Biomarkers Of Acute Kidney Injury Research Articles

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

Tetramethylpyrazine attenuates renal tubular epithelial cell ferroptosis in contrast-induced nephropathy by inhibiting transferrin receptor and intracellular reactive oxygen species.

Contrast-induced nephropathy (CIN) is a leading cause of hospital-acquired acute kidney injury (AKI). Recently, ferroptosis was reported to be crucial for AKI pathogenesis. Our previous studies indicated antioxidant tetramethylpyrazine (TMP) prevent CIN in vivo. However, whether ferroptosis is involved in TMP nephroprotective mechanism against CIN is unclear. In the present study, we investigated the role of renal tubular epithelial cell ferroptosis in TMP reno-protective effect against CIN and the molecular mechanisms by which TMP regulates ferroptosis. Classical contrast-medium, Iohexol, was used to construct CIN models in rats and HK-2 cells. Results showed that tubular cell injury was accompanied by ferroptosis both in vivo and in vitro, including the typical features of ferroptosis, Fe2+ accumulation, lipid peroxidation and decreased glutathione peroxidase 4 (GPX4). Ferroptosis inhibition by classic inhibitors Fer-1 and DFO promoted cell viability and reduced intracellular ROS production. Additionally, TMP significantly inhibited renal dysfunction, reduced AKI biomarkers, prevented ROS production, inhibited renal Fe2+ accumulation and increased GPX4 expression. Expressions of various proteins associated with iron ion metabolism, including transferrin receptor (TFRC), divalent metal transporter 1, iron-responsive element binding protein 2, ferritin heavy chain 1, ferroportin 1, and heat shock factor binding protein 1, were examined using mechanistic analyses. Among these, TFRC changes were the most significant after TMP pretreatment. Results of siRNA knockdown and plasmid overexpression of TFRC indicated that TFRC is essential for TMP to alleviate ferroptosis and reduce LDH release, Fe2+ accumulation and intracellular ROS. Our findings provide crucial insights about the potential of TMP in treating AKI associated with ferroptosis.

Gut Microbiota and Neonatal Acute Kidney Injury.

To characterize the relationship between gut microbiota and neonatal acute kidney injury biomarkers based on the gut-kidney axis. The Pubmed database was primarily searched to include relevant literature on gut microbiota and neonatal acute kidney injury biomarkers, which was subsequently organized and analyzed and a manuscript was written. Gut microbiota was associated with neonatal acute kidney injury biomarkers. These biomarkers included TIMP-2, IGFBP-7, VEGF, calbindin, GST, B2MG, ghrelin, and clusterin. The gut microbiota is strongly associated with neonatal acute kidney injury biomarkers, and controlling the gut microbiota may be a potential target for ameliorating neonatal acute kidney injury. · There is a bidirectional association between gut microbiota and AKI.. · Gut microbiota is closely associated with biomarkers of nAKI.. · Manipulation of gut microbiota may improve nAKI..

Sensing Dying Cells in Health and Disease: The Importance of Kidney Injury Molecule-1.

Kidney injury molecule-1 (KIM-1), also known as T-cell Ig and mucin domain-1 (TIM-1), is a widely recognized biomarker for AKI, but its biological function is less appreciated. KIM-1/TIM-1 belongs to the T-cell Ig and mucin domain family of conserved transmembrane proteins, which bear the characteristic six-cysteine Ig-like variable domain. The latter enables binding of KIM-1/TIM-1 to its natural ligand, phosphatidylserine, expressed on the surface of apoptotic cells and necrotic cells. KIM-1/TIM-1 is expressed in a variety of tissues and plays fundamental roles in regulating sterile inflammation and adaptive immune responses. In the kidney, KIM-1 is upregulated on injured renal proximal tubule cells, which transforms them into phagocytes for clearance of dying cells and helps to dampen sterile inflammation. TIM-1, expressed in T cells, B cells, and natural killer T cells, is essential for cell activation and immune regulatory functions in the host. Functional polymorphisms in the gene for KIM-1/TIM-1, HAVCR1 , have been associated with susceptibility to immunoinflammatory conditions and hepatitis A virus-induced liver failure, which is thought to be due to a differential ability of KIM-1/TIM-1 variants to bind phosphatidylserine. This review will summarize the role of KIM-1/TIM-1 in health and disease and its potential clinical applications as a biomarker and therapeutic target in humans.

