Kidney injury molecule-1 KIM

Serum creatinine and BUN, the most common indicators of renal function used in both clinical and preclinical safety laboratory panels, are relatively insensitive markers of injury, particularly for the renal tubules. Urinary measurements of alanine aminopeptidase and A-acetyl-beta-D-glucosaminidase and kidney injury molecule-1 (KIM-1) can provide much more sensitivity when nephrotoxicity is a potential safety concern [28,29], These are also suitable for safety monitoring in early-phase human trials if preclinical studies validate such use to monitor product nephrotoxicity. 

Zhang Z, Humphreys BD, Bonventre JV. Shedding of the urinary biomarker kidney injury molecule-1 (KIM-1) is regulated by MAP kinases and juxtamembrane region. J Am Soc Nephrol. 2007 18 2704-14. 

IchimuraT, Bonventre JV, Bailly V, Wei H, Hession CA, Cate RL, Sanicola M Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cellsafterinjury. J Biol Chem 1998 273 4135-4142. 

Han WK, Bailly V, Abichandani R,Thadhani R, Bonventre JV. Kidney Injury Molecule-1 (KIM-1) a novel biomarker for human renal proximal tubule injury Kidney Int 2002 62 237-244. 

Han WK, Bailey V, Abichandami R, Thadhani Rl, Ichimura T, Bonventre JV Kidney injury molecule-1 (KIM-1) is a new biomarker for human renal proximal tubule injury. J Am Soc Nephrol 2000 11 129A. 

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... 

Biomarkers such as cystatin C (CyC), neutrophil-gelatinase-assosiated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) have previously been investigated for a more sensitive and earlier detection of contrast induced nephropathy. 

---