Assay of Methylguanidine As a Hydroxyl Radical Marker in Serum of Patients on Hemodialysis

Abstract

Serum methylguanidine (MG) concentrations in patients on hemodialysis (HD) were determined by an improved enzymatic method. A significant correlation was found between MG (γ) and creatinine (χ) values in serum with a linear regression equation of γ=6.836χ-3.030 and a correlation coefficient of 0.705. The patients on HD could be divided into 3 groups based on Δ MG (the difference between the observed MG and the calculated MG from the above equation with measured creatinine):Δ MG≥1.37μmol/l, 1.37μmol/l>Δ MG>-1.37μmol/l, and Δ MG≤-1.37μmol/l. In about 70% of the patients with joint pain, infection and gastrointestinal bleeding, Δ MG was 1.37μmol/l or more. MG and Δ MG were significantly increased in patients on hemodialysis for 10 years or longer. We found overproduction of MG in those hemodialysis patients with inflammatory complications. The patients on hemodialysis for a long duration frequently complained of pain in various joints. In patients on HD for 10 years or longer duration, significant positive correlations were found between MG and the number of red blood cells, and between MG and hemoglobin and myoglobin levels. The generation of hydroxyl radicals in the presence of hydrogen peroxide and hemoglobin (or myoglobin) was observed by the electron spin resonance spectrometry (ESR) spin trapping technique. These findings suggest that the production of MG from creatinine in patients on HD is caused by the increase of blood heme protein level. The measurement of MG in serum of patients, on HD, may provide useful information concerning the generation of hydroxyl radicals.