The case for uric acid-lowering treatment in patients with hyperuricaemia and CKD


Hyperuricaemia is common among patients with chronic kidney disease (CKD), and increases in severity with the deterioration of kidney function. Although existing guidelines for CKD management do not recommend testing for or treatment of hyperuricaemia in the absence of a diagnosis of gout or urate nephrolithiasis, an emerging body of evidence supports a direct causal relationship between serum urate levels and the development of CKD. Here, we review randomized clinical trials that have evaluated the effect of urate-lowering therapy (ULT) on the rate of CKD progression. Among trials in which individuals in the control arm experienced progressive deterioration of kidney function (which we define as ≥4 ml/min/1.73 m² over the course of the study — typically 6 months to 2 years), treatment with ULT conferred consistent clinical benefits. In contrast, among trials where clinical progression was not observed in the control arm, treatment with ULT was ineffective, but this finding should not be used as an argument against the use of uric acid-lowering therapy. Although additional studies are needed to identify threshold values of serum urate for treatment initiation and to confirm optimal target levels, we believe that sufficient evidence exists to recommend routine measurement of serum urate levels in patients with CKD and consider initiation of ULT among those who are hyperuricaemic with evidence of deteriorating renal function, unless specific contraindications exist.

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Fig. 1: Effects of uric acid on the kidney.
Fig. 2: Purine nucleotide degradation and fructose metabolism generate uric acid.


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Y.S. was a JSPS Overseas Research Fellow in the laboratories of R.J.J and M.A.L. D.-H.K. was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean Government (MSIP) (NRF-2015R1A2A1A15053374, NRF-2017R1A2B2005849).

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Y.S., D.I.F., A.G.S., D.-H.K., L.G.S.-L. and R.J.J. researched data for the article, contributed substantially to discussion of the article’s content and wrote the article. All authors contributed to review/editing of the manuscript before submission.

Correspondence to Richard J. Johnson.

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A.G.S. has had an unrestricted educational grant from the Menarini International Operations Luxemburg and has consulted for Menarini and Grunenthal Pharma. L.G.S.-L has received funding from Relburn Metabolomic and Danone Research Foundation. R.J.J. has equity with XORT Therapeutics, which is developing novel xanthine oxidase inhibitors and is an inventor involved in several patents on the role of uric acid in hypertension, metabolic syndrome and diabetic nephropathy that have resulted from his research (US Patent No. 7,799,794; US Patent No. 8,236,488; US Patent No. 8,557,831; US Patent No. 9,155,740B). He has also consulted for Danone Research Foundation, for Horizon Pharmaceuticals and for AstraZeneca. The other authors declare no competing interests.

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Sato, Y., Feig, D.I., Stack, A.G. et al. The case for uric acid-lowering treatment in patients with hyperuricaemia and CKD. Nat Rev Nephrol 15, 767–775 (2019) doi:10.1038/s41581-019-0174-z

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