Quantitative gene expression analysis in a nonhuman primate model of antibiotic-induced nephrotoxicity

Davis, John W.; Goodsaid, Federico; Bral, Christopher M.; Obert, Leslie; Mandakas, George; Garner, C. Edwin; Collins, Nathaniel D.; Smith, Roger; Rosenblum, Ira

doi:10.1016/j.taap.2004.02.001

Cited by 60 publications

(38 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…*P < 0.05 and **P < 0.01. ,Mki67,Fga,Fgg,Krt8,Krt18, and Krt19, were selected as candidate biomarkers because (i) there was the strong evidence supporting their usefulness as nephrotoxicity biomarkers in rats and other species (Alchi et al, 2005., Davis et al, 2004Dieterich et al, 2009;Kharasch et al, 2006;Thukral et al, 2005;Wang et al, 2008) and (ii) these selected genes were considered to be biologically related to the gene categories, such as tissue remodeling, inflammatory responses, and cell growth. The usefulness of these genes as nephrotoxicity biomarkers in mice was evaluated further through expression profiling under several experimental conditions using real time RT-PCR.…”

Section: Discussionmentioning

confidence: 99%

Predictive genomic biomarkers for drug-induced nephrotoxicity in mice

et al. 2012

View full text Add to dashboard Cite

-The present study aimed to establish candidate biomarker genes for the early detection of nephrotoxicity in mice, with a particular focus on nephrotoxicity caused by polyene macrolides. Comprehensive gene expression changes were evaluated using microarrays in a mouse model in which acute nephrotoxicity was induced by amphotericin B deoxycholate, trade name Fungizone. The upregulated genes identified through microarray analysis of kidney tissue of Fungizone-treated mice included several genes that have been reported as nephrotoxicity biomarkers in rats, and 14 genes were selected as candidate nephrotoxicity biomarkers. The usefulness of these genes as nephrotoxicity biomarkers in mice was evaluated further through expression profiling under several experimental conditions using real time RT-PCR. Expression of genes encoding kidney injury molecule 1, lipocalin 2, tissue inhibitor of metalloproteinase 1, and secreted phosphoprotein 1 was highly upregulated by Fungizone, nystatin, natamycin, amphotericin B methyl ester, and liposomal amphotericin B, and their area under the ROC curve values were more than 0.95. These genes were more sensitive at detecting nephrotoxicity than traditional clinical chemistry and histopathology parameters. This study provides novel evidence that these nephrotoxicity biomarker genes identified are translatable to mice, and that they are useful for early and sensitive detection of nephrotoxicity.

show abstract

Section: Discussionmentioning

confidence: 99%

Predictive genomic biomarkers for drug-induced nephrotoxicity in mice

et al. 2012

View full text Add to dashboard Cite

show abstract

“…Urinary levels of clusterin, KIM-1, and NGAL all rose in rats given cisplatin (125)(126)(127) or gentamicin (128,129). In a rodent model of chronic gentamicin toxicity, urinary clusterin rose together with NAG but stayed elevated longer (130).…”

Section: Renal Transplantationmentioning

confidence: 99%

Cell-Specific Biomarkers in Renal Medicine and Research

Shaw¹

2010

Methods in Molecular Biology

View full text Add to dashboard Cite

Histopathology is the gold standard for defining renal injury, but it is invasive, time-consuming and expensive, plus it is seldom used in subjects with mild renal injury. Using biomarkers linked to distinct, defined cell types and tissues provides a direct link to histopathology without its drawbacks, plus it provides increased sensitivity, and specificity. The nephron consists of several sections, each with its own specific biomarkers; therefore, by the use of a battery of tests injuries can be localised to distinct areas of it. Using urine samples simplifies repeated sampling from the same subject or animal leading to better defined toxicokinetics and disease monitoring.Serum creatinine is the most widely used renal biomarker in spite of its known shortcomings. Cell-specific biomarkers are more specific and sensitive and have been known for over 40 years, but they are still underused in renal medicine and research. In particular, while many studies have shown cell-specific biomarkers to be valuable in diagnosis, there are few studies where they have been used to guide therapy or linked to quantitative changes in the kidney. Furthermore, the great majority of cell-specific biomarkers are from the proximal tubule, which may have hindered research into the study of conditions where the distal tubules are affected. Recently, the range of biomarkers and their applications has been expanded by the introduction of indicators of cellular regeneration.This chapter will discuss how using biomarkers with a known cellular origin, renal effects may be found earlier and at lower levels of injury. Their use in both renal medicine and drug research will be presented. Knowledge of these existing markers lays the foundation for evaluation, comparison, and characterisation of new markers that will be identified in the future.

