scholarly journals The need for disruptive innovation in acute kidney injury

2020 ◽  
Vol 24 (11) ◽  
pp. 979-988
Author(s):  
Kent Doi
Keyword(s):  
Acute Kidney Injury ◽  
Medical Condition ◽  
Kidney Injury ◽  
Basic Research ◽  
Disruptive Innovation ◽  
Multiple Organ ◽  
Organ Crosstalk ◽  
Research Findings ◽  
Poor Outcomes ◽  
New Biomarkers

Abstract Acute kidney injury (AKI) is a threatening medical condition associated with poor outcomes at different settings. The development of standardized diagnostic criteria and new biomarkers addressed significant clinical impacts of AKI and the need for an early AKI detection, respectively. There have been some breakthroughs in understanding the pathogenesis of AKI through basic research; however, treatments against AKI aside from renal replacement therapy (RRT) have not shown adequate successful results. Biomarkers that could identify good responders to certain treatment are expected to facilitate translation of basic research findings. Most patients with severe AKI treated with RRT died due to multiple-organ failure, not renal dysfunction. Hence, it is essential to identify other organ dysfunctions induced by AKI as organ crosstalk. Also, a multidisciplinary approach of critical care nephrology is needed to evaluate a complex organ crosstalk in AKI. For disruptive innovation for AKI, we further explore these new aspects of AKI, which previously were considered outside the scope of nephrology.

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.

Complement C5 inhibition protects against hemolytic anemia and acute kidney injury in anthrax peptidoglycan-induced sepsis in baboons

2021 ◽  
Vol 118 (37) ◽  
pp. e2104347118
Author(s):  
Ravi Shankar Keshari ◽  
Narcis Ioan Popescu ◽  
Robert Silasi ◽  
Girija Regmi ◽  
Cristina Lupu ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Hemolytic Anemia ◽  
Complement Activation ◽  
Inflammatory Responses ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Kidney Injury ◽  
Multiple Organ ◽  
Immune Recognition ◽  
Gram Positive ◽  
Terminal Complement

Late-stage anthrax infections are characterized by dysregulated immune responses and hematogenous spread of Bacillus anthracis, leading to extreme bacteremia, sepsis, multiple organ failure, and, ultimately, death. Despite the bacterium being nonhemolytic, some fulminant anthrax patients develop a secondary atypical hemolytic uremic syndrome (aHUS) through unknown mechanisms. We recapitulated the pathology in baboons challenged with cell wall peptidoglycan (PGN), a polymeric, pathogen-associated molecular pattern responsible for the hemostatic dysregulation in anthrax sepsis. Similar to aHUS anthrax patients, PGN induces an initial hematocrit elevation followed by progressive hemolytic anemia and associated renal failure. Etiologically, PGN induces erythrolysis through direct excessive activation of all three complement pathways. Blunting terminal complement activation with a C5 neutralizing peptide prevented the progressive deposition of membrane attack complexes on red blood cells (RBC) and subsequent intravascular hemolysis, heme cytotoxicity, and acute kidney injury. Importantly, C5 neutralization did not prevent immune recognition of PGN and shifted the systemic inflammatory responses, consistent with improved survival in sepsis. Whereas PGN-induced hemostatic dysregulation was unchanged, C5 inhibition augmented fibrinolysis and improved the thromboischemic resolution. Overall, our study identifies PGN-driven complement activation as the pathologic mechanism underlying hemolytic anemia in anthrax and likely other gram-positive infections in which PGN is abundantly represented. Neutralization of terminal complement reactions reduces the hemolytic uremic pathology induced by PGN and could alleviate heme cytotoxicity and its associated kidney failure in gram-positive infections.

scholarly journals New Biomarkers for the Quick Detection of Acute Kidney Injury

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Abdulmuttalip Simsek ◽  
Volkan Tugcu ◽  
Ali Ihsan Tasci
Keyword(s):  
Acute Kidney Injury ◽  
Serum Creatinine ◽  
Critically Ill ◽  
Cystatin C ◽  
Critically Ill Patients ◽  
Clinical Training ◽  
Kidney Injury ◽  
Urinary Proteins ◽  
New Biomarkers ◽  
Urine And Serum

