Renal Cell Therapy in the Treatment of Patients with Acute and Chronic Renal Failure

Abstract

Hemodialysis and hemofiltration have been important technologies in saving the lives of patients with acute (ARF) and chronic renal failure by clearing small solutes from plasma and thereby preventing death from acidemia, hyperkalemia, volume overload, and uremia. These therapeutic approaches, however, are still suboptimal, as patients with ARF have mortality rates exceeding 50%, and patients with end-stage renal disease (ESRD) have, on average, a life expectancy of 4–5 years. The preeminent cause of death in patients with ARF is the development of sepsis or the systemic inflammatory response syndrome with resulting systemic vasodilation, hypotension, ischemic injury to solid organs, multi-organ failure, and death. This vasodilation is due to persistent and excessive pro-inflammation. Similarly, the reduced survival times of patients with ESRD on chronic dialysis have been associated with a persistent and chronic systemic pro-inflammatory state. We have hypothesized that the loss of renal tubule cell mass acutely in acute tubule necrosis and chronically in ESRD results in an immunologically dysregulated state leading to excessive pro-inflammation. The replacement of renal tubule cell function may thus change the current dismal prognosis of patients with these disorders. In this regard, this report presents the first patient ever treated with a bioartificial kidney consisting of a synthetic hemofilter in series with a renal tubule assist device (RAD) containing approximately 10⁹ human renal tubule cells. This treatment in a critically ill patient with multi-organ failure and ARF in the intensive care unit was associated temporally with improved cardiovascular parameters and enhanced native kidney function. Multiple systemic plasma cytokine levels and gene expression profiles of peripheral white blood cells were also temporally changed with cell therapy. Clinical trials in patients suffering from either ARF or ESRD are currently ongoing to evaluate the influence of the RAD on the inflammatory response in these groups of patients.

Staged in vitro reconstitution and implantation of engineered rat kidney tissue

“…For example, the extracorporeal renal tubule assist device utilizes a synthetic hemofilter connected in series with a bioreactor cartridge containing human proximal tubule cells (2). In addition, renal primordia obtained at a sufficiently early developmental stage have been demonstrated to undergo differentiation and grow when transplanted into animal hosts (3)(4)(5)(6)(7)(8).…”

Construction of bioartificial renal tubule assist device In Vitro and its function of transporting sodium and glucose

“…It was reported that RAD is able to replace the functions of renal tubular epithelial cells [19][20][21] . ARF accompanied with MODS were treated with RAD constructed with rabbit primary proximal tubule epithelial cells, and the results showed that RAD was capable of reabsorbing Na + , glucose and para-aminohippuric acid, which could be inhibited respectively by ouabain (Na + -K + -ATPase inhibitor), phlorizin (glucose transport inhibitor) and probenecid.…”

Endothelial Bioreactor Ameliorates Endotoxemia Sepsis in Swine

“…The results suggested that the pathogenesis of sepsis is not due to the dysfunction of a single protein but develops due to alterations in the complex interactions of a variety of cell components; it is unimaginable to expect supplying one therapeutic compound would have success. Therefore, a cell-based therapy may be a more successful strategy by providing a dynamic, interactive, and individualized therapeutic approach responding to the specific pathophysiological condition of the patient [11,19] .…”