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American Journal of Kidney Diseases

Uric Acid and the Risks of Kidney Failure and Death in Individuals With CKD

  • Anand Srivastava
    Correspondence
    Address for Correspondence: Anand Srivastava, MD, MPH, Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, 633 N St Clair St, Ste 18-083, Chicago, IL 60611.
    Affiliations
    Renal Division, Brigham & Women’s Hospital, Boston, MA

    Division of Nephrology and Hypertension, Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL
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  • Arnaud D. Kaze
    Affiliations
    Renal Division, Brigham & Women’s Hospital, Boston, MA
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  • Ciaran J. McMullan
    Affiliations
    Renal Division, Brigham & Women’s Hospital, Boston, MA
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  • Tamara Isakova
    Affiliations
    Division of Nephrology and Hypertension, Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL
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  • Sushrut S. Waikar
    Affiliations
    Renal Division, Brigham & Women’s Hospital, Boston, MA
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Published:November 10, 2017DOI:https://doi.org/10.1053/j.ajkd.2017.08.017

      Background

      Serum uric acid concentrations increase in chronic kidney disease (CKD) and may lead to tubular injury, endothelial dysfunction, oxidative stress, and intrarenal inflammation. Whether uric acid concentrations are associated with kidney failure and death in CKD is unknown.

      Study Design

      Prospective observational cohort study.

      Settings & Participants

      3,885 individuals with CKD stages 2 to 4 enrolled in the Chronic Renal Insufficiency Cohort (CRIC) between June 2003 and September 2008 and followed up through March 2013.

      Predictor

      Baseline uric acid concentrations.

      Outcomes

      Kidney failure (initiation of dialysis therapy or transplantation) and all-cause mortality.

      Results

      During a median follow-up of 7.9 years, 885 participants progressed to kidney failure and 789 participants died. After adjustment for demographic, cardiovascular, and kidney-specific covariates, higher uric acid concentrations were independently associated with risk for kidney failure in participants with estimated glomerular filtration rates (eGFRs) ≥ 45 mL/min/1.73 m2 (adjusted HR per 1−standard deviation greater baseline uric acid, 1.40; 95% CI, 1.12-1.75), but not in those with eGFRs < 30 mL/min/1.73 m2. There was a nominally higher HR in participants with eGFRs of 30 to 44 mL/min/1.73 m2 (adjusted HR, 1.13; 95% CI, 0.99-1.29), but this did not reach statistical significance. The relationship between uric acid concentration and all-cause mortality was J-shaped (P = 0.007).

      Limitations

      Potential residual confounding through unavailable confounders; lack of follow-up measurements to adjust for changes in uric acid concentrations over time.

      Conclusions

      Uric acid concentration is an independent risk factor for kidney failure in earlier stages of CKD and has a J-shaped relationship with all-cause mortality in CKD. Adequately powered randomized placebo-controlled trials in CKD are needed to test whether urate lowering may prove to be an effective approach to prevent complications and progression of CKD.

      Index Words

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