Mehmet Kanbay1, Baris Afsar2, Dimitrie Siriopol3,4, Hilmi Umut Unal5, Murat Karaman5, Mutlu Saglam6, Tayfun Eyileten5, Mustafa Gezer5, Samet Verim6, Yusuf Oguz5, Abdulgaffar Vural5, Alberto Ortiz7, Richard J Johnson8, Adrian Covic3,4, Mahmut Ilker Yilmaz5. 1. Division of Nephrology, Department of Medicine, Koc University School of Medicine, Sariyer, Istanbul, Turkey. drkanbay@yahoo.com. 2. Division of Nephrology, Department of Medicine, Konya Numune State Hospital, Konya, Turkey. 3. Nephrology Clinic, Dialysis and Renal Transplant Center, 'C.I. PARHON' University Hospital, Iasi, Romania. 4. 'Grigore T. Popa' University of Medicine, Iasi, Romania. 5. Department of Nephrology, Gulhane School of Medicine, Ankara, Turkey. 6. Department of Radiology, Gulhane School of Medicine, Ankara, Turkey. 7. IISFundacion Jimenez Diaz, School of Medicine, UAM, REDINREN, FRIAT, Madrid, Spain. 8. Division of Renal Diseases and Hypertension, University of Colorado, Denver, CO, USA.
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.
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.
Authors: Nihat Sen; Mehmet Fatih Ozlu; Emin Ozgur Akgul; Selcuk Kanat; Tuncer Cayci; Osman Turak; Halil Yaman; Erdogan Sokmen; Firat Ozcan; Orhan Maden; Ahmet Duran Demir; Adrian Covic; Mehmet Kanbay Journal: Atherosclerosis Date: 2011-06-17 Impact factor: 5.162
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Authors: Aslihan Yerlikaya; Tuncay Dagel; Christopher King; Masanari Kuwabara; Miguel A Lanaspa; Ana Andres-Hernando; Adrian Covic; Jacek Manitius; Alan A Sag; Mehmet Kanbay Journal: Int Urol Nephrol Date: 2017-02-16 Impact factor: 2.370