Soluble uric acid suppresses neutrophil-mediated host defense in sepsis

However, neutrophil dysfunction is a hallmark of the acquired immunodeficiency in kidney disease, contributing to an increased susceptibility to infections such as peritonitis, sepsis, and pneumonia. We speculated that the impaired renal clearance of the metabolite soluble uric acid (sUA) may account for neutrophil dysfunction.

Indeed, hyperuricemia (HU, serum UA of 9-14 mg/dL) related or unrelated to kidney disease significantly exacerbated the inflammatory immune response to infection by impairing neutrophil dynamics and functions in mice with mono- and polybacterial sepsis. This aggravated inflammatory response was partially reversible by lowering UA levels with febuxostat. We validated these findings in vitro using either neutrophils or serum from healthy individuals or hyperuricemic patients with chronic kidney disease.