Early Diagnosis Of Acute Kidney Injury Research Articles

Diagnostic efficacy of urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 for early detection of acute kidney injury in dogs with leptospirosis or babesiosis.

This study evaluates the diagnostic efficacy of urinary biomarkers, Neutrophil Gelatinase-Associated Lipocalin (uNGAL), and Kidney Injury Molecule-1 (uKIM-1), in identifying Acute Kidney Injury (AKI) in dogs affected with leptospirosis or babesiosis. Acute kidney injury was diagnosed based on the increase in serum creatinine levels above 0.3mg/dL within 48h and dogs were categorized according to AKI grades based on International Renal Interest Society guidelines. Traditional biomarkers (serum creatinine and blood urea nitrogen) and novel biomarkers like urinary NGAL and urinary KIM-1 levels were measured and compared to concentrations obtained in control dogs. Statistical analysis assessed significant differences (P < 0.01) across AKI grades, specifically noting elevated urinary NGAL and KIM-1 in IRIS grade I AKI (P < 0.001). The study highlights the diagnostic significance of urinary NGAL and KIM-1 as early indicators of renal damage, particularly valuable in non-azotemic AKI cases, offering promising markers for early AKI diagnosis in veterinary clinical settings. These biomarkers demonstrate clinical utility and underscore their potential for improving AKI management in veterinary medicine. Further validation studies involving larger cohorts and diverse etiologies of AKI are needed to confirm the diagnostic accuracy and clinical utility of urinary NGAL and KIM-1 in veterinary practice.

Acute kidney injury comorbidity analysis based on international classification of diseases-10 codes.

Acute kidney injury (AKI) is a clinical syndrome that occurs as a result of a dramatic decline in kidney function caused by a variety of etiological factors. Its main biomarkers, serum creatinine and urine output, are not effective in diagnosing early AKI. For this reason, this study provides insight into this syndrome by exploring the comorbidities of AKI, which may facilitate the early diagnosis of AKI. In addition, organ crosstalk in AKI was systematically explored based on comorbidities to obtain clinically reliable results. We collected data from the Medical Information Mart for Intensive Care-IV database on patients aged [Formula: see text] 18 years in intensive care units (ICU) who were diagnosed with AKI using the criteria proposed by Kidney Disease: Improving Global Outcomes. The Apriori algorithm was used to mine association rules on the diagnoses of 55,486 AKI and non-AKI patients in the ICU. The comorbidities of AKI mined were validated through the Electronic Intensive Care Unit database, the Colombian Open Health Database, and medical literature, after which comorbidity results were visualized using a disease network. Finally, organ diseases were identified and classified from comorbidities to investigate renal crosstalk with other distant organs in AKI. We found 579 AKI comorbidities, and the main ones were disorders of lipoprotein metabolism, essential hypertension, and disorders of fluid, electrolyte, and acid-base balance. Of the 579 comorbidities, 554 were verifiable and 25 were new and not previously reported. In addition, crosstalk between the kidneys and distant non-renal organs including the liver, heart, brain, lungs, and gut was observed in AKI with the strongest heart-kidney crosstalk, followed by lung-kidney crosstalk. The comorbidities mined in this study using association rules are scientific and may be used for the early diagnosis of AKI and the construction of AKI predictive models. Furthermore, the organ crosstalk results obtained through comorbidities may provide supporting information for the management of short- and long-term treatment practices for organ dysfunction.

Discovering a New Drug Against Acute Kidney Injury by Using a Tailored Photoacoustic Imaging Probe.

Acute kidney injury (AKI) has become an increasing concern for patients due to the widespread clinical use of nephrotoxic drugs. Currently, the early diagnosis of AKI is still challenging and the available therapeutic drugs cannot meet the clinical demand. Herein, this work has investigated the key redox couple involved in AKI and develops a tailored photoacoustic (PA) imaging probe (AB-DiOH) which can reversibly respond to hypochlorite (ClO-)/glutathione (GSH) with high specificity and sensitivity. This probe enables the real-time monitoring of AKI by noninvasive PA imaging, with better detection sensitivity than the blood test. Furthermore, this probe is utilized for screening nephroprotective drugs among natural products. For the first time, astragalin is discovered to be a potential new drug for the treatment of AKI. After oral administration, astragalin can be efficiently absorbed by the animal body, alleviate kidney injury, and meanwhile induce no damage to other normal tissues. The treatment mechanism of astragalin has also been revealed to be the simultaneous inhibition of oxidative stress, ferroptosis, and cuproposis. The developed PA imaging probe and the discovered drug candidate provide a promising new tool and strategy for the early diagnosis and effective treatment of AKI.

