Diagnosis Of AKI Research Articles

Outcome of early versus late CRRT in critically ill patients with acute kidney injury

AKI is a common but serious complication in acutely unwell patients and results in high morbidity and mortality. This review considers the issue of the effects of early versus late initiation of CRRT on patient outcomes. Early CRRT may be defined as inception shortly after the diagnosis of AKI has been established, especially in the case of signs related to fluid overload or severe electrolyte disturbances. Early CRRT would offer potential benefits like an improved survival rate, complications avoided as regards pulmonary edema and cardiac failure, better nutritional support, and a reduced need for more intensive renal replacement support later. On the other hand, late CRRT is performed in clinical practice when more severe AKI manifestations have occurred, which are usually associated with higher mortality and complications due to fluid overload and metabolic disturbances. Key studies referred to report worse outcomes for late initiation, considering higher multi-organ failure and prolongation of the length of stay in the ICU. Most observational studies report better outcomes with early CRRT, while randomized controlled trials exhibit variable results, with some finding no clinically significant difference in mortality between the timing of early and delayed initiation.

Urinary Cytokeratin 20 as a Biomarker for AKI-CKD Transition among Patients with Acute Decompensated Heart Failure and AKI.

Predicting the risk of AKI-CKD transition remains a major challenge in management of acute decompensated heart failure and AKI. This study investigated the clinical utility of urinary cytokeratin 20 (CK20), a novel biomarker reflecting severity of histological acute tubular injury, for identifying patients at risk of AKI-CKD progression. This prospective cohort study included a Test set comprising 279 consecutive hospitalized patients with acute decompensated heart failure and AKI in 5 centers and a Validation set enrolling 206 similar patients at an external center. Urinary CK20 and seven reported renal tubular injury biomarkers at the time of AKI diagnosis were measured. The primary outcome was a composite of AKI-CKD transition 90 days after AKI or all-cause death within 90 days. The secondary outcome was AKI-CKD progression 90 days after AKI. In the Test set, 115 (41%) patients reached the primary endpoint. Concentrations of urinary CK20 peaked on the day of AKI diagnosis and remained elevated 14 days after AKI. After multivariable adjustment, the highest tertile of urinary CK20 was associated with 21-fold higher risk of the primary outcome and 29-fold higher risk of the secondary outcome. For predicting the primary and the secondary outcomes, urinary CK20 at the time of AKI diagnosis had area under the receiver-operating characteristic curves (AUC) of 0.82 (95% confidence interval [CI], 0.77-0.87) and 0.81 (95% CI, 0.75-0.87), and outperformed other reported biomarkers reflecting acute tubular injury and the risk of CKD. Adding urinary CK20 to the clinical variables improved the ability for predicting the primary outcome with an AUC of 0.90 (95% CI, 0.85-0.94), and largely improved the risk reclassification. The ability of urinary CK20 in predicting AKI-CKD transition was further confirmed in the Validation set. Urinary CK20 improved prediction of the risk for transition from AKI to CKD in patients with acute decompensated heart failure and AKI.

Modified furosemide responsiveness index and biomarkers for AKI progression and prognosis: a prospective observational study.

Modified furosemide responsiveness index (mFRI) is a novel biomarker for assessing diuretic response and AKI progression in patients with early AKI. However, the comparative predictive performance of mFRI and novel renal biomarkers for adverse renal outcomes remains unclear. In a single-center prospective study, we aimed to evaluate the discriminatory abilities of mFRI and other novel renal biomarkers in predicting AKI progression and prognosis in patients with initial mild and moderate AKI (KDIGO stage 1 to 2). Patients with initial mild and moderate AKI within 48h following cardiac surgery were included in this study. The mFRI, renal biomarkers (including serum or urinary neutrophil gelatinase-associated lipocalin [sNGAL or uNGAL], serum cystatin C, urinary N-acetyl-beta-D-glycosaminidase [uNAG], urinary albumin-to-creatinine ratio) and cytokines (TNF, IL-1β, IL-2R, IL-6, IL-8, and IL-10) were measured at AKI diagnosis. The mFRI was calculated for each patient, which was defined as 2-hour urine output divided by furosemide dose and body weight. Of 1013 included patients, 154 (15.2%) experienced AKI progression, with 59 (5.8%) progressing to stage 3 and 33 (3.3%) meeting the composite outcome of hospital mortality or receipt of renal replacement therapy (RRT). The mFRI showed non-inferiority or potential superiority to renal biomarkers and cytokines in predicting AKI progression (area under the curve [AUC] 0.80, 95% confidence interval [CI] 0.77-0.82), progression to stage 3 (AUC 0.87, 95% CI 0.85-0.89), and composite outcome of death and receipt of RRT (AUC 0.85, 95% CI 0.82-0.87). Furthermore, the combination of a functional biomarker (mFRI) and a urinary injury biomarker (uNAG or uNGAL) resulted in a significant improvement in the prediction of adverse renal outcomes than either individual biomarker (all P < 0.05). Moreover, incorporating these panels into clinical model significantly enhanced its predictive capacity for adverse renal outcomes, as demonstrated by the C index, integrated discrimination improvement, and net reclassification improvement (all P < 0.05). As a rapid, cost-effective and easily accessible biomarker, mFRI, exhibited superior or comparable predictive capabilities for AKI progression and prognosis compared to renal biomarkers in cardiac surgical patients with mild to moderate AKI. Clinicaltrials.gov, NCT04962412. Registered July 15, 2021, https://clinicaltrials.gov/ct2/show/NCT04962412?cond=NCT04962412&draw=2&rank=1 .

