Urinary NGAL Outperforms 99mTc-MAG3 Renography in Predicting DCD Kidney Graft Function.

Abstract

Recipients of donation after circulatory death (DCD) kidneys are at high risk for delayed graft function (DGF) due to severe ischemia-reperfusion injury. We compared urinary biomarkers in predicting the duration of DGF with the tubular function slope (TFS) as the gold standard. In 89 DCD kidney transplant recipients, urinary TIMP-2, IGFBP7, B2M, NGAL, KIM1, CXCL9, and UMOD were quantified by LC-MS/MS analysis on postoperative days (PODs) 1, 4 and 10. Interstitial fibrosis and tubular atrophy (IF/TA) were assessed with protocol biopsies at POD 10. TFS was calculated with ^99mTc-MAG3 renography. Predictive performance was compared with AUCs from ROC analyses. Of all 89 recipients, 22% experienced no (<7), 22% mild (≥7-14), 29% moderate (≥14-<21) and 26% severe (≥21 days) fDGF. The OR for the presence of IF/TA was 1.9 (95% CI:0.4; 10.0) for mild to moderate and 15.0 (95% CI:2.7; 84.8) for severe compared to no fDGF. At POD 4, urinary NGAL and fractional NGAL excretion (FE-NGAL) outperformed TFS and other biomarkers in predicting fDGF with AUCs of 0.97, 0.98 and 0.92, respectively. At POD10, FE-NGAL and PCR best predicted severe vs. mild to moderate fDGF, with AUCs of 0.74 and 0.76 versus 0.65 for TFS. Therefore, urinary NGAL and FE-NGAL may provide a viable alternative to ^99mTcMAG3 renography for monitoring fDGF clearance or guiding kidney transplant biopsy to exclude additional acute rejection.