Kidney tissue injury biomarkers

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... 

One thing that is clear from the table is that in vivo assessments of renal function in humans are limited due to the need for them to be noninvasive. In contrast, in vitro cell culture models enable processes to be examined at the cellular and molecular levels where they occur. Additionally, many of the responses and processes that are measured in vivo can be similarly measured in the in vitro model. Notable among these is the measurement of sensitive biomarkers of renal injury in urine in the in vivo model and in the extracellular medium in the in vitro cell culture model. Kidney injury molecule-1 (Kim-1) is an excellent example that has been characterized by Bonventre and colleagues (Ichimura et al., 1998,2004 Han et al., 2002 Vaidya et al., 2006 Hoffmann et al., 2010). Kim-1 is a type 1 transmembrane protein that is undetectable in normal kidney tissue but is expressed at very high levels in dedifferentiated PT epithelial cells of human and rodent kidneys after either ischanic or chemically induced injury. It appears to satisfy several of the criteria for being an ideal biomarker of effect for renal injury Kim-1 is stable in urine for prolonged periods of time, it is specific to the kidneys, its expression increases markedly from a baseline of essentially zero, and its increased expression occurs early... 

IchimuraT, Hung CC, Yang SA, et al. Kidney injury molecule-1 a tissue and urinary biomarker for nephrotoxicant-induced renal injury. Am JRenal Physiol 2004 286(3) F552-63. 

Fatty acid-binding proteins (FABPs) are low molecular weight ( 15kDa) cytoplasmic proteins expressed in all tissues with active fatty acid metabolism (Glatz and Van Der Vusse, 1996). L-FABP has been identified in the human kidney in the proximal tubule, and urinary L-FABP has been found to be a potential biomarker in preclinical models of renal interstitial injury associated with increased expression and urinary excretion of L-FABP (Kamijo et al., 2004,2006) and clinical conditions (Maatman et al., 1992). Additional studies are needed to determine the utility of L-FABP when monitoring for DIKI (Vaidya et al., 2008). 

A Cd biomarker is any substance or molecule that can serve as an indicator of the functional state or level of toxic injury in an organism, organ, tissue or cell [190]. Practically, sampling of Cd biomarkers should be easy and without expensive, invasive or damaging procedures because it should be apphed to large populations. Measurements should be limited to urine (and/or blood) samples because the kidney is the sentinel of Cd toxicity [190] (see Section 4.3.1). For the above reasons a recent suggestion to measure renal autophagy as an early biomarker of subtoxic Cd exposure is not practical [412]. 

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