Urine Output (UO) and AKI Diagnosis in Neonates and Infants: A Prospective Study in Cardiac Surgery Patients with Indwelling Urinary Catheters

Urine Output (UO) and AKI Diagnosis in Neonates and Infants: A Prospective Study in Cardiac Surgery Patients with Indwelling Urinary Catheters

Acute Kidney Injury in Hospitalized Patients With Exertional Rhabdomyolysis

An association between serum creatine kinase (CK) levels and the risk of kidney failure in patients with exertional rhabdomyolysis (ERM) has been suggested. However, the actual incidence of AKI in hospitalized patients with ERM along with the contributing cofactors that may increase the risk of AKI have rarely been investigated. To examine the incidence of kidney injury in hospitalized patients with ERM and to identify additional cofactors that might contribute to the development of kidney injury in patients with ERM. This retrospective cohort study was conducted in a diverse community population of patients 18 years or older with ERM who were hospitalized across Kaiser Permanente Northern California between January 1, 2009, and December 31, 2019. Patients were initially identified through electronic screening for all-cause rhabdomyolysis admissions, followed by manual medical record reviews to verify their eligibility for the study. The diagnosis of AKI and chronic kidney disease (CKD) was determined using KDIGO (Kidney Disease Improving Global Outcomes) criteria and confirmed by medical record review. Data analysis was performed from October 1, 2023, to January 31, 2024. History of strenuous physical exercise before hospitalization for ERM. Development of AKI, CKD, and compartment syndrome and number of deaths. Among 3790 patients hospitalized for rhabdomyolysis between 2009 and 2019 in Kaiser Permanente Northern California, 200 (mean [SD] age, 30.5 [8.5] years; 145 [72.5%] male) were confirmed to have ERM via medical record review. Seventeen patients (8.5%) developed AKI, none developed CKD, 1 (0.5%) developed compartment syndrome, and there were no fatalities. There was no association between serum CK levels and the risk of AKI. However, the risk of AKI was significantly higher in patients with ERM who used nonsteroidal anti-inflammatory drugs (NSAIDs) before admission (11 of 17 with AKI [64.7%] vs 40 of 183 without AKI [21.9%], P < .001) or experienced dehydration (9 of 183 without AKI [52.9%] vs 9 of 17 with AKI [4.9%], P < .001). This analysis suggests that eliminating preadmission NSAID use and dehydration could reduce the risk of potential AKI in patients with ERM by 92.6% (95% CI, 85.7%-96.1%) in this population. The findings of this cohort study of hospitalized patients with ERM suggest that serum CK elevation alone is insufficient as an indicator of AKI in patients with ERM. Concurrent risk factors, such as NSAID use or dehydration, may be associated with AKI development in patients with ERM.

Human Proenkephalin A 119-159 (penKid) in Extracorporeal Therapies: Ex vivo Sieving Coefficient, Diffusive Clearance, and Hemoadsorption Kinetics

