Cell-free DNA in urine: a marker for kidney graft rejection, but not for prenatal diagnosis?

Intrigued by the rapid clearance of free fetal DNA from the maternal circulation, we have investigated whether this fetal genetic material could be cleared via the kidney. For this purpose, we examined for the presence of Y chromosome-specific DNA sequences in urine samples obtained from 8 women pregnant with male fetuses. No male-specific sequences could be detected, despite the use of a very sensitive nested PCR assay nor a highly reproducible real-time PCR assay. We did, however, detect maternal DNA sequences. To determine if this cell-free DNA was derived from the kidney or another source, we next examined urine from female kidney transplant patients who had received male kidneys. Y chromosome-specific sequences were indeed detectable by both nested and real-time PCR in these samples, thereby confirming a recent report describing urinary DNA microchimerism. Quantitative analysis of serially obtained samples furthermore suggests that transplant-derived sequences are elevated during periods of graft rejection. These results imply that the measurement of graft-derived urinary DNA may serve as a new marker for kidney graft tolerance.