Assessment and Prognosis in CSA-AKI Using Novel Kidney Injury Biomarkers: A Prospective Observational Study.
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ABSTRACT: Background
There is a need for early diagnostic solutions for cardiac surgery associated acute kidney injury (CSA-AKI) as serum creatinine changes do not occur dynamically enough. Moreover, new approaches are needed for kidney protective strategy in patients undergoing cardiac surgery procedures; Methods: Samples of serum and urine were taken from the selected group of patients undergoing elective cardiac surgery procedures. The aim of this study was to assess the utility of specific inflammation and kidney injury biomarkers in the early diagnostic of CSA-AKI and in the prognosis of long-term postoperative kidney function; Results: At 6 h after weaning from cardiopulmonary bypass, there were significant differences in IL-6, IL-8, TNF-α, MMP-9 and NGAL concentrations in patients with CSA-AKI, compared to the control group. Serum IL-8 and urine NGAL 6 h after weaning from CPB proved to be independent acute kidney injury predictors. The TNF-α, MMP-9, IL-18, TIMP-1 and MMP-9/TIMP-1 ratio in the early postoperative period correlated with long-term kidney function impairment; Conclusions: Novel kidney injury biomarkers are an eligible tool for early diagnosis of CSA-AKI. They are also reliable indicators of long-term postoperative kidney function impairment risk after cardiac surgery procedures.
SUBMITTER: Udzik J
PROVIDER: S-EPMC8470477 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:We previously reported that children undergoing cardiac surgery are at high risk for long-term chronic kidney disease (CKD) and hypertension, although postoperative acute kidney injury (AKI) is not a risk factor for worse long-term kidney outcomes. We report here our evaluation of renal injury biomarkers 5 years after cardiac surgery to determine whether they are associated with postoperative AKI or long-term CKD and hypertension. METHODS:Children aged 1 month to 18 years old undergoing cardiopulmonary bypass were recruited to this prospective cohort study. At 5 years after cardiac surgery, we measured urine interleukin-18, kidney injury molecule-1, monocyte chemoattractant protein-1, YKL-40, and neutrophil gelatinase-associated lipocalin (NGAL). Biomarker levels were compared between patients with AKI and those without. We also performed a cross-sectional analysis of the association between these biomarkers with CKD and hypertension. RESULTS:Of the 305 subjects who survived hospitalization, four (1.3%) died after discharge, and 110 (36%) participated in the 5-year follow-up. Of these 110 patients, 49 (45%) had AKI. Patients with versus those without postoperative AKI did not have significantly different biomarker concentrations at 5 years after cardiac surgery. None of the biomarker concentrations were associated with CKD or hypertension at 5 years of follow-up, although CKD and hypertension were associated with a higher proportion of participants with abnormal NGAL levels. CONCLUSIONS:Postoperative pediatric AKI is not associated with urinary kidney injury biomarkers 5 years after surgery. This may represent a lack of chronic renal injury after AKI, imprecise estimation of the glomerular filtration rate, the need for longer follow-up to detect chronic renal damage, or that our studied biomarkers are inadequate for evaluating subclinical chronic renal injury.
| S-EPMC5945328 | biostudies-literature
Project description:BackgroundThis study aims to identify potential biomarkers associated with acute kidney injury (AKI) post kidney transplantation.Material and methodsTwo mRNA expression profiles from Gene Expression Omnibus repertory were downloaded, including 20 delayed graft function (DGF) and 68 immediate graft function (IGF) samples. Differentially expressed genes (DEGs) were identified between DGF and IGF group. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis of DEGs were performed. Then, a protein-protein interaction analysis was performed to extract hub genes. The key genes were searched by literature retrieval and cross-validated based on the training dataset. An external dataset was used to validate the expression levels of key genes. Receiver operating characteristic curve analyses were performed to evaluate diagnostic performance of key genes for AKI.ResultsA total of 330 DEGs were identified between DGF and IGF samples, including 179 up-regulated and 151 down-regulated genes. Of these, OLIG3, EBF3 and ETV1 were transcription factor genes. Moreover, LEP, EIF4A3, WDR3, MC4R, PPP2CB, DDX21 and GPT served as hub genes in PPI network. EBF3 was significantly up-regulated in validation GSE139061 dataset, which was consistently with our initial gene differential expression analysis. Finally, we found that LEP had a great diagnostic value for AKI (AUC = 0.740).ConclusionEBF3 may be associated with the development of AKI following kidney transplantation. Furthermore, LEP had a good diagnostic value for AKI. These findings provide deeper insights into the diagnosis and management of AKI post renal transplantation.
