THE EFFECTS OF ALLOPURINOL ON THE PROGRESSION OF CHRONIC KIDNEY DISEASE ACCORDING TO BASELINE SERUM URATE LEVEL: RESULTS FROM POST HOC ANALYSES OF THE CKD-FIX TRIAL

A TIKU1, E PASCOE2, N BOUDVILLE3, A CASS4, N DALBETH5, R DAY6, J DE ZOYSA5, B DOUGLAS2, R FAULL7, D HARRIS8, C HAWLEY2, G JONES9, J KANELLIS10, S PALMER11, V PERKOVIC1, G RANGAN12, D REIDLINGER2, L ROBISON2, R WALKER11, G WALTERS13, D 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 of estimated glomerular filtration rate (eGFR) over 104 weeks in patients with chronic kidney disease (CKD) at risk of progression.
Aim: To assess the effect of allopurinol on change in eGFR by baseline serum urate level.
Methods: Three hundred and sixty nine adults with CKD stage 3 or 4, no history of gout, and risk of progression (urinary albumin-to-creatinine ratio ≥265 mg/g or eGFR decrease ≥3.0 mL/min/1.73 m2 in the preceding year) were randomized to receive allopurinol or placebo. Primary outcome was rate of change in eGFR up to 104 weeks using the CKD-EPI creatinine equation. This post hoc subgroup analysis describes outcomes in 352 participants by baseline serum urate level (normouricaemic and hyperuricaemic [serum urate >6 mg/dL in women and >7 mg/dL in men], and tertiles).
Results: At baseline, 65 (18.5%) patients were normouricaemic and 287 (81.5%) hyperuricemic. Mean serum urate was 5.9 mg/dL in the normouricemic group and 8.7 mg/dL in the hyperuricaemic group. There were no significant differences in change in eGFR between allopurinol and placebo in normouricemic (mean difference [MD] 0.35, 95%CI -2.72 to 3.42 mL/min/1.73 m2/year) and hyperuricemic (MD -0.06, 95%CI -1.20 to 1.08 mL/min/1.73 m2/year) participants (interaction P value = 0.84). Mean serum urate levels in the lowest, middle and highest tertiles were 6.3 mg/dL, 8.0 mg/dL and 10.0 mg/dL, respectively. The result for the primary outcome was consistent across all tertiles of baseline serum urate level (interaction P value for subgroup analysis = 0.49).
Conclusion: In CKD patients at risk of progression, the effect of allopurinol on eGFR decline was not modified by baseline serum urate level.


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