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.

KIM-1, IL-18, and NGAL, in the Machine Learning Prediction of Kidney Injury among Children Undergoing Hematopoietic Stem Cell Transplantation-A Pilot Study.

Children undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are prone to developing acute kidney injury (AKI). Markers of kidney damage: kidney injury molecule (KIM)-1, interleukin (IL)-18, and neutrophil gelatinase-associated lipocalin (NGAL) may ease early diagnosis of AKI. The aim of this study was to assess serum concentrations of KIM-1, IL-18, and NGAL in children undergoing HSCT in relation to classical markers of kidney function (creatinine, cystatin C, estimated glomerular filtration rate (eGFR)) and to analyze their usefulness as predictors of kidney damage with the use of artificial intelligence tools. Serum concentrations of KIM-1, IL-18, NGAL, and cystatin C were assessed by ELISA in 27 children undergoing HSCT before transplantation and up to 4 weeks after the procedure. The data was used to build a Random Forest Classifier (RFC) model of renal injury prediction. The RFC model established on the basis of 3 input variables, KIM-1, IL-18, and NGAL concentrations in the serum of children before HSCT, was able to effectively assess the rate of patients with hyperfiltration, a surrogate marker of kidney injury 4 weeks after the procedure. With the use of the RFC model, serum KIM-1, IL-18, and NGAL may serve as markers of incipient renal dysfunction in children after HSCT.

Illumination of Hydroxyl Radical in Kidney Injury and High-Throughput Screening of Natural Protectants Using a Fluorescent/Photoacoustic Probe.

The hydroxyl radical (•OH) is shown to play a crucial role in the occurrence and progression of acute kidney injury (AKI). Therefore, the development of a robust •OH probe holds great promise for the early diagnosis of AKI, high-throughput screening (HTS) of natural protectants, and elucidating the molecular mechanism of intervention in AKI. Herein, the design and synthesis of an activatable fluorescent/photoacoustic (PA) probe (CDIA) for sensitive and selective imaging of •OH in AKI is reported. CDIA has near-infrared fluorescence/PA channels and fast activation kinetics, enabling the detection of the onset of •OH in an AKI model. The positive detection time of 12 h using this probe is superior to the 48-hour detection time for typical clinical assays, such as blood urea nitrogen and serum creatinine detection. Furthermore, a method is established using CDIA for HTS of natural •OH inhibitors from herbal medicines. Puerarin is screened out by activating the Sirt1/Nrf2/Keap1 signaling pathway to protect renal cells in AKI. Overall, this work provides a versatile and dual-mode tool for illuminating the •OH-related pathological process in AKI and screening additional compounds to prevent and treat AKI.

Vanin-1-Activated Chemiluminescent Probe: Help to Early Diagnosis of Acute Kidney Injury with High Signal-to-Noise Ratio through Urinalysis.

Acute kidney injury (AKI) is a common medical condition with high morbidity and mortality. Although urinalysis provides a noninvasive and convenient diagnostic method for AKI at the molecular level, the low sensitivity of current chemical probes used in urinalysis hinders the time diagnosis of AKI. Herein, we achieved the sensitive and early diagnosis of AKI by the development of a chemiluminescent probe CL-Pa suitable for detection of urinary Vanin-1. Vanin-1 is considered as an early and sensitive biomarker for AKI, while few chemical probes have been applied to for its efficient detection. By virtue of the low autofluorescence interference during urine imaging in the chemiluminescence model, CL-Pa could realize the monitoring of the up-regulated urinary Vanin-1 with a high signal-to-noise ratio (∼588). Importantly, under the help of CL-Pa, the up-regulation of urinary Vanin-1 of cisplatin-induced AKI mice at 12 h post cisplatin injection was detected, which was much earlier than clinical biomarkers (sCr and BUN) and change of kidney histology (48 h post cisplatin injection). Furthermore, using this probe, the fluctuation of urinary Vanin-1 of mice with different degrees of AKI was monitored. This study demonstrated the ability of CL-Pa in sensitively detecting drug-induced AKI through urinalysis and suggested the great potential of CL-Pa for early diagnosis of AKI and evaluate the efficiency of anti-AKI drugs clinically.