| S-EPMC7703406 | biostudies-literature
Project description:BackgroundWe previously demonstrated that assessment of the duration of AKI, in addition to magnitude of rise in creatinine alone, adds prognostic information for long-term survival. We evaluated whether post-operative kidney injury biomarkers in urine collected immediately after cardiac surgery associate with duration of serum creatinine elevation.MethodsWe studied 1199 adults undergoing cardiac surgery in a prospective cohort study (TRIBE-AKI) and examined the association between the levels of five urinary biomarkers individually at 0-6 hours after surgery: interleukin-18 (IL-18), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver fatty acid binding protein (L-FABP) and albumin with duration of serum creatinine-based AKIN criteria for AKI (0 (no AKI), 1-2, 3-6, ?7 days).ResultsOverall, 407 (34%) patients had at least stage 1 AKI, of whom 251 (61.7%) had duration of 1-2 days, 118 (28.9%) had duration 3-6 days, and 38 (9.3%) had duration of ?7 days. Higher concentrations of all biomarkers (per log increase) were independently associated with a greater odds of a longer duration of AKI; odds ratios and 95% confidence intervals using ordinal logistic regression were the following: IL-18: 1.22, 1.13-1.32; KIM-1: 1.36, 1.21-1.52; albumin 1.20, 1.09-1.32; L-FABP 1.11, 1.04-1.19; NGAL 1.06, 1.00-1.14). AKI duration of 7 days or longer was associated with a 5-fold adjusted risk of mortality at 3 years.ConclusionsThere was an independent dose-response association between urinary levels of injury biomarkers immediately after cardiac surgery and longer duration of AKI. Duration of AKI was also associated with long term mortality. Future studies should explore the potential utility of these urinary kidney injury biomarkers to enrich enrollment of patients at risk for longer duration of AKI into trials of interventions to prevent or treat post-operative AKI.
| S-EPMC4990204 | biostudies-literature
Project description:ObjectivesTo test the methodology of recruitment, retention and data completeness in a prospective cohort recruited after a hospitalised episode of acute kidney injury (AKI), to inform a future prospective cohort study examining the effect of obesity on AKI outcomes.DesignFeasibility study.SettingSingle centre, multi-site UK tertiary hospital.Participants101 participants (67M; 34F) with a median age of 64 (IQR 53-73) years, with and without obesity, recruited within 3 months of a hospitalised episode of AKI.Outcome measuresFeasibility outcomes were recruitment (>15%?meeting inclusion criteria recruited), participant retention at 6 and 12 months (?80%) and completeness of data collection. Exploratory measures included recovery from AKI (regaining >75% of pre-AKI estimated glomerular filtration rate [eGFR]) at 6 months, development or progression of chronic kidney disease (CKD) (kidney function decrease of ?25% + ?rise in CKD category) at 12 months, and associations with poorer kidney outcomes.Results41% of eligible patients consented to take part, exceeding the target recruitment uptake rate of 15%. Retention was 86% at 6 months and 78% at 12 months; 10 patients died and three commenced dialysis during the study. Data were 90%-100%?complete. Median BMI was 27.9?kg/m2 (range 18.1?kg/m2-54.3?kg/m2). 50% of the cohort had stage 3 AKI and 49% had pre-existing CKD. 46% of the cohort met the AKI recovery definition at 6 months. At 12 months, 20/51 patients developed CKD (39%) and CKD progression occurred in 11/49 patients (22%). Post-AKI interleukin-6 and cystatin-C were associated with 12?months decline in eGFR.ConclusionsFeasibility to conduct a long-term observational study addressing AKI outcomes associated with obesity was demonstrated. A fully powered prospective cohort study to examine the relationships between obesity and outcomes of AKI is warranted.
