From Transrenal DNA to Stem Cell Differentiation: An Unexpected Twist

In this issue of Clinical Chemistry , Hung et al. describe the results of a study originally devoted to investigation of the transrenal DNA (Tr-DNA)1 phenomenon. These authors report on the presence of donor-derived, cell-free DNA and cells in the urine of sex-mismatched hematopoietic stem cell transplant (HSCT) recipients(1).The term Tr-DNA defines DNA molecules that appear in the urine from sources located outside of the urinary system. The investigators who found such molecules in urine for the first time suggested that DNA fragments from cells dying throughout the body appear in the bloodstream as so-called cell-free circulating DNA (cfcDNA) and then cross the kidney barrier into the urine(2). Otherwise, it is difficult to explain how fetal DNA appears in the urine of pregnant women or how tumor-specific DNA markers appear in the urine of patients with tumors located outside of the urinary system. This original observation was reproduced in many laboratories(2)(3)(4)(5)(6)(7). At the same time, several groups could not detect fetal DNA in the urine of pregnant women(8)(9), raising doubts about the concept of Tr-DNA. The latter results can be explained by the fact that Tr-DNA fragments are shorter than cfcDNA, and shorter amplicons should be used for their detection(4)(7)(10), especially in prenatal models in which concentrations of fetal DNA in maternal urine are low. It is also important to remember that urinary DNA from other sources complicates analysis of Tr-DNA. Other sources of urinary DNA include epithelial cells shed from the organs of the urinary system, often lymphocytes and …