Patient characteristics.

<p>NOTE: The results are given as mean ± standard deviation. Statistical analysis was performed using the Mann-Whitney U test and Kruskal-Wallis test.</p><p><b>Abbreviations:</b> BUN, blood urea nitrogen; eGFR, estimated glomerular filtration rate; MELD, Model for End-stage Liver Disease; Scr, serum creatinine; POD, postoperative day.</p><p>Patient characteristics.</p

Characteristics of the urinary biomarkers.

<p><b>Abbreviations:</b> AUC, area under the curve; CI, confidence interval; IL-18, interleukin-18; L-FABP, liver-type fatty acid-binding protein; MCP-1, monocyte chemotactic protein-1; NGAL, neutrophil gelatinase-associated lipocalin.</p><p>Characteristics of the urinary biomarkers.</p

Time-dependent changes tacrolimus concentration, Scr levels and urinary NGAL concentrations.

<p>The average ± SD values of tacrolimus trough concentrations, Scr levels and urinary NGAL concentrations in the liver transplant patients who experienced AKI during the period of postoperative day 1–5 (B, F, J), during the postoperative day 6–10 (C, G, K), after the postoperative day 11 (D, H, L) and AKI-free patients (A, E, I) are summarized. The cut-off values of urinary NGAL calculated from ROC analysis were 61.0 ng/mg creatinine (red dotted line).</p

Comparison of the urinary levels of NGAL (A), MCP-1 (B), L-FABP (C), IL-18 (D), osteopontin (E), cystatin C (F), and clusterin (G) between AKI-free group (37 measurements of 11 subjects) and AKI group (40 measurements of 20 subjects).

<p>Data were from urinary samples in the post-transplant tacrolimus therapy. Data were normalized to urinary creatinine concentration and plotted on a logarithmic Y axis. Statistical analyses were performed using the Mann-Whitney U test and Kruskal-Wallis test. *P<0.05, ***P<0.001. NGAL, neutrophil gelatinase-associated lipocalin; MCP-1, monocyte chemotactic protein-1; L-FABP, liver-type fatty acid-binding protein; IL-18, interleukin-18, N.D., not detected.</p

Urinary levels of NGAL in AKI and AKI-free patients.

<p>The cut-off values of urinary NGAL at postoperative day 1 (A, dotted line: 12.8 ng/mg creatinine) and postoperative day 7 (B, dotted line: 62.6 ng/mg creatinine) were evaluated using ROC curve analysis. Although the urinary level of NGAL in the AKI group was similar to that of the AKI-free group at postoperative day 1 (<b>A</b>), that at postoperative day 7 was markedly higher in the AKI group than in the AKI-free group (<b>B</b>). The probability of AKI developing between postoperative days 1 and 7 (<b>C</b>) and between postoperative days 8 and 14 (<b>D</b>) was examined using Kaplan-Meier analysis and a log-rank test. Statistical analysis was performed using the Mann-Whitney U test. **P<0.01. NGAL, neutrophil gelatinase-associated lipocalin.</p

Diagnostic algorithm of tacrolimus-induced AKI in the patients after liver transplantation.

<p>Between August 2010 and July 2013, 93 patients were enrolled with the written informed consent. Nine patients with perioperative renal impairment before the administration of tacrolimus-based posttransplant immunosuppressive treatment and patients with any renal replacement therapy were excluded. Patients with renal impairment by some other causes including septic ischemia, antibiotics and hepatorenal syndrome were also excluded from this study. In addition, the patients of renal impairment with low tacrolimus levels, whose Scr levels were not changed even by the decrease of tacrolimus dosage, were also excluded indicating other causes-derived renal impairment such as tubular necrosis post-surgery. Among 24 patients with normal kidney function, 13 patients with post-transplant infectious disease, surgery for hemostasis, post-surgical diabetes mellitus and acute rejection episode were excluded for the temporal discontinuation of tacrolimus administration. Finally, the clinical data of the 11 control patients and 20 patients with tacrolimus-induced AKI were used.</p

Comparison of the urinary levels of NGAL (A), MCP-1 (B), L-FABP (C), IL-18 (D), osteopontin (E), cystatin C (F), and clusterin (G) among healthy volunteers (8 measurements of 8 subjects), AKI-free group (11 measurements of 11 subjects) and AKI group (20 measurements of 20 subjects).

<p>Data were from urinary samples on postoperative day 1 immediately before the administration of tacrolimus in liver transplant patients (AKI-free group and AKI group). Data were normalized to urinary creatinine concentration and plotted on a logarithmic Y axis. Statistical analyses were performed using the Mann-Whitney U test and Kruskal-Wallis test. *<0.05, **P<0.01, ***P<0.001. NGAL, neutrophil gelatinase-associated lipocalin; MCP-1, monocyte chemotactic protein-1; L-FABP, liver-type fatty acid-binding protein; IL-18, interleukin-18, N.D., not detected.</p