Challenges of conducting a trial of uric-acid-lowering therapy in CKD

Nat Rev Nephrol. 2011 May;7(5):295-300. doi: 10.1038/nrneph.2010.186. Epub 2011 Feb 15.

Abstract

Observational studies have shown that asymptomatic hyperuricemia is associated with increased risks of hypertension, chronic kidney disease (CKD), end-stage renal disease, cardiovascular events, and mortality. Whether these factors represent cause, consequence or incidental associations, however, remains uncertain. Hyperuricemia could be a consequence of impaired kidney function, diuretic therapy or oxidative stress, such that elevated serum urate level represents a marker, rather than a cause, of CKD. On the other hand, small, short-term, single-center studies have shown improvements in blood-pressure control and slowing of CKD progression following serum urate lowering with allopurinol. An adequately powered randomized controlled trial is required to determine whether uric-acid-lowering therapy slows the progression of CKD. This article discusses the rationale for and the feasibility of such a trial. International collaboration is required to plan and conduct a large-scale multicenter trial in order to better inform clinical practice and public health policy about the optimal management of asymptomatic hyperuricemia in patients with CKD.

Publication types

  • Review

MeSH terms

  • Allopurinol / therapeutic use*
  • Gout Suppressants / therapeutic use*
  • Humans
  • Hyperuricemia / drug therapy*
  • Hyperuricemia / epidemiology
  • Hyperuricemia / metabolism
  • Kidney Failure, Chronic / drug therapy*
  • Kidney Failure, Chronic / epidemiology
  • Kidney Failure, Chronic / metabolism
  • Randomized Controlled Trials as Topic / methods
  • Research Design
  • Risk Factors
  • Uric Acid / blood*

Substances

  • Gout Suppressants
  • Uric Acid
  • Allopurinol