Molekulare Grundlagen der primär-renalen Hyperurikämie

Abstract

In highly industrialized countries hyperuricemia is one of the most common metabolic disorders. High uric acid blood levels may lead to the manifestation of gout owing to the precipitation of urate crystals in connective tissue, the skeletal system and kidneys. A primary reduction of renal uric acid excretion can be detected in more than 90% of all cases of hyperuricemia. Despite the identification of several uric acid transporting proteins their pathogenetic role for the induction of primary reduced renal uric acid excretion has not yet been verified. As a result of a case-control study on individuals with normal and reduced renal uric acid excretion, an association of polymorphisms in the human urate transporter 1 gene (hURAT1) with primary reduced urate excretion has been demonstrated for the first time. The hURAT1 gene is an organic anion transporter (SLC22A12), which is preferentially expressed in the apical membrane of proximal renal tubule cells. Functioning as an antiporter, hURAT1 mediates the uptake of urate from the lumen into proximal tubule cells in exchange for organic and inorganic anions. Loss-of-function mutations in the hURAT1 gene are a cause of hereditary renal hypouricemia. The precisely regulated hURAT1 is a candidate gene for hyperuricemia and an important target for the development and optimization of new diagnostic approaches and pharmacological interventions of primary reduced renal uric acid excretion.

Lesinurad: A significant advancement or just another addition to existing therapies of gout?

“…Considering under-excretion of uric acid as major cause of hyperuricemia, in recent years important urate transport proteins such as the human uric acid transporter 1 (URAT1) and the fructose transporter SLC2A9 have been characterized. [1112] Lesinurad, a newer drug to treat chronic refractory gout by targeting the URAT1 transporter, has been approved recently by the US Food and Drug Administration in combination with an XOI. [13] It has also been currently approved by the European Commission for marketing authorization throughout the European Union in February 2016.…”