A TIKU1, E PASCOE2, N BOUDVILLE3, A CASS4, N DALBETH5, R O. DAY6, J DE ZOYSA5, B DOUGLAS2, R FAULL7, D HARRIS8, C HAWLEY2, G R. JONES9, J KANELLIS10, S PALMER11, V PERKOVIC1, G RANGAN12, D REIDLINGER2, L ROBISON2, R J. WALKER11, G WALTERS13, D W. JOHNSON2, S BADVE1
1The George Institute for Global Health, Sydney, Australia, 2The University of Queensland, Brisbane, Australia, 3The University of Western Australia, Perth, Australia, 4Menzies School of Health Research, Darwin, Australia, 5The University of Auckland, Auckland, New Zealand, 6St Vincent’s Hospital, Sydney, Australia, 7The University of Adelaide, Adelaide, Australia, 8The University of Sydney, Sydney, Australia, 9UNSW Sydney, Sydney, Australia, 10Monash University, Melbourne, Australia, 11University of Otago, Dunedin, New Zealand, 12Westmead Hospital, Sydney, Australia, 13The Australian National University, Canberra, Australia
Background: The CKD-FIX trial showed that allopurinol did not slow decline in estimated glomerular filtration rate (eGFR) over 2 years in patients with chronic kidney disease (CKD) and risk of progression.
Aim: To assess the effect of allopurinol on change in eGFR by baseline albuminuria level.
Methods: In this trial, 369 adults with CKD stage 3 or 4, no history of gout and either urinary albumin-to-creatinine ratio (UACR) ≥265 mg/g or eGFR decrease ≥3.0 mL/min/1.73 m2 in the preceding year, were randomized to receive allopurinol or placebo. The primary outcome was change in eGFR up to 104 weeks using the CKD-EPI creatinine equation.
Results: At baseline, 104 (29%) participants had UACR < 300 mg/g and 254 (71%) had UACR ≥ 300 mg/g. In patients with UACR < 300 mg/g (mean UACR 96.6 mg/g, mean serum urate 8.0 mg/dL) change in eGFR did not differ between allopurinol (-1.62 mL/min/1.73 m2/year, 95% CI -2.83 to -0.40) and placebo (-0.90 mL/min/1.73 m2/year, 95% CI -2.16 to 0.35) groups (mean difference [MD], -0.71 mL/min/1.73 m2/year, 95% CI -2.45 to 1.03). In patients with UACR ≥ 300 mg/g (mean UACR 1,846.4 mg/g, mean serum urate 8.2 mg/dL) change in eGFR did not differ between allopurinol (-3.78 mL/min/1.73 m2/year, 95% CI -4.69 to -2.86) and placebo (-4.02 mL/min/1.73 m2/year, 95% CI -4.90 to -3.14) groups (MD, 0.25 mL/min/1.73 m2/year, 95% CI -1.02 to 1.51). The interaction P value for subgroup analysis was 0.30.
Conclusion: In CKD patients at risk of progression, the effect of allopurinol on eGFR decline was not modified by baseline level of albuminuria.
Dr Anushree Tiku is a nephrologist who trained at various tertiary hospitals throughout Sydney including the East Coast Renal Network and Royal Prince Alfred Hospital. She is currently doing a PhD with the Australasian Kidney Trials Network and The George Institute examining the role of urate-lowering therapy in chronic kidney disease.