Assessment of urine CCL2 as a potential diagnostic biomarker for acute kidney injury and septic acute kidney injury in intensive care unit patients

Acute kidney injury (AKI) is a prevalent and serious condition in the intensive care unit (ICU), associated with significant morbidity and mortality. Septic acute kidney injury (SAKI) contributes substantially to AKI cases in the ICU. However, current diagnostic methods have limitations, necessitating the exploration of novel biomarkers. In this study, we investigated the potential of plasma and urine CCL2 levels as diagnostic markers for AKI and SAKI in 216 ICU patients. Our findings revealed significant differences in plasma (p < 0.01) and urine CCL2 (p < 0.0001) levels between AKI and non-AKI patients in the ICU. Notably, urine CCL2 demonstrated promising predictive value for AKI, exhibiting high specificity and sensitivity (AUC = 0.8976; p < 0.0001). Furthermore, we observed higher urine CCL2 levels in SAKI compared to non-septic AKI (p < 0.001) and urine CCL2 could also differentiate SAKI from non-septic AKI (AUC = 0.7597; p < 0.0001). These results suggest that urine CCL2 levels hold promise as early biomarkers for AKI and SAKI, offering valuable insights for timely intervention and improved management of ICU patients.

Bioactive adrenomedullin and interleukin-6 in COVID-19: potential biomarkers of acute kidney injury and critical illness

BackgroundThe aim of this study was to investigate whether bioactive adrenomedullin (bio-ADM) and interleukin-6 (IL-6) are related to acute kidney injury (AKI) and severe illness in COVID-19 patients.Methods153 patients with COVID-19 admitted to the emergency department (ED) were included. Blood samples were collected from each patient at admission. Bio-ADM and IL-6, as well as DPP3 and routinely measured markers were evaluated regarding the endpoints AKI (22/128 hospitalized patients) and a composite endpoint of admission to intensive care unit and/or in-hospital death (n = 26/153 patients).ResultsBio-ADM and IL-6 were significantly elevated in COVID-19 patients with AKI compared to COVID-19 patients without AKI (each p < 0.001). According to ROC analyses IL-6 and bio-ADM had the largest AUC (0.84 and 0.81) regarding the detection of AKI.Furthermore, bio-ADM and IL-6 were significantly elevated in COVID-19 patients reaching the composite endpoint (each p < 0.001). Regarding the composite endpoint ROC analysis showed an AUC of 0.89 for IL-6 and 0.83 for bio-ADM in COVID-19 patients.In the multivariable logistic model bio-ADM and IL-6 presented as independent significant predictors regarding both endpoints AKI and the composite endpoint in COVID-19 patients (as well as creatinine regarding the composite endpoint; each p < 0.05), opposite to leukocytes, C-reactive protein (CRP) and dipeptidyl peptidase 3 (DPP3; each p = n.s.).ConclusionElevated levels of bio-ADM and IL-6 are associated with AKI and critical illness in patients with COVID-19. Therefore, both biomarkers may be potential tools in risk stratification in COVID-19 patients at presentation in the ED.

Validation of plasma neutrophil gelatinase-associated lipocalin as a biomarker for diabetes-related acute kidney injury.

