Association Between Mortality and Serum Uric Acid Levels in Non-diabetes-related Chronic Kidney Disease: An Analysis of the National Health and Nutrition Examination Survey, USA, 1999-2010

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/m), 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/1.732m), 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/1.732m), 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/1.832m), 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).