Implantation of Autologous Selected Renal Cells in Diabetic Chronic Kidney Disease Stages 3 and 4-Clinical Experience of a "First in Human" Study.

INTRODUCTION

Animal models of chronic kidney disease demonstrate that a redundant population of therapeutically bioactive selected renal cells (SRCs) can be delivered to the kidney through intraparenchymal injection and arrest disease progression. Direct injection of SRCs has been shown to attenuate nuclear factor-κB, which is known to drive tissue inflammation, as well as the transforming growth factor-β-mediated plasminogen activator inhibitor-1 response that drives tissue fibrosis.

METHODS

We present experience from the first-in-human clinical study with SRCs. Seven male type 2 diabetic patients (63 ± 2 years of age) with chronic kidney disease stage 3 to 4 (estimated glomerular filtration rate 25 ± 2 ml/min) were recruited. After blood and urine sampling, iohexol clearance, magnetic resonance imaging, and renal scintigraphy, patients underwent ultrasound-guided renal biopsy. Two cores of renal tissue were shipped to the manufacturing plant for cell isolation, culture, and product preparation. Formulated SRCs were transported back to study sites (range 59-87 days after biopsy) for intracortical injection using a retroperitoneoscopic technique.

RESULTS

Laparoscopically assisted implantation of SRCs was uneventful in all patients. However, postoperative complications were common and suggest that other techniques of SRC delivery should be used. Kidney volume, split function, and glomerular filtration rate did not change during 12 months of follow-up. An extended 24-month follow-up in 5 of the patients showed a decline in estimated glomerular filtration rate (cystatin C).

DISCUSSION: Postoperative complications following retroperitoneoscopic implantation of SRC in the kidney cortex seem to be related to the surgical procedure rather than to injection of the cell product. No changes in renal function were observed during the original 12-month protocol. Beyond the first 12 months after cell implantation, individual renal function began to deteriorate during further follow-up.