Problem: Chronic kidney disease (CKD) is a global public health concern involving progressive loss in renal function over a period of months or years. The disparity between the numbers of patients on dialysis awaiting kidney transplant and organs actually transplanted highlights the need for new treatments that address renal function directly. Existing pre-transplant therapies merely address the symptoms of the consequences of renal function loss, not the loss itself. Reconstituting renal function lost as a result of CKD is key to reducing morbidity in these patients. Background: Although allogeneic transplant is the current definitive treatment that improves renal function in CKD patients, it requires immunosuppressive therapy for the remainder of the patient’s life. Regenerative medicine approaches offer the hope of an autologous therapy that restores renal function. Specifically, therapeutically-relevant renal cell subpopulations have been identified that extended survival and improved renal function in a 5/6 nephrectomized rodent model (5/6 NX) of CKD (NKA treatment). Furthermore, these therapeutically-relevant renal cell subpopulations can be isolated from the kidneys of large mammal and humans with established CKD, providing proof-of-concept that an autologous treatment for CKD is feasible. Hypothesis: The underlying mechanisms by which NKA treatment improved renal function are not well characterized. Our studies on NKA treatment’s mechanism of action have focused on cell-cell signalling, engraftment, and fibrotic pathways. This study focused on how NKA treatment might increase the organ’s intrinsic regenerative capacity – perhaps by mobilizing renal stem cells. We hypothesize that the extended survival and improvement in renal function observed in NKA-treated 5/6 NX rats is associated with molecular expression of specific stem cell markers. Research: Molecular assays to evaluate the mobilization of resident stem and progenitor cells in 5/6 NX rats were developed and used to investigate the temporal response of these markers to NKA treatment. Observations: NKA treatment was specifically associated with up-regulation of the key stem cell markers CD24, CD133, UTF-1, SOX-2 and NODAL at mRNA transcript and protein levels. Up-regulation was detected by 1 week post-injection and had peaked by 12 weeks post-injection. Activation of stem and progenitor cell markers was associated with extended survival and improvement of renal filtration and was significant relative to untreated 5/6 NX control animals. Conclusion: Mobilization of resident stem and progenitor cell populations in response to NKA treatment may contribute to the restoration of kidney function in 5/6 NX animals by regenerating damaged kidney tissue and organ architecture. The molecular assays used in this study might therefore provide a rapid, straightforward, and predictive assay of regenerative outcomes for evaluating tissue engineering and regenerative medicine treatments for CKD.