Rheumatology 2001; 40: 1193-1194
© 2001 British Society for Rheumatology
Letters to the Editor |
Metabolic abnormalities associated with microalbuminuria in systemic lupus erythematosus
Department of Medicine and Therapeutics and
2Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong and
1Department of Nursing and Health Sciences, The Hong Kong Polytechnic University, Hong Kong
SIR, Microalbuminuria (MAU) is a sign of early vascular damage and has been recognized as an important risk factor associated with coronary artery disease (CAD) in patients with diabetes mellitus and in general populations [1, 2]. MAU is associated with other metabolic and haemodynamic abnormalities, including impaired glucose tolerance, atherogenic lipid profile, hyperuricaemia and altered diurnal blood pressure rhythm [3]. In patients with systemic lupus erythematosus (SLE), MAU did not correlate with renal histology or predict the subsequent development of clinical nephritis [4, 5], and it is not known whether MAU may predict the development of atheromatous disease in these patients as in other patient groups. This study was performed to elucidate whether MAU in patients with SLE is associated with metabolic abnormalities or parameters of oxidative stress that may be predictive of subsequent vascular disease.
Seventy-one consecutive Chinese lupus patients without a history of nephritis were recruited. Patients with conditions that may affect lipid or other metabolic profiles, including thyroid disease, liver disease and diabetes mellitus, and patients using beta-blockers, thiazide diuretics, lipid-lowering agents or oral contraceptives were excluded. After a 12-h fast, blood samples were collected for determination of the lipid profile, parameters of oxidative stress and antioxidant balance and other CAD risk factors. The serum lipid profile assessment included total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1, apolipoprotein B and lipoprotein (a). The ferric-reducing antioxidant power (FRAP) assay was used to assess plasma antioxidant power [6]. Allantoin, the non-enzymatic oxidation product of urate, was measured as an in vivo marker of free radical generation reflecting oxidative stress [7]. Other antioxidants measured included erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPX), which were measured with reagent kits (Randox Laboratories, Antrim, UK), and ascorbic acid and vitamin E, which were measured by spectrophotometric and fluorimetric methods [8, 9]. Spot urine samples collected in the morning were used to quantify MAU, which was defined by an albumin:creatinine ratio between 3.5 and 30.
Six patients were excluded as they had a positive urine dipstick test for protein, indicating macroalbuminuria. The mean age of the remaining 65 patients was 39 yr. Two patients were male and 63 patients were female. The mean disease duration was 7.2 yr, mean body mass index (BMI) 21.7 kg/m2 and mean SLE disease activity index (SLEDAI) 1.6. Two-thirds of the patients were on hydroxychloroquine (HCQ), with a mean dose of 244 mg/day, and 52.3% were on prednisone, with a mean dose of 4.3 mg/day.
Thirteen (20%) patients were found to have MAU, including one male patient. There were no significant differences between patients with and without MAU in mean age, BMI, SLEDAI, plasma creatinine level, presence of autoantibodies (including antiphospholipid antibody and anti-double-stranded DNA antibody) or the use of prednisone or HCQ. Nonetheless, the former group had slightly longer disease duration (8.8±7.8 vs 6.8±5.4 yr, P=0.047) and a higher mean blood pressure (89.0±14.6 vs 81.7±10.4 mmHg, P=0.046), although the systolic or diastolic blood pressures were not significantly different.
The association of MAU with metabolic risk factors for atherosclerosis and oxidative stress parameters was examined. MAU was not associated with any significant differences in any of the lipid parameters or in oxidative stress as measured by the allantoin level or allantoin/urate ratio (Table 1
). Nonetheless, compared with the group without MAU, the group with MAU had significantly higher plasma antioxidant power (FRAP level), mainly because of elevated urate levels. Other antioxidant measurements, including ascorbic acid, vitamin E, SOD and GPX activity, were not different in patients with or without MAU. Glucose levels were similar in the two groups of patients, whereas plasma homocysteine levels were significantly higher in patients with MAU than in those without MAU, although plasma vitamin B12 and folic acid were not different.
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Increased urate has been a common finding in other patients with MAU [3]. Urate, being a physiological antioxidant, makes a large contribution (about 60%) to the measured total antioxidant capacity of plasma [6]. Our study did not show increased oxidative stress in SLE patients with MAU, but this should be confirmed by using other markers of oxidative stress. Our findings of the associations of MAU with metabolic and haemodynamic variables are consistent with studies in other conditions, but this has not been reported previously in SLE patients. Whether these findings indicate an adverse effect on the risk of CAD in patients with MAU is unknown until further studies are done to confirm these associations and examine their long-term prognostic value.
Notes
Correspondence to: L. S. Tam, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong. 
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