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Kidney Week

Abstract: FR-OR137

Preventing Early Renal Loss in Diabetes (PERL) Study: Outcome of a 3-Year Trial of Serum Uric Acid Reduction with Allopurinol

Session Information

  • High-Impact Clinical Trials
    November 08, 2019 | Location: Ballroom C, Walter E. Washington Convention Center
    Abstract Time: 03:30 PM - 03:45 PM

Category: Diabetic Kidney Disease

Authors

  • Doria, Alessandro, Joslin Diabetes Center, Boston, Massachusetts, United States
  • Galecki, Andrzej, University of Michigan, Ann Arbor, Michigan, United States
  • Spino, Cathie, University of Michigan, Ann Arbor, Michigan, United States
  • Mauer, Michael, University of Minnesota, Minneapolis, Minnesota, United States

Group or Team Name

  • PERL Consortium
Background

Observational studies have shown that higher serum uric acid (SUA) is associated with a higher risk of diabetic kidney disease (DKD) in type 1 diabetes (T1D). PERL (NCT02017171) evaluated whether lowering SUA with allopurinol could slow glomerular filtration rate (GFR) decline in patients with T1D and mild to moderate DKD.

Methods

This double-blind, placebo-controlled, multicenter, international trial randomized 530 persons with T1D, estimated GFR (eGFR) 40-99.9 mL/min/1.73 m2, SUA ≥4.5 mg/dL, and micro- to macroalbuminuria (79.1%) or normoalbuminuria with historical eGFR decline ≥3 mL/min/1.73 m2/year (20.9%) to allopurinol (A, n=267) or placebo (P, n=263). The primary outcome was baseline-adjusted iohexol GFR (iGFR) after 3 years of treatment plus a 2-month drug washout period. Treatments were compared by means of a linear model with correlated errors using the intention-to-treat population.

Results

Participants were 66% male and 84% white. Baseline median age was 52 years, T1D duration was 35 years, and HbA1c was 8.0 %; 93% had hypertension and 90% were on RAS blockers. These factors were balanced between A and P. The mean (± SD) baseline iGFR was 68.7 ± 17 in A and 67.3 ± 17 mL/min/1.73 m2 in P. Baseline SUA was 6.1 ± 1.5 mg/dL in both groups. During the trial, SUA averaged 4.1 ± 1.2 in A and 6.2 ± 1.3 mg/dL in P (p <0.0001). Baseline-adjusted iGFRs at the end of the drug washout period were virtually identical in A and P (least square mean ± SE = 61.2 ± 1.6 mL/min/1.73 m2 in both, p=0.99). Rates of iGFR decline over the 3 years of treatment were -3.0 in A and -2.5 mL/min/1.73 m2/year in P (p=0.25), at or close to the loss of -3.0 mL/min/1.73 m2/year expected in untreated subjects. No statistically significant treatment differences were seen in the secondary outcomes of iGFR before drug washout, eGFR slope, or time to serum creatinine doubling or ESKD. Albuminuria levels at washout were higher in A than in P (baseline-adjusted geometric means: 42.9 vs. 31.7 μg/min, p=0.035).

Conclusion

PERL – the largest CKD trial of allopurinol to date – found no significant benefit of SUA reduction on kidney outcomes in T1D persons with mild to moderate GFR reduction and SUA levels above the median. Secondary analyses are in progress to assess whether results are similar across pre-specified clinical sub-groups.

Funding

  • NIDDK Support