Introduction: Enkephalins, endogenous opioid peptides, are involved in the regulation of renal function. One derived molecule, proenkephalin A, also known as penKid, has been demonstrated to be a reliable biomarker for kidney function and its plasma concentration correlates with measured glomerular filtration rate. penKid is used for prediction and diagnosis of AKI and need of renal replacement therapy (RRT). penKid has also been used to predict the successful weaning from RRT in patients with AKI. Whether the concentration of penKid is affected or not by RRT is a controversial point and there are no studies describing the kinetics of the molecule in such conditions. The low molecular weight (4.5 kDa) would imply free removal by the glomerulus and the dialysis membranes. During RRT, this reduction could not be detected in clinical practice due to the complex kinetics involving either low dialytic clearance or increased production in response to impaired kidney function. The aim of this study was to determine the sieving coefficient and the diffusive clearance of the penKid molecule in conditions of in vitro continuous veno-venous hemofiltration (CVVH) and continuous veno-venous hemodialysis (CVVHD), respectively, and also the penKid removal ratio in conditions of in vitro hemoadsorption (HA) using a synthetic microporous resin. Methods: Blood spiked with a lyophilized penKid peptide solved in 20 mm dipotassium phosphate and 6 mm disodium EDTA [pH 8] to reach target concentrations is used as testing solution. In each experiment, the blood batch was adjusted at a volume of 1,000 mL, maintained at 37°, and continuously stirred. Samples were collected from blood, ultrafiltrate, and spent dialysate at different times during the experiments. Sieving, clearance, and removal ratio were calculated. Results: Significant removal of penKid was observed in CVVH (sieving 1.04 ± 0.27), in CVVHD (clearance 23.08 ± 0.89), and in HA (removal ratio 76.1 ± 1% after 120 min). Conclusion: penKid is effectively removed by extracorporeal therapies. In presence of anuria, penKid generation kinetics can be calculated based on extracorporeal removal and volume variation. In steady state conditions, declining values may be the result of an initial renal function recovery and may suggest discontinuation and successful liberation from RRT.

FACTORS RELATED TO MIDDLE- LONG-TERM MORTALITY IN ACUTE KIDNEY INJURY

Aim: To determine the clinical and laboratory parameters that affect the mid-long term mortality of patients hospitalized for AKI. Material and method: Patients hospitalized with the diagnosis of AKI in the intensive care unit and clinic of Nephrology for four years were retrospectively screened. The files of these patients were scanned. Demographic data, comorbidities, vital signs and laboratory parameters were scanned. It was determined in terms of factors affecting mortality in these patients (living and dying) over a 4-year period. Results: The effects of the variables found to be significant (age, presence of hypertension and coronary artery disease (CAD), sedimentation, C-reactive protein (CRP), urea, potassium (K), magnesium (Mg), pH and CRP-albumin ratio (CAR) by univariate analysis on mortality was performed using multiple logistic regression analysis, which was used to identify the independent risk factors of mortality. Multiple logistic regression analysis using Stepwise selection method revealed that increasing age (IQR=1.04, 95% CI=1.01 – 1.07, p=.004), presence of CAD (IQR =2.16, 95% CI=1.16 – 4.02, p=.016), increased Mg (IQR =2.64, 95% CI=1.18 – 5.92, p=.018) and K (IQR =1.70, 95% CI=1.21 – 2.41, p=.002) were independent risk factors for mortality. The accuracy rate for the predictive performance of this prediction model in predicting mortality was 71.1%, with a sensitivity of 26.5%, a specificity of 90%, and an AUC of 0.753. Conclusion: In our predictive model, in the medium-long term, we found old age, the presence of coronary artery disease, increased K and Mg as the independent risk factors for mortality in AKI patients.

#2548 In vitro evaluation of proenkephalin kinetics in hemofiltration and hemodialysis

