Identification of Novel Biomarkers for Predicting Kidney Injury Due to Drugs Using "Omic" Strategies.
Ontology highlight
ABSTRACT:
SUBMITTER: Awdishu L
PROVIDER: S-EPMC7719321 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Identification of Novel Biomarkers for Predicting Kidney Injury Due to Drugs Using "Omic" Strategies.
Awdishu Linda L Atilano-Roque Amandla A Tuey Stacey S Joy Melanie S MS
Pharmacogenomics and personalized medicine 20201202
Drug-induced kidney injury accounts for 20% of community- and hospital-acquired cases of acute kidney injury (AKI). The incidence is higher among older individuals, who often have co-existing morbidities and are exposed to more diagnostic procedures and therapies. While demographic and clinical components have been identified as risk factors, the proposed cellular mechanisms of drug-induced kidney injury are numerous and complicated. There are also limitations recognized in the use of traditiona ...[more]
Similar Datasets
Project description:AimTo evaluate the performance of kidney-specific biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cystatin-C) in early detection of acute kidney injury (AKI) following cardiac arrest (CA) when compared to serum creatinine.MethodsAdult CA patients who had kidney-specific biomarkers of AKI collected within 12 h of return of spontaneous circulation (ROSC) were included. The association between renal biomarker levels post-ROSC and the development of KDIGO stage III AKI within 7 days of enrollment were assessed as well as their predictive value of future AKI development, neurological outcomes, and survival to discharge.ResultsOf 153 patients, 54 (35%) developed stage III AKI within 7 days, and 98 (64%) died prior to hospital discharge. Patients who developed stage III AKI, compared to those who did not, had higher median levels of creatinine, NGAL, and cystatin-C (p < 0.001 for all). There was no statistically significant difference in KIM-1 between groups. No biomarker outperformed creatinine in the ability to predict stage III AKI, neurological outcomes, or survival outcomes (p > 0.05 for all). However, NGAL, cystatin-C, and creatinine all performed better than KIM-1 in their ability to predict AKI development (p < 0.01 for all).ConclusionIn post-CA patients, creatinine, NGAL, and cystatin-C (but not KIM-1) measured shortly after ROSC were higher in patients who subsequently developed AKI. No biomarker was statistically superior to creatinine on its own for predicting the development of post-arrest AKI.
| S-EPMC10529996 | biostudies-literature
Project description:BackgroundWe 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.MethodsChildren 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.ResultsOf 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.ConclusionsPostoperative 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:Chronic kidney disease (CKD) is a worldwide health problem. The disease is most often progressive of nature with a high impact on patients and society. It is increasingly recognized that CKD can be detected in the early stages and should be managed as early as possible. Treatment of the cause, but in particular control of the main risk markers, such as high blood pressure, glucose and albuminuria, has been instrumental in delaying the progression to end-stage renal disease (ESRD). However, despite the state of the art therapy, the absolute risk of renal and cardiovascular morbidity and mortality in CKD patients remains devastatingly high. Novel drugs are therefore highly desirable to halt effectively the progressive renal (and cardiovascular) function loss. Recently, several novel strategies have been tested targeting traditional risk factors such as blood pressure (combination therapy of angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) and novel mineralocorticoid receptor antagonists) as well as dyslipidaemia (statins) with surprising results. In addition, drug targets specifically related to the kidney, such as vitamin D, uric acid, erythropoietin and phosphate, have been the subject of clinical trials, in some instances with unexpected results. Finally, novel targets including endothelin receptors and inflammatory pathways are increasingly explored as potential avenues to improve renal and cardiovascular protection, albeit that the drugs tested have not been unequivocally successful. In this article we review novel drugs or intervention strategies for the management of CKD, we try to provide explanations for the failure of some promising drugs and hypothesize on the potential success of new strategies.
