Pharmacological urate-lowering approaches in chronic kidney disease

Eur J Med Chem. 2019 Mar 15:166:186-196. doi: 10.1016/j.ejmech.2019.01.043. Epub 2019 Jan 23.

Abstract

Chronic kidney disease (CKD) has become a global public health issue and uric acid (UA) remains a major risk factor of CKD. As the main organ for the elimination of UA, kidney owned a group of urate transporters in tubular epithelium. Kidney disease hampered the UA excretion, and the accumulation of serum UA in return harmed the renal function. Commercially, there are three kinds of agents targeting at urate-lowering, xanthine oxidoreductase inhibitor which prevents the production of UA, uricosuric which increases the concentration of UA in urine thus decreasing serum UA level, and uricase which converts UA to allantoin resulting in the dramatic decrement of serum UA. Of note, in patients with CKD, administration of above-mentioned agents, alone or combined, needs special attention. New evidence is emerging for the efficacy of several urate-lowering drugs for the treatment of hyperuricemia in patients with CKD. Besides, loads of novel and promising drug candidates and phytochemicals are in the different phases of research and development. As of today, there is insufficient evidence to recommend the widespread use of UA-lowering therapy to prevent or slow down the progression of CKD. The review summarized the evidence and perspectives about the treatment of hyperuricemia with CKD for medicinal chemist and nephrologist.

Keywords: Chronic kidney disease; Urate-lowering treatment; Uric acid; Xanthine oxidase.

Publication types

  • Review

MeSH terms

  • Biological Products / pharmacology
  • Biological Products / therapeutic use
  • Drug Discovery / methods*
  • Flavonoids / pharmacology
  • Flavonoids / therapeutic use
  • Humans
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / metabolism*
  • Uric Acid / metabolism*

Substances

  • Biological Products
  • Flavonoids
  • Uric Acid