Chitinase-like protein Brp-39/YKL-40 modulates the renal response to ischemic injury and predicts delayed allograft function

Insa M. Schmidt, Isaac E. Hall, Sujata Kale, Sik Lee, Chuan Hua He, Yashang Lee, Geoffrey L. Chupp, Gilbert W. Moeckel, Chun Geun Lee, Jack A. Elias, Chirag R. Parikh, Lloyd G. Cantley

Research output: Contribution to journalArticle

Abstract

Kidney hypoperfusion during episodes of systemic hypotension or after surgical procurement for transplantation can lead to tubular cell death via necrosis and apoptosis, which trigger a series of responses that promote repair. The factors that contribute to the repair phase after kidney injury are notwell understood. Using a urine proteomic screen in mice, we identified themacrophage-secreted chitinase-like protein Brp-39, the murine protein product of the chitinase 3-like 1 gene, as a critical component of this reparative response that serves to limit tubular cell apoptotic death via activation of Akt, improving animal survival after kidney ischemia/reperfusion. Examination of graded times of renal ischemia revealed a direct correlation between the degree of kidney injury and both Chi3l1/Brp-39 expression in the kidney and its levels in the urine. In samples collected from patients undergoing deceased-donor kidney transplantation, we found higher levels of the orthologous human protein, YKL-40, in urine and blood fromallografts subjected to sufficient peri-transplant ischemia to cause delayed graft function than from allografts with slow or immediate graft function. Urinary levels of YKL-40 obtained within hours of transplant predicted the need for subsequent dialysis in these patients. In summary, these data suggest that Brp-39/YKL-40 is a sensor of the degree of injury, a critical mediator of the reparative response, and a possible biomarker to identify patients at greatest risk of sustained renal failure after transplantation.

Original languageEnglish (US)
Pages (from-to)309-319
Number of pages11
JournalJournal of the American Society of Nephrology
Volume24
Issue number2
DOIs
StatePublished - Jan 31 2013

ASJC Scopus subject areas

  • Nephrology

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    Schmidt, I. M., Hall, I. E., Kale, S., Lee, S., He, C. H., Lee, Y., Chupp, G. L., Moeckel, G. W., Lee, C. G., Elias, J. A., Parikh, C. R., & Cantley, L. G. (2013). Chitinase-like protein Brp-39/YKL-40 modulates the renal response to ischemic injury and predicts delayed allograft function. Journal of the American Society of Nephrology, 24(2), 309-319. https://doi.org/10.1681/ASN.2012060579