Cofilin-1 induces acute kidney injury via the promotion of endoplasmic reticulum stress-mediated ferroptosis

Ischemia–reperfusion injury (IRI) leads to acute kidney injury (AKI), which poses serious threat to public health and society. Many clinical studies were conducted to evaluate several biomarkers in AKI, among which Cofilin-1 remains to be a very promising one. To explore the potential mechanism of Cofilin-1 in AKI, we established an oxygen-glucose-deprivation (OGD)-induced AKI cell model. The overexpression and knock-down Cofilin-1 were used for gain- and loss-of-function. Pharmacological inhibitors were employed to study the related pathways. The results showed that Cofilin-1 was significantly upregulated in AKI cells, knocking down Cofilin-1 protected cells against the effect of OGD treatment and alleviated AKI phenotypes. Overexpression of Cofilin-1 might induce AKI by triggering ferroptosis, inhibiting NF-κB signaling or ER stress pathway attenuated Cofilin-1 induced lipid peroxidation and AKI. We also validated our findings in IRI-induced AKI mouse models in vivo. Our work elucidated that Cofilin-1 might induce AKI via promoting ER stress-mediated ferroptosis and argues it as a biomarker for early diagnosis of AKI. We also expect to offer novel insights on future therapeutic interventions.

Plasma neutrophil gelatinase-associated lipocalin role as a developing biomarker of acute renal failure following coronary artery bypass surgery

Introduction: Acute kidney injury (AKI) following coronary artery bypass graft (CABG) procure is related with elevated morbidity and mortality, early diagnosis of which is important for effective management of these patients. Neutrophil gelatinase-associated lipocalin (NGAL) is a secreted glycoprotein in response to inflammation. Objectives: The current study aimed to evaluate the role of serum NGAL in predicting AKI in a group of Iranian patients undergoing CABG. Patients and Methods: This study was a cross-sectional prospective study conducted on 79 patients undergoing CABG from Mousavi hospital, Zanjan, Iran. The blood samples for serum creatinine and plasma NGAL levels were collected before anesthesia induction and at 12th, 24th and 48th hour’s post-operative. The plasma NGAL level was measured using enzyme-linked immunosorbent assay method. The incidence of AKI was known by the risk-injury-failure-loss-end-stage renal disease (RIFLE) criteria. Results: In 23 cases (29%) AKI development was detected. In a 24-hour follow-up, the mean serum creatinine values did not change in patients while the mean plasma NGAL level was elevated within 12 hours post-operatively (207.2±180.8 ng/mL and 119.26±103.5 ng/mL in the AKI and non-AKI groups, respectively). The plasma NGAL level measured after CABG (with the cut-off point equal to 126.4 ng/mL) showed a sensitivity of 77% and a specificity of 81% for the prediction of AKI. In AKI group, no patient had grade 3 AKI and neither required dialysis. Conclusion: These data indicated that the plasma NGAL levels could be potentially utilized for early diagnosis of AKI in patients undergoing CABG.

Early assessment of acute kidney injury in severe acute pancreatitis with multimodal DWI: an animal model.