This retrospective study aimed to investigate the correlation between neutrophil gelatinase-associated lipocalin (NGAL) levels and the clinical progression and severity of diabetes-related acute kidney injury (AKI). The quantitative determination of NGAL in plasma on the Beckman Coulter AU480 analyzer was measured using the Bioporto NGAL TestTM, a particle-enhanced turbidimetric immunoassay with hospitalized patients at an East Central Georgia Medical Center. The clinical determination of plasma NGAL included a retrospective cohort study where 45 adult patients were selectively recruited. The selective criteria were patients with and without diabetes mellitus (DM) at risk for developing AKI admitted to the Medical Center between January and November 2023. All patients included in the study had pNGAL levels measured upon admission and up to 96 h post-admission. Receiver operating characteristics and likelihood ratio methods were used to determine optimal sensitivity, specificity, and cutoff value of pNGAL in AKI patients associated with and without DM. The intra-assay and interassay imprecision percent relative standard deviation was between 2.7% and 4.2%. pNGAL levels were higher for patients with AKI compared to non-AKI patients, regardless of DM status. The optimal cutoff value for pNGAL to predict AKI for patients with DM was 293 ng/mL, with a sensitivity of 80% and specificity of 87%. In a multivariate logistic regression model, pNGAL levels at 48 h post-admission were determined to be associated with diabetes-related AKI patients. Plasma NGAL levels at 48 h are associated with patients with diabetes-related AKI. The specific cutoff values for AKI for early diagnosis and risk stratification and its association with comorbidities must be determined to improve patient outcomes.

From Acute to Chronic: Unraveling the Pathophysiological Mechanisms of the Progression from Acute Kidney Injury to Acute Kidney Disease to Chronic Kidney Disease.

This article provides a thorough overview of the biomarkers, pathophysiology, and molecular pathways involved in the transition from acute kidney injury (AKI) and acute kidney disease (AKD) to chronic kidney disease (CKD). It categorizes the biomarkers of AKI into stress, damage, and functional markers, highlighting their importance in early detection, prognosis, and clinical applications. This review also highlights the links between renal injury and the pathophysiological mechanisms underlying AKI and AKD, including renal hypoperfusion, sepsis, nephrotoxicity, and immune responses. In addition, various molecules play pivotal roles in inflammation and hypoxia, triggering maladaptive repair, mitochondrial dysfunction, immune system reactions, and the cellular senescence of renal cells. Key signaling pathways, such as Wnt/β-catenin, TGF-β/SMAD, and Hippo/YAP/TAZ, promote fibrosis and impact renal function. The renin-angiotensin-aldosterone system (RAAS) triggers a cascade leading to renal fibrosis, with aldosterone exacerbating the oxidative stress and cellular changes that promote fibrosis. The clinical evidence suggests that RAS inhibitors may protect against CKD progression, especially post-AKI, though more extensive trials are needed to confirm their full impact.

Impact of low pneumoperitoneum on renal function and acute kidney injury biomarkers during robot-assisted radical prostatectomy (RARP): a randomised clinical trial

The objective of this study was to evaluate the effect of low pneumoperitoneum pressure (Pnp) on renal function and renal injury biomarkers during robot-assisted radical prostatectomy (RARP). A single-centre, triple-blinded, randomised clinical trial was conducted with 98 patients undergoing RARP, who were assigned to either standard Pnp of 12 mmHg or low Pnp of 7 mmHg. The primary outcome was urinary neutrophil gelatinase-associated lipocalin (u-NGAL), and several other kidney injury biomarkers were assessed as secondary outcomes. Acute kidney injury (AKI) was evaluated using the Kidney Disease Improving Global Outcomes (KDIGO) criteria, the gold standard method for defining AKI. The trial was registered on ClinicalTrials.gov (NCT04755452). Patients in the low Pnp group had significantly lower levels of u-NGAL (mean difference − 39.9, 95% CI − 73.7 to − 6.1, p = 0.02) compared to the standard Pnp group. No significant differences were observed for other urinary biomarkers. Interestingly, there was a significant difference in intraoperative urine production between the groups (low Pnp median: 200 mL, IQR: 100–325 vs. standard Pnp median: 100 mL, IQR: 50–200, p = 0.01). Similarly, total postoperative urine production also varied significantly (low Pnp median: 1325 mL, IQR: 1025–1800 vs. standard Pnp median: 1000 mL, IQR: 850–1287, p = 0.001). The occurrence of AKI, as defined by the KDIGO criteria, did not differ significantly between the groups. Low Pnp during RARP resulted in lower u-NGAL levels, suggesting a potential benefit in terms of reduced renal injury. However, the lack of a notable difference in AKI as defined by the KDIGO criteria indicates that the clinical significance of this finding may be limited. Further research is needed to validate and expand on these results, ultimately defining the optimal Pnp strategy for RARP and improving patient outcomes.

