Clinical prospects of biomarkers for the early detection and/or prediction of organ injury associated with pharmacotherapy

Tajima, Soichiro; Yamamoto, Nanae; Masuda, Satohiro

doi:10.1016/j.bcp.2019.113664

Cited by 37 publications

(43 citation statements)

References 146 publications

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“…Most reports described the mechanistic background responsible for cellular or subcellular origin of the parameter under consideration and reported on conflicting data open for further discussions. Little support existed for the provided parameters listed in other publications [26][27][28][29][30][31][32][33][34]. This included a recent commentary carefully discussing biomarker options without considering new regulatory aspects of EMA (European Medicines Agency) [34], as previously discussed [17].…”

Section: Current Challengesmentioning

confidence: 99%

“…Therefore, the EMA decided to retract its Letter of Support affecting virtually all biomarkers listed in Table 1. As a consequence, related regulatory or consortia Letters of Support previously provided by the FDA and SAFE-T (Safer and Faster Evidence-based Translation) Consortium disappeared from their websites that were previously cited in the literature [14,17,24,34]. All such conditions require new considerations.…”

Section: Proposals For Future Approachesmentioning

confidence: 99%

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Diagnostic Biomarkers in Liver Injury by Drugs, Herbs, and Alcohol: Tricky Dilemma after EMA Correctly and Officially Retracted Letter of Support

Teschke

Eickhoff

Brown

et al. 2019

IJMS

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Liver injuries caused by the use of exogenous compounds such as drugs, herbs, and alcohol are commonly well diagnosed using laboratory tests, toxin analyses, or eventually reactive intermediates generated during metabolic degradation of the respective chemical in the liver and subject to covalent binding by target proteins. Conditions are somewhat different for idiosyncratic drug induced liver injury (DILI), for which metabolic intermediates as diagnostic aids are rarely available. Although the diagnosis of idiosyncratic DILI can well be established using the validated, liver specific, structured, and quantitative RUCAM (Roussel Uclaf Causality Assessment Method), there is an ongoing search for new diagnostic biomarkers that could assist in and also confirm RUCAM-based DILI diagnoses. With respect to idiosyncratic DILI and following previous regulatory letters of recommendations, selected biomarkers reached the clinical focus, including microRNA-122, microRNA-192, cytokeratin analogues, glutamate dehydrogenase, total HMGB-1 (High Mobility Group Box), and hyperacetylated HMGB-1 proteins. However, the new parameters total HMGB-1, and even more so the acetylated HMGB-1, came under critical scientific fire after misconduct at one of the collaborating partner centers, leading the EMA to recommend no longer the exploratory hyperacetylated HMGB1 isoform biomarkers in clinical studies. The overall promising nature of the recommended biomarkers was considered by EMA as highly dependent on the outstanding results of the now incriminated biomarker hyperacetylated HMGB-1. The EMA therefore correctly decided to officially retract its Letter of Support affecting all biomarkers listed above. New biomarkers are now under heavy scrutiny that will require re-evaluations prior to newly adapted recommendations. With Integrin beta 3 (ITGB3), however, a new diagnostic biomarker may emerge, possibly being drug specific but tested in only 16 patients; due to substantial remaining uncertainties, final recommendations would be premature. In conclusion, most of the currently recommended new biomarkers have lost regulatory support due to scientific misconduct, requiring now innovative approaches and re-evaluation before they can be assimilated into clinical practice.

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Section: Current Challengesmentioning

confidence: 99%

Section: Proposals For Future Approachesmentioning

confidence: 99%

Diagnostic Biomarkers in Liver Injury by Drugs, Herbs, and Alcohol: Tricky Dilemma after EMA Correctly and Officially Retracted Letter of Support

Teschke

Eickhoff

Brown

et al. 2019

IJMS

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“…Furthermore, serum NGAL level was an independent risk factor for mortality in the multivariate Cox regression analysis. NGAL was first discovered in mature neutrophil granules [1] but is now known to be expressed in the proximal and distal tubular cells in the kidney [24], hepatocytes [25], smooth muscle cells [26], cardiomyocytes [27], endothelial cells [28], neurons [29], and various immune cells [5,30]. NGAL levels are thought to increase in these cells in the early stages of organ damage in ischemia-reperfusion injury.…”

