Safety and feasibility of computed tomography (CT)-guided percutaneous locoregional implantation of novel renal autologous cell therapy (REACT) for high-risk diabetic-related chronic kidney disease (DKD)

To demonstrate the safety and feasibility of depositing REACT into the renal cortex of patients with DKD stages 3-4, using a small caliber co-axial needle placed with CT guidance.

Materials and Methods: Renal biopsy tissue is harvested and REACT is produced ex vivo with autologous cell expansion/preparation over 30 days for same donor injection. From an ongoing phase 2 multi-center open-label trial (NCT:02836574), we randomized 83 patients (67% males) with eGFRs of 20-50 ml/min/1.73² into an active (REACT injections ~30 days post-biopsy) or deferred (12-months standard of care followed by REACT injection) cohort. Each REACT percutaneous injection into the ipsilateral renal cortex is CT-guided with conscious sedation in outpatient settings, using an outer 18/20- and inner 22/25-gauge coaxial needle system (Cook, Bloomington IN and IMD Huntsville, UT, USA). The first injection was intended at > 30 days post-biopsy and the second at ~ 180 days later. Recovery and 24-hour post-injection laboratory tests and renal ultrasound were obtained. All Serious Adverse Events (SAEs) were recorded.

Results: There was no baseline difference between the cohorts in age, BMI, eGFR, and albuminuria. We performed 130 injections in 73 patients (1^st injection) and 57 (2^nd injection). All injections with CT needle confirmation in the renal cortex were technically successful. There were 9 kidney-related SAEs in 4/83 patients: hematoma < 1% (n=1), pain 2.3% (n=3), transfusion < 1% (n=1) and cortical scarring 1% (n=1%). Furthermore, 97% of patients had a stable eGFR and the remaining 3% (n=3) did not require dialysis. There was no hematuria or need for angiographic interventions. Recovery and 24-hour renal ultrasounds on the remaining patients were unremarkable. Hemoglobin level changes pre/post 1^st (12.3/11.9) and 2^nd (12.3/12.1) injections were deemed secondary to IV fluid hemodilution and clinically insignificant.

Conclusion: Demonstrating technique safety profiles and delivery feasibility with novel cell therapy trials in high-risk chronic disease populations, is critical for regulatory approval. In this trial, CT-guided REACT injections into the renal cortices of stages 3-4 DKD patients were feasible and had low complication rates.