The Killer-Cell Immunoglobulin-Like Receptor (kir) Genotype Correlates with Acute Kidney Failure in the Early Post-Liver Transplantation Period

Introduction: Acute kidney injury (ARI) and acute renal failure (ARF) are major complications following liver transplantation (LT) leading up to chronic end-stage renal disease. The etiology of post-LT impairment is multi-factorial but it is suggested that e.g. during ischemia initial insults provoke morphological and functional changes within the vascular endothelium and tubular epithelium. Methods: As it has been demonstrated, that ischemic ARF can occur in the absence of classical T cell function and that Natural Killer (NK) cells can kill syngeneic tubular epithelial cell (TEC) in vitro, we aimed to elucidate the role of NK cells and their receptors in the context of early post-liver transplant ARI and ARF more precisely. Results: For instance, patients with impaired kidney function (serum creatinine levels >1.2 mg/dl, n=13) illustrated heightened peripheral NK cell frequencies prior LT compared with patients showing stable renal function (n=9) (17.22% ± 10.56 versus 12.98% ± 9.09). We further tested retrospectively 89 liver transplant recipients for their killer-cell immunoglobulin-like receptor (KIR) genotype and the risk of ARI and ARF. During the first week post liver-transplantation ARI occurred in 12% and ARF in 22% of the patients, respectively. ARI was a significant risk factor for acute rejection (p=0.0009) and ARF led to elevated serum creatinine levels (>1.2 mg/dl) at the time of hospital discharge (p=0.008). Interestingly, significantly less patients having a homozygous KIR haplotype A/A (characterized by the presence of only one activating KIR gene) displayed a stable early postoperative kidney function, compared to patients with a KIR haplotype B/x (more than one activating receptor) (p=0.025, odds ratio 2.3, CI=1.3-3.9). Moreover, the absence of KIR2DL2/DS2 genes significantly influenced the risk of acute renal failure (p=0.05). A multivariate regression model of both clinical and genomic risk factors for acute kidney injury/failure confirmed a link between the KIR haplotype A/A and post-LT acute renal failure (p=0.04). Conclusion: In summary, we observed a higher percentage of NK cells prior to LT in patients with impaired renal function and identified the KIR haplotype A/A as an independent genetic risk factor for ARF within the first postoperative week. Our data therefore provide new aspects of an innate immune response within the setting of post-LT kidney injury and failure.