show abstract

“…Clusterin is induced in the kidney and urine of rats, dogs, and primates after various forms of preclinical AKI such as ischemia/reperfusion injury (59,60), toxicant-induced kidney injury, unilateral ureteral obstruction, or subtotal nephrectomy (61)(62)(63). Clusterin, like Kim-1, is expressed on the dedifferentiated tubular cells after injury and is also induced in polycystic kidney disease (64) and renal cell carcinoma (65).…”

Section: Clusterinmentioning

confidence: 99%

Biomarkers of Acute Kidney Injury

Vaidya

Ferguson

Bonventre

2008

Annu. Rev. Pharmacol. Toxicol.

633

457

View full text Add to dashboard Cite

Acute kidney injury (AKI) is a common condition with a high risk of death. The standard metrics used to define and monitor the progression of AKI, such as serum creatinine and blood urea nitrogen levels, are insensitive, nonspecific, and change significantly only after significant kidney injury and then with a substantial time delay. This delay in diagnosis not only prevents timely patient management decisions, including administration of putative therapeutic agents, but also significantly affects the preclinical evaluation of toxicity thereby allowing potentially nephrotoxic drug candidates to pass the preclinical safety criteria only to be found to be clinically nephrotoxic with great human costs. Studies to establish effective therapies for AKI will be greatly facilitated by two factors: (a) development of sensitive, specific, and reliable biomarkers for early diagnosis/prognosis of AKI in preclinical and clinical studies, and (b) development and validation of high-throughput innovative technologies that allow rapid multiplexed detection of multiple markers at the bedside. Keywordsacute renal failure; clusterin; cystatin-C; cysteine-rich protein-61 (CYR-61); ELISA; ; kidney injury molecule-1 (Kim-1); microfluidics; nanotechnology; neutrophil gelatinaseassociated lipocalin (NGAL) ACUTE KIDNEY INJURY Definition and PrevalenceAcute kidney injury (AKI) is currently recognized as the preferred nomenclature for the clinical disorder formally called acute renal failure (ARF). This transition in terminology served to emphasize that the spectrum of disease is much broader than that subset of patients who experience failure requiring dialysis support (1). This new nomenclature underscores the fact that kidney injury exists along a continuum: The more severe the injury, the more likely the overall outcome will be unfavorable. The Acute Kidney Injury Network (AKIN), which was formed recently in an effort to facilitate improved care of patients who are at risk for AKI, described AKI as "functional or structural abnormalities or markers of kidney damage Copyright © 2008 by Annual Reviews. All rights reserved The Annual Review of Pharmacology and Toxicology is online at http://pharmtox.annualreviews.org DISCLOSURE STATEMENT Dr. Bonventre is a co-inventor on patents involving KIM-1. NIH Public Access Author ManuscriptAnnu Rev Pharmacol Toxicol. Author manuscript; available in PMC 2009 September 11. Published in final edited form as:Annu Rev Pharmacol Toxicol. 2008 ; 48: 463-493. doi:10.1146/annurev.pharmtox.48.113006.094615. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript including abnormalities in blood, urine, or tissue tests or imaging studies present for less than three months." AKI is associated with the retention of creatinine, urea, and other metabolic waste products that are normally excreted by the kidney. Although severe AKI may result in oliguria or even anuria, urine volume may be normal or even increased (2).Recent epidemiologic data suggest that the progress observed in the un...

show abstract

Quantitative gene expression analysis in a nonhuman primate model of antibiotic-induced nephrotoxicity

Cited by 60 publications

References 29 publications

Predictive genomic biomarkers for drug-induced nephrotoxicity in mice

Predictive genomic biomarkers for drug-induced nephrotoxicity in mice

Cell-Specific Biomarkers in Renal Medicine and Research

Biomarkers of Acute Kidney Injury

Contact Info

Product

Resources

About