Section: Discussionmentioning

confidence: 99%

Mortality prediction of serum neutrophil gelatinase-associated lipocalin in patients requiring continuous renal replacement therapy

Park

Ban

Kim

et al. 2021

Korean J Intern Med

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Background/Aims: We investigated whether serum neutrophil gelatinase-associated lipocalin (NGAL) can predict mortality in patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). Methods: This study enrolled 169 patients who underwent serum NGAL testing at CRRT initiation from June 2017 to January 2019. The predictive power of serum NGAL level for 28-day mortality was compared to the Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score and Sequential Organ Failure Assessment (SOFA) score via area under the receiver operating characteristic curve (AuROC) value. Results: There were 55 survivors and 114 non-survivors at 28 days post-CRRT initiation. Median serum NGAL level was significantly higher in the non-survivor group than in the survivor group (743.0 ng/mL vs. 504.0 ng/mL, p = 0.003). The AuROC value of serum NGAL level was 0.640, which was lower than APACHE-II score and SOFA score values (0.767 and 0.715, respectively). However, in the low APACHE-II score group (< 27.5), AuROC value of serum NGAL was significantly increased (0.698), and it was an independent risk factor for 28 day-mortality (hazard ratio, 2.405; 95% confidence interval, 1.209 to 4.783; p = 0.012). Conclusions: In patients with AKI requiring CRRT, serum NGAL levels may be useful for predicting short-term mortality in those with low APACHE-II scores.

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“…In recent epidemiology studies, the introduction of associated biological markers not only enhanced the accuracy of the analysis but also enabled early diagnosis of the diseases ( Sjaarda et al, 2018 ; Elliott et al, 2019 ). Furthermore, in the studies covering a stimulus and disease with organ-specific cytotoxicity, the significance of measuring organ-specific biomarkers greatly increases ( Tajima et al, 2019 ; Lieske et al, 2020 ). Therefore, further epidemiological LDR research is warranted to consider the utilization of biological markers for its risk estimation and pro/retrospective analysis.…”

Section: Discussionmentioning

confidence: 99%

Organ-Specific Effects of Low Dose Radiation Exposure: A Comprehensive Review

et al. 2020

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Ionizing radiation (IR) is a high-energy radiation whose biological effects depend on the irradiation doses. Low-dose radiation (LDR) is delivered during medical diagnoses or by an exposure to radioactive elements and has been linked to the occurrence of chronic diseases, such as leukemia and cardiovascular diseases. Though epidemiological research is indispensable for predicting and dealing with LDR-induced abnormalities in individuals exposed to LDR, little is known about epidemiological markers of LDR exposure. Moreover, difference in the LDR-induced molecular events in each organ has been an obstacle to a thorough investigation of the LDR effects and a validation of the experimental results in in vivo models. In this review, we summarized the recent reports on LDR-induced risk of organ-specifically arranged the alterations for a comprehensive understanding of the biological effects of LDR. We suggested that LDR basically caused the accumulation of DNA damages, controlled systemic immune systems, induced oxidative damages on peripheral organs, and even benefited the viability in some organs. Furthermore, we concluded that understanding of organ-specific responses and the biological markers involved in the responses is needed to investigate the precise biological effects of LDR.

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Clinical prospects of biomarkers for the early detection and/or prediction of organ injury associated with pharmacotherapy

Cited by 37 publications

References 146 publications

Diagnostic Biomarkers in Liver Injury by Drugs, Herbs, and Alcohol: Tricky Dilemma after EMA Correctly and Officially Retracted Letter of Support

Diagnostic Biomarkers in Liver Injury by Drugs, Herbs, and Alcohol: Tricky Dilemma after EMA Correctly and Officially Retracted Letter of Support

Mortality prediction of serum neutrophil gelatinase-associated lipocalin in patients requiring continuous renal replacement therapy

Organ-Specific Effects of Low Dose Radiation Exposure: A Comprehensive Review

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