Acute kidney injury (AKI) is a common and strong problem in the diagnosis of which based on measurement of BUN and serum creatinine. These traditional methods are not sensitive and specific for the diagnosis of AKI. AKI is associated with increased morbidity and mortality in critically ill patients and a quick detection is impossible with BUN and serum creatinine. A number of serum and urinary proteins have been identified that may messenger AKI prior to a rise in BUN and serum creatinine. New biomarkers of AKI, including NGAL, KIM-1, cystatin-C, IL-18, and L-FABP, are more favourable tests than creatinine which have been identified and studied in several experimental and clinical training. This paper will discuss some of these new biomarkers and their potential as useful signs of AKI. We searched the literature using PubMed and MEDLINE with acute kidney injury, urine, and serum new biomarkers and the articles were selected only from publication types in English.

scholarly journals Acute Kidney Injury and Acute Liver Failure in Leptospira Infection and Weil’s Syndrome

2020 ◽  
Vol 4 (2) ◽  
pp. 21-28
Author(s):  
Jonathan S Chávez-Iñiguez ◽  
Jose Said Cabrera-Aguilar ◽  
Guillermo Garcia-Garcia ◽  
Juan Armendáriz-Borunda
Keyword(s):  
Acute Kidney Injury ◽  
Clinical Presentation ◽  
Clinical Signs ◽  
Kidney Injury ◽  
Organ Damage ◽  
Multiple Organ ◽  
Serological Tests ◽  
Microbiological Criteria ◽  
Sanitary Conditions ◽  
The Impact

Leptospirosis is considered a zoonosis acquired predominantly from contaminated surfaces and water, more commonly in emerging countries with limited sanitary conditions. Leptospira in the host unleashes an immune response that explains the symptoms and clinical signs; once it reaches the kidney and liver tissue, it can manifest with alterations that lead to acute and chronic diseases in both organs. Weil’s syndrome is the best known clinical manifestation with jaundice and acute kidney injury that could lead to multiple organ failure and death. For its diagnosis, there are simplified scores such as the SPiRO score, the microbiological criteria by microscopy or serological tests; the treatment focuses on antibiotics and, if necessary, provides organic support until the infection is curtailed. The purpose of this review was to address the impact of Lep-tospira infection on the kidney and liver, the mechanisms of organ damage, the clinical presentation, and diagnosis and management of this disease.

scholarly journals Biomarker-Based Management of AKI: Fact or Fantasy?

Nephron ◽  
2021 ◽  
pp. 1-7
Author(s):  
Marlies Ostermann ◽  
Emma Karsten ◽  
Nuttha Lumlertgul
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Current Role ◽  
Kinetic Profile ◽  
Origin Function ◽  
New Biomarkers

New biomarkers for acute kidney injury (AKI) have improved our understanding of the etiology and pathogenesis of AKI. Depending on their origin, function, and kinetic profile, biomarkers have a role in screening, diagnosis, prognostication, and monitoring of AKI. This offers opportunities to improve the management of AKI, but concerns and limitations remain. In this review, we summarize the current role of new AKI biomarkers in the management of AKI and outline some of the ongoing limitations and challenges.

scholarly journals The Indirect Implication of SARS-CoV-2 Resulting in Kayexalate Toxicity in a Patient with Acute Kidney Injury

2021 ◽  
Vol 5 (1) ◽  
pp. 6-13
Author(s):  
Charles E. Middleton IV ◽  
William Daley ◽  
Neha Varshney
Keyword(s):  
Acute Kidney Injury ◽  
Virus Disease ◽  
Severe Disease ◽  
Kidney Injury ◽  
Multiple Organ ◽  
Subsequent Treatment ◽  
Gastrointestinal Complications ◽  
Treatment Regimens ◽  
Organ Systems ◽  
Life Threatening

The clinical features of corona virus disease 2019 (COVID-19) are variable, but the majority of patients experience mild flu-like symptoms. The cases of severe disease include complications such as progressive pneumonia, acute kidney injury, multi-organ failure, and even death. This paper explores the association between COVID-19 and its effect on multiple organ systems and how the subsequent treatment of this disease can itself lead to morbidity and mortality. We present a case which emphasizes the life threatening gastrointestinal complications associated with treatment of acute kidney injury (AKI) in a patient with COVID-19. We conclude that the patients whose treatment regimens utilize medical resins should be closely monitored for gastrointestinal complications so as to mitigate the known adverse effects associated with these drugs, such as colonic mucosal ulceration, perforation, or even death.