| S-EPMC3791977 | biostudies-literature
Project description:BackgroundThe 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.Study designCross-sectional prospective.Setting & participantsHospitalized patients from 2 sites: Yale New Haven Hospital (n=50) and University of California, San Francisco Medical Center (n=36).PredictorsWe 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.OutcomesUrine 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.MeasurementsWe 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).ResultsNeither 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).LimitationsNo comparisons to fresh, unfrozen samples; no evaluation of the effect of protease inhibitors.ConclusionsAll 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-literature
Project description:BackgroundNumerous studies have suggested a possible role for acute kidney injury (AKI) biomarkers in predicting renal recovery both before and after renal replacement therapy (RRT). However, definitions for recovery and whether to include patients dying but free of RRT may influence results.ObjectivesTo validate plasma neutrophil gelatinase-associated lipocalin (pNGAL) as a useful biomarker for predicting or improving the ability of clinical predictors alone to predict recovery following AKI, including in our model plasma B-type natriuretic peptide (pBNP) to account for cardiovascular events.MethodsWe analyzed 69 patients enrolled in the Acute Renal Failure Trial Network study. pNGAL and pBNP were measured on days 2, 7, and 14. We analyzed their predictive ability for subsequent recovery, defined as alive and independent from dialysis in 60 days. In sensitivity analyses, we explored changes in results with alternative definitions of recovery.ResultsTwenty-nine patients (42%) recovered from AKI. Neither pNGAL nor pBNP, alone or in combination, was accurate predictors of renal recovery-the best area under the receiver-operating characteristics curve (AUC) was for pNGAL using the largest relative change (AUC 0.59, 95% CI 0.45-0.74). The best clinical model achieved superior performance to biomarkers (AUC 0.69, 95% CI 0.56-0.81). The AUC was greatest (0.75, 95% CI 0.60-0.91) when pNGAL + pBNP on day 14 were added to the clinical model but this increase did not achieve statistical significance. However, integrated discrimination improvement analysis showed that the addition of pNGAL and pBNP on day 14 to the clinical model significantly improved the prediction of renal recovery (p = 0.008).ConclusionspNGAL and pBNP can improve the accuracy of clinical parameters in predicting AKI recovery and a full model using biomarkers together with age achieved adequate discrimination.
| S-EPMC6773527 | biostudies-literature
Project description:Acute kidney injury (AKI) is a common and severe complication after cardiac surgery. Currently, a series of novel biomarkers have favored the assessment of AKI after cardiac surgery in addition to the conventional indicators. The biomartkers, such as urinary liver fatty acid binding protein (L-FABP), urinary neutrophil gelatinase-associated lipocalin (NGAL), serum L-FABP, heart-type FABP, kidney injury molecule 1 (KIM-1), and interleukin-18 were found to be significantly higher in patients who developed AKI after cardiac surgery than those who did not. Apart from urinary interleukin-18, the novel biomarkers have been recognized as reliable indicators for predicting the diagnosis, adverse outcome, and even mortality of AKI after cardiac surgery. The timing of the renal replacement therapy is a significant predictor relating to patients' prognoses. In patients with AKI after cardiac surgery, renal replacement therapy should be performed as early as possible in order to achieve promising outcomes. In children, AKI after cardiac surgery can be managed with peritoneal dialysis. AKI after cardiac surgery has received extensive attention as it may increase early mortality and impact long-term survival of patients as well. The purpose of this article was to analyze the changes of the pertinent biomarkers, to explore the related risk factors leading to the occurrence of AKI after cardiac surgery, and to provide a basis for the clinical prevention and reduction of AKI.
| S-EPMC6629228 | biostudies-literature
Project description: Not available
| S-EPMC9705447 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19) arising from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a global pandemic since its first report in December 2019. So far, SARS-CoV-2 nucleic acid detection has been deemed as the golden standard of COVID-19 diagnosis. However, this detection method often leads to false negatives, thus triggering missed COVID-19 diagnosis. Therefore, it is urgent to find new biomarkers to increase the accuracy of COVID-19 diagnosis. To explore new biomarkers of COVID-19 in this study, expression profiles were firstly accessed from the GEO database. On this basis, 500 feature genes were screened by the minimum-redundancy maximum-relevancy (mRMR) feature selection method. Afterwards, the incremental feature selection (IFS) method was used to choose a classifier with the best performance from different feature gene-based support vector machine (SVM) classifiers. The corresponding 66 feature genes were set as the optimal feature genes. Lastly, the optimal feature genes were subjected to GO functional enrichment analysis, principal component analysis (PCA), and protein-protein interaction (PPI) network analysis. All in all, it was posited that the 66 feature genes could effectively classify positive and negative COVID-19 and work as new biomarkers of the disease.
