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, but difficult to diagnose with serum creatinine and urinary output. 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 liver transplantation cohort. u[TIMP-2]*[IGFBP-7] was measured 6 and 36 hours after graft reperfusion, with AKI and acute kidney disease diagnosed according to KDIGO and ADQI criteria at 7-day 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%, and 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 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). Serum creatinine/urinary output criteria predicted AKI only in 10% and 18% at 6 and 36 hours, respectively. Subclinical patients with AKI (24%) had higher risks of acute kidney disease (42% vs. 26%), early allograft dysfunction (32% vs. 18%), graft loss (16% vs. 4%), and longer intensive care unit stays. u[TIMP-2]*[IGFBP-7] is a valuable biomarker for early AKI risk stratification after liver transplantation, with subclinical AKI representing a distinct, clinically relevant phenotype.