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Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies
Open accessAbstract
Kidney toxicity accounts both for the failure of many drug candidates as well as considerable patient morbidity. Whereas histopathology remains the gold standard for nephrotoxicity in animal systems, serum creatinine (SCr) and blood urea nitrogen (BUN) are the primary options for monitoring kidney dysfunction in humans. The transmembrane tubular protein kidney injury molecule-1 (Kim-1) was previously reported to be markedly induced in response to renal injury. Owing to the poor sensitivity and specificity of SCr and BUN, we used rat toxicology studies to compare the diagnostic performance of urinary Kim-1 to BUN, SCr and urinary N-acetyl-β-D-glucosaminidase (NAG) as predictors of kidney tubular damage scored by histopathology. Kim-1 outperforms SCr, BUN and urinary NAG in multiple rat models of kidney injury. Urinary Kim-1 measurements may facilitate sensitive, specific and accurate prediction of human nephrotoxicity in preclinical drug screens. This should enable early identification and elimination of compounds that are potentially nephrotoxic.
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A note on a general definition of the coefficient of determination
NAGELKERKE, N. J. D. (1991) · Biometrika · doi:10.1093/biomet/78.3.691 · Cited by 5,927
Cited by
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Bonventre, J. V., Vaidya, V. S., Schmouder, R., Feig, P., & Dieterle, F. (2010) · Nature Biotechnology · doi:10.1038/nbt0510-436 · Cited by 538
Self-citationKidney-on-a-Chip technology for drug-induced nephrotoxicity screening
Wilmer, M. J., Ng, C. P., Lanz, H. L., Vulto, P., Suter-Dick, L., & Masereeuw, R. (2016) · Trends in Biotechnology · doi:10.1016/j.tibtech.2015.11.001 · Cited by 354
A Better Coefficient of Determination for Genetic Profile Analysis
Lee, S. H., Goddard, M. E., Wray, N. R., & Visscher, P. M. (2012) · Genetic Epidemiology · doi:10.1002/gepi.21614 · Cited by 349
Tuntland, T., Ethell, B., Kosaka, T., Blasco, F., Zang, R. X., Jain, M., Gould, T., & Hoffmaster, K. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00174 · Cited by 239
Tanase, D. M., Gosav, E. M., Radu, S., Costea, C. F., Ciocoiu, M., Carauleanu, A., Lacatusu, C. M., Maranduca, M. A., Floria, M., & Rezus, C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20205238 · Cited by 191
Metadata
- Authors
- Vaidya, V. S., Ozer, J. S., Dieterle, F., Collings, F. B., Ramirez, V., Troth, S., Muniappa, N., Thudium, D., Gerhold, D., Holder, D. J., Bobadilla, N. A., Marrer, E., Perentes, E., Cordier, A., Vonderscher, J., Maurer, G., Goering, P. L., Sistare, F. D., & Bonventre, J. V.
- Venue
- Nature Biotechnology
- Published
- 2010-05
- Volume
- 28
- Issue
- 5
- Pages
- 478-485
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2164819474
- Cited by
- 660
- References
- 1
- FWCI
- 33.11
- Type
- journal article
- Language
- en
- Open access
- green
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- Vaidya, V. S., Ozer, J. S., Dieterle, F., Collings, F. B., Ramirez, V., Troth, S., Muniappa, N., Thudium, D., Gerhold, D., Holder, D. J., Bobadilla, N. A., Marrer, E., Perentes, E., Cordier, A., Vonderscher, J., Maurer, G., Goering, P. L., Sistare, F. D., & Bonventre, J. V. (2010). Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies. Nature Biotechnology. https://doi.org/10.1038/nbt.1623
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