Restenosis in Hemodialytic Fistulas and Chronic Kidney Disease-Associated Vascular Disease: Two Pathologies Driven by Metakaryotic Stem Cells

Chronic kidney disease (CKD) exacerbating vascular disease poses a major challenge to nephrology. Surgically placed vascular fistulas, as an aid to hemodialysis prior to kidney transplant, have extended many lives, while post-surgical restenosis closure of the fistula by smooth muscle cells affects many lives. When post-surgical restenosis is developed, palliative measures are almost always surgical: there are no effective drug treatments. In this study, we offer a testable hypothesis that effects of CKD on widely distributed vascular diseases and the phenomenon of fistula restenosis are both driven by the pathologic creation of non-dividing smooth muscle cells via asymmetric division of exponentially increasing metakaryotic stem cells. In slow growing atherosclerotic plaques, the Benditts demonstrated clonality of smooth muscle cells that we posit originate in a single mutated metakaryotic stem cell of fetal/juvenile vasculogenesis. In the fast process of fistula restenosis, we posit quiescent metakaryotic stem cells "on call" for wound healing among which are rare stem cells that have lost the ability to cease division. These hypotheses and suggestions for specific research paths toward development of effective drug therapies are built on (a) our shared discoveries of the role of metakaryotic stem cells in organogenesis, carcinogenesis, and atherosclerotic plaque formation and (b) the recent finding that metakaryotic cancer stem cells are constitutively resistant to radio- and chemotherapies yet sensitive to killing by a wide range of existing drugs. We propose to test these hypotheses in discarded fistulas and stem cells derived therefrom, and, if supported, to test drug-eluting devices to block fistula restenosis.