TWO-YEAR FOLLOW-UP STUDY OF THE RELATIONSHIP BETWEEN SERUM HOMOCYSTEINE, URIC ACID AND RENAL FUNCTION IN GOUTY PATIENTS

Abstract

Background Gout is known to be associated with metabolic syndrome and cardiovascular disease (CVD), which are major cause of increasing mortality in gouty patients. Homocysteine (Hcy) is related with endothelial cell damage and is regarded as an important risk factor for CVD. Although both hyperhomocysteinemia and gout are closely related to CVD, the only few cases about serum Hcy in gouty patients have been reported.

Objectives We investigated the associations between serum Hcy level and the other parameters such as serum uric acid level, renal function, and cholesterol profiles in gouty patients with 2 year follow-up data.

Methods Ninety-one male patients with gout and 97 age-matched healthy male controls were included in this study. The average age of each was 51.19±15.08 and 51.57±17.01 years old, respectively. Among them, 33 patients with gout and 39 healthy controls underwent follow-up tests for Hcy levels with 24.00±9.12 months on average. Serum Hcy levels were measured by a competitive immunoassay using direct chemiluminescent. The estimated glomurular filtration rate (eGFR) was calculated using modification of diet in renal disease equation, and then chronic kidney disease (CKD) was defined as an eGFR below 60 ml/min/1.73m2.

Results Patients with gout showed significantly higher levels in serum Hcy than those in controls (13.96±4.05 μmol/L vs 12.67±3.51 μmol/L, p=0.022). However there was no significant difference between gouty patients and controls in the serum uric acid level (6.15±2.23 mg/dL vs 5.82±1.22 mg/dL, p=0.214). In patients with gout, serum Hcy level was negatively correlated with eGFR (γ=-0.413, p<0.001), while it was uncorrelated with serum uric acid levels or cholesterol profiles. Serum Hcy levels were not different between the groups treated with allopurinol and with benzbromarone. When we observed the follow-up results in gouty group, the change of serum Hcy level was positively correlated with the change of serum creatinine level (γ=0.560, p<0.001), and negatively correlated with the change of eGFR (γ=-0.556, p<0.001). However the change of serum Hcy level was uncorrelated with the changes of uric acid level or the lipid profiles. The gouty patients with CKD showed significantly higher serum Hcy level than those without CKD (17.45±4.68 μmol/L vs 13.15±3.46 μmol/L, p<0.001), and the follow-up result also showed similar tendency (19.12±4.29 μmol/L vs 15.69±5.73 μmol/L, p=0.059). In multiple linear analyses, serum Hcy level was affected by eGFR (β=-0.385, p<0.001), however, was not affected by the serum uric acid level.

Conclusions Serum Hcy level was elevated in gouty patients than in controls. The change of serum Hcy level was negatively correlated with the change of eGFR. High level of serum Hcy in gouty patients was related with decreased renal function, and was not with serum uric acid or lipid profiles.