Abstract Background and Aims Proenkephalin A 119-159 (penKid) is a stable surrogate marker for enkephalins (endogenous opioids regulating kidney function). PenKid plasma concentration correlates to GFR and increases in AKI, for this reason it can be used for prediction and diagnosis of AKI (even subclinical forms) and need of RRT. Furthermore, it seems to be also a reliable biomarker to predict the successful liberation from RRT and may therefore aid in the successful weaning of patients from RRT. PenKid has the perk of maintaining stable its concentration during RRT, suggesting that is barely filtered, in contrast to other biomarkers. However, with its small size of 4.5 kDa, penKid can be assumed to be freely filtered through the glomerulus and dialysis membranes. To address the issue about stable penKid plasma concentrations in RRT (no extracorporeal removal or increased production in response to impaired kidney function), we planned ex vivo experiments simulating different conditions of RRT. The aim of this study is to determine the sieving coefficient and the diffusive clearance of the penKid molecule in conditions of in vitro continuous veno-venous hemofiltration (CVVH) and continuous veno-venous hemodialysis (CVVHD), respectively. Method The lyophilized peptide was solved in 20 mM Dipotassium phosphate, 6 mM Disodium EDTA [pH 8], avoiding concentrations higher than 1 mg/mL. The compound was diluted in 50 mL of plasma to ensure homogeneous distribution. For each experimental modality, a batch of blood of 1000 mL with adjusted hematocrit at 30% and albumin concentration of 3 g% was utilized. Blood was spiked with lyophilized synthetic penKid to achieve two target concentrations of 150 and 500 pmol/L in CVVH and CVVHD modalities, respectively. Blood was adjusted for a volume of 1000 mL, maintained at 37° and continuously stirred during the experiments. CVVH was performed with blood flow (QB) = 150 mL/min and ultrafiltration rate (QUF) = 20 mL/min to reproduce a filtration fraction of 20%. The ultrafiltrate was reinfused in the venous line to maintain initial volume. This allowed to define convective clearance and solute sieving coefficient in pure convective mode. CVVHD was performed with QB = 150 mL/min and dialysate flow (QD) = 35 mL/min (Net QUF = 0 mL/min). This allowed the calculation of diffusive clearance. A polysulfone dialyzer (AV1000 FMC, Bad Homburg, Germany) was utilized. Samples were taken at 10, 30, 60 minutes from the initiation of the circulation, in both modalities. Results Initial penKid concentrations in blood corresponded to the desired targets in all the experiments. Sieving coefficients displayed values between 0.69 and 1.5 and they appear to remain stable over time (Fig. 1). Diffusive clearance displayed values between 35 and 15.7 mL/min. Values appear to present a slight decrease over time (Fig. 2). The observed variability can be attributed to several factors: difference in plasma protein interference in various moments of the experiments, difference in concentration of penKid in plasma water versus plasma or blood, variability in the sample measurements. Conclusion Significant removal of penKid can be obtained by extracorporeal therapies both in convection (CVVH) and diffusion (CVVHD). Further investigation is needed to assess if these findings are confirmed during in vivo treatments in which penKid kinetics is affected by generation, elimination and changes in distribution volume.

#1900 Should we prescind of KDIGO Stage 2 in AKI severity classification?

Abstract Background and Aims The most worldwide used classification system for staging AKI is KDIGO-2012, it was based on a combination of the RIFLE and AKIN criteria. KDIGO severity stages are defined: Stage 1 ↑ in SCr by &amp;gt;0.3 mg/dl or increase in SCr to &amp;gt;1.5x baseline. Stage 2 ↑ in SCr ≥2.0–2.9x baseline. Stage 3 ↑ in SCr ≥3.0x baseline, ↑ in SCr to &amp;gt;4.0 mg/dl, or initiation of RRT. Some authors advocate for the elimination of the Stage 2 level and its incorporation in the severer stage; the justification is that this stage has a smaller number of individuals, and they show poorer clinical outcomes. We tested this hypothesis in a real-world setting. Method We retrospectively included all patients admitted to nephrology ward and nephrology consultations with AKI diagnosis by KDIGO-2012 classification, during a 3-y period. We compared clinical outcomes between KDIGO-AKI Stage 2 and 3. We excluded need for HD (because it is a criterion for Stage 3) and HD dependence at discharge (a consequence of initiating HD). In addition, we calculated the proportion of patients classified in Stage 2 by the rate of SCr increment, that were re-classified into Stage 3 by KDIGO criteria. Results 1130 individuals met inclusion criteria. 458 (41%) Stage-1, 148 (13%) Stage-2, 524 (46%) in Stage-3. We found no statistically significant differences in age, Charlson's Index, HTN and DM prevalence, hospitalization in medical wards, and hospital acquired AKI between groups. We found significant differences in sex distribution (61% Stage-2, 70% Stage-3) (see Table A: Features). Hospital stay was significantly shorter in Stage1-15d (±12) but not significantly different between Stage-2 19d (±16) and Stage-3 20d (±17). Median of time to nephrology consultation was 6-7d in all groups. Rate of in-hospital mortality incremented gradually in every severity stage: 9% Stage-1, 18% Stage-2 and 31% Stage-3 (see Table B: Results). When using only the rate of SCr increment as the classification criterion, 265 (24%) of patients would have been catalogued in the moderate AKI stratum. Of the 117 patients that were reclassified as AKI Stage-3, 36 needed HD, and 81 reached a SCr &amp;gt;4.0 mg/dl. Conclusion The proportion of subjects classified in KDIGO AKI Stage-2 is small but not negligible. We found that Stage-2 individuals show longer hospital stay and increased mortality than Stage-1, and slightly better outcomes than Stage-3; therefore, we consider that an increase in SCr ≥2.0–2.9x from baseline still leads to deleterious consequences. We also observed that possibly KDIGO AKI Stage 3 criteria lead to a skew to classification in the severer stage, (almost half of individuals are reclassified). With these findings, should we prescind of KDIGO Stage-2 in AKI severity classification?