To evaluate the feasibility of multimodal diffusion-weighted imaging (DWI) for detecting the occurrence and severity of acute kidney injury (AKI) caused by severe acute pancreatitis (SAP) in rats. SAP was induced in thirty rats by the retrograde injection of 5.0% sodium taurocholate through the biliopancreatic duct. Six rats underwent MRI of the kidneys 24h before and 2, 4, 6, and 8h after this AKI model was generated. Conventional and functional MRI sequences were used, including intravoxel incoherent motion imaging (IVIM), diffusion tensor imaging (DTI), and diffusion kurtosis imaging (DTI). The main DWI parameters and histological results were analyzed. The fast apparent diffusion coefficient (ADC) of the renal cortex was significantly reduced at 2h, as was the fractional anisotropy (FA) value of the renal cortex on DTI. The mean kurtosis (MK) values for the renal cortex and medulla gradually increased after model generation. The renal histopathological score was negatively correlated with the medullary slow ADC, fast ADC, and perfusion scores for both the renal cortex and medulla, as were the ADC and FA values of the renal medulla in DTI, whereas the MK values of the cortex and medulla were positively correlated (r = 0.733, 0.812). Thus, the cortical fast ADC, medullary MK, FADTI, and slow ADC were optimal parameters for diagnosing AKI. Of these parameters, cortical fast ADC had the highest diagnostic efficacy (AUC = 0.950). The fast ADC of the renal cortex is the core indicator of early AKI, and the medullary MK value might serve as a sensitive biomarker for grading renal injury in SAP rats. The multimodal parameters of renal IVIM, DTI, and DKI are potential beneficial for the early diagnosis and severity grading of renal injury in SAP patients. • The multimodal parameters of renal DWI, including IVIM, DTI, and DKI, may be valuable for the noninvasive detection of early AKI and the severity grading of renal injury in SAP rats. • Cortical fast ADC, medullary MK, FA, and slow ADC are optimal parameters for early diagnosis of AKI, and cortical fast ADC has the highest diagnostic efficacy. • Medullary fast ADC, MK, and FA as well as cortical MK are useful for predicting the severity grade of AKI, and the renal medullary MK value exhibits the strongest correlation with pathological scores.

Paper-based multiplex colorimetric vertical flow assay with smartphone readout for point-of-care detection of acute kidney injury biomarkers

Acute kidney injury (AKI) is a serious renal emergency that is often underdiagnosed and associated with high mortality rates. Early diagnosis of AKI is crucial to improve patient prognosis and reduce healthcare costs. In this study, a paper-based colloidal gold multiplex vertical flow assay was developed for rapid detection of three AKI biomarkers, namely, NGAL, CysC, and RBP4, in a single test kit. In this system, specific capture antibodies were pre-immobilized on the sensing membrane at four spatially isolated immunoreactive sites. Gold nanoparticles were conjugated with detection antibodies as the colorimetrical labels. The resultant images could be read out qualitatively by the naked eyes or quantitatively by a smartphone-based readout device. Three AKI biomarkers could be simultaneously detected in 10–15 min. The detection sensitivity and specificity for clinical serum samples collected from 25 patients with AKI and 25 healthy individuals were determined as 92% and 88%. This vertical flow assay platform is easy to use, rapid, and low cost. It is a promising diagnostic tool for multiplex detection of disease biomarkers at point of care.

Predictive value of urinary cell cycle arrest biomarkers for all cause-acute kidney injury: a meta-analysis

The cell cycle arrest markers tissue inhibitor metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been identified as potential biomarkers of acute kidney injury (AKI) in critically ill adults in intensive care units and cardiac surgery-associated AKI (CSA-AKI). However, the clinical impact on all-cause AKI remains unclear. Here, we report a meta-analysis performed to evaluate the predictive value of this biomarker for all-cause AKI. The PubMed, Cochrane, and EMBASE databases were systematically searched up to April 1, 2022. We used the Quality Assessment Tool for Diagnosis Accuracy Studies (QUADAS-2) to assess the quality. We extracted useful information from these studies and calculated the sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). Twenty studies with 3625 patients were included in the meta-analysis. The estimated sensitivity of urinary [TIMP-2] × [IGFBP7] in the diagnosis of all-cause AKI was 0.79 (95% CI 0.72, 0.84), and the specificity was 0.70 (95% CI 0.62, 0.76). The value of urine [TIMP-2] × [IGFBP7] in the early diagnosis of AKI was assessed using a random effects model. The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 2.6 (95% CI 2.1, 3.3), 0.31 (95% CI 0.23, 0.40), and 8 (95% CI 6, 13), respectively. The AUROC was 0.81 (95% CI 0.78–0.84). No significant publication bias was observed in eligible studies. Subgroup analysis indicated that the diagnostic value was related to the severity of AKI, time measurement, and clinical setting. This study shows that urinary [TIMP-2] × [IGFBP7] is a reliable effective predictive test for all cause-AKI. However, whether and how urinary [TIMP-2] × [IGFBP7] can be used in clinical diagnosis still requires further research and clinical trials.

