Neutrophil Gelatinase-Associated Lipocalin Is Not Associated with Tacrolimus-Induced Acute Kidney Injury in Liver Transplant Patients Who Received Mycophenolate Mofetil with Delayed Introduction of Tacrolimus

Int J Mol Sci. 2019 Jun 25;20(12):3103. doi: 10.3390/ijms20123103.

Abstract

Tacrolimus is widely used as an immunosuppressant in liver transplantation, and tacrolimus-induced acute kidney injury (AKI) is a serious complication. The urinary neutrophil gelatinase-associated lipocalin (NGAL) level has been linked to tacrolimus-induced AKI in patients starting tacrolimus treatment the morning after liver transplantation. Here we tested this association using a different immunosuppression protocol: Mycophenolate mofetil administration beginning on Postoperative Day 1 and tacrolimus administration beginning on Postoperative Day 2 or 3. Urine samples were collected from 26 living donor liver transplant recipients before (Postoperative Day 1) and after (Postoperative Day 7 or 14) tacrolimus administration. NGAL levels were measured via enzyme-linked immunosorbent assays, as were those of three additional urinary biomarkers for kidney diseases: Monocyte chemotactic protein-1 (MCP-1), liver-type fatty acid-binding protein (L-FABP), and human epididymis secretory protein 4 (HE4). HE4 levels after tacrolimus administration were significantly higher in patients who developed AKI (n = 6) than in those who did not (n = 20), whereas NGAL, MCP-1, and L-FABP levels did not differ significantly before or after tacrolimus administration. These findings indicate that NGAL may not be a universal biomarker of AKI in tacrolimus-treated liver transplant recipients. To reduce the likelihood of tacrolimus-induced AKI, our immunosuppression protocol is recommended.

Keywords: acute kidney injury; biomarker; liver transplantation; neutrophil gelatinase-associated lipocalin; tacrolimus.

MeSH terms

  • Acute Kidney Injury / diagnosis*
  • Acute Kidney Injury / etiology*
  • Adult
  • Algorithms
  • Biomarkers / metabolism
  • Biomarkers / urine
  • Female
  • Humans
  • Kidney Function Tests
  • Lipocalin-2 / genetics*
  • Lipocalin-2 / metabolism
  • Liver Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Mycophenolic Acid / adverse effects*
  • Tacrolimus / adverse effects*
  • WAP Four-Disulfide Core Domain Protein 2

Substances

  • Biomarkers
  • Lipocalin-2
  • WAP Four-Disulfide Core Domain Protein 2
  • WFDC2 protein, human
  • Mycophenolic Acid
  • Tacrolimus