Can Xanthine Oxidoreductase Inhibitor Protect Kidney against Progressive Injury?

Hyperuricemia has been shown to associate with high incidence of cardiovascular or kidney disease [1,2] and the beneficial effect of the treatment with allopurinol has been shown in hyperuricemic chronic kidney disease (CKD) patients [3]. Moreover, recent investigations have demonstrated that monosodium urate crystals activate natural immune system through its binding to Toll-like receptors (TLRs) and nucleotide binding and oligomerization domain-like receptors (NLRs) [4]. These indicate that xanthine oxidoreductase (XOR) inhibitor is a good candidate for renoprotective agents. However, there is evidence that, in contrast to the pro-inflammatory action of monosodium urate crystals, soluble form of uric acid in plasma acts as a major anti-oxidant in body [5]. Furthermore, allopurinol has been speculated to have nonspecific action on purine nucleotide metabolism pathway, because it is generated as purine nucleotide derivative. Thus, presently it is unclear whether treating non-symptomatic hyperuricemic subject with XOR inhibitor has beneficial effects on the progression of cardiovascular or kidney disease.