Renal support therapy

2021 ◽  
pp. 338-350
Author(s):  
Claudio Ronco ◽  
Stefano Romagnoli ◽  
Zaccaria Ricci
Keyword(s):  
Acute Kidney Injury ◽  
Renal Replacement Therapy ◽  
Multiple Organ Failure ◽  
Replacement Therapy ◽  
Kidney Injury ◽  
Multiple Organ ◽  
Acute Illness ◽  
Renal Support Therapy ◽  
Critical Patients ◽  
Renal Support

Renal dysfunction is known to be frequently a component of multiple organ failure, a complex syndrome affecting the most severely ill critical patients. Bidirectional interaction between the kidneys and other organs has always been suspected; evidence suggests that severe kidney injury is an important protagonist in acute illness, even when managed by dialysis. In fact, if it seems that increasing the dose of renal replacement therapy does not reduce mortality, it could be inferred that acute kidney injury influences mortality through means that are not reversed by conventional renal support, either because the putative culprit toxins are not removed by renal replacement therapy or because renal replacement therapy is started too late to prevent these effects. It is known that the kidneys exert effects on other organs, such as the lung, liver, heart, and brain, in a process called 'crosstalk'. This effect means that the kidney is not only a victim, but also a culprit regarding the malfunction of other organs. This chapter will detail some traditional aspects of different renal replacement therapy modalities and prescription schedules, but it will also describe the most recent evidence on the management and support of the kidney during failure of other organs.

scholarly journals Acute kidney injury in pediatric patients: experience of a single center during an 11-year period

Medicina ◽  
2010 ◽  
Vol 46 (8) ◽  
pp. 511 ◽  
Author(s):  
Birutė Pundzienė ◽  
Diana Dobilienė ◽  
Šarūnas Rudaitis
Keyword(s):  
Intensive Care Unit ◽  
Acute Kidney Injury ◽  
Intensive Care ◽  
Organ Dysfunction ◽  
Multiple Organ Dysfunction Syndrome ◽  
Kidney Injury ◽  
Pediatric Intensive Care ◽  
Multiple Organ ◽  
Multiple Organ Dysfunction ◽  
Second Period

The aim of our study was to determine the causes of acute kidney injury (AKI) in children, to compare outcomes between two periods – 1998–2003 and 2004-2008 – and to evaluate the influence of new methods of renal replacement therapy on mortality. Material and methods. A retrospective analysis of medical record data of all children treated for AKI at the Clinic of Children Diseases, Hospital of Kaunas University of Medicine, during the period of 1998–2008 was made. Both periods were compared regarding various variables. Results. Of the 179 children with AKI, 75 (41.9%) were treated during 1998–2003 and 104 (58.1%) during 2004–2008. Primary glomerular disease and sepsis were the leading causes of AKI in both the periods. AKI without involvement of other organs was diagnosed for 106 (59.2%) children: for 42 (56.0%) children in the first period and 64 (61.5%) in the second. A total of 124 (69.3%) children were treated in a pediatric intensive care unit. Multiple organ dysfunction syndrome with AKI was diagnosed for 33 (44%) patients in the first period and for 40 (38.5%) in the second. A significant decrease in mortality among patients with multiple organ dysfunction syndrome during the second period was observed (78.8% vs. 37.5%). Conclusions. More than half of patients had secondary acute kidney injury of nonrenal origin. More than two-thirds (69.3%) of patients with AKI were treated in the pediatric intensive care unit. Multiple organ dysfunction syndrome was diagnosed for 40.8% of children with AKI. Renal replacement therapy was indicated for one-third of patients with AKI. A 2.5-fold decrease in mortality was observed in the second period as compared to the first one.

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