Urine high mobility group box 1 for prompt predicting acute graft dysfunction among kidney transplant recipients

Abstract

Objective

Because renal graft dysfunction usually leads to inevitable graft failure, prompt diagnosis and treatment of kidney transplant recipients (KTRs) experiencing graft dysfunction are crucial for improving long-term graft survival. A biomarker for early and accurate prediction of the development of acute graft dysfunction among KTRs is essential.

Methods

We conducted a prospective study on KTRs with more than two years of graft function to identify biomarkers for the early prediction of acute graft dysfunction. Urine biomarkers, such as high mobility group box 1 (HMGB1), kidney injury molecule-1 (KIM-1), migration inhibitory factor (MIF), and vascular endothelial growth factor (VEGF), were evaluated.

Results

Among the 86 enrolled KTRs, 18.6 % developed acute graft dysfunction. Urinary biomarkers, including HMGB1, KIM-1, MIF, and VEGF, were evaluated. While the KIM-1/creatinine, MIF/creatinine, and VEGF/creatinine ratios were similar between patient groups, the HMGB1/creatinine ratio was distinctly distributed. A receiver operating characteristic curve yielded an area under the curve of 0.747, with a cutoff value of 53.6 (pg/ml)/(mg/dl)) for the urinary HMGB1/creatinine ratio. Kaplan–Meier analysis with Cox regression demonstrated that KTRs with ratios >53.6 were significantly more prone to acute graft dysfunction (P < 0.05) than those with ratios ≤53.6 were.

Conclusions

Among KTRs with maintained graft function, the urine ratio of HMGB1/creatinine, a noninvasive and easily accessible assay, was effective for early prediction of acute graft dysfunction.