Does Tamm-Horsfall protein-uric acid binding play a significant role in urate homeostasis?

BACKGROUND Mutations in Tamm-Horsfall protein (THP), also known as uromodulin, lead to a group of diseases known as the uromodulin storage disorders. Clinically, these diseases present with tubulo-interstitial damage, progressive renal dysfunction, hyperuricaemia, and gout. However, it remains unclear how a mutation in THP, a protein produced in the thick ascending limb, can cause hyperuricaemia when most of the uric acid transport is believed to occur in the proximal tubule. However, one study in humans suggests that uric acid could also be secreted in the distal tubule. Thus, an attractive hypothesis could be that THP would bind to uric acid in the distal tubule, and decrease its subsequent reabsorption in the distal nephron. METHODS We screened for uric acid binding to THP using four independent binding assays. RESULTS There was no evidence that uric acid could bind to THP. CONCLUSION THP-uric acid binding does not seem to play a significant role in the regulation of urate homeostasis.