#259 Predictive capacity and comparison of new biomarkers for AKI in patients undergoing non-cardiac surgery

Abstract Background and Aims The diagnosis of AKI, according to the KDIGO guidelines, is still based on a tangible increase in serum creatinine which, however, cannot be detected until 24-48 hours after renal damage. Unfortunately, it has not been possible to identify among the various new biomarkers the one that is potentially able to detect AKI early, to intervene promptly to preserve renal function. The aim of this study was to analyze, in a population of patients undergoing major non-cardiac surgery, the most recent urinary biomarkers to evaluate their predictive potential for AKI and compare them with creatinine levels. Method 22 patients (18 males, 4 females) with an average age of 76 (67-85) years were enrolled for the study. 22 urine samples were analyzed by: Results Carrying out a correlation between the new biomarkers for AKI (Nephrocheck, NGALds and SEPP1) with creatinine levels at different times (pre-operative, post-operative and 24 h post-operative) shows a significant correlation only with NGALds (respectively p = 0.017, p = 0.035 and p = 0.012) (Table). Subdividing patients based on the increase in creatinine levels from pre-operation to 24 hours post-operation, the only biomarker that showed an increase in values ​​was NGALds, while the others showed levels discordant with creatinine. Conclusion By analyzing the new biomarkers and comparing them with the creatinine data, it emerged that NGALds alone significantly correlated with the latter at different times. The other urinary biomarkers (Nephrocheck and SEPP1) showed no correlation with creatinine levels. Based on this outcome, it could be assumed that NGALds is the biomarker which, due to its characteristics already stated in numerous studies and its correlation with creatinine, could be used and replace the latter as an early biomarker of AKI.

Clinical case of mechanical and non-mechanical rhabdomyolysis complicated by acute kidney injury. Case report

To date, the problem of rhabdomyolysis remains relevant in Russia. Despite the introduction of modern methods of diagnosis, prevention and treatment, mortality remains high, up to 40%, especially with the addition of acute kidney injury. This article presents a clinical case of rhabdomyolysis, which arose as a result of the combined effects of non-traumatic (toxic effects of methadone, alcohol) and traumatic (vibration and non-physiological position during sleep) factors. This syndrome eventually led to the development of acute kidney damage up to anuria. In this clinical case, intensive infusion and detoxification therapy, including hemodialysis procedures, was carried out, which led to an almost complete restoration of the functional state of the kidneys. Thus, early diagnosis of rhabdomyolysis and AKI based on anamnesis, timely laboratory and instrumental diagnosis can prevent severe kidney damage up to terminal uremia and fatal consequences.

A novel ESIPT fluorescent probe for early detection and assessment of ferroptosis-mediated acute kidney injury via peroxynitrite fluctuation

BackgroundAcute kidney injury (AKI) poses a severe risk to public health, mostly manifested by damage and death of renal tubular epithelial cells. However, routine blood examination, a conventional approach for clinical detection of AKI, is not available for identifying early-stage AKI. Plenty of reported methods were lack of early biomarkers and real time evaluation tools, which resulted in a vital challenge for early diagnosis of AKI. Therefore, developing novel probes for early detection and assessment of AKI is exceedingly crucial. ResultsBased on ESIPT mechanism, a new fluorescent probe (MEO-NO) with 2-(2′-hydroxyphenyl) benzothiazole (HBT) derivatives as fluorophore has been synthesized for dynamic imaging peroxynitrite (ONOO−) levels in ferroptosis-mediated AKI. Upon the addition of ONOO−, MEO-NO exhibited obvious fluorescence changes, a significant Stokes shift (130 nm) and rapid response (approximately 45 s), and featured exceptional sensitivity (LOD = 7.28 nM) as well as high selectivity from the competitive species at physiological pH. In addition, MEO-NO was conducive to the biological depth imaging ONOO− in cells, zebrafish, and mice. Importantly, MEO-NO could monitor ONOO− levels during sorafenib-induced ferroptosis and CP-induced AKI. With the assistance of MEO-NO, we successfully visualized and tracked ONOO− variations for early detection and assessment of ferroptosis-mediated AKI in cells, zebrafish and mice models. Significance and noveltyBenefiting from the superior performance of MEO-NO, experimental results further demonstrated that the levels of ONOO− was overexpressed during ferroptosis-mediated AKI in cells, zebrafish, and mice models. The developed novel probe MEO-NO provided a strong visualization tool for imagining ONOO−, which might be a potential method for the prevention, diagnosis, and treatment of ferroptosis-mediated AKI.

