The augmenter of liver regeneration protects the kidneys after orthotopic liver transplantation possibly by upregulating HIF-1α and O2-sensitive K+ channels

Purpose: The augmenter of liver regeneration (ALR) might promote better renal function after orthotopic liver transplantation (OLT). Using a rat allogeneic OLT model, we investigated if ALR can mediate renal protection and its potential mechanisms.

Methods: Orthotopic liver transplant recipients were assigned to a cyclosporine A (CsA)-treated group (CsA group) and an ALR+CsA group (ALR group). Transplanted liver, kidneys, and serum were harvested on post-transplantation days 1, 3, and 7 for histological examination, and hepatic function and renal function analysis. We also measured the expression of hypoxiainducible factor-1 (HIF-1α) and O(2)-sensitive K(+) cannels (KV1.5 and KV2.1), and free Ca(2+) in the smooth muscle cells (SMCs) of intrarenal arterioles in the kidneys.

Results: All transplanted livers suffered mild acute rejection after OLT. Recipient kidney damage was more severe in the CsA group, characterized by increased serum creatinine, tubular epithelial apoptosis and necrosis, and the formation of casts. In the ALR group, HIF-1α, KV1.5, and KV2.1 were upregulated, accompanied by lower Ca(2+) concentration, in the SMCs shortly after OLT.

Conclusion: Augmenter of liver regeneration might increase the expression of HIF-1α and K(+) channels and decrease intracellular free Ca(2+), thereby inhibiting arterial contraction and promoting kidney perfusion immediately after OLT.