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Abstract: TH-PO1198

Effect of Allopurinol on the Progression of CKD: The CKD-FIX Study

Session Information

Category: CKD (Non-Dialysis)

Authors

  • Badve, Sunil, St George Hospital, Sydney, New South Wales, Australia
  • Tiku, Anushree, St George Hospital, Sydney, New South Wales, Australia
  • Pascoe, Elaine, The University of Queensland, New Farm, Queensland, Australia
  • Boudville, Neil, University of Western Australia, Nedlands, Western Australia, Australia
  • Cass, Alan, Menzies School of Health Research, Darwin, Northern Territory, Australia
  • Dalbeth, Nicola, University of Auckland, Auckland, New Zealand
  • Day, Richard O., St Vincents Hospital & UNSW, Darlinghurst, New South Wales, Australia
  • de Zoysa, Janak, Waitemata District Health Board, Auckland, New Zealand
  • Douglas, Bettina, Princess Alexandra Hospital, Brisbane, Queensland, Australia
  • Faull, Randall, Royal Adelaide Hospital, Adelaide, South Australia, Australia
  • Harris, David, Sydney Medical School - University of Sydney, Duffys Forest, New South Wales, Australia
  • Hawley, Carmel, Princess Alexandra Hospital, Brisbane, Queensland, Australia
  • Jones, Graham R D, St Vincent''s Hospital, Sydney, Darlinghurst, New South Wales, Australia
  • Kanellis, John, Monash Medical Centre, Clayton, Victoria, Australia
  • Palmer, Suetonia, University of Otago, Christchurch, New Zealand
  • Perkovic, Vlado, The George Institute for Global Health, Newtown, New South Wales, Australia
  • Rangan, Gopi, Westmead Institute for Medical Research, The University of Sydney, Sydney, New South Wales, Australia
  • Reidlinger, Donna, The University of Queensland, New Farm, Queensland, Australia
  • Robison, Laura, University of Queensland, Brisbane, New South Wales, Australia
  • Walker, Robert J., University of Otago, Christchurch, New Zealand
  • Walters, Giles, ACT Health, Garran, Australian Capital Territory, Australia
  • Johnson, David W., Princess Alexandra Hospital, Brisbane, Queensland, Australia
Background

Hyperuricemia is a common finding in chronic kidney disease (CKD) and associated with increased risk of progression of CKD. The effect of urate-lowering therapy on CKD progression remains uncertain. We therefore assessed whether allopurinol attenuates the decline of estimated glomerular filtration rate (eGFR) over 2 years in people with high CKD-progression risk.

Methods

In this double-blind randomized controlled trial, adults with CKD stage 3 or 4, urinary albumin-to-creatinine ratio (UACR) ≥30 mg/mmol or decrease in eGFR ≥3.0 mL/min/1.73 m2 in the preceding ≤12 months, and no history of gout, were randomized to allopurinol (100-300 mg once daily) or placebo. The primary outcome was change in eGFR (mL/min/1.73 m2/yr) up to 104 weeks. The key secondary endpoints were 40% reduction in GFR, progression to end-stage kidney disease (ESKD), blood pressure, albuminuria, and adverse events.

Results

369 participants were randomised to the allopurinol group (n=185) or placebo group (n=184). Six withdrew before the baseline visit (3 in each group). The rate of eGFR decline did not differ significantly between the allopurinol (-3.33 mL/min/1.73 m2/yr, 95% CI -4.11 to -2.55) and placebo (-3.23 mL/min/1.73 m2/yr, 95% CI -3.98 to -2.47) groups (difference -0.10 mL/min/1.73 m2/yr, 95% CI -1.18 to 0.97, P=0.85). 63 (35%) and 51 (28%) participants in the allopurinol and placebo groups experienced a secondary composite endpoint of 40% eGFR decline, ESKD, or death from any cause (RR 1.23, 95% CI 0.90 to 1.67). There were no significant differences in change in UACR (P=0.25), and systolic blood pressure (P=0.30) between the two groups. Serum urate was significantly lower in the allopurinol group (mean difference -0.16 mmol/L, 95% CI -0.17 to -0.15, P<0.001). Serious adverse events were reported in 84 (46%) and 79 (44%) participants in the allopurinol and placebo groups, respectively (P=0.63).

Conclusion

In CKD patients with elevated CKD-progression risk, urate-lowering treatment with allopurinol did not result in slower eGFR decline than placebo. These results do not support the use of urate-lowering therapy to slow CKD progression.

Funding

  • NIDDK Support