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Plasma 3-deoxyglucosone elevation in chronic renal failure is associated with increased aldose reductase in
Yukiko Hasuike1, Takeshi Nakanishi, Yoshinaga Otaki
1Department of Internal Medicine, Division of Kidney and Dialysis, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Background:
Serum concentrations of 3-deoxyglucosone (3DG), a highly reactive dicarbonyl compound, are elevated in uremic patients. Aldose reductase (AR) is an enzyme involved in both the detoxification of 3DG and producing precursors of 3DG.
Methods:
We examined the relationship between plasma 3DG and erythrocyte AR content in uremic patients. Patients were divided into three groups: (1) progressive renal disease without hemodialysis (HD; chronic renal failure [CRF] group), (2) patients without diabetes mellitus (DM) treated with maintenance HD (HD group), and (3) patients with DM treated with maintenance HD (DM-HD group). High-performance liquid chromatography was used to measure 3DG, and erythrocyte AR was measured by means of enzyme-linked immunosorbent assay.
Results:
Both 3DG and erythrocyte AR levels were significantly greater in the CRF, HD, and DM-HD groups than in healthy controls. These results did not change after HD sessions in the HD or DM-HD groups. Serum creatinine levels correlated with 3DG and erythrocyte AR levels in the control and CRF groups (3DG: r = 0.67; P < 0.001; erythrocyte AR: r = 0.71; P < 0.001). Both erythrocyte AR and 3DG levels then increased as renal function declined. A positive correlation was seen between 3DG and erythrocyte AR levels in all groups (r = 0.65; P < 0.001), and also between plasma osmolality and erythrocyte AR level (r = 0.46; P < 0.001).
Conclusion:
Both erythrocyte AR and 3DG levels are increased in uremic patients, and these increases could possibly contribute to the development of uremic symptoms.