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


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.

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Figure 1: Schematic diagram of a potential RCT to evaluate the effects of urate-lowering therapy on renal and cardiovascular outcomes in patients with stages 2–3 CKD.


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We are grateful to C. Thompson, a Biostatistician at the Australasian Kidney Trials Network, University of Queensland, Brisbane, Qld 4102, Australia, for his invaluable statistical assistance.

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Authors and Affiliations



S. V. Badve, F. Brown, J. Kanellis, G. K. Rangan, V. Perkavic contributed equally to researching data for the article, writing and reviewing the manuscript before submission. C. M. Hawley made a substantial contribution to discussion of content, writing and review of the manuscript. D. W. Johnson was involved in writing and review of the manuscript before submission.

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Correspondence to Sunil V. Badve.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Summary of studies that have examined the relationship between uric acid level and various clinical outcomes (DOC 70 kb)

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Badve, S., Brown, F., Hawley, C. et al. Challenges of conducting a trial of uric-acid-lowering therapy in CKD. Nat Rev Nephrol 7, 295–300 (2011).

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