Evaluation of Renal Function with Urinary NGAL and Doppler Ultrasonography in ICU Patients: A 1-Year Observational Pilot Study.

We estimated the diagnostic accuracy of urinary NGAL for the diagnosis of AKI. Urinary NGAL and Creatinine were measured daily for up to 3 days. Doppler ultrasonography was performed within 24 h of admission and for the following 3 days. Of the 21 patients, 44% had AKI during their ICU stay. The AKI group presented with higher values of serum Creatinine, renal length, MDRD as well as SAPS II already at admission. Urinary NGAL was significantly higher among patients with AKI and patients AKI-no at T0 (p < 0.0001) and increased steadily on T1 and T2. Urinary NGAL seemed to be a notable diagnostic marker for AKI from the first measurement (T0) with an area under the ROC of 0.93 (95% CI = 0.78-0.99) with a sensitivity of 99%. RRI levels were slightly higher in the AKI group at each time and increased gradually from T0 to T2 but reached statistical significance only at T2 (p = 0.02). Renal length and SAPS II at T0 showed high AuRoc and sensitivity. Urinary NGAL is a valuable marker for AKI in intensive care settings. It seemed that a pre-existing chronic renal disease, the SAPS II and the NGAL at admission represented the principal predictors of AKI.

Epidemiology, Risk Factors, and Clinical Outcomes of AKI in Pediatric Hematopoietic Stem Cell Transplant Patients.

Key Points The cumulative incidence of AKI diagnosis post–hematopoietic stem cell transplantation was 12.9%. Calcineurin inhibitor use was associated with the highest cumulative incidence, 21.6%, after hematopoietic stem cell transplantation.Patients with AKI with hypertension/hypertensive disease had a 30-day survival probability of 63.9% (hazard ratio, 4.86, 95% confidence interval, 3.58 to 6.60).Patients with AKI were 2.5 times more likely to experience composite hospitalization and/or mortality at 30 days. Of patients who developed AKI, dialysis dependence has nearly tripled since 2014. Background AKI is a common complication in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT), with a reported prevalence ranging from 68% to 84%. Few multicenter pediatric studies comprehensively assess the epidemiologic associations and clinical outcomes associated with AKI development. Methods An observational, retrospective analysis was conducted using an aggregated electronic health record data platform. The study population consisted of pediatric patients (age &lt;18 years) who underwent HSCT over a 20-year period. The study groups consisted of patients with an encounter diagnosis of AKI (n=713) and those without AKI (n=4455). Both groups were propensity matched for age, sex, race, prior cancer diagnosis, and other comorbidities. End points were incidence, mortality risk, clinical outcomes, and prevalence of dialysis dependence. Competing risks analysis, Cox proportional hazard analyses, Kaplan–Meier survival curves, and incidence/prevalence rates were calculated. Results After matching, 688 patients were identified. Cumulative incidence of AKI diagnosis post-HSCT was 13.7%. Hypertensive disease, calcineurin inhibitors, and vancomycin were the most prevalent risk factors for AKI, with calcineurin inhibitors showing the highest cumulative incidence (21.6%). Patients with AKI with hypertensive disease had a survival probability of 63.9% at 30 days, followed by calcineurin inhibitors (64.4%) and vancomycin (65.9%). Patients with AKI were 1.7 times more likely to experience composite hospitalization and/or mortality at 30 days. At 365 days post-HSCT, patients with AKI had higher rates of all-cause emergency department visits, intensive care unit admissions, and mechanical ventilation compared with non-AKI. Of patients who developed AKI, the prevalence of dialysis dependence has nearly tripled since 2014. Conclusions The findings highlight a strong association between specific risk factors, such as hypertension, calcineurin inhibitor use, and vancomycin use, with increased mortality and adverse clinical outcomes in patients with AKI after HSCT. These results emphasize the need for preventative actions such as 24-hour BP monitoring and discontinuation of potential nephrotoxic medications.

