TY - JOUR
T1 - Uric Acid and the Risks of Kidney Failure and Death in Individuals With CKD
AU - Srivastava, Anand
AU - Kaze, Arnaud D.
AU - McMullan, Ciaran J.
AU - Isakova, Tamara
AU - Waikar, Sushrut S.
N1 - Funding Information:
Support: This work was supported by NIDDK grants F32DK111066 (Dr Srivastava) and U01DK085660 (Dr Waikar). The authors are supported by NHLBI grant R01HL105440 (Dr McMullan) and NIDDK grants R01DK110087 (Dr Isakova) and R01DK093574, R01DK103784, and U01DK104308 (Dr Waikar). CRIC was conducted by the CRIC Investigators and supported by the NIDDK. The funders of this study had no role in the analysis, interpretation of data, writing of the manuscript, or the decision to submit the report for publication.
Publisher Copyright:
© 2017 National Kidney Foundation, Inc.
PY - 2018/3
Y1 - 2018/3
N2 - 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 m 2 (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 m 2 . There was a nominally higher HR in participants with eGFRs of 30 to 44 mL/min/1.73 m 2 (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.
AB - 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 m 2 (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 m 2 . There was a nominally higher HR in participants with eGFRs of 30 to 44 mL/min/1.73 m 2 (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.
KW - CKD progression
KW - Chronic Renal Insufficiency Cohort (CRIC)
KW - Uric acid
KW - chronic kidney disease (CKD)
KW - death
KW - eGFR decline
KW - end-stage renal disease (ESRD)
KW - hyperuricemia
KW - kidney failure
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U2 - 10.1053/j.ajkd.2017.08.017
DO - 10.1053/j.ajkd.2017.08.017
M3 - Article
C2 - 29132945
AN - SCOPUS:85033445876
SN - 0272-6386
VL - 71
SP - 362
EP - 370
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 3
ER -