Use of Renal Near-Infrared Spectroscopy and Urinary Neutrophil Gelatinase-Associated Lipocalin Monitoring as Indicators of Acute Kidney Injury in Pediatric Cardiac Surgery.

Acute kidney injury (AKI) is a common complication following cardiac surgery under cardiopulmonary bypass (CPB) in children. A prospective study for examining urinary neutrophil gelatinase-associated lipocalin (NGAL) and renal near-infrared spectroscopy (NIRS) trends during AKI was conducted among pediatric patients undergoing cardiac surgery with CPB. Urinary NGAL showed a significant difference between intensive care unit admission (0 h) and 2 h post-admission (p < 0.001) and remained significant up to 4 h (p < 0.05). The renal NIRS in the AKI group showed a significant rate of decrease and lower values during the intraoperative period (p < 0.05). The cumulative median saturation of renal regional saturation of oxygen (rSO2) during CPB was 1637.5% min in the AKI group and 943.0% min in the non-AKI group. The median renal rSO2 scores at a reduction of 20% and 25% were significantly higher (p < 0.001) in the AKI group. Our results suggest that monitoring renal rSO2 scores and limiting their decline might be useful in preventing AKI. The combination of NGAL, renal rSO2, and renal rSO2 scores might be useful in the early diagnosis of AKI during pediatric cardiac surgery.

Biomarkers for prediction of acute kidney injury in pediatric patients: a systematic review and meta-analysis of diagnostic test accuracy studies.

Severity of acute kidney injury (AKI) confers higher odds of mortality. Timely recognition and early initiation of preventive measures may help mitigate the injury further. Novel biomarkers may aid in the early detection of AKI. The utility of these biomarkers across various clinical settings in children has not been evaluated systematically. To synthesize the currently available evidence on different novel biomarkers for the early diagnosis of AKI in pediatric patients. We searched four electronic databases (PubMed, Web of Science, Embase, and Cochrane Library) for studies published between 2004 and May 2022. Cohort and cross-sectional studies evaluating the diagnostic performance of biomarkers in predicting AKI in children were included. Participants in the study included children (aged less than 18years) at risk of AKI. We used the QUADAS-2 tool for the quality assessment of the included studies. The area under the receiver operating characteristics (AUROC) was meta-analyzed using the random-effect inverse-variance method. Pooled sensitivity and specificity were generated using the hierarchical summary receiver operating characteristic (HSROC) model. We included 92 studies evaluating 13,097 participants. Urinary NGAL and serum cystatin C were the two most studied biomarkers, with summary AUROC of 0.82 (0.77-0.86) and 0.80 (0.76-0.85), respectively. Among others, urine TIMP-2*IGFBP7, L-FABP, and IL-18 showed fair to good predicting ability for AKI. We observed good diagnostic performance for predicting severe AKI by urine L-FABP, NGAL, and serum cystatin C. Limitations were significant heterogeneity and lack of well-defined cutoff value for various biomarkers. Urine NGAL, L-FABP, TIMP-2*IGFBP7, and cystatin C showed satisfactory diagnostic accuracy in the early prediction of AKI. To further improve the performance of biomarkers, they need to be integrated with other risk stratification models. PROSPERO (CRD42021222698). A higher resolution version of the Graphical abstract is available as "Supplementary information".

THE DIAGNOSTIC VALUE OF URINE GELATINASE-ASSOCIATED LIPOCALIN AS A BIOMARKER FOR ACUTE KIDNEY INJURY IN PRETERM INFANTS WITH HEMODYNAMICALLY SIGNIFICANT PATENT DUCTUS ARTERIOSUS

THE DIAGNOSTIC VALUE OF URINE GELATINASE-ASSOCIATED LIPOCALIN AS A BIOMARKER FOR ACUTE KIDNEY INJURY IN PRETERM INFANTS WITH HEMODYNAMICALLY SIGNIFICANT PATENT DUCTUS ARTERIOSUS

Neutrophil Gelatinase-Associated Lipocalin as a Predictor of Acute Kidney Injury in Children With Shock: A Prospective Study.

