Injury biomarkers

Gill, S., Murphy, M., Clausen, I, Richard, D., Quilliam, M., MacKinnon, S., LaBlanc, P, Mueller, R. and Pulido, O., 2003. Neural injury biomarkers of novel shellfish toxins, spirolides a pilot study using immunochemical and transcriptional... 

Washburn KK, Zappitelli M, Arikan AA, Loftis L, Yalavarthy R, Parikh CR, Edelstein CL, Goldstein SL. Urinary interleukin-18 is an Acute Kidney injury Biomarker in Critically III Children. Nephrol Dial Transplant. 2007 Oct 1. 

CSF Visinin-like protein-1 (VILIP-1), a calcium-mediated neuronal injury biomarker, has been described as a novel biomarker for AD. CSF VILIP-1 levels are increased in AD patients compared with both normal controls and DLB patients. CSF VILIP-1 levels positively correlate with t-tau and p-tauisip and with a-synuclein. CSF VILIP-1 and VILIP-l/APp levels show diagnostic accuracy to allow the detection and differential diagnosis of AD [126]. 

Luo X, Hou L, Shi H, Zhong X, Zhang Y, Zheng D et al (2013) CSF levels of the neuronal injury biomarker visinin-like protein-1 in Alzheimer s disease and dementia with Lewy bodies. JNeurochem. 127 681-690... 

Animal models of human cardiac disease have been widely used to validate and develop understanding of cTn as a cardiac injury biomarker. Such studies have shown correlation of increases in blood cTn with loss from myocardium, compromised cardiac function, and structural injury to myocardium. The value of cTn in clinical assessment of cardiotoxicity from anticancer drugs was first demonstrated in mice (O Brien et al. 1997a), rats (Herman et al. 1998), and dogs (Christiansen et al. 2002) with doxorubicin. 

Another major cardiac injury biomarker is myoglobin, the cytoplasmic protein storing and shuttling oxygen from the cell surface to the mitochondria. This small protein can be easily measured by species-specific immunoassays (Spangenfhal and Ellis... 

Gill S. et al. Neural injury biomarkers of novel shellfish toxins, spirolides a pilot study using immunochemical and transcriptional analysis, Neurotoxicology 24, 593, 2003. 

Ennulat D and Adler S (2015) Recent successes in the identification, development, and qualification of translational biomarkers the next generation of kidney injury biomarkers. Toxicol Pathol. 43(l) 62-9. 

Rouse R, Min M, Francke S, Mog S, Zhang J, Shea K, Stewart S and Colatsky T (2014) Impact of pathologists and evaluation methods on performance assessment of the kidney injury biomarker, kim-1. Toxicol Pathol. 43(5) 662-74. 

Exocrine Injury Biomarkers in Humans and Preclinical Species... 

In contrast with pancreatic exocrine injury biomarkers discussed in the previous section, there are currently no injury markers reported for the endcxaine pancaeas or islets. Available islet-specific bicmarkers routinely used to understand islet health in general include parameters that test the functionality of islets relative to the synthesis of insulin and concurrent regulation of blcxid glucose concentrations. 

The lack of tissue specificity of the total serum CK assay and the reliance on histopathology to definitively diagnose drug-induced skeletal muscle injury in preclinical drug development have highlighted the need to identily better biomarkers. Beyond the characteristics desired in all safety biomarkers (reviewed in Robinson et al. (2008)), the ideal skeletal muscle injury biomarker should have a number of specific characteristics. First, it should be specific for skeletal muscle tissue injury and, most importantly, allow the discrimination between cardiac and skeletal muscle... 

European Medicines Agency (2015, March 6). Letter of Support for Skeletal Muscle Injury Biomarkers. fiom http //www.ema. europa.eu/docs/en GB/document library/Other/2015/03/ WC500184458.pdf (accessed October 20, 2015). 

The lessons learned from the preclinical qualification of renal safety biomarkers have demonstrated that it is also clear that no single biomarker will be the answer and that a panel approach of novel biomarkers alongside a more intelligent use of currently used biomarkers represents the way forward to inform all stakeholders. Moreover, novel translational biomarkers that reflect the mechanistic basis of DILI are fundamental to efforts in translational research. Despite significant progress in preclinical renal injury biomarker qualification, to date, clinical biomaiker qualification studies are ongoing to achieve this objective. 

Antoine, D.J., et al.. Are we eloser to finding biomarkers for identifying acute dmg-indueed liver injury Biomark Med, 2013b. 7(3) p. 383-6. 

Urinary Total Protein and Albumin Urinary total protein and albumin have been nsed for decades as glomerular injury biomarkers and, more recently, were qualified as measurements of glomerular filtration and tubular reabsorption function (Ferguson et al., 2008 Bonventre et al., 2010). Compared with blood concentrations of protein/albumin, a small amount of protein and albumin (microalbumin, which is below the albumin detection threshold by the conventional urinary dipstick 30-300 mg/L) enters the filtrate by the glomerulus and is reabsorbed and subsequently catabolized in the normal kidney proximal tubnle (Vaidya et al., 2008 Charlton et al., 2014). Therefore, increased urinary protein/albumin can reflect glomerular injury, tubular injury, or combined effects, though albuminuria can be observed in rats secondary to other effects such as dehydration or hypertensive conditions (Haschek et al., 2013). 

More recently, kidney tissue injury biomarkers including urinary NAG, a-GST, calbindin D28, RPA-1, and other constituents of renal tubule epithelial cell brush border membranes and cytoplasm are used for the evaluation of drug-induced direct kidney tissue damage (de Geus et al., 2012 Peres et al., 2013 Charlton et al., 2014). Injured tubule epithelial cells release their membrane and cytoplasmic... 

Charlton JR, Portilla D, Okusa MD. (2014) A basic science view of acute kidney injury biomarkers. Nephrol Dial Transplant. 201 1-11. 

Urbschat A, Obermtiller N, Haferkam A. (2011) Biomarkers of kidney injury. Biomarkers. 16(S1) S22-S30. 

Waikar SS, Betensky RA, Bonventre JV. (2009) Creatmine as the gold standard for kidney injury biomarker studies Nephrol Dial Transplant. 24(ll) 3263-3265. 

TRADITIONAL KIDNEY SAFETY PROTEIN BIOMARKERS AND NEXT-GENERATION DRUG-INDUCED KIDNEY INJURY BIOMARKERS IN NONHUMAN PRIMATES... 

MicroRNAs AS NEXT-GENERATION KIDNEY TUBULAR INJURY BIOMARKERS IN RATS... 

CASE STUDY FULLY AUTOMATED IMAGE ANALYSIS OF PODOCYTE INJURY BIOMARKER EXPRESSION IN RATS... 

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