Kidney injury molecule

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. 

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. 

Kidney injury molecule 1 (KlM-1) is a type 1 transmembrane protein with an immunoglobulin and mucin domain. The KlM-1 ectodomain is cleaved, shed from cells, detectable in urine, and reflects renal damage [298]. The cleavage of KlM-1 is mediated by ERK activation and is accelerated by p38 MAP kinase activation [299]. KlM-1 is not expressed in the normal kidney but is markedly up-regulated in renal proximal tubule cells by stimuli that promote dedifferentiation, including ischemic and toxic [300,301] injury. Because it is expressed in proliferating and dedifferentiated... 

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. 

Lin F, Zhang PL, Yang XJ, Shi J, BlasickT, Han WK, Wang HL, Shen SS, Teh BT, Bonventre JV Human kidney injury molecule-1 (hKIM-1) A useful immunohistochemical marker for diagnosing renal cell carcinoma and ovarian clear cell carcinoma. Am J Surg Pathol 31 371 -381,2007. 

Han WK, Allnani A, Wu CL, Michaelson D, Loda M, McGovern FJ,Thadhani R, Bonventre JV Human kidney injury molecule-1 is a tissue and urinary tumor marker of renal cell carcinoma. J Am Soc Nephrol 16 1126-1134,2005. 

Kuehn EW, Park KM, Somlo S, Bonventre JV Kidney injury molecule-1 expression in murine polycystic kidney disease. Am J Physiol Renal Physiol 283 FI 326 -FI 336, 2002. 

LiangosO, Perianayagam MC, Vaidya VS, Han WK, Wald R,Tighiouart H, MacKinnon RW, Li L, Balakrishnan VS, Pereira BJ, Bonventre JV, Jaber BL. Urinary N-acetyl-beta-(D)-glucosaminidase activity and kidney injury molecule-1 level are associated with adverse outcomes in acute renal failure J Am Soc Nephrol 2007 18 904-912. 

Vaidya VS, RamirezV, IchimuraT, Bobadilla NA, Bonventre JV Urinary kidney injury molecule-1 A sensitive quantitative biomarker for early detection of kidney tubular injury. Am J Physiol Renal Physiol 2006 290 F517 -F529. 

KIM kidney injury molecule MRI magnetic resonance imaging... 

Kuehn EW, Hirt MN, John AK, et al. Kidney injury molecule 1 (Kiml) is a novel ciliary molecule and interactor of polycystin 2. Biochem Biophys Res Commun. 2007 364(4) 861-866. 

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. 

Wang, H. T, Kang, B. S., Ren, E, Pearton, S. J., Johnson, J. W, Rajagopal, R, Roberts, J. C., Piner, E. L. and Linthicum, K. J. (2007c) Electrical detection of kidney injury molecule-1 with AlGaN/GaN high electron mobility transistors , AppZ/ed Physics Letters, 91(22). 

Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies. Nat. Biotechnol. 28(5) 478. 

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... 

Han, W.K., Bailly, V, Abichandani, R., Thadhani, R., and Bonventre, J.V. (2002) Kidney injury molecule-1 (KlM-1) A novel biomarker for human renal proximal tubule injury. Kidney Int. 62, 237-244. 

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