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Relevance of uric acid and asymmetric dimethylarginine for modeling cardiovascular risk prediction in chronic kidney disease patients

  • Nephrology - Original Paper
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Abstract

Background

Both elevated serum uric acid and serum asymmetric dimethylarginine (ADMA) are risk factors for cardiovascular disease. We hypothesized that combined elevation of uric acid and ADMA amplifies the risk of all-cause mortality and/or cardiovascular events (CVE) in patients with chronic kidney disease (CKD).

Methods

A total of 259 patients with CKD stages 1–5 were followed up in a time-to-event analysis for all-cause mortality and fatal and non-fatal CVE (including death, stroke, and myocardial infarction). Baseline measurements included serum uric acid and ADMA and endothelial function [ultrasound determined flow-mediated dilatation (FMD)].

Results

As a measure of endothelial function, log FMD value was positively associated with log eGFR, but negatively associated with log ADMA and log uric acid levels. During follow-up (median 38 months), 24 (9.3 %) deaths, 90 (34.7 %) CVE, and 95 (36.7 %) deaths and CVE (composite outcome) occurred. In the univariate Cox analysis, patients with both serum uric acid and ADMA levels above the median had an increased risk of all-cause mortality, CVE, and the composite outcome (HR 5.06, 95 % CI 2.01–12.76; HR 4.75, 95 % CI 2.98–7.59; and HR 4.13, 95 % CI 2.66–6.43, respectively). However, after adjustment for renal-specific risk factors (glomerular filtration rate, proteinuria, and hsCRP), this association was maintained only for CVE and the composite outcome. The addition of both biomarkers into a model with traditional and renal-specific risk factors did not increase the prediction abilities of the model for none of the three outcomes.

Conclusion

Elevated serum uric acid and ADMA levels are associated with an increased cardiovascular risk, but their combination does not improve risk prediction. The effects are not additive, possibly because uric acid may lie in the causal pathway by which ADMA acts.

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Authors and Affiliations

  1. Division of Nephrology, Department of Medicine, Koc University School of Medicine, Sariyer, Istanbul, Turkey

    Mehmet Kanbay

  2. Division of Nephrology, Department of Medicine, Konya Numune State Hospital, Konya, Turkey

    Baris Afsar

  3. Nephrology Clinic, Dialysis and Renal Transplant Center, ‘C.I. PARHON’ University Hospital, Iasi, Romania

    Dimitrie Siriopol & Adrian Covic

  4. ‘Grigore T. Popa’ University of Medicine, Iasi, Romania

    Dimitrie Siriopol & Adrian Covic

  5. Department of Nephrology, Gulhane School of Medicine, Ankara, Turkey

    Hilmi Umut Unal, Murat Karaman, Tayfun Eyileten, Mustafa Gezer, Yusuf Oguz, Abdulgaffar Vural & Mahmut Ilker Yilmaz

  6. Department of Radiology, Gulhane School of Medicine, Ankara, Turkey

    Mutlu Saglam & Samet Verim

  7. IISFundacion Jimenez Diaz, School of Medicine, UAM, REDINREN, FRIAT, Madrid, Spain

    Alberto Ortiz

  8. Division of Renal Diseases and Hypertension, University of Colorado, Denver, CO, USA

    Richard J. Johnson

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  1. Mehmet Kanbay
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Correspondence to Mehmet Kanbay.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Kanbay, M., Afsar, B., Siriopol, D. et al. Relevance of uric acid and asymmetric dimethylarginine for modeling cardiovascular risk prediction in chronic kidney disease patients. Int Urol Nephrol 48, 1129–1136 (2016). https://doi.org/10.1007/s11255-016-1271-6

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