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The case for uric acid-lowering treatment in patients with hyperuricaemia and CKD
Yuka Sato1, Daniel I Feig2, Austin G Stack3,4
1Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Insights
High serum urate levels are common in chronic kidney disease (CKD). Urate-lowering therapy (ULT) can slow CKD progression in patients with worsening kidney function.
Area of Science:
- Nephrology
- Internal Medicine
- Pharmacology
Background:
- Hyperuricaemia is prevalent in chronic kidney disease (CKD) and worsens with declining kidney function.
- Current CKD guidelines do not mandate hyperuricaemia management without gout or urate nephrolithiasis.
- Emerging evidence suggests a direct link between serum urate and CKD development.
Purpose of the Study:
- To review randomized clinical trials assessing urate-lowering therapy (ULT) effects on CKD progression.
- To evaluate the efficacy of ULT in slowing the decline of renal function in CKD patients.
Main Methods:
- Systematic review of randomized clinical trials.
- Analysis of studies where control groups showed kidney function deterioration (≥4 ml/min/1.73 m²).
- Comparison of ULT efficacy in trials with and without observed progression in control arms.
Main Results:
- ULT demonstrated consistent clinical benefits in trials where control groups experienced significant kidney function decline.
- ULT was ineffective in trials without observed progression in the control arm, suggesting context-dependent efficacy.
- The findings support the benefit of ULT when CKD is actively progressing.
Conclusions:
- Routine serum urate measurement in CKD patients is recommended.
- Consider initiating ULT for hyperuricaemic CKD patients with evidence of renal function deterioration.
- Further research is needed to establish optimal serum urate thresholds for ULT initiation and targets.
Abstract:
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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