Serum KIM-1 and Cyctatin levels as predictors of acute kidney injury in asphyxiated neonates

Urinary liver fatty acid-binding protein: another novel biomarker of acute kidney injury

Background: Acute kidney injury (AKI) is a common complication after liver transplantation (LT), and considerably increases the morbidity and mortality of the procedure. The gold standard of measuring the kidney function, the serum creatinine level (sCr), has poor specificity and sensitivity for the early diagnosis of AKI. Novel biomarkers for the prediction or early diagnosis of AKI, would potentially increase the opportunities for therapeutic interventions.Objective: To compare the diagnostic value of the standard renal marker, sCr and neutrophil gelatinase-associated lipocalin (NGAL) to predict AKI within 48 hours of LT.Methods: During a 9-month period from 2010 to 2011, NGAL was measured two times in 90 patients who underwent LT from deceased donors—after induction of anesthesia (NGAL1) and 2 hours after reperfusion of the liver graft (NGAL2). Patients were grouped according to the presence of risk factors for developing AKI according to the Acute Kidney Injury Network criteria (increase of ≥0.3 mg/dL in plasma creatinine above the baseline value within 48 hours).Results: 60 men and 30 women with mean±SD age of 40.2±14.2 years were included in this study. The incidence of AKI was 34% (95% CI: 24%–44%). The difference between the NGAL1 and NGAL2 (ΔNGAL) and the baseline NGAL concentration was predictive of AKI in all patients. Receiver operating characteristic (ROC) curve and area under curves (AUCs) of ΔNGAL and sCr levels during the first 48 hours of LT were similar in predicting AKI. The AUCs of the ΔNGAL to predict AKI was 0.64 (95% CI: 0.52–0.76). The development of AKI was significantly correlated with the number of units of fresh frozen plasma transfused intra-operatively (p=0.017) and cold ischemic time (p=0.042).Conclusion: Serum NGAL concentrations obtained during surgery is a predictor of AKI in patients undergoing LT.

This systematic review evaluates the clinical utility of a novel biomarker kidney injury molecule 1 (Kim-1) in the prediction, diagnosis and prognosis of acute kidney injury (AKI). We searched literature in electronic databases from January 2002 to December 2009 by the key words "kidney injury molecule 1" or "Kim-1" and "acute kidney injury" or "acute renal failure". Studies were eligible for inclusion if they were primary studies published in English, in which Kim-1 was measured for the purpose of prediction, diagnosis or prognosis of AKI in patients. Eight articles met the selection criteria for inclusion in the study. Compared to non AKI patients, Kim-1 increased significantly (at least p<0.05) in AKI patients by 2 hours after cardiac surgery. In the prediction of AKI in patients within 24 hours of cardiac surgery, the sensitivity of Kim-1 ranged from 92% to 100% and AUC between 0.78 and 0.91. Kim-1 increased significantly (at least p<0.05) in AKI established patients, especially in patients with acute tubular necrosis (ATN). The AUC of Kim-1 in the diagnosis of AKI was from 0.9 to 0.95. However, Kim-1 showed weak association with the need of renal replacement therapy and death of AKI patient. Kim-1 is a potential novel urinary biomarker in the early detection of AKI within 24 hours after kidney insult. It might be especially beneficial in the diagnosis of ischemic ATN.

Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker that can potentially be used for the detection of acute renal failure earlier and more accurately than current standard examinations, such as serum levels of creatinine and urea which are less sensitive and less specific. The objective of this research was to assess the ability of NGAL as a biomarker of acute renal failure by comparing the levels of serum urea and creatinine in rats with induced acute renal failure. Twelve male Wistar rats (Rattus norvegicus), 2 months of age with a body weight (BW) of 150–200 g, were allocated into two groups. Group I (n = 2), as the control group, were injected with sterile distilled water 10 mL/kg BW intramuscularly and group II (n = 10) were injected with 50 % glycerol 10 mL/kg BW intramuscular, the rats in all group had been fasting 12 h before injection. In group II, two rats were selected at each time point (0, 6, 12, 24 and 48 h after injection) bloods collected for analysis of urea and creatinine concentration and identification of NGAL and they were necropsied and the kidney removed for histopathological analysis and NGAL identification. The levels of creatinine and urea were analysed by independent t test. Identification of NGAL was conducted by one-step reverse transcriptase polymerase chain reaction and sequencing. Results showed that the glycerol injection significantly elevated the levels of urea at 6, 12 and 24 h compared to the control group (p < 0.05). Creatinine levels were significantly increased at 24 h compared to the control group (p < 0.05). The expression of NGAL in kidney and blood samples could be detected at 6, 12 and 24 h after induction. In conclusion, the blood NGAL could be detected before increasing of creatinine levels and could be used as an early detection of acute renal failure.

The present observational study was undertaken in order to evaluate the diagnostic value of urinary N-acetyl-β-D-glucosaminidase (NAG) for the prediction of acute kidney injury (AKI) in patients after percutaneous nephrolithotripsy (PNL). Pre- and post-operative patient data were collected for 90 patients who underwent PNL between September 2008 and December 2010. The patients included 64 males and 26 females with an average age of 52.8±9.7 years. Pre- and post-operative urinary NAG was measured by colorimetric assay and serum creatinine levels were determined for comparative analysis. Urinary NAG levels significantly increased after PNL compared to pre-operative levels (P<0.05). AKI occurred in 11 cases after surgery. A comparison of the AKI and non-AKI groups revealed no significant differences in age, gender ratio or baseline creatinine levels (P>0.05); however, there were significant differences between the groups as regards surgical duration, post-operative infection rate, C-reactive protein levels and number of hospital days (P<0.05). NAG levels were significantly higher in the AKI compared to the non-AKI group after surgery (P<0.05). The diagnostic utility of the increase in urinary NAG 24 h after surgery was assessed by receiver operating characteristic (ROC) analysis. For an increase in NAG of 235.44%, the area under the ROC curve was 0.878 (P<0.01) and the sensitivity and specificity for AKI diagnosis were 81.8 and 91.1%, respectively. Urinary NAG significantly increased in patients suffering from AKI after surgery. This parameter is more sensitive than serum creatinine and can reflect the impairment of kidney function at an earlier stage. The surgical duration and post-operative infection rate are possible risk factors for AKI. Urinary NAG may have some clinical value in the early diagnosis of AKI after surgery.

ESPITE more than half a century of investigation,acute kidney injury (AKI) remains a major healthcareissue in medicine today. Reported to occur in 1–32% of allhospital admissions and 10–90% of intensive care unit ad-missions, the wide variation reflects different criteria used todefineAKI.However,independentofdefinition,adiagnosisof AKI is consistently associated with an increase in bothshort- and long-term morbidity and mortality. Even themildest forms of AKI are independently associated with in-creased early as well as long-term mortality, the risk increas-ing as severity of renal injury increases.

Urinary IL-18 is an early predictive biomarker of acute kidney injury after cardiac surgery