Exploration of potential biomarkers and therapeutic targets for trauma-related acute kidney injury

PurposeAcute kidney injury (AKI) is one of the most common functional injuries observed in trauma patients. However, certain trauma medications may exacerbate renal injury. Therefore, the early detection of trauma-related AKI holds paramount importance in improving trauma prognosis. MethodsQualified datasets were selected from public databases, and common differentially expressed genes related to trauma-induced AKI and hub genes were identified through enrichment analysis and the establishment of protein-protein interaction (PPI) networks. Additionally, the specificity of these hub genes was investigated using the sepsis dataset and conducted a comprehensive literature review to assess their plausibility. The raw data from both datasets were downloaded using R software (version 4.2.1) and processed with the "affy" package19 for correction and normalization. ResultsOur analysis revealed 585 upregulated and 629 downregulated differentially expressed genes in the AKI dataset, along with 586 upregulated and 948 downregulated differentially expressed genes in the trauma dataset. Concurrently, the establishment of the PPI network and subsequent topological analysis highlighted key hub genes, including CD44, CD163, TIMP metallopeptidase inhibitor 1, cytochrome b-245 beta chain, versican, membrane spanning 4-domains A4A, mitogen-activated protein kinase 14, and early growth response 1. Notably, their receiver operating characteristic curves displayed areas exceeding 75%, indicating good diagnostic performance. Moreover, our findings postulated a unique molecular mechanism underlying trauma-related AKI. ConclusionThis study presents an alternative strategy for the early diagnosis and treatment of trauma-related AKI, based on the identification of potential biomarkers and therapeutic targets. Additionally, this study provides theoretical references for elucidating the mechanisms of trauma-related AKI.

Kidney replacement therapy in COVID-19-Related acute kidney injury: The impact of timing on mortality.

The objective of this study was to determine the impact of the timing of KRT, dichotomized by a temporal criterion or by creatinine level, in patients with COVID-19-related AKI. This was a retrospective study involving 512 adult patients admitted to the ICU. All participants had laboratory-confirmed COVID-19 and a confirmed diagnosis of AKI. The potential predictors were the determination of the timing of KRT based on a temporal criterion (days since hospital admission) and that based on a serum creatinine cutoff criterion. Covariates included age, sex, and the SOFA score, as well as the need for mechanical ventilation and vasopressors. The main outcome measure was in-hospital mortality. We evaluated 512 patients, of whom 69.1% were men. The median age was 64 years. Of the 512 patients, 76.6% required dialysis after admission. The overall in-hospital mortality rate was 72.5%. When the timing of KRT was determined by the temporal criterion, the risk of in-hospital mortality was significantly higher for later KRT than for earlier KRT-84% higher in the univariate analysis (OR = 1.84, 95%, [CI]: 1.10-3.09) and 140% higher after adjustment for age, sex, and SOFA score (OR = 2.40, 95% CI: 1.36-4.24). When it was determined by the creatinine cutoff criterion, there was no such difference between high and low creatinine at KRT initiation. In patients with COVID-19-related AKI, earlier KRT might be associated with lower in-hospital mortality.

Tissue inhibitor of metalloproteinase-2 in patients aged 1 month to 1 year with and without cardiac surgery-associated acute kidney injury in congenital heart disease surgery with cardiopulmonary bypass: a single-center retrospective study

Introduction: Acute kidney injury is a common complication of cardiac surgery after management of congenital heart defects. Cardiac surgery-associated acute kidney injury (CS-AKI) results in longer stays of patients in the intensive care unit and hospital. However, using an increase in postoperative creatinine as a means of detecting AKI has some limitations, since significant changes occur after the loss of more than 50% of renal function. In children, the creatinine level is influenced by various factors such as muscle mass, cardiac output, etc. These factors vary significantly among young children and complicate the early diagnosis of AKI. Recent studies have explored biomarkers as potential predictors for the early detection of CS-AKI after cardiac surgery for management of congenital heart disease in children.Objective: To evaluate the urinary tissue inhibitor of metalloproteinase-2 (TIMP2) as a predictor of CS-AKI following management of congenital heart defects in children aged 1 month to 1 year who underwent cardiopulmonary bypass.Methods: A single-center retrospective study included patients aged 1 month to 1 year who underwent cardiopulmonary bypass for the correction of congenital heart defects. The groups were formed based on the presence of CS-AKI. The study group comprised of patients who had CS-AKI (group 1, n = 52), while those without CC-AKI constituted the control group (group 2, n = 98). To ensure minimal systematic errors and comparability between two groups, propensity score matching analysis was performed (52 patients in groups 1 and 2). Preoperative, intraoperative, and postoperative parameters and characteristics were compared.Results: The results showed no differences in baseline or demographic characteristics between the patients. In the study group, 34.6% of patients were diagnosed with CS-AKI. Among them, 67.4% (n = 35) were stage 1, 28.8% (n = 15) were stage 2, and 3.8% (n = 2) were stage 3. The results of the regression analysis show a decrease by 24% and an increase by 9 and 16% in CS-AKI respectively, with an increase in creatinine levels by 1 µmol/l, at baseline and on days 3 and 4. Additionally, male patients have a 76% lower likelihood to develop CS-AKI. It was observed that there was no significant difference in the tissue inhibitor of metalloprotease-2 levels between the groups with and without CS-AKI.Conclusion: Urinary TIMP2 levels were found to be unable to predict the early onset of CS-AKI in congenital heart defect patients ages 1 month to 1 year who underwent cardiopulmonary bypass surgery. Received 24 April 2023. Revised 27 November 2023. Accepted 28 November 2023. Funding: The study did not have sponsorship. Conflict of interest: The authors declare no conflict of interest. Contribution of the authors: The authors contributed equally to this article.

