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Issue 945 coverCIRCULATING NUCLEIC ACIDS IN PLASMA OR SERUM II Copyright © 2001 by the New York Academy of Sciences
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Annals of the New York Academy of Sciences 945:250-257 (2001)
© 2001 New York Academy of Sciences

Cell-Free DNA in Urine

A Marker for Kidney Graft Rejection, but Not for Prenatal Diagnosis?

XIAO YAN ZHONGa, DEIRDRÉ HAHNb, CAROLYN TROEGERa, ANDRÉ KLEMMc, GÜNTER STEINc, PETER THOMSONb, WOLFGANG HOLZGREVEa AND SINUHE HAHNa

aDepartment of Obstetrics and Gynecology, University of Basel, CH 4031 Basel, Switzerland
bDepartment of Pediatric Nephrology, Wits University, Johannesburg, South Africa
cDivision of Nephrology, University of Jena, Jena, Germany

Address for correspondence: Dr. Sinuhe Hahn, Laboratory for Prenatal Medicine, Department of Obstetrics and Gynecology, University of Basel, Schanzenstrasse 46, CH 4031 Basel, Switzerland. Voice: +41 61 325 9224/9595; fax: +41 61 325 9399.
shahn{at}uhbs.ch

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.

Key Words: Cell-free DNA • Transplant • Graft rejection




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