Abstract

The relationship between serum uric acid (SUA) and cardiovascular (CV) mortality in patients with chronic kidney disease (CKD) has been described as either a J- or U-shaped function. However, its effect in non-diabetic CKD (and varying severities of CKD) remains unclear. We analyzed the database of the National Health and Nutrition Examination Survey, USA, from the years 1999 to 2010. We then grouped the subjects into 4 categories according to their SUA levels: (a) < 5 mg/dl, (b) 5–7 mg/dl, (c) 7–9 mg/dl and (d) ≥ 9 mg/dl. For mortality comparison purposes (CV related, cancer related and all-cause mortality), we set the SUA group of 5–7 mg/dl as the reference. We also separated this population into moderate (stage 3) and severe (stages 4 and 5) CKD. A total of 1860 participants were included in this study. Results showed that the group with the lowest SUA levels (< 5 mg/dl), were the least male gender (19.25%), had the lowest body mass index (26.41(95% CI = 25.66–27.16) kg/m2), highest systolic blood pressure (139.02 (95% CI 135.72–142.32) mmHg), highest high-density cholesterol (59.55 (95% CI 57.37–61.74) mg/dl), lowest blood glucose (95.46 (95% CI 93.16–97.76) mg/dl), highest total cholesterol (210.31 (95% CI 203.36–217.25) mg/dl), lowest serum albumin (4.09 (95% CI 4.04–4.14) g/dl), highest estimated glomerular filtration rate (eGFR) (47.91 (95% CI 45.45–50.49) ml/min/1.732m2), least history of hypertension (54.4%), and least total energy intake (1643.7 (95% CI 1536.13–1751.27) kcal/day). In the group with SUA ≥ 9 mg/dl, patients had higher all-cause mortality (HR = 2.15) whatever their baseline CVD status. In non-DM CKD patients with a CVD history, the group with SUA ≥ 9 mg/dl had the highest all-cause mortality (HR = 5.39), CVD mortality (HR = 8.18) and CVD or cancer (HR = 8.25) related mortality. In non-DM patients with severe CKD (eGFR < 30 ml/min/1.732m2), the group with SUA < 5 had a significantly increased all-cause mortality. On the contrary, in non-DM patients with moderate CKD (eGFR = 30–60 ml/min/1.832m2), the group with SUA ≥ 9 had a significantly increased all-cause mortality. In moderate non-DM CKD, SUA ≥ 9 mg/dl is associated with higher all-cause mortality. However, once progressing to severe non-DM CKD, SUA < 5 mg/dl is associated with higher all-cause mortality (even though it has the least risk factors for metabolic syndrome).

Highlights

  • High serum uric acid (SUA) levels predict myocardial infarction, a finding that was first reported in ­19511

  • The National Health and Nutrition Examination Survey (NHANES) is one of a series of healthrelated programs in the USA conducted periodically by the Centers for Disease Control (CDC) and Prevention’s National Center for Health Statistics (NCHS), which release their data to the public

  • In the group with the lowest SUA levels, most of them had the lowest body mass index (BMI) (26.41 kg/m2), highest systolic blood pressure (SBP)

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Summary

Introduction

High serum uric acid (SUA) levels predict myocardial infarction, a finding that was first reported in ­19511. There is still no consensus regarding this causal association between SUA and CVD related mortality Until now, only those guidelines followed in Japan recommend that treatment of asymptomatic hyperuricemia be used in order to obtain cardiovascular and renal b­ enefits[9]. Only those guidelines followed in Japan recommend that treatment of asymptomatic hyperuricemia be used in order to obtain cardiovascular and renal b­ enefits[9] Such conflicting results are in part due to differences in baseline risk factors surrounding atherosclerosis (such as pre-existing CVD, diuretic ­treatment7, ­obesity10, ­hypertension[11] and diabetes mellitus (DM)[12]). The aim of the present study was to investigate the predictive role of different levels of SUA on mortality (including CVD and those cancer related) in patients with various different severities of non-diabetic CKD

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