Biomarkers Of Acute Kidney Injury Research Articles

NGAL in the Development of Acute Kidney Injury in a Murine Model of Remote Ischaemic Preconditioning and Liver Ischaemia Reperfusion

Acute kidney injury (AKI) is common following liver transplantation and is associated with liver ischeamia reperfusion (IR) injury. The purpose of this study was to use a mouse model of liver IR injury and AKI to study the role of Neutrophil Gelatinase Associated Lipocalin (NGAL), a biomarker of AKI, in liver IR injury and AKI. We demonstrate an adapted, reproducible model of liver IR injury and AKI in which remote ischemic preconditioning (RIPC) by repeated episodes of hindleg ischemia prior to liver IR reduced the severity of the IR injury. In this model, serum NGAL at 2 h post reperfusion correlated with AKI development early following IR injury. This early rise in serum NGAL was associated with hepatic but not renal upregulation of NGAL mRNA, suggesting NGAL production in the liver but not the kidney in the early phase post liver IR injury.

A Clinical Study on Urinary Clusterin and Cystatin B in Dogs with Spontaneous Acute Kidney Injury

Novel biomarkers are needed in diagnosing reliably acute kidney injury (AKI) in dogs and in predicting morbidity and mortality after AKI. Our hypothesis was that two novel tubular biomarkers, urinary clusterin (uClust) and cystatin B (uCysB), are elevated in dogs with AKI of different etiologies. In a prospective, longitudinal observational study, we collected serum and urine samples from 18 dogs with AKI of different severity and of various etiology and from 10 healthy control dogs. Urinary clusterin and uCysB were compared at inclusion between dogs with AKI and healthy controls and remeasured one and three months later. Dogs with AKI had higher initial levels of uClust (median 3593 ng/mL; interquartile range [IQR]; 1489–10,483) and uCysB (554 ng/mL; 29–821) compared to healthy dogs (70 ng/mL; 70–70 and 15 ng/mL; 15–15; p < 0.001, respectively). Initial uCysB were higher in dogs that died during the one-month follow-up period (n = 10) (731 ng/mL; 517–940), compared to survivors (n = 8) (25 ng/mL; 15–417 (p = 0.009). Based on these results, uClust and especially uCysB are promising biomarkers of AKI. Further, they might reflect the severity of tubular injury, which is known to be central to the pathology of AKI.

One Novel Urinary Biomarkers of Acute Kidney Injury in Patients After Allogeneic Hematopoetic Stem Cell Transplantation

Hematopoietic stem cell transplantation could be complicated by acute kidney injury and chronic kidney disease. It may be due to either previous chemotherapy or exposure to a variety of nephrotoxic drug or other causes. The aim of the study was to assess biomarkers of kidney injury in patients at least 3 months after hematopoetic stem cell transplantation (HSCT) under ambulatory care of the Hematology, Transplantation and Internal Medicine Department. We studied 80 prevalent patients after allogeneic HSCT and 32 healthy volunteers to obtain normal ranges of biomarkers. In this cross-sectional study we assessed retinol-binding protein 4 (RBP4), a biomarker of kidney injury in urine using commercially available assays. It was significantly higher in patients after HSCT when compared to healthy volunteers. When we divided patients according to kidney function (below and over 60 mL/min/1.72 m2), we found that the concentration of RBP4 was significantly higher in 23 patients with chronic kidney disease stage 3 compared to patients with estimated glomerular filtration (eGFR) over 60 mL/min/1.72 m2. In univariate correlations RBP4 was positively related to serum creatinine (r = 0.34, P < .01) and inversely to eGFR (r = −0.20, P < .05). Patients after allogeneic HSCT despite normal or near normal kidney function show evidence of kidney injury.

Long Non-coding RNA Neat1, NLRP3 Inflammasome, and Acute Kidney Injury.

