Rilparencel (Renal Autologous Cell Therapy-REACT®) for Chronic Kidney Disease and Type 1 and Type 2 Diabetes: Phase 2 Trial Design Evaluating Bilateral Kidney Dosing and Redosing Triggers.

INTRODUCTION: Autologous cell-based therapies (CBT) to treat chronic kidney disease (CKD) with diabetes are novel and can potentially preserve renal function and decelerate disease progression. CBT dosing schedules are in early development and may benefit from individual bilateral organ dosing and kidney-dependent function to improve efficacy and durability. The objective of this open-label, phase 2 randomized controlled trial (RCT) is to evaluate participants' responses to rilparencel (Renal Autologous Cell Therapy-REACT®) following bