Association of hyperhomocysteinemia with plasma sulfate and urine sulfate excretion in patients with progressive renal disease

Abstract

Background: Plasma total homocysteine (tHcy) level is increased in patients with renal disease, parallel to serum creatinine concentration. In renal failure, the final product of sulfated amino acid metabolism, sulfate, also accumulates as renal function declines. We hypothesized that the elevation in sulfate level could cause hyperhomocysteinemia and tested the relation between tHcy level and both urinary excretion and plasma levels of sulfate.

Methods: Forty patients with renal disease were divided into three groups: patients without renal failure (nRF; creatinine clearance [CCr] > or = 80 mL/min/1.73 m2 [> or =1.33 mL/s/1.73 m2]), patients with mild renal failure (mRF; 80 > CCr > or = 25 mL/min/1.73 m2 [1.33 > CCr >/ or 0.42 mL/s/1.73 m2]), and patients with severe renal failure (sRF; CCr < 25 mL/min/1.73 m2 [<0.42 mL/s/1.73 m2]). Daily urinary excretion and plasma levels of tHcy, total cysteine (tCys), and sulfate were measured. A healthy control (HC) group also was tested. Serum methionine, taurine, vitamin B12, and folate levels also were determined in patients with renal disease.

Results: Plasma tHcy and sulfate concentrations in the groups with mRF and sRF were greater than in the HC group. Plasma tCys concentrations in the mRF and sRF groups were greater than in the nRF group. Daily urinary Hcy and Cys excretion did not differ among the four groups. Daily urine sulfate and urea nitrogen excretion in the sRF group were significantly less than in the HC and nRF groups. Multiple regression analyses showed that plasma creatinine (beta = 0.40) and sulfate (beta = 0.43) levels were independently associated with plasma Hcy level; among urine parameters, only daily urine sulfate excretion (beta = -0.52) was independently associated with plasma Hcy level.

Conclusion: The elevated plasma sulfate level, in accordance with renal function, is associated with plasma tHcy level. Decreased sulfate excretion, which might parallel the intake of sulfated amino acid or protein, may increase tHcy levels.