THE EFFECTS OF ALLOPURINOL ON THE PROGRESSION OF CHRONIC KIDNEY DISEASE ACCORDING TO BASELINE KIDNEY FUNCTION: PRE-SPECIFIED 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 allopurinol did not slow decline in estimated glomerular filtration rate (eGFR) over 2 years in patients with chronic kidney disease (CKD) also at risk of progression.
Aim: To assess the effect of allopurinol on change in eGFR by baseline CKD stage.
Methods: In this trial, 369 adults with CKD stage 3 or 4, no history of gout and either 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 pre-specified subgroup analysis describes outcomes in patients with CKD stages 3 and 4.
Results: At baseline, 178 (49%) patients had CKD stage 3 (mean eGFR 41 mL/min/1.73 m2, mean serum urate 7.9 mg/dL) and 185 (51%) patients had CKD stage 4 (mean eGFR 23.1 mL/min/1.73 m2, mean serum urate 8.4 mg/dL). In patients with CKD stage 3, change in eGFR did not differ between the allopurinol (-3.67 mL/min/1.73 m2/year, 95% CI -4·97 to -2·38) and placebo (-3.34 mL/min/1.73 m2/year, 95% CI -4·59 to -2·09) groups (mean difference [MD], -0.33 mL/min/1.73 m2/year, 95% CI -2.13 to 1.47). In patients with CKD stage 4, there was no difference in change in eGFR between the allopurinol (-2.89 mL/min/1.73 m2/year, 95% CI -3·74 to -2·03) and placebo (-2.89 mL/min/1.73 m2/year, 95% CI -3·73 to -2·04) groups (MD, 0.00 mL/min/1.73 m2/year, 95% CI -1.18 to 1.17). The interaction P value for subgroup analysis was 0.87.
Conclusion: In CKD patients at risk of progression, baseline kidney function did not modify the effect of allopurinol on eGFR decline.


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