Genetic variation implicates plasma angiopoietin-2 in the development of acute kidney injury sub-phenotypes.

BMC Nephrology
Pavan K BhatrajuMark M Wurfel

Abstract

We previously identified two acute kidney injury (AKI) sub-phenotypes (AKI-SP1 and AKI-SP2) with different risk of poor clinical outcomes and response to vasopressor therapy. Plasma biomarkers of endothelial dysfunction (tumor necrosis factor receptor-1, angiopoietin-1 and 2) differentiated the AKI sub-phenotypes. However, it is unknown whether these biomarkers are simply markers or causal mediators in the development of AKI sub-phenotypes. We tested for associations between single-nucleotide polymorphisms within the Angiopoietin-1, Angiopoietin-2, and Tumor Necrosis Factor Receptor 1A genes and AKI- SP2 in 421 critically ill subjects of European ancestry. Top performing single-nucleotide polymorphisms (FDR < 0.05) were tested for cis-biomarker expression and whether genetic risk for AKI-SP2 is mediated through circulating biomarkers. We also completed in vitro studies using human kidney microvascular endothelial cells. Finally, we calculated the renal clearance of plasma biomarkers using 20 different timed urine collections. A genetic variant, rs2920656C > T, near ANGPT2 was associated with reduced risk of AKI-SP2 (odds ratio, 0.45; 95% CI, 0.31-0.66; adjusted FDR = 0.003) and decreased plasma angiopoietin-2 (p = 0.002). Causa...Continue Reading

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Citations

Oct 10, 2020·Clinical Journal of the American Society of Nephrology : CJASN·Samantha Gunning, Jay L Koyner
Oct 13, 2020·Current Opinion in Critical Care·Zoltan H Endre, Ravindra L Mehta

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Methods Mentioned

BETA
genotyping
urine collection
urine sample collections
blood collection

Software Mentioned

IMPUTE2
Goldenhelix
STATA

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