Chitinase-Like Protein Brp-39/YKL-40 Modulates the Renal Response to Ischemic Injury and Predicts Delayed Allograft Function

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 n...

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Bibliographic Details
Published in:Journal of the American Society of Nephrology 2013-02, Vol.24 (2), p.309-319
Main Authors: SCHMIDT, Insa M, HALL, Isaac E, PARIKH, Chirag R, CANTLEY, Lloyd G, KALE, Sujata, LEE, Sik, HE, Chuan-Hua, LEE, Yashang, CHUPP, Geoffrey L, MOECKEL, Gilbert W, CHUN GEUN LEE, ELIAS, Jack A
Format: Article
Language:English
Subjects:
Adipokines - genetics
Adipokines - metabolism
Animals
Apoptosis - physiology
Biological and medical sciences
Biomarkers - blood
Biomarkers - urine
Cells, Cultured
Chitinase-3-Like Protein 1
Clinical Research
Delayed Graft Function - metabolism
Delayed Graft Function - mortality
Delayed Graft Function - physiopathology
Disease Models, Animal
Epithelial Cells - cytology
Glycoproteins - genetics
Glycoproteins - metabolism
Humans
Kidney - cytology
Kidney Transplantation
Lectins - genetics
Lectins - metabolism
Macrophages - metabolism
Male
Medical sciences
Mice
Mice, Inbred C57BL
Nephrology. Urinary tract diseases
Nephropathies. Renovascular diseases. Renal failure
Phosphatidylinositol 3-Kinases - metabolism
Predictive Value of Tests
Proto-Oncogene Proteins c-akt - metabolism
Renovascular diseases
Reperfusion Injury - metabolism
Reperfusion Injury - mortality
Reperfusion Injury - physiopathology
Signal Transduction - physiology
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Surgery of the urinary system
Transplantation, Homologous
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Summary: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 not well understood. Using a urine proteomic screen in mice, we identified the macrophage-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 from allografts 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.
ISSN:1046-6673
1533-3450
DOI:10.1681/asn.2012060579