| S-EPMC8485143 | biostudies-literature
Project description:PURPOSE:The aim of the RUBY study was to evaluate novel candidate biomarkers to enable prediction of persistence of renal dysfunction as well as further understand potential mechanisms of kidney tissue damage and repair in acute kidney injury (AKI). METHODS:The RUBY study was a multi-center international prospective observational study to identify biomarkers of the persistence of stage 3 AKI as defined by the KDIGO criteria. Patients in the intensive care unit (ICU) with moderate or severe AKI (KDIGO stage 2 or 3) were enrolled. Patients were to be enrolled within 36 h of meeting KDIGO stage 2 criteria. The primary study endpoint was the development of persistent severe AKI (KDIGO stage 3) lasting for 72 h or more (NCT01868724). RESULTS:364 patients were enrolled of whom 331 (91%) were available for the primary analysis. One hundred ten (33%) of the analysis cohort met the primary endpoint of persistent stage 3 AKI. Of the biomarkers tested in this study, urinary C-C motif chemokine ligand 14 (CCL14) was the most predictive of persistent stage 3 AKI with an area under the receiver operating characteristic curve (AUC) (95% CI) of 0.83 (0.78-0.87). This AUC was significantly greater than values for other biomarkers associated with AKI including urinary KIM-1, plasma cystatin C, and urinary NGAL, none of which achieved an AUC?>?0.75. CONCLUSION:Elevated urinary CCL14 predicts persistent AKI in a large heterogeneous cohort of critically ill patients with severe AKI. The discovery of CCL14 as a predictor of persistent AKI and thus, renal non-recovery, is novel and could help identify new therapeutic approaches to AKI.
| S-EPMC7210248 | biostudies-literature
Project description:Acute kidney injury (AKI) is a global public health concern associated with high morbidity, mortality, and health-care costs, and the therapeutic measures are still limited. This study aims to investigate crucial genes correlated with AKI, and their potential functions, which might contribute to a better understanding of AKI pathogenesis. The high-throughput data GSE52004 and GSE98622 were downloaded from Gene Expression Omnibus; four group sets were extracted and integrated. Differentially expressed genes (DEGs) in the four group sets were identified by limma package in R software. The overlapping DEGs among four group sets were further analyzed by the VennDiagram package, and their potential functions were analyzed by the GO and KEGG pathway enrichment analyses using the DAVID database. Furthermore, the protein-protein interaction (PPI) network was constructed by STRING, and the functional modules of the PPI network were filtered by MCODE and ClusterOne in Cytoscape. Hub genes of overlapping DEGs were identified by Cyto-Hubba and cytoNCA. The expression of 35 key genes was validated by quantitative real-time PCR (qRT-PCR). Western blot and immunofluorescence were performed to validate an important gene Egr1. A total of 722 overlapping DEGs were differentially expressed in at least three group sets. These genes mainly enriched in cell proliferation and fibroblast proliferation. Additionally, 5 significant modules and 21 hub genes, such as Havcr1, Krt20, Sox9, Egr1, Timp1, Serpine1, Edn1, and Apln were screened by analyzing the PPI networks. The 5 significant modules were mainly enriched in complement and coagulation cascades and Metabolic pathways, and the top 21 hub genes were mainly enriched in positive regulation of cell proliferation. Through validation, Krt20 were identified as the top 1 upregulated genes with a log2 (fold change) larger than 10 in all these 35 genes, and 21 genes were validated as significantly upregulated; Egr1 was validated as an upregulated gene in AKI in both RNA and protein level. In conclusion, by integrated analysis of different high-throughput data and validation by experiment, several crucial genes were identified in AKI, such as Havcr1, Krt20, Sox9, Egr1, Timp1, Serpine1, Edn1, and Apln. These genes were very important in the process of AKI, which could be further utilized to explore novel diagnostic and therapeutic strategies.
| S-EPMC7247857 | biostudies-literature