Acute kidney injury (AKI) is common in hospitalized patients and is associated with high mortality. Inflammation plays a key role in the pathophysiology of AKI. Long non-coding RNAs (lncRNAs) are increasingly recognized as regulators of the inflammatory and immune response, but its role in AKI remains unclear. We explored the role of lncRNA Neat1 in (1) a cross-sectional and a longitudinal cohort of AKI in human; (2) three murine models of septic and aseptic AKI and (3) cultured C1.1 mouse kidney tubular cells. In human, hospitalized patients with AKI (n=66) demonstrated significantly increased lncRNA Neat1 levels in urinary sediment cells and buffy coat versus control participants (n=152) from a primary care clinic; and among 6 kidney transplant recipients, Neat1 levels were highest immediately after transplant surgery followed by a prompt decline to normal levels in parallel with recovery of kidney function. In mice with AKI induced by sepsis (via LPS injection or cecal ligation and puncture) and renal ischemia-reperfusion, kidney tubular Neat1 was increased versus sham-operated mice. Knockdown of Neat1 in the kidney using short hairpin RNA preserved kidney function, suppressed overexpression of the AKI biomarker NGAL, leukocyte infiltration and both intrarenal and systemic inflammatory cytokines IL-6, CCL-2 and IL-1β. In LPS-treated C1.1 cells, Neat1 was overexpressed via TLR4/NF-κB signaling, and translocated from the cell nucleus into the cytoplasm where it promoted activation of NLRP3 inflammasomes via binding with the scaffold protein Rack1. Silencing Neat1 ameliorated LPS-induced cell inflammation, whereas its overexpression upregulated IL-6 and CCL-2 expression even without LPS stimulation. Our findings demonstrate a pathogenic role of Neat1 induction in human and mice during AKI with alleviation of kidney injury in 3 experimental models of septic and aseptic AKI after knockdown of Neat1. LPS/TLR4-induced Neat1 overexpression in tubular epithelial cells increases the inflammatory response by binding with the scaffold protein, Rack1, to activate NLRP3 inflammasomes.

Unlocking renal Restoration: Mesaconine from Aconitum plants restore mitochondrial function to halt cell apoptosis in acute kidney injury

Acute kidney injury (AKI) is characterized by a sudden decline in renal function. Traditional Chinese medicine has employed Fuzi for kidney diseases; however, concerns about neurotoxicity and cardiotoxicity have constrained its clinical use. This study explored mesaconine, derived from processed Fuzi, as a promising low-toxicity alternative for AKI treatment. In this study, we assessed the protective effects of mesaconine in gentamicin (GM)-induced NRK-52E cells and AKI rat models in vitro and in vivo, respectively. Mesaconine promotes the proliferation of damaged NRK-52E cells and down-regulates intracellular transforming growth factor β1 (TGF-β1) and kidney injury molecule 1 (KIM-1) to promote renal cell repair. Concurrently, mesaconine restored mitochondrial morphology and permeability transition pores, reversed the decrease in mitochondrial membrane potential, mitigated mitochondrial dysfunction, decreased ATP production, inhibited inflammatory factor release, and reduced early apoptosis rates. In vivo, GM-induced AKI rat models exhibited elevated AKI biomarkers, in which mesaconine was effectively reduced, indicating improved renal function. Mesaconine enhanced superoxide dismutase activity, reduced malondialdehyde content, alleviated inflammatory infiltrate, mitigated tubular and glomerular lesions, and downregulated NF-κB (nuclear factor-κb) p65 expression, leading to decreased tumor necrosis factor-α (TNF-α) and IL-1β (interleukin-1β) levels in GM-induced AKI animals. Furthermore, mesaconine inhibited the expression of renal pro-apoptotic proteins (Bax, cytochrome c, cleaved-caspase 9, and cleaved-caspase 3) and induced the release of the anti-apoptotic protein bcl-2, further suppressing apoptosis. This study highlighted the therapeutic potential of mesaconine in GM-induced AKI. Its multifaceted mechanisms, including the restoration of mitochondrial dysfunction, anti-inflammatory and antioxidant effects, and apoptosis mitigation, make mesaconine a promising candidate for further exploration in AKI management.