Acute kidney injury occurs early in PICU admission and increases risks for poor outcomes. We evaluated the feasibility of a multicenter acute kidney injury biomarker urine collection protocol and measured diagnostic characteristics of urine neutrophil gelatinase-associated lipocalin, interleukin-18, and liver fatty acid binding protein to predict acute kidney injury and prolonged acute kidney injury. Prospective observational pilot cohort study. Four Canadian tertiary healthcare PICUs. Eighty-one children 1 month to 18 years old. Exclusion criteria were as follows: cardiac surgery, baseline severe kidney disease, and inadequate urine or serum for PICU days 1-3. PICUs performed standardized urine collection protocol to obtain early PICU admission urine samples, with deferred consent. Study barriers and facilitators were recorded. Acute kidney injury was defined based on Kidney Disease: Improving Global Outcomes serum creatinine criteria (acute kidney injuryserum creatinine) and by serum creatinine and urine output criteria (acute kidney injuryserum creatinine+urine output) Prolonged acute kidney injury was defined as acute kidney injury duration of 48 hours or more. PICU days 1-3 neutrophil gelatinase-associated lipocalin, interleukin-18, and liver fatty acid binding protein were evaluated for acute kidney injury prediction (area under the curve). Biomarkers on the first day of acute kidney injury attainment (day 1 acute kidney injury) were evaluated for predicting prolonged acute kidney injury. Eighty-two to 95% of subjects had urine collected from PICU days 1-3. Acute kidney injuryserum creatinine developed in 16 subjects (20%); acute kidney injuryserum creatinine+urine output developed in 38 (47%). On PICU day 1, interleukin-18 predicted acute kidney injuryserum creatinine with area under the curve=0.82, but neutrophil gelatinase-associated lipocalin and liver fatty acid binding protein predicted acute kidney injuryserum creatinine with area under the curve of less than or equal to 0.69; on PICU day 2, area under the curve was higher (not shown). Interleukin-18 and liver fatty acid binding protein on day 1 acute kidney injury predicted prolonged acute kidney injuryserum creatinine (area under the curve=0.74 and 0.83, respectively). When acute kidney injuryserum creatinine+urine output was used to define acute kidney injury, biomarker area under the curves were globally lower. Protocol urine collection to procure early admission samples is feasible. Individual biomarker acute kidney injury prediction performance is highly variable and modest. Larger studies should evaluate utility and cost effectiveness of using early acute kidney injury biomarkers.

Background: acute kidney injury (AKI) is a syndrome characterized by a rapid (hours to days) deterioration of kidney functions. It is often diagnosed in the context of other acute illnesses and is particularly common in critically ill patients. The clinical consequences of AKI include the accumulation of waste products, electrolytes, and fluid, but also less obvious effects, including reduced immunity and dysfunction of non-renal organs (organ cross-talk). Aim of the Work: was to assess the role of serum Cystatin C in early prediction of Acute Kidney Injury in critically ill patients. Patients and Methods: This a prospective cohort study included a total of 30 critically ill patients who suffered of Acute Kidney Injury and 30 subjects confined to the same age as control, attending at ICU, Al-Azhar University Hospitals. Blood samples were taken for estimation of serum cystatin C and serum creatinine at (2, 24, 48 and 72 hours). Results: showed that at day zero at 2 hours all patient showed normal kidney functions, and no one has acute kidney injury after 24 hours about 10 patient developed acute kidney injury according to KDIGO classification with a percentage of 33.3%. after 48 hours all 30 patients developed acute kidney injury according to KDIGO classification with a percentage of 100% and after 72 hours the patients state began to improve and only 28 patients have acute kidney injury with a percentage of 93.3% and level of serum creatinine started to decrease to all patients. This was due to treatment and interference to the patients. Conclusion: Cystatin C level is a valuable biomarker in prediction and early detection of acute kidney injury. Moreover, cystatin C level may be also used for prognosis of cases of acute kidney injury. Further a large-scale study may be needed to validate its predictive value.

Early predictors of acute kidney injury in patients with cirrhosis and bacterial infection: urinary neutrophil gelatinase-associated lipocalin and cardiac output as reliable tools

