Comet-assay analysis identifies genomic damage in lymphocytes of uremic patients

This study investigates genomic damage in peripheral lymphocytes from patie nts with moderate to severe chronic renal insufficiency and those on long-t erm maintenance hemodialysis (MHD) and hemodiafiltration therapy. As a meas ure for genomic damage, the comet assay (single-cell gel electrophoresis) w as applied. This test detects single- and double-strand breaks and alkali l abile sites through electrophoretic mobility of the resulting fragments. Th e average damage (percentage of DNA in the tail region of the comet) observ ed In cells of the control group of 21 healthy subjects was 10.5% +/- 0.8%. There was a significant increase to 14.7% +/- 3.5% in cells of 23 patients with chronic renal failure, and a further increase to 17.1% +/- 3.5% in th e subgroup of 12 patients with serum creatinine values greater than 6 mg/dL . Damage was 16.7% +/- 4.2% in cells of the MHD group (26 patients) and 20. 1% +/- 3.0% in the subgroup with MHD therapy longer than 10 years (8 patien ts). Cellular DNA damage In the group of 15 maintenance hemodiafiltration p atients was 15.6% +/- 2.1%, ranging between predialysis and MHD patients, a nd did not seem to increase with treatment time. These results, together wi th previously observed elevated frequencies of micronuclei, decreased DNA r epair, and Increased cancer incidence described for these patient groups, e mphasize the need to further optimize the current therapy for reducing the degree of genomic damage. (C) 2001 by the National Kidney Foundation, Inc.