestinal tissues.

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