| S-EPMC6528015 | biostudies-literature
Project description:ImportanceAmong patients who had acute kidney injury (AKI) during hospitalization, there is a need to improve risk prediction such that those at highest risk for subsequent loss of kidney function are identified for appropriate follow-up.ObjectiveTo evaluate the association of post-AKI proteinuria with increased risk of future loss of renal function.Design, setting, and participantsThe Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Study was a multicenter prospective cohort study including 4 clinical centers in North America included 1538 patients enrolled 3 months after hospital discharge between December 2009 and February 2015.ExposuresUrine albumin-to-creatinine ratio (ACR) quantified 3 months after hospital discharge.Main outcomes and measuresKidney disease progression defined as halving of estimated glomerular filtration rate (eGFR) or end-stage renal disease.ResultsOf the 1538 participants, 769 (50%) had AKI durring hospitalization. The baseline study visit took place at a mean (SD) 91 (23) days after discharge. The mean (SD) age was 65 (13) years; the median eGFR was 68 mL/min/1.73 m2; and the median urine ACR was 15 mg/g. Overall, 547 (37%) study participants were women and 195 (13%) were black. After a median follow-up of 4.7 years, 138 (9%) participants had kidney disease progression. Higher post-AKI urine ACR level was associated with increased risk of kidney disease progression (hazard ratio [HR], 1.53 for each doubling; 95% CI, 1.45-1.62), and urine ACR measurement was a strong discriminator for future kidney disease progression (C statistic, 0.82). The performance of urine ACR was stronger in patients who had had AKI than in those who had not (C statistic, 0.70). A comprehensive model of clinical risk factors (eGFR, blood pressure, and demographics) including ACR provided better discrimination for predicting kidney disease progression after hospital discharge among those who had had AKI (C statistic, 0.85) vs those who had not (C statistic, 0.76). In the entire matched cohort, after taking into account urine ACR, eGFR, demographics, and traditional chronic kidney risk factors determined 3 months after discharge, AKI (HR, 1.46; 95% CI, 0.51-4.13 for AKI vs non-AKI) or severity of AKI (HR, 1.54; 95% CI, 0.50-4.72 for AKI stage 1 vs non-AKI; HR, 0.56; 95% CI, 0.07-4.84 for AKI stage 2 vs non-AKI; HR, 2.24; 95% CI, 0.33-15.29 for AKI stage 3 vs non-AKI) was not independently associated with more rapid kidney disease progression.Conclusions and relevanceProteinuria level is a valuable risk-stratification tool in the post-AKI period. These results suggest there should be more widespread and routine quantification of proteinuria after hospitalized AKI.
| S-EPMC6990681 | biostudies-literature
Project description:Acute kidney injury (AKI) currently is diagnosed by a temporal trend of a single blood analyte: serum creatinine. This measurement is neither sensitive nor specific to kidney injury or its protean forms. Newer biomarkers, neutrophil gelatinase-associated lipocalin (NGAL, Lipocalin 2, Siderocalin), or kidney injury molecule-1 (KIM-1, Hepatitis A Virus Cellular Receptor 1), accelerate the diagnosis of AKI as well as prospectively distinguish rapidly reversible from prolonged causes of serum creatinine increase. Nonetheless, these biomarkers lack the capacity to subfractionate AKI further (eg, sepsis versus ischemia versus nephrotoxicity from medications, enzymes, or metals) or inform us about the primary and secondary sites of injury. It also is unknown whether all nephrons are injured in AKI, whether all cells in a nephron are affected, and whether injury responses can be stimulus-specific or cell type-specific or both. In this review, we summarize fully agnostic tissue interrogation approaches that may help to redefine AKI in cellular and molecular terms, including single-cell and single-nuclei RNA sequencing technology. These approaches will empower a shift in the current paradigm of AKI diagnosis, classification, and staging, and provide the renal community with a significant advance toward precision medicine in the analysis AKI.
| S-EPMC5753434 | biostudies-literature
Project description:AKI is an increasingly common disorder that is strongly linked to short- and long-term morbidity and mortality. Despite a growing heterogeneity in its causes, providing a timely and certain diagnosis of AKI remains challenging. In this review, we summarize the evolution of AKI biomarker studies over the past few years, focusing on two major areas of investigation: the early detection and prognosis of AKI. We highlight some of the lessons learned in conducting AKI biomarker studies, including ongoing attempts to address the limitations of creatinine as a reference standard and the recent shift toward evaluating the prognostic potential of these markers. Lastly, we suggest current gaps in knowledge and barriers that may be hindering their incorporation into care and a full ascertainment of their value.
| S-EPMC5220647 | biostudies-literature
Project description:ObjectivesTo summarise the evidence from studies of acute kidney injury (AKI) with regard to the effect of pre-AKI renal function and post-AKI renal function recovery on long-term mortality and renal outcomes, and to assess whether these factors should be taken into account in future prognostic studies.Design/settingA systematic review of observational studies listed in Medline and EMBASE from 1990 to October 2012.ParticipantsAll AKI studies in adults with data on baseline kidney function to identify AKI; with outcomes either stratified by pre-AKI and/or post-AKI kidney function, or described by the timing of the outcomes.OutcomesLong-term mortality and worsening chronic kidney disease (CKD).ResultsOf 7385 citations, few studies met inclusion criteria, reported baseline kidney function and stratified by pre-AKI or post-AKI function. For mortality outcomes, three studies compared patients by pre-AKI renal function and six by post-AKI function. For CKD outcomes, two studies compared patients by pre-AKI function and two by post-AKI function. The presence of CKD pre-AKI (compared with AKI alone) was associated with doubling of mortality and a fourfold to fivefold increase in CKD outcomes. Non-recovery of kidney function was associated with greater mortality and CKD outcomes in some studies, but findings were inconsistent varying with study design. Two studies also reported that risk of poor outcome reduced over time post-AKI. Meta-analysis was precluded by variations in definitions for AKI, CKD and recovery.ConclusionsThe long-term prognosis after AKI varies depending on cause and clinical setting, but it may also, in part, be explained by underlying pre-AKI and post-AKI renal function rather than the AKI episode itself. While carefully considered in clinical practice, few studies address these factors and with inconsistent study design. Future AKI studies should report pre-AKI and post-AKI function consistently as additional factors that may modify AKI prognosis.
