THE EFFECTS OF ALLOPURINOL ON THE PROGRESSION OF CHRONIC KIDNEY DISEASE ACCORDING TO ALBUMINURIA AT BASELINE: RESULTS FROM PRE-SPECIFIED ANALYSES OF THE CKD-FIX TRIAL

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.

Biography:
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.