Uric Acid Levels, Kidney Function, and Cardiovascular Mortality in US Adults: National Health and Nutrition Examination Survey (NHANES) 1988-1994 and 1999-2002

doi:10.1053/j.ajkd.2014.04.024

American Journal of Kidney Diseases

Volume 64, Issue 4, October 2014, Pages 550-557

https://doi.org/10.1053/j.ajkd.2014.04.024 Get rights and content

Background

Chronic kidney disease (CKD) and hyperuricemia often coexist, and both conditions are increasing in prevalence in the United States. However, their shared role in cardiovascular risk remains highly debated.

Study Design

Cross-sectional and longitudinal.

Setting & Participants

Participants in the National Health and Nutrition Examination Survey (NHANES) from 1988 to 2002 (n = 10,956); data were linked to mortality data from the National Death Index through December 31, 2006.

Predictors

Serum uric acid concentration, categorized as the sex-specific lowest (<25th), middle (25th-<75th), and highest (≥75th) percentiles; and kidney function assessed by estimated glomerular filtration rate (eGFR) based on the CKD-EPI (CKD Epidemiology Collaboration) creatinine-cystatin C equation and urinary albumin-creatinine ratio (ACR).

Outcomes

Cardiovascular death and all-cause mortality.

Results

Uric acid levels were correlated with eGFR_cr-cys (r = −0.29; P < 0.001) and were correlated only slightly with ACR (r = 0.04; P < 0.001). There were 2,203 deaths up until December 31, 2006, of which 981 were due to cardiovascular causes. Overall, there was a U-shaped association between uric acid levels and cardiovascular mortality in both women and men, although the lowest risk of cardiovascular mortality occurred at a lower level of uric acid for women compared with men. There was an association between the highest quartile of uric acid level and cardiovascular mortality even after adjustment for potential confounders (HR, 1.48; 95% CI, 1.13-1.96), although this association was attenuated after adjustment for ACR and eGFR_cr-cys (HR, 1.25; 95% CI, 0.89-1.75). The pattern of association between uric acid levels and all-cause mortality was similar.

Limitations

GFR not measured; mediating events were not observed.

Conclusions

High uric acid level is associated with cardiovascular and all-cause mortality, although this relationship was no longer statistically significant after accounting for kidney function.

Section snippets

Study Population

The present study includes data from NHANES participants 20 years and older surveyed in NHANES III (1988-1994) and continuous NHANES (1999-2002). Participants were excluded if they were pregnant or did not complete both the interview and examination. In NHANES III and NHANES 1999-2002, there were 16,429 and 8,909 participants, respectively, who met the inclusion criteria. In NHANES III, creatinine and uric acid were measured in 15,394 participants and cystatin C was measured in 6,842

Results

During a maximum of 10 (median, 7.7; range, 0.1-10) years of follow-up, there were 2,203 deaths, of which 981 were due to cardiovascular causes. In the pooled sample of NHANES III and NHANES 1999-2002, women with higher uric acid levels were older and more likely to be 65 years and older (Table 1). Women were more likely to have never smoked compared with men (P < 0.001), although differences across uric acid levels were minimal within women or men. On average, women and men with higher uric acid

Discussion

To our knowledge, this is the first study to examine uric acid levels in the US population, based on the new KDIGO-recommended classification system and on 3 renal markers. We found that uric acid levels were associated with eGFR and were highest in persons with the lowest eGFRs. There was a U-shaped association between uric acid levels and cardiovascular morality, although the association of low uric acid levels and mortality was attenuated in adjusted models. Associations of high uric acid

Acknowledgements

Support: Dr Odden is supported by the American Heart Association Western States Affiliate (grant 11CRP7210088) and the National Institute on Aging (grant K01AG039387); no funding agency had any role in the study design; collection, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication.

Financial Disclosure: The authors declare that they have no other relevant financial interests.

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Original InvestigationPathogenesis and Treatment of Kidney DiseaseUric Acid Levels, Kidney Function, and Cardiovascular Mortality in US Adults: National Health and Nutrition Examination Survey (NHANES) 1988-1994 and 1999-2002

Background

Study Design

Setting & Participants

Predictors

Outcomes

Results

Limitations

Conclusions

Section snippets

Study Population

Results

Discussion

Acknowledgements

Semin Nephrol

Am J Kidney Dis

Am J Kidney Dis

Am J Kidney Dis

Ann Epidemiol

Am J Kidney Dis

Am J Kidney Dis

Lancet

Kidney Int

Am J Kidney Dis

Kidney Int

Am J Kidney Dis

Am J Kidney Dis

Prevalence of chronic kidney disease in the United States

JAMA

Original Investigation
Pathogenesis and Treatment of Kidney Disease
Uric Acid Levels, Kidney Function, and Cardiovascular Mortality in US Adults: National Health and Nutrition Examination Survey (NHANES) 1988-1994 and 1999-2002