Many factors such as trauma and COVID-19 cause acute kidney injury (AKI). Late AKI have a very high incidence and mortality rate. Early diagnosis of AKI provides a critical therapeutic time window for AKI treatment to prevent progression to chronic renal failure. However, the current clinical detection based on creatinine and urine output isn't effective in diagnosing early AKI. In recent years, the early diagnosis of AKI has made great progress with the advancement of information technology, nanotechnology, and biomedicine. These emerging methods are mainly divided into two aspects: First, predicting AKI through models construct by machine learning; Second, early diagnosis of AKI through detection of newly-discovered early biomarkers. Currently, these methods have shown great potential and become an attractive tool for the early diagnosis of AKI. Therefore, it is very important to discuss and summarize these methods for the early diagnosis of AKI. In this review, we first systematically summarize the application of machine learning in AKI prediction algorithms and specific scenarios. In addition, we introduce the key role of early biomarkers in the progress of AKI, and then comprehensively summarize the application of emerging detection technologies for early AKI. Finally, we discuss current challenges and prospects of machine learning and biomarker detection. The review is expected to provide new insights for early diagnosis of AKI, and provided important inspiration for the design of early diagnosis of other major diseases.

BackgroundAlthough the present diagnosis of acute kidney injury (AKI) involves measurement of acute increases in serum creatinine (SC) and reduced urine output (UO), measurement of UO is underutilized for diagnosis of AKI in clinical practice. The purpose of this investigation was to conduct a systematic literature review of published studies that evaluate both UO and SC in the detection of AKI to better understand incidence, healthcare resource use, and mortality in relation to these diagnostic measures and how these outcomes may vary by population subtype.MethodsThe systematic literature review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Data were extracted from comparative studies focused on the diagnostic accuracy of UO and SC, relevant clinical outcomes, and resource usage. Quality and validity were assessed using the National Institute for Health and Care Excellence (NICE) single technology appraisal quality checklist for randomized controlled trials and the Newcastle–Ottawa Quality Assessment Scale for observational studies.ResultsA total of 1729 publications were screened, with 50 studies eligible for inclusion. A majority of studies (76%) used the Kidney Disease: Improving Global Outcomes (KDIGO) criteria to classify AKI and focused on the comparison of UO alone versus SC alone, while few studies analyzed a diagnosis of AKI based on the presence of both UO and SC, or the presence of at least one of UO or SC indicators. Of the included studies, 33% analyzed patients treated for cardiovascular diseases and 30% analyzed patients treated in a general intensive care unit. The use of UO criteria was more often associated with increased incidence of AKI (36%), than was the application of SC criteria (21%), which was consistent across the subgroup analyses performed. Furthermore, the use of UO criteria was associated with an earlier diagnosis of AKI (2.4–46.0 h). Both diagnostic modalities accurately predicted risk of AKI-related mortality.ConclusionsEvidence suggests that the inclusion of UO criteria provides substantial diagnostic and prognostic value to the detection of AKI.

Derivation and validation of the renal angina index to improve the prediction of acute kidney injury in critically ill children

Objective To evaluate the clinical significance of serum Klotho protein levels in the early diagnosis and prognosis of acute kidney injury (AKI) among adult patients in the intensive care units (ICU). Methods The study was prospective and observational. Blood samples and clinical data of AKI patients admitted to the ICU of the First Affiliated Hospital of Xinjiang Medical University between July 1 and August 31, 2016 were collected. ELISA was used for the detection of Klotho and NGAL. Receiver operating characteristic curve (ROC) and the area under the curve (AUC) were used to compare the predictive performance among Klotho, NGAL and serum creatinine, evaluating the sensitivity and specificity of Klotho on the diagnosis of AKI. The correlation between Klotho and prognosis of AKI was investigated by comparing serum Klotho levels and early AKI predictors. Results The patients were divided into AKI group of 52 cases and non-AKI group of 98 cases. The baseline serum Klotho level in AKI group was significantly lower than that in non-AKI group (P 0.05). There was no significant correlation between the Klotho level at diagnosis of AKI and peak Scr, peak eGFR, Scr at discharge and eGFR at discharge (r=0.026, P=0.853; r=-0.127, P=0.368; r=0.243, P=0.082; r=-0.187, P=0.184). Conclusion Serum Klotho may be a potential biomarker for early diagnosis of AKI, but the association between serum klotho and the prognosis of AKI requires further study. Key words: Renal insufficiency, acute; Diagnosis; Prognosis; Klotho protein

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.