NET UPTAKE OF PLASMA HOMOCYSTEINE BY THE RAT-KIDNEY IN-VIVO

Hyperhomocysteinemia is a common finding in dialysis-dependent end-sta ge renal disease (ESRD) patients, but its etiology and refractoriness to standard homocysteine-lowering B-vitamin therapy are poorly underst ood. In the absence of actual in vivo data, it has been hypothesized t hat loss of normal renal parenchymal uptake and metabolism of homocyst eine is an important determinant of hyperhomocysteinemia in ESRD, give n that urinary homocysteine excretion by healthy kidneys is trivial. W e assessed net renal uptake and metabolism of homocysteine using an es tablished rat model for measuring arteriovenous amino acid differences across the rat kidney, along with simultaneous determination of renal plasma flow, urine flow, and urinary homocysteine concentration. Subs tantial homocysteine uptake and metabolism by normal rat kidneys was d emonstrated, and we also confirmed that urinary homocysteine excretion is minimal. These data suggest that loss of the sizable homocysteine metabolizing capacity of the intact kidneys may be an important determ inant of the refractory, potentially atherothrombotic hyperhomocystein emia frequently observed in ESRD.