Reactive oxygen species are generated during
ischemia-reperfusion tissue injury. Oxidation of
thymidine by
hydroxyl radicals (HO*) causes formation of
5,6-dihydroxy-5,6-dihydrothymidine (
thymidine glycol).
Thymidine glycol excreted in urine can be used as a
biomarker of oxidative DNA damage. The aim of this study was to investigate the oxidative DNA damage in patients showing immediate allograft function after
kidney transplantation, and to find out whether this damage correlates with glomerular and tubular lesions. Time dependent changes in urinary excretion rates of
thymidine glycol, but also of total
protein,
albumin, low molecular weight (alpha1-microglobulin, beta2-microglobulin) and high molecular weight
proteins (
transferrin,
IgG,
alpha2-macroglobulin) were analyzed quantitatively and by
polyacrylamide-gel electrophoresis in six patients. Urinary
thymidine glycol was determined by a fluorimetric assay in combination with affinity chromatography and HPLC. After
kidney transplantation the urinary excretion rate of
thymidine glycol increased gradually reaching a maximum within the first 48 hours (16.56+/-11.3 nmol/m mol
creatinine, ref. 4.3+/-0.97). Severe
proteinuria with an excretion rate of up to 7.2 g/mmol
creatinine was observed and declined within the first 24 hours of allograft function (0.35+/-0.26 g/mmol
creatinine). The gel-electrophoretic pattern showed a nonselective glomerular and tubular
proteinuria. The initial nonselective glomerular
proteinuria disappeared within 48 hours, changing to a mild selective glomerular
proteinuria. In this period (12-48 hours) higher levels of
thymidine glycol excretion were observed, when compared to the initial posttransplant phase (13.66+/-9.76 vs. 4.31+/-3.61 nmol/mmol
creatinine; p<0.05). An increased excretion of
thymidine glycol is seen after
kidney transplantation and is explained by the
ischemia-reperfusion induced oxidative DNA damage in the kidney. In the second phase higher levels of excretion were observed parallel to the change from a nonselective to a selective glomerular and tubular
proteinuria. An explanation may be sought in the repair process of
DNA in the glomerular and tubular epithelial cells, appearing simultaneously with functional recovery.