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) and risk of progression.
Aim: To assess the effect of allopurinol on change in eGFR based on diabetic kidney disease at baseline.
Methods: Three hundred and sixty nine adults with CKD stage 3 or 4, no history of gout, and risk of progression (based on 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. Primary outcome was rate of change in eGFR up to 104 weeks using the CKD-EPI creatinine equation.
Results: At baseline, 165 (45%) patients had diabetic kidney disease (mean serum urate 8.4 g/dL, mean UACR 1,802.1 mg/g) and 198 (55%) had non-diabetic kidney disease (mean serum urate 8.0 mg/dL, mean UACR 950.2 mg/g). In patients with diabetic kidney disease, change in eGFR did not differ between the allopurinol (-2.23 mL/min/1.73 m2/year, 95% CI -3.21 to -1.25) and placebo (-2.77 mL/min/1.73 m2/year, 95% CI -3.78 to -1.75) groups (mean difference [MD], 0.53 mL/min/1.73 m2/year, 95% CI -0.87 to 1.93). In patients with non-diabetic kidney disease, there was no difference in change in eGFR between the allopurinol (-4.84 mL/min/1.73 m2/year, 95% CI -6.06 to -3.63) and placebo (-3.78 mL/min/1.73 m2/year, 95% CI -4.88 to -2.69) groups (MD, -1.06 mL/min/1.73 m2/year, 95% CI -2.68 to 0.56). The interaction P value for subgroup analysis was 0.11.
Conclusion: In CKD patients at risk of progression, the effect of allopurinol on eGFR decline was not modified by diabetic kidney disease at baseline.
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.