Elevated levels of serum sulfite in patients with chronic renal failure

Sulfite, a well known air pollutant, is toxic for humans, especially those with sulfite hypersensitivity. Sulfite is also generated endogenously, during normal metabolism of sulfur-containing amino acids. Mammalian tissues contain the enzyme sulfite oxidase, which detoxifies both endogenous and exogenous sulfite by oxidation to sulfate. Deficiency of sulfite oxidase in humans is fatal, demonstrating its physiologic importance. Nevertheless, information about serum and tissue levels of sulfite in normal and pathologic conditions is limited. Using a sensitive HPLC assay, it is shown here that sera from patients with chronic renal failure (CRF) contain significantly higher amounts of sulfite than those from healthy subjects. Mean +/- SD of serum sulfite in healthy subjects (n = 20) was 1.55 +/- 0.54 microM, whereas those in patients under maintenance hemodialysis (HD patients; n = 44) and CRF patients before introducing dialysis therapy (pre-HD patients; n = 33) were 3. 23 +/- 1.02 microM (P < 0.01) and 3.80 +/- 3.32 microM (P < 0.01), respectively. Among pre-HD patients, serum sulfite was positively correlated with serum creatinine (r = 0.714, P < 0.0001), and negatively with serum albumin (r = -0.407, P = 0.0188), hematocrit (r = -0.524, P = 0.0017), and total cholesterol (r = -0.375, P = 0. 0318). There was no significant association between sulfite and patient age, gender, or leukocyte counts. Multiple regression analysis revealed serum creatinine as the sole independent predictor of serum sulfite levels. Each HD treatment was associated with approximately 27% reduction in serum sulfite levels, suggesting the presence of a dialyzable form in serum. Thus, these results indicate that reduced glomerular filtration is a factor that determines serum sulfite levels. Chronic elevation in serum sulfite levels might contribute to tissue or organ dysfunction in patients with CRF.