Case Report on a Cocktail Drug Abuser Developing Rhabdomyolysis

Rhabdomyolysis is a medical emergency characterized by the break down of skeletal muscle leading to the release of intracellular contents into the blood stream, which can lead to acute kidney injury and even death. Drug abuse is one of the potential causes of rhabdomyolysis. This case report describes a 18-year-old male with a history of drug abuse who presented to the emergency department with severe muscle pain, weakness, dark and reduced amount of urine. The patient was diagnosed with rhabdomyolysis, which was likely due to a combination of high doses Marijuana, Chlorpheniramine, Dextromethorphan (Corex Syrup), Dicyclomine, Tramadol, Acetaminophen and cigarette smoking over period of 4-5 years, landed up in rhabdomyolysis after joining gym. The patient was immediately started on aggressive intravenous fluid resuscitation, and his urine output and electrolyte levels were closely monitored. Patient required initiation of Hemodialysis over period of 15 days. Patient's muscle pain and weakness gradually improved over the next few days, and he was discharged with a diagnosis of AKI due to Rhabdomyolysis due to drug abuse. Prompt recognition and treatment of rhabdomyolysis are crucial to prevent serious complications, and addiction treatment should be pursued to prevent future episodes of rhabdomyolysis and other drugrelated complications.

Do Novel Biomarkers Have Utility in the Diagnosis and Prognosis of AKI?: Commentary.

Do Novel Biomarkers Have Utility in the Diagnosis and Prognosis of AKI?: Commentary.

Untargeted and spatial-resolved metabolomics characterize serum and tissue-specific metabolic reprogramming in acute kidney injury

BackgroundAcute kidney injury (AKI) is one of the most common clinical emergencies characterized by rapid progression, difficulty in early diagnosis, and high mortality. Currently, there are no effective AKI early diagnostic methods and treatments. Therefore, identifying new mechanisms of AKI have become urgent for development new targets for early diagnosis and treatment of AKI in the current clinical setting. MethodsIn this study, systematic analysis and comparison of serum metabolic profiles of clinical AKI patients, chronic kidney disease (CKD) patients, and healthy subjects were performed using untargeted metabolomics. Moreover, the first spatial metabolomic analysis of kidney tissues in an AKI mouse model using MALDI-TOF MS technology was conducted. Differentially expressed metabolites were identified using a comprehensive, publicly available database. The metabolic data obtained were evaluated using principal component analysis, (orthogonal) partial least squares discriminant analysis, and metabolic pathway analysis to explore the unique serum metabolic profile of the patients, as well as to characterize the spatial distribution of differential metabolites in the kidneys of AKI mice. ResultsSignificant changes in the metabolite levels of amino acids, carnitine, and lipids were observed in the AKI and CKD groups versus the healthy population, suggesting that kidney injury may lead to abnormalities in various metabolic pathways, such as amino acids, fatty acids, and lipids. The significant difference between the AKI and CKD groups were found for the first time in these indexes including amino acid, carnitine, fatty acid, and lipid levels. Additionally, spatial metabolomics results revealed that amino acid, carnitine, organic acid, and fatty acid metabolites were more likely significantly altered in the renal cortex, while lipid metabolites were both differentially distributed in the cortex and medulla of the AKI group. ConclusionAbnormalities in the serum metabolism of amino acids, carnitine, and lipids in patients with kidney diseases, such as AKI and CKD, are closely associated with the physiological dysfunction of kidney injury. Metabolic differences between patients with AKI and CKD were compared for the first time, showing that fatty acid oxidative inhibition was more severe in patients with AKI. Furthermore, spatial metabolomics has revealed metabolic reprogramming with tissue heterogeneity in AKI mice model. Our study provides valuable information in the molecular pathological features of AKI in the kidney tissues.