Urinary cell-cycle arrest proteins for early prediction and phenotyping of subclinical and clinical acute kidney injury after liver transplantation

Acute kidney injury (AKI) is common after liver transplantation (LT) but difficult to diagnose with serum creatinine (sCr) and urinary output (UO). This study evaluated the early risk stratification capability of urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor binding protein-7 (u[TIMP-2]*[IGFBP-7]) in a prospective adult LT cohort. u[TIMP-2]*[IGFBP-7] was measured 6 and 36 hours post-graft reperfusion, with AKI and acute kidney disease (AKD) diagnosed according to KDIGO and ADQI criteria at 7 and 90-day windows. Subclinical AKI was defined as u[TIMP-2]*[IGFBP-7]>0.30 without clinical AKI. Among 78 included patients, AKI occurred in 45% (10.3%, 11.7%, 23.4% for stages 1, 2, and 3). At 6 hours, 46% had u[TIMP-2]*[IGFBP-7]>0.30, predicting AKI (stage ≥1) with an odds ratio (OR) of 3.23 (p=0.01); at 36 hours, 37% had u[TIMP-2]*[IGFBP-7]>0.30, predicting stage 3 AKI with an OR of 4.22 (p=0.009). sCr/UO criteria predicted AKI only in 10% and 18% at 6 and 36 hours. Subclinical AKI patients (24%) had higher risks of AKD (42% vs. 26%), early allograft dysfunction (32% vs. 18%), graft loss (16% vs. 4%), and longer ICU stays. u[TIMP-2]*[IGFBP-7] is a valuable biomarker for early AKI risk stratification after LT, with subclinical AKI representing a distinct, clinically relevant phenotype.