Kidney injury molecule-1 expression with segment-specific nephrotoxicants

Kidney injury molecule-1 (KIM-1) is a type 1 transmembrane protein that is not detectable in healthy kidney tissue. Transcript levels for the gene that encodes KIM-1 are strongly up-regulated in dedifferentiated proximal tubule epithelial cells after ischemic or toxic injury (1); furthermore, the gene is significantly up-regulated by several nephrotoxicants. In situ hybridization and immunohistochemistry revealed that Kim-1 gene is expressed in damaged regions of proximal tubular epithelial cells, especially in the S3 segment in the outer stripe of the outer medulla, a region that is highly susceptible to injury as a result of ischemia or toxins (1). The use of different nephrotoxicants such as S-(1,1,2,2-tetrafluoroethyl)-L-cysteine, folic acid, and cis-platin showed that the first caused a Kim-1 gene expression pattern similar to that in the post ischemic kidney, the second a clearly localization to the apical brush border of well-differentiated proximal tubular epithelial cells, and the latter a diffuse expression in S3 cells of proximal tubules (2). KIM-1 is also up-regulated by segment-specific nephrotoxicants such as hexachloro-1:3-butadiene, potassium dichromate, and cephaloridine, substances that are toxic for S3, S1-S2 and S2 segments, respectively (3). Interestingly, even no or low severity microscopic injuries were evidenced by gene expression changes, capturing different levels of damage such as degeneration, necrosis and regeneration which could provide a more sensitive biomarker of damage compared with traditional clinical measurements. Moreover, according to its increased expression also with minimal or no morphologic modifications, Kim-1 gene expression is likely to represent a potential tool for early screening of nephrotoxicants.