The current definition of acute kidney injury (AKI) is based on serum creatinine (SrCr) and urine output, limited by delayed identification of such patients. Plasma neutrophil gelatinase-associated lipocalin (NGAL) is considered an early diagnostic and highly predictive biomarker of AKI. To determine the diagnostic accuracy of NGAL for AKI compared with creatinine clearance for early detection of AKI in children with shock receiving inotropic support. Critically ill children requiring inotropic support in the pediatric intensive care unit were enrolled prospectively. SrCr and NGAL values were obtained three times at six, 12, and 48 hours after vasopressor initiation. Patients with AKI were defined as having loss of >25% renal function based on creatinine clearance within 48 hours. NGAL level of more than 150 ng/dl was suggestive of the diagnosis of AKI. Receiver operator characteristic curves were generated for NGAL and SrCr to compare the predictive ability of both at 0, 12, and 48 hours of starting vasopressor support. Results: A total of 94 patients were enrolled. The mean age was 43±50.95 months. Most common primary diagnoses were related to the cardiovascular system (46%). Twenty-nine patients (31%) died during the hospital stay. Thirty-four patients (36%) developed AKI within 48hours following shock. The area under the curve (AUC) for NGAL at a cutoff of 150 ng/ml was 0.70, 0.74, and 0.73 at six-hour, 12-hour, and 48-hour follow-up, respectively. NGAL had a sensitivity of 85.3% and specificity of 50% at 0 hours of follow-up for diagnosis of AKI. Serum NGAL has better sensitivity and AUC compared to SrCr for early diagnosis of AKI in children admitted with shock.

Нарушение функции почек у детей с острыми кишечными инфекциями без развития гемолитико-уремического синдрома

Issues of nephrological complications of the acute period of acute intestinal infections (AII) are currently concentrated mainly on the problem of critical conditions associated with the development of hemolytic-uremic syndrome (HUS). Taking into account the introduction into clinical practice of new highly specific biological markers of acute kidney injury (AKI), which make it possible to diagnose this condition before the development of uremia, new prospects for the early diagnosis of AKI are opening up, which will allow timely modification of treatment tactics that prevent its progression to chronic kidney disease and reduce disability in patients, which is important at the present stage of development of pediatrics and infectious diseases. Objective. To assess the prevalence of AKI in children with moderate AII without the formation of HUS, as well as to asses the diagnostic significance of modern biological markers of kidney damage. Patients and methods. 270 patients aged 1 to 7 years with moderate AII without the development of HUS (study group), as well as 55 somatic healthy children (comparison group) were examined. Over time, standard laboratory and instrumental studies were carried out, assessment of the levels of biomarkers of structural kidney damage (lipocalin-2, cystatin C, acute kidney injury molecules-1 (KIM-1)), as well as calculation of glomerular filtration rate using various formulas. Results. It was found that upon admission, 38% of children in the main group had reduced diuresis, 13% had an increase in serum creatinine levels, while the urea level was increased in only 3% of children. When assessing the level of AKI markers in patients with AII upon admission, an increase in the level of KIM-1 in the urine was detected in 90% of patients, cystatin C and lipocalin-2 in the blood serum in 18.9% of patients. A comprehensive assessment of identified renal dysfunction (based on decreased diuresis, increased serum creatinine, decreased glomerular filtration rate) in AEI without the development of HUS made it possible to diagnose the development of AKI in 13.7%, predominantly (in 97.3% of cases) – 1th stage according to KDIGO. Among the factors of unfavorable premorbid background in children of the main group who developed AKI, anemia (in 62.2% of patients) suffered during the last 6 months was significantly more common. AII (51.4%) and SARS (51.4%) (p &lt; 0.001). Conclusion. With moderate AII in children, the development of AKI is registered in 13.7% of cases. Clinical factors associated with the development of AKI are: febrile fever lasting 4–6 days, degree II exacerbation, repeated vomiting lasting more than 3 days, diarrhea lasting 5–8 days, and the predominance of viral etiology of the disease. In order to optimize the diagnosis of AKI in children with AII, it is advisable to include in the examination plan the determination of the level of cystatin C and lipocalin-2 in the blood serum, which have a significantly higher sensitivity (94.6 and 97.3%) and specificity (84.5 and 85.8% respectively) compared to creatinine levels. Key words: children, acute intestinal infection, acute kidney injury, cystatin C, lipocalin-2, NGAL, KIM-1

Renal Endothelial Cell-Targeted Extracellular Vesicles Protect the Kidney from Ischemic Injury.

