title: Presence of donor-derived DNA and cells in the urine of sex-mismatched hematopoietic stem cell transplant recipients: implication for the transrenal hypothesis.
abstract: BACKGROUND
  The term "transrenal DNA" was coined in 2000 to signify that DNA in urine may come from the passage of plasma DNA through the kidney barrier. Although DNA in the urine has the potential to provide a completely noninvasive source of nucleic acids for molecular diagnosis, its existence remains controversial.
  
  
  METHODS
  We obtained blood and urine samples from 22 hematopoietic stem cell transplant (HSCT) recipients and used fluorescence in situ hybridization, PCR for short tandem repeats, mass spectrometry, quantitative PCR, and immunofluorescence detection to study donor-derived DNA in the urine.
  
  
  RESULTS
  All HSCT recipients exhibited high amounts of donor-derived DNA in buffy coat and plasma samples. Male donor-derived DNA was detected in supernatants of urine samples from all 5 female sex-mismatched HSCT recipients. Surprisingly, the amount of DNA in urine supernatants was not correlated with the plasma value. Moreover, cell-free urine supernatants contained DNA fragments >350 bp that were absent in plasma. Donor-derived polymorphs were detected in urine by fluorescence in situ hybridization. Coincidentally, donor-derived cytokeratin-producing epithelial cells were discovered in urine samples from 3 of 10 sex-mismatched HSCT recipients as long as 14.2 years after transplantation.
  
  
  CONCLUSIONS
  This report is the first to demonstrate the presence of donor-derived DNA in the urine of HSCT recipients; however, we show that much of this DNA originates from donor-derived cells, rather than from the transrenal passage of cell-free plasma DNA. Our discovery of donor-derived cytokeratin-producing epithelial cells raises interesting biological and therapeutic implications, e.g., the capacity of marrow stem cells to serve as an extrarenal source for renal tubule regeneration.
authors.affiliation: Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China.
authors.forename: Emily C W
authors.initials: EC
authors.lastname: Hung
authors.forename: Tristan K F
authors.initials: TK
authors.lastname: Shing
authors.forename: Stephen S C
authors.initials: SS
authors.lastname: Chim
authors.forename: Philip C
authors.initials: PC
authors.lastname: Yeung
authors.forename: Rebecca W Y
authors.initials: RW
authors.lastname: Chan
authors.forename: Ki W
authors.initials: KW
authors.lastname: Chik
authors.forename: Vincent
authors.initials: V
authors.lastname: Lee
authors.forename: Nancy B Y
authors.initials: NB
authors.lastname: Tsui
authors.forename: Chi-Kong
authors.initials: CK
authors.lastname: Li
authors.forename: Cesar S C
authors.initials: CS
authors.lastname: Wong
authors.forename: Rossa W K
authors.initials: RW
authors.lastname: Chiu
authors.forename: Y M Dennis
authors.initials: YM
authors.lastname: Lo
mesh_terms: D004247:DNA / Q000097:blood / Q000235:genetics / Q000652:urine*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007668:Kidney / Q000502:physiology*; D008297:Male; D008954:Models, Biological; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D004247:DNA