Plasma NGAL (Neutrophil Gelatinase Associated Lipocalin) Levels in Septic Patients With &amp; Without Acute Kidney Injury: A Plausible Biomarker

Introduction: Acute kidney injury is extremely common among septic patients. Its early recognition among critically ill patients can help in better prognosis and decrease the risk of longer hospital stay and dialysis requirement. Creatinine is considered as a gold standard for diagnosis of Acute Kidney Injury but it has its own disadvantages. New biomarkers for Acute Kidney Injury that can help in its early recognition are the need of time. Many plasma and urinary markers including Neutrophil Gelatinase Associated Lipocalin are being studied. Its role in earlier detection of septic Acute Kidney Injury in septic patients in our set of population still needs extensive research where incidence of sepsis associated complications leading to death is extremely high. Aims and Objectives: To measure plasma Neutrophil Gelatinase Associated Lipocalin levels in septic patients with and without acute injury compare pNGAL levels in two groups, and to measure specificity and sensitivity of plasma Neutrophil Gelatinase Associated Lipocalin levels in both sets of patients. Place and Duration of study: A cross sectional analytical study was carried out in National Health Research Complex, Shaikh Zayed Hospital, Lahore over a period of 3 years from 2016-2019 Material and Methods: This is a cross-sectional analytical study carried out in ninety two patients that are divided in two groups on the basis of creatinine levels measured at 72hrs. First group consists of septic patients who developed Acute Kidney Injury (AKI) and second group consists of septic patients Without Acute Kidney Injury(WAKI). Plasma NGAL levels are compared in two groups. SPSS v 20 was used for analysis, p-value ? 0.05 was considered significant. Results: The plasma NGAL level at 24 hours for group without Acute Kidney Injury was 126.4±15.4 ng/ml and for the group which developed Acute kidney Injury was 191.1±15.9 ng/ml and the difference was clearly significant with p- value &lt;0.001. Conclusion: pNGAL levels are significantly raised than the cut-off value of 150ng/ml at 0hrs in septic patients who developed AKI as compared to septic patients who didn’t develop AKI.

Assessing the role of Chemokine (C–C motif) ligand 14 in AKI: a European consensus meeting

Background Urinary Chemokine (C–C motif) ligand 14 (CCL14) is a biomarker associated with persistent severe acute kidney injury (AKI). There is limited data to support the implementation of this AKI biomarker to guide therapeutic actions. Methods Sixteen AKI experts with clinical CCL14 experience participated in a Delphi-based method to reach consensus on when and how to potentially use CCL14. Consensus was defined as ≥ 80% agreement (participants answered with ‘Yes’, or three to four points on a five-point Likert Scale). Results Key consensus areas for CCL14 test implementation were: identifying challenges and mitigations, developing a comprehensive protocol and pairing it with a treatment plan, and defining the target population. The majority agreed that CCL14 results can help to prioritize AKI management decisions. CCL14 levels above the high cutoff (> 13 ng/mL) significantly changed the level of concern for modifying the AKI treatment plan (p < 0.001). The highest level of concern to modify the treatment plan was for discussions on renal replacement therapy (RRT) initiation for CCL14 levels > 13 ng/mL. The level of concern for discussion on RRT initiation between High and Low, and between Medium and Low CCL14 levels, showed significant differences. Conclusion Real world urinary CCL14 use appears to provide improved care options to patients at risk for persistent severe AKI. Experts believe there is a role for CCL14 in AKI management and it may potentially reduce AKI-disease burden. There is, however, an urgent need for evidence on treatment decisions and adjustments based on CCL14 results.

Early fluid plus norepinephrine resuscitation diminishes kidney hypoperfusion and inflammation in septic newborn pigs.

Sepsis is the most frequent risk factor for acute kidney injury (AKI) in critically ill infants. Sepsis-induced dysregulation of kidney microcirculation in newborns is unresolved. The objective of this study was to use the translational swine model to evaluate changes in kidney function during the early phase of sepsis in newborns and the impact of fluid plus norepinephrine (NE) resuscitation. Newborn pigs (3-7-day-old) were allocated randomly to three groups: 1) Sham, 2) Sepsis (cecal ligation and puncture; CLP) without subsequent resuscitation, and 3) Sepsis with Lactated Ringer plus NE resuscitation. All animals underwent standard anesthesia and mechanical ventilation. Cardiac output (COP) and glomerular filtration rate (GFR) were measured non-invasively. Mean arterial pressure (MAP), total renal blood flow (RBF), cortical perfusion (coPf), medullary perfusion (mePf), and medullary tissue oxygen tension (mtPO2) were determined for 12 h. CLP decreased MAP and COP by more than 50%, with a proportional increase in renal vascular resistance (RVR) and a 60-80% reduction in RBF, coPf, mePf, and mtPO2 compared to sham. CLP also decreased GFR by ~79% and increased AKI biomarkers. Isolated foci of tubular necrosis were observed in the septic piglets. Except for mtPO2, changes in all these parameters were ameliorated in resuscitated piglets. Resuscitation also attenuated sepsis-induced increases in the levels of plasma C-reactive protein, proinflammatory cytokines, lactate dehydrogenase, alanine transaminase, aspartate aminotransferase, and renal NLRP3 inflammasome. These data suggest that newborn pigs subjected to CLP develop hypodynamic septic AKI. Early implementation of resuscitation lessens the degree of inflammation, AKI, and liver injury.

Biomarkers of acute kidney injury: From discovery to the future of clinical practice

Purpose of this reviewAcute kidney injury (AKI) is a complex syndrome whose development is associated with an increased morbidity and mortality. Recent studies show that this syndrome is a common complication in critically ill and surgical patients the trajectory of which may differ. As AKI can be induced by different triggers, it is complex and therefore challenging to manage patients with AKI. This review strives to provide a brief historical perspective on AKI, elucidate recent developments in diagnosing and managing AKI, and show the current usage of novel biomarkers in both clinical routine and research. In addition, we provide a perspective on potential future developments and their impact of AKI understanding and management.Recent findings/developmentsRecent studies show the merits of stress and damage biomarkers, highlighting limitations of the current KDIGO definition that only uses the functional biomarkers serum creatinine and urine output. The use of novel biomarkers led to the introduction of the concept of “subclinical AKI”. This new classification may allow a more distinct management of affected or at risk patients. Ongoing studies, such as BigpAK-2 and PrevProgAKI, investigate the implementation of biomarker-guided interventions in clinical practice and may demonstrate an improvement in patients' outcome.SummaryThe ongoing scientific efforts surrounding AKI have deepened our understanding of the syndrome prompting an expansion of existing concepts. A future integration of stress and damage biomarkers in AKI management, may lead to an individualized therapy in this area.

Navigating the landscape: a comprehensive review of biomarkers in acute kidney injury

This comprehensive review explored the evolving landscape of biomarkers of acute kidney injury (AKI), emphasizing their critical role in early detection, monitoring, and prognostication. The examination included functional biomarkers (serum cystatin C, NGAL, KIM-1), tubular injury biomarkers (NAG, L-FABP, and IL-18), inflammatory biomarkers (CRP, TNF-α, and IL-6), and oxidative stress biomarkers (MDA, SOD, and catalase). These biomarkers offer nuanced insights into specific facets of renal injury, aiding in differentiating prerenal and intrinsic renal injury and providing a more holistic understanding of AKI pathophysiology. The implications for clinical practice are profound, with biomarkers presenting valuable tools for personalized patient management, early intervention, and improved outcomes. Future research directions should focus on identifying emerging biomarkers, technological advancements, refining integration strategies, and addressing standardization and cost-effectiveness for seamless integration into routine clinical practice. This comprehensive approach positions AKI biomarkers as pivotal in advancing diagnostic precision and intervention strategies in the dynamic landscape of acute kidney injury.

Discovery and verification of mmu_Circ_26986/hsa_Circ_0072463 as a potential biomarker and intervention target for sepsis-associated acute kidney injury

Approximately 60% of septic patients developed acute kidney injury (AKI). The mortality rate of septic AKI (SA-AKI) is two to three times higher than that of septic without AKI (SA-non-AKI). The actual functions and mechanisms of CircRNAs in the pathophysiology of SA-AKI remain incompletely understood. Herein, we observed that the mmu_Circ_26986 could be induced by lipopolysaccharide (LPS) and cecum ligation and puncture (CLP) in BUMPT cell line and C57BL/6 mouse kidney, respectively. Functionally, mmu_Circ_26986 suppressed BUMPT cell apoptosis induced by LPS. Mechanistically, mmu_Circ_26986 sponged miRNA-29b-1-5p to upregulate the expression of PAK7. Overexpression of mmu_Circ_26986 ameliorated the progression of CLP-stimulated AKI through miRNA-29b-1-5p/PAK7 axis. In addition, we found that hsa_Circ_0072463, homologous to mmu_Circ_26986, suppressed LPS-induced HK-2 cells apoptosis via regulation of miRNA-29b-1-5p/PAK7 axis. Furthermore, sepsis patients with AKI had a higher level of hsa_Circ_0072463 compared to those without AKI. The sensitivity, specificity and AUC of hsa_Circ_0072463 were 78.8%, 87.9% and 0.866, respectively. Spearman's test indicated a noticeable positive correlation between plasma hsa_Circ_0072463 and serum creatinine in sepsis patients (r = 0.725). In summary, this study reveals that the mmu_Circ_26986/hsa_Circ_0072463 miRNA-29b-1-5p/PAK7 axis mediates septic AKI, and hsa_Circ_0072463 is a potential diagnostic marker for septic AKI.

Performances of acute kidney injury biomarkers vary according to sex.

Before implementing individualized strategies to treat acute kidney injury (AKI), identifying clusters of patients with divergent pathophysiological mechanisms, diagnosis criteria or outcomes is of the utmost importance. Here we studied sex-related molecular mechanisms in cardiac bypass (CBP) surgery patients developing AKI. We compared the characteristics of 1170 patients referred for CBP surgery using multivariate logistic regression and propensity score-based analysis. Performances of the candidate urinary biomarkers at <4h post-surgery, urinary neutrophil gelatinase-associated lipocalin (uNGAL), [IGFBP7]·[TIMP-2] product (NephroCheck) and a recently developed AKI signature of 204 urinary peptides (AKI204) to predict AKI were compared in both sexes. Incidence (∼25%) and severity of AKI were similar in men and women, even after adjustment for the usual risk factors of AKI, including baseline estimated glomerular filtration rate, age, diabetes mellitus, length of CBP and red blood cell transfusion. However, at the molecular level, performances of uNGAL, NephroCheck and AKI204 to predict AKI strongly diverged between men and women. In the full cohort, as well as in subgroups of men and women, the multimarker AKI204 signature outperformed uNGAL and NephroCheck and predicted the development of AKI significantly better in women than in men. Analysis of AKI204 at the single-peptide level suggested divergences of AKI mechanisms between sexes due to increased kidney inflammation in women (increased abundance of urinary fragments of osteopontin and uromodulin). In patients referred for CBP surgery, significant clinical and biological differences between men and women as well as sexual dimorphism of AKI biomarker performances were identified. The urinary peptide signature points to sex-related molecular mechanisms underlying AKI.

Identification and validation of ferroptosis-related gene SLC2A1 as a novel prognostic biomarker in AKI.

Emerging evidence reveals the key role of ferroptosis in the pathophysiological process of acute kidney injury (AKI). Our study aimed to investigate the potential ferroptosis-related gene in AKI through bioinformatics and experimental validation. The AKI single-cell sequencing dataset was retrieved from the GEO database and ferroptosis-related genes were extracted from the GENECARD website. The potential differentially expressed ferroptosis-related genes of AKI were selected. Functional enrichment analysis was performed. Machine learning algorithms were used to identify key ferroptosis-related genes associated with AKI. A multi-factor Cox regression analysis was used to construct a risk score model. The accuracy of the risk score model was validated using receiver operating characteristic (ROC) curve analysis. We extensively explored the immune landscape of AKI using CIBERSORT tool. Finally, expressions of ferroptosis DEGs were validated in vivo and in vitro by Western blot, ICH and transfection experiments. Three hub genes (BAP1, MDM4, SLC2A1) were identified and validated by constructing drug regulatory network and subsequent screening using experimentally determined interactions. The risk mode showed the low-risk group had significantly better prognosis compared to high-risk group. The risk score was independently associated with overall survival. The ROC curve analysis showed that the prognosis model had good predictive ability. Additionally, CIBERSORT immune infiltration analysis suggest that the hub gene may influence cell recruitment and infiltration in AKI. Validation experiments revealed that SLC2A1 functions by regulating ferroptosis. In summary, our study not only identifies SLC2A1 as diagnostic biomarker for AKI, but also sheds light on the role of it in AKI progression, providing novel insights for the clinical diagnosis and treatment of AKI.

Urine biomarkers of acute kidney injury and association with brain MRI abnormalities in neonatal hypoxic-ischemic encephalopathy.

Determine whether urine biomarkers NGAL (neutrophil gelatinase-associated lipocalin), KIM-1 (kidney injury molecule 1) and IL-18 (interleukin-18) are associated with abnormal MRI findings in neonates with hypoxic-ischemic encephalopathy (HIE) who underwent therapeutic hypothermia (TH). Secondary analysis of a multicenter, prospective study of neonates with HIE requiring TH. Urine biomarkers were obtained at 12 and 24 h of life (HOL). Brain MRI was scored per NICHD criteria. Association between biomarkers and MRI stage was determined. In 57 neonates with HIE, only IL-18 at 24 HOL was significantly increased in neonates with MRI Stage 2B or greater, compared to Stage 2A or less (mean 398.7 vs. 182.9 pg/mL, p = 0.024.) A multivariate model including IL-18 at 24 HOL and 5-min Apgar performed best, with an AUC of 0.84 (SE = 0.07, p = 0.02). Elevated urine IL-18 at 24 HOL was associated with more severe brain MRI abnormalities among neonates with HIE.

Selenium binding protein 1 protects renal tubular epithelial cells from ferroptosis by upregulating glutathione peroxidase 4

Ferroptosis is a form of programmed cell death involved in various types of acute kidney injury (AKI). It is characterized by inactivation of the selenoprotein, glutathione peroxidase 4 (GPX4), and upregulation of acyl-CoA synthetase long-chain family member 4 (ACSL4). Since urinary selenium binding protein 1 (SBP1/SELENBP1) is a potential biomarker for AKI, this study investigated whether SBP1 plays a role in AKI. First, we showed that SBP1 is expressed in proximal tubular cells in normal human kidney, but is significant downregulated in cases of AKI in association with reduced GPX4 expression and increased ACSL4 expression. In mouse renal ischemia-reperfusion injury (I/R), the rapid downregulation of SBP1 protein levels preceded downregulation of GPX4 and the onset of necrosis. In vitro, hypoxia/reoxygenation (H/R) stimulation in human proximal tubular epithelial (HK-2) cells induced ferroptotic cell death in associated with an acute reduction in SBP1 and GPX4 expression, and increased oxidative stress. Knockdown of SBP1 reduced GPX4 expression and increased the susceptibility of HK-2 cells to H/R-induced cell death, whereas overexpression of SBP1 reduced oxidative stress, maintained GPX4 expression, reduced mitochondrial damage, and reduced H/R-induced cell death. Finally, selenium deficiency reduced GPX4 expression and promoted H/R-induced cell death, whereas addition of selenium was protective against H/R-induced oxidative stress. In conclusion, SBP1 plays a functional role in hypoxia-induced tubular cell death. Enhancing SBP1 expression is a potential therapeutic approach for the treatment of AKI.

Biomarkers in Contrast-Induced Acute Kidney Injury: Towards A New Perspective.

Contrast-Induced Acute Kidney Injury (CI-AKI) remains a frequent iatrogenic condition since radiological procedures using intra-vascular iodinated contrast media (CM) are being widely administered for diagnostic and therapeutic purposes. Despite the improvement of the medical healthcare system worldwide, CI-AKI is still associated with direct short-term and indirect long-term outcomes including increased morbidity and mortality, especially in patients with underlying pre-existing renal function impairment, cardiovascular disease, or diabetes that could rapidly progress into Chronic Kidney Disease. Although the RIFLE (Risk, Injury, Failure, Loss, End-Stage Kidney Disease), AKIN (Acute Kidney Injury Network), and KDIGO (Kidney Disease Improving Global Outcomes) clinical criteria and recommendation guidelines are based on traditional "gold standard" biomarkers known as serum creatinine, glomerular filtration rate, and urinary output, new reliable serum and urinary biomarkers are still needed for an effective unified diagnostic strategy for AKI. Starting from previous and recent publications on the benefits and limitations of validated biomarkers responding to kidney injury, glomerular filtration, and inflammation among others, this review unravels the role of new emerging biomarkers used alone or in combination as reliable tools for early diagnosis and prognosis of CI-AKI, taking into account patients and procedures-risk factors towards a new clinical perspective.

Kidney damage in burn disease. Part 2. Biochemical markers (literature review)

Recently discovered specific markers open up new possibilities for the diagnosis of acute kidney injury (AKI) in burn disease in order to optimize the treatment of such patients. Early diagnosis with the involvement of biomarkers prevents the sudden death of burn patients and allows predicting the course of the pathological condition. There are several characteristics that an “ideal” AKI biomarker should conform to: being non-invasive, locally specific, highly sensitive, being a stable molecule at different temperatures and pH values, having the ability to rapidly increase in response to kidney injury (quantify it), remaining at high levels during the episode and decreasing during the recovery period. There is a difference between the biomarkers that can be freely filtered in the glomerulus, so any increase in their plasma concentration (due to damage to other renal tissues) can lead to a high concentration of indicators in the urine (loss of specificity), and high-molecular-weight markers that are not freely filtered and therefore are more specific when measured in urine. Renal function in burn patients is usually determined by blood and urine tests, as biopsy can cause iatrogenic damage and is not commonly used in this cohort. After the onset of AKI, the level of biomarkers remains elevated for a certain period. None of the described indicators is monospecific for AKI; this makes estimating the time of AKI quite difficult. It has been proven that the combination of three biomarkers at two different time points in adults and the combination of two indicators at two time intervals in children allows to increase the reliability of determining AKI up to 0.78

Combined Plasma Olink Proteomics and Transcriptomics Identifies CXCL1 and TNFRSF12A as Potential Predictive and Diagnostic Inflammatory Markers for Acute Kidney Injury.

Acute kidney injury (AKI) poses a significant global public health challenge. Current methods for detecting AKI rely on monitoring changes in serum creatinine (Scr), blood urea nitrogen (BUN), urinary output and some commonly employed biomarkers. However, these indicators are usually neither specific nor sensitive to AKI, especially in cases of mild kidney injury. AKI is accompanied by severe inflammatory reactions, resulting in the upregulation of numerous inflammation-associated proteins in the plasma. Plasma biomarkers are a noninvasive method for detecting kidney injury, and to date, plasma inflammation-associated cytokines have not been adequately studied in AKI patients. The objective of our research was to identify novel inflammatory biomarkers for AKI. We utilized Olink proteomics to analyze the alterations in plasma inflammation-related proteins in the serum of healthy mice (n = 2) or mice treated with cisplatin (n = 6). Additionally, transcriptome datasets for the lipopolysaccharide (LPS), cisplatin, and ischemia‒reperfusion injury (IRI) groups were obtained from the National Center of Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. We calculated the intersection of differentially expressed proteins (DEPs) and genes (DEGs) from both datasets. In the Olink proteomics analysis, the AKI group had significantly greater levels of 11 DEPs than did the control group. In addition, 56 common upregulated DEGs were obtained from the transcriptome dataset. The expression of CXCL1 and TNFRSF12A overlapped across all the datasets. The transcription and protein expression levels of CXCL1 and TNFRSF12A were detected in vivo. The gene and protein levels of CXCL1 and TNFRSF12A were significantly increased in different AKI mouse models and clinical patients, suggesting that these genes and proteins could be potential specific biomarkers for the identification of AKI.

Prognostic Biomarkers and AKI: Potential to Enhance the Identification of Post-Operative Patients at Risk of Loss of Renal Function.

Acute kidney injury (AKI) is a common complication after surgery and the more complex the surgery, the greater the risk. During surgery, patients are exposed to a combination of factors all of which are associated with the development of AKI. These include hypotension and hypovolaemia, sepsis, systemic inflammation, the use of nephrotoxic agents, tissue injury, the infusion of blood or blood products, ischaemia, oxidative stress and reperfusion injury. Given the risks of AKI, it would seem logical to conclude that early identification of patients at risk of AKI would translate into benefit. The conventional markers of AKI, namely serum creatinine and urine output are the mainstay of defining chronic kidney disease but are less suited to the acute phase. Such concerns are compounded in surgical patients given they often have significantly reduced mobility, suboptimal levels of nutrition and reduced muscle bulk. Many patients may also have misleadingly low serum creatinine and high urine output due to aggressive fluid resuscitation, particularly in intensive care units. Over the last two decades, considerable information has accrued with regard to the performance of what was termed "novel" biomarkers of AKI, and here, we discuss the most examined molecules and performance in surgical settings. We also discuss the application of biomarkers to guide patients' postoperative care.

Proenkephalin A 119–159, a Possible Early Biomarker of Acute Kidney Injury in Complex Endovascular Aortic Repair: a Single Centre Observational, Cross Sectional Study

Proenkephalin A 119–159, a Possible Early Biomarker of Acute Kidney Injury in Complex Endovascular Aortic Repair: a Single Centre Observational, Cross Sectional Study