Endothelial cell injury plays a critical part in ischemic acute kidney injury (AKI) and participates in the progression of AKI. Targeting renal endothelial cell therapy may ameliorate vascular injury and further improve the prognosis of ischemic AKI. Here, P-selectin as a biomarker of ischemic AKI in endothelial cells is identified and P-selectin binding peptide (PBP)-engineered extracellular vesicles (PBP-EVs) with imaging and therapeutic functions are developed. The results show that PBP-EVs exhibit a selective targeting tendency to injured kidneys, while providing spatiotemporal information for the early diagnosis of AKI by quantifying the expression of P-selectin in the kidneys by molecular imaging. Meanwhile, PBP-EVs reveal superior nephroprotective functions in the promotion of renal repair and inhibition of fibrosis by alleviating inflammatory infiltration, improving reparative angiogenesis, and ameliorating maladaptive repair of the renal parenchyma. In conclusion, PBP-EVs, as an ischemic AKI theranostic system that is designed in this study, provide a spatiotemporal diagnosis in the early stages of AKI to help guide personalized therapy and exhibit superior nephroprotective effects, offering proof-of-concept data to design EV-based theranostic strategies to promote renal recovery and further improve long-term outcomes following AKI.

Serum procalcitonin, C-reactive protein, and neutrophil gelatinase-associated lipocalin in early diagnosis of acute kidney injury after upper urinary tract calculi.

To investigate the value of serum procalcitonin(PCT), C-reactive protein(CRP), and neutrophil gelatinase-associated lipocalin(NGAL) in the early diagnosis of acute kidney injury(AKI) after upper urinary tract calculi(UUTC). The clinical data of 86 patients who underwent UUTC surgery in our hospital from March 2020 to April 2021 were analyzed retrospectively(Approval number: 20211205L, Date: 2021-12-21). Patients were divided into an AKI group (AKI≥7 days after the operation) and a Non-AKI group. PCT, CRP, and NGAL concentrations were compared before and two hours after the operation. Multivariate logistic regression analysis was used to identify risk factors affecting the early occurrence of AKI post-operation. The receiver operating characteristic curve evaluated PCT, CRP, and NGAL in the early AKI diagnosis. A total of 86 patients (30 with AKI and 56 with Non-AKI) were included. Kidney injury molecule-1(KIM-1) and urinary microalbumin(mAlb) concentrations were significantly higher in the AKI group (P<0.05). PCT, CRP, and NGAL concentrations were significantly higher two hours after the operation than before the operation (P<0.05). KIM-1 levels and elevated PCT, CRP and NGAL concentrations affected the establishment of AKI after UUTC. The sensitivity of PCT, CRP, and NGAL in evaluating AKI after UUTC were 81.17%, 84.42%, and 79.02%; the specificity was 62.31%, 71.48%, and 73.32%; and the AUC was 0.812, 0.885 and 0.804 respectively. PCT, CRP, and NGAL concentrations in patients with AKI after UUTC were significantly increased two hours after the operation, which can be used for the early diagnosis of AKI after UUTC operation.

New Biomarkers in Early Diagnosis of Acute Kidney Injury in Children

Acute Kidney Injury (AKI) is a common condition with a high risk of mortality and morbidity, so, early diagnosis and management of AKI is very important in clinical practice. Despite significant progress in the management of AKI, it still carries high morbidity and mortality. BUN and serum creatinine are not very sensitive nor specific for the diagnosis of AKI because they are affected by many renal and non-renal factors that are independent of kidney injury or kidney function and change significantly only after significant kidney injury and with a substantial time delay. Detection of biomarkers of AKI made predominantly by the injured kidney tissue are essential for the early diagnosis of AKI. An ideal biomarker should be one that could be easily measured, with no interference with other biologic variables, and be able to clarify early phases of kidney damage. The most common biomarkers studied are Neutrophil Gelatinase-Associated Lipocalin (NGAL), Interleukin-18 (IL-18), Kidney Injury Molecule-1 (KIM-1), Cystatin-C, L type Fatty Acid-Binding Protein (L-FABP), N-Acetyl-β-D Glucosaminidase (NAG), netrin-1, vanin-1, and Monocyte Chemoattractant Protein-1 (MCP-1) and calprotectin.