Introduction: Pediatric donor kidneys are increasingly used to address the global organ shortage, with satisfactory transplant outcomes. However, the risk of undiagnosed inherited kidney diseases (IKDs) in pediatric donors remains a concern due to the lack of overt clinical or imaging findings at an early age. When donor DNA is unavailable, identifying an alternative, non-invasive DNA source of donor origin becomes critical.
Methods: Urine-derived stem cells (USCs) were isolated from kidney transplant recipients as a potential alternative source of donor genetic material in the absence of available donor DNA (HLA, 2021, 98(5): 431–447). To investigate the analytical validity of USC-derived DNA for comprehensive genetic testing, whole exome sequencing (WES) was performed on matched samples from three donor-recipient pairs, including donor peripheral blood, recipient peripheral blood, and USCs obtained from post-transplant urine samples. This methodology was subsequently applied to a cohort of transplant recipients presenting with clinical suspicion of donor derived IKDs, aiming to establish a non-invasive, accurate, and clinically applicable approach for post-transplant genetic assessment.
Results: USC-derived DNA showed sufficient quality and quantity for WES, comparable to donor blood DNA. In three representative cases, pathogenic variants were identified in genes associated with known inherited kidney or systemic diseases: PKD1 (autosomal dominant polycystic kidney disease), NDUFAF6 (Leigh syndrome), and LRP5 (polycystic liver disease 4 without renal cysts). In all cases where donor DNA was available, the genetic findings from USC-derived DNA were concordant. These results support the analytical reliability of USC-derived DNA as a viable alternative for post-transplant genetic analysis in the absence of donor DNA.
Conclusion: USCs from kidney transplant recipients provide a viable, non-invasive, and donor-specific DNA source for WES in suspected donor-derived IKDs. This approach is especially valuable when donor DNA is unavailable and helps preserve limited renal biopsy material for future diagnostic use.