Acute Kidney Injury Patterns Following Transplantation of Steatotic Liver Allografts

Abstract

Background: Steatotic grafts are increasingly being used for liver transplant (LT); however, the impact of graft steatosis on renal function has not been well described.

Methods: A total of 511 allografts from Mayo Clinic Arizona and Minnesota were assessed. We evaluated post-LT acute kidney injury (AKI) patterns, perioperative variables and one-year outcomes for patients receiving moderately steatotic allografts (>30% macrovesicular steatosis, n = 40) and compared them to non-steatotic graft recipients.

Results: Post-LT AKI occurred in 52.5% of steatotic graft recipients versus 16.7% in non-steatotic recipients (p < 0.001). Ten percent of steatotic graft recipients required new dialysis post-LT (p = 0.003). At five years, there were no differences for AKI vs. no AKI patient survival (HR 0.95, 95% CI 0.08-10.6, p = 0.95) or allograft survival (HR 1.73, 95% CI 0.23-13.23, p = 0.59) for those using steatotic grafts. Lipopeliosis on biopsy was common in those who developed AKI (61.0% vs. 31.6%, p = 0.04), particularly when the Model for End-Stage Liver Disease (MELD) was ≥20 (88.9%; p = 0.04). Lipopeliosis was a predictor of post-LT AKI (OR 6.0, 95% CI 1.1-34.6, p = 0.04).

Conclusion: One-year outcomes for moderately steatotic grafts are satisfactory; however, a higher percentage of post-LT AKI and initiation of dialysis can be expected. Presence of lipopeliosis on biopsy appears to be predictive of post-LT AKI.

Keywords: acute kidney injury; allograft steatosis; lipopeliosis.

Figure 1

Liver Graft Biopsy Findings Liver Biopsy Findings. (A) Representative biopsy of a >30% macrovesicular steatotic allograft. (B) Representative biopsy of a non-steatotic allograft. (C) Approximately 30% macrovesicular steatosis with a mixture of large (arrows) and small (arrowheads) droplet fat (hematoxylin and eosin (H&E), 200×). (D) Microvesicular steatosis characterized by diffuse deposition of fat droplets in the hepatocyte cytoplasm without any macrovesicular steatosis (H&E, 200×). (E) Approximately 40% macrovesicular steatosis seen on a pre-implantation biopsy (H&E frozen section, 400×). (F) Zonal distribution of macrovesicular steatosis with fat deposition accentuated in zone three (asterisks) around the central veins (H&E, frozen section, 100×). (G), Lipopeliosis characterized by the rupture of hepatocytes with coalescence of fat droplets (arrow) in the sinusoidal spaces (H&E, frozen section, 600×). (H), Lipopeliosis (arrow) in post-reperfusion biopsy (H&E, 600×).

Figure 2

Post-Liver Transplant Patterns in Steatotic and Non-Steatotic Grafts. (A) Post-LT aspartate aminotransferase (AST) levels. Compared to non-steatotic graft, AST levels were 2-times higher in steatotic grafts without post-LT AKI and 4-times higher for steatotic grafts with AKI. (B) Post-LT creatinine levels.

Figure 3

Survival. (A) Patient survival post-LT. Hazard ratio (HR); Confidence Interval (CI). (B) Liver allograft survival post-transplant. Moderately steatotic grafts with AKI (>30% Macro-AKI); Moderately steatotic grafts without AKI (>30% Macro-No AKI); Non-steatotic grafts (<30% Macro).

Figure 4

Relationship between MELD, Lipopeliosis and Post-LT AKI.