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Uric Acid and the Risks of Kidney Failure and Death in Individuals With CKD.
Am J Kidney Dis. 2018 03; 71(3):362-370.AJ

Abstract

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) ≥ 45mL/min/1.73m2 (adjusted HR per 1-standard deviation greater baseline uric acid, 1.40; 95% CI, 1.12-1.75), but not in those with eGFRs<30mL/min/1.73m2. There was a nominally higher HR in participants with eGFRs of 30 to 44mL/min/1.73m2 (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.

Authors+Show 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. Electronic address: anand.srivastava@northwestern.edu.Renal Division, Brigham & Women's Hospital, Boston, MA.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.Renal Division, Brigham & Women's Hospital, Boston, MA.

Pub Type(s)

Journal Article
Multicenter Study
Observational Study
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

29132945

Citation

Srivastava, Anand, et al. "Uric Acid and the Risks of Kidney Failure and Death in Individuals With CKD." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 71, no. 3, 2018, pp. 362-370.
Srivastava A, Kaze AD, McMullan CJ, et al. Uric Acid and the Risks of Kidney Failure and Death in Individuals With CKD. Am J Kidney Dis. 2018;71(3):362-370.
Srivastava, A., Kaze, A. D., McMullan, C. J., Isakova, T., & Waikar, S. S. (2018). Uric Acid and the Risks of Kidney Failure and Death in Individuals With CKD. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 71(3), 362-370. https://doi.org/10.1053/j.ajkd.2017.08.017
Srivastava A, et al. Uric Acid and the Risks of Kidney Failure and Death in Individuals With CKD. Am J Kidney Dis. 2018;71(3):362-370. PubMed PMID: 29132945.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2017/11/11/ PY - 2017/05/13/received PY - 2017/08/10/accepted PY - 2017/11/15/pubmed PY - 2019/8/15/medline PY - 2017/11/15/entrez 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 SP - 362 EP - 370 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am J Kidney Dis VL - 71 IS - 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) ≥ 45mL/min/1.73m2 (adjusted HR per 1-standard deviation greater baseline uric acid, 1.40; 95% CI, 1.12-1.75), but not in those with eGFRs<30mL/min/1.73m2. There was a nominally higher HR in participants with eGFRs of 30 to 44mL/min/1.73m2 (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. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/29132945/Uric_Acid_and_the_Risks_of_Kidney_Failure_and_Death_in_Individuals_With_CKD_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0272-6386(17)30948-4 DB - PRIME DP - Unbound Medicine ER -