| S-EPMC4289733 | biostudies-literature
Project description:Background and objectivesHow to best medically manage patients who survived hospitalized AKI is unclear. Use of renin-angiotensin system blockers in this setting may increase risk of recurrent AKI.Design, setting, participants, & measurementsThis is a cohort study of 10,242 members of an integrated health care delivery system in Northern California who experienced AKI and survived a hospitalization between January 1, 2006 and December 31, 2013. All study participants did not have prior heart failure or use of angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) up to 5 years prior. New receipt and time-updated exposure of ACE-Is/ARBs was identified on the basis of dispensed prescriptions found in outpatient health plan pharmacy databases. The main outcome of interest was subsequent episode of hospitalized AKI after discharge from an initial index hospitalization complicated by AKI. Recurrent AKI episode was defined using acute changes in serum creatinine concentrations. Marginal structural models were used to adjust for baseline and potential time-dependent confounders.ResultsForty-seven percent of the study population had a documented eGFR<60 ml/min per 1.73 m2 or documented proteinuria before hospitalization. With a median of 3 (interquartile range, 1-5) years of follow-up, 1853 (18%) patients initiated use of ACE-Is/ARBs and 2124 (21%) patients experienced recurrent AKI. Crude rate of recurrent AKI was 6.1 (95% confidence interval [95% CI], 5.9 to 6.4) per 100 person-years off ACE-Is/ARBs and 5.7 (95% CI, 4.9 to 6.5) per 100 person-years on ACE-Is/ARBs. In marginal structural causal inference models that adjusted for baseline and potential time-dependent confounders, exposure to ACE-I/ARB use was not associated with higher incidence of recurrent AKI (adjusted odds ratio, 0.71; 95% CI, 0.45 to 1.12).ConclusionsIn this study of AKI survivors without heart failure, new use of ACE-I/ARB therapy was not independently associated with increased risk of recurrent hospitalized AKI.
| S-EPMC6946085 | biostudies-literature
Project description:The study of novel urinary biomarkers of acute kidney injury has expanded exponentially. Effective interpretation of data and meaningful comparisons between studies require awareness of factors that can adversely affect measurement. We examined how variations in short-term storage and processing might affect the measurement of urine biomarkers.Cross-sectional prospective.Hospitalized patients from 2 sites: Yale New Haven Hospital (n=50) and University of California, San Francisco Medical Center (n=36).We tested the impact of 3 urine processing conditions on these biomarkers: (1) centrifugation and storage at 4°C for 48 hours before freezing at -80°C, (2) centrifugation and storage at 25°C for 48 hours before freezing at -80°C, and (3) uncentrifuged samples immediately frozen at -80°C.Urine concentrations of 5 biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), and cystatin C.We measured urine biomarkers by established enzyme-linked immunosorbent assay methods. Biomarker values were log-transformed, and agreement with a reference standard of immediate centrifugation and storage at -80°C was compared using concordance correlation coefficients (CCCs).Neither storing samples at 4°C for 48 hours nor centrifugation had a significant effect on measured levels, with CCCs higher than 0.9 for all biomarkers tested. For samples stored at 25°C for 48 hours, excellent CCC values (>0.9) also were noted between the test sample and the reference standard for NGAL, cystatin C, L-FABP and KIM-1. However, the CCC for IL-18 between samples stored at 25°C for 48 hours and the reference standard was 0.81 (95% CI, 0.66-0.96).No comparisons to fresh, unfrozen samples; no evaluation of the effect of protease inhibitors.All candidate markers tested using the specified assays showed high stability with both short-term storage at 4°C and without centrifugation prior to freezing. For optimal fidelity, urine for IL-18 measurement should not be stored at 25°C before long-term storage or analysis.
| S-EPMC3969397 | biostudies-other