Toward Precision Medicine: Exploring the Landscape of Biomarkers in Acute Kidney Injury.

Acute kidney injury (AKI) remains a complex challenge with diverse underlying pathological mechanisms and etiologies. Current detection methods predominantly rely on serum creatinine, which exhibits substantial limitations in specificity and poses the issue of late-stage detection of kidney injury. In this review, we propose an up-to-date and comprehensive summary of advancements that identified novel biomarker candidates in blood and urine and ideal criteria for AKI biomarkers such as renal injury specificity, mechanistic insight, prognostic capacity, and affordability. Recently identified biomarkers not only indicate injury location but also offer valuable insights into a range of pathological processes, encompassing reduced glomerular filtration rate, tubular function, inflammation, and adaptive response to injury. The clinical applications of AKI biomarkers are becoming extensive and serving as relevant tools in distinguishing acute tubular necrosis from other acute renal conditions. Also, these biomarkers can offer significant insights into the risk of progression to chronic kidney disease CKD and in the context of kidney transplantation. Integration of these biomarkers into clinical practice has the potential to improve early diagnosis of AKI and revolutionize the design of clinical trials, offering valuable endpoints for therapeutic interventions and enhancing patient care and outcomes.

Association between platelet count and neonatal acute kidney injury: a cohort study using the medical information mart for intensive care III database

Objective A decrease in platelet count has been reported to be associated with several neonatal inflammatory diseases, including sepsis and necrotizing enterocolitis; while its association with neonatal acute kidney injury (AKI) has not been reported. This study aims to explore the association between platelet count and neonatal AKI. Methods This was a retrospective cohort study based on the Medical Information Mart for Intensive Care III (MIMIC-III) database. Data were extracted based on baseline characteristics, comorbidities, vital signs, laboratory parameters, and intervention measures. Logistic regression analysis was used to assess the association between platelet count and AKI, and results were shown as odds ratios (OR) with 95% confidence intervals (CI). Results A total of 1,576 neonates were finally included in the analysis. After adjusting birth weight, sepsis, patent ductus arteriosus, hematocrit, percentage of neutrophils, and vasopressor use, we found that platelet count in the lowest quartile (Q1) was significantly associated with the higher odds of AKI than platelet count in the highest quartile (Q4) (OR = 1.70, 95% CI: 1.01-2.87). Conclusions Low platelet count was associated with the high odds of AKI in the neonatal intensive care unit (NICU), indicating that platelet count might be a biomarker for neonatal AKI. Large-scale multicenter studies should be performed to verify the results.

Review of the limitations of current biomarkers in acute kidney injury clinical practices.

Acute kidney injury is a prevalent disease in hospitalized patients and is continuously increasing worldwide. Various efforts have been made to define and classify acute kidney injury to understand the progression of this disease. Furthermore, deviations from structure and kidney function and the current diagnostic guidelines are not adequately placed due to baseline serum creatinine values, which are rarely known and estimated based on glomerular function rate, resulting in misclassification of acute kidney injury staging. Hence, the current guidelines are still developing to improve and understand the clinical implications of risk factors and earlier predictive biomarkers of acute kidney injury. Yet, studies have indicated disadvantages and limitations with the current acute kidney injury biomarkers, including lack of sensitivity and specificity. Therefore, the present narrative review brings together the most current evidenced-based practice and literature associated with the limitations of the gold standard for acute kidney injury diagnoses, the need for novel acute kidney injury biomarkers, and the process for biomarkers to be qualified for diagnostic use under the following sections and themes. The introduction section situates the anatomy and normal and abnormal kidney functions related to acute kidney injury disorders. Guidelines in providing acute kidney injury definitions and classification are then considered, followed by a discussion of the disadvantages of standard markers used to diagnose acute kidney injury. Characteristics of an ideal acute kidney injury biomarker are discussed concerning sensitivity, specificity, and anatomic location of injury. A particular focus on the role and function of emerging biomarkers is discussed in relation to their applications and significance to the prognosis and severity of acute kidney injury. Findings show emerging markers are early indicators of acute kidney injury prediction in different clinical settings. Finally, the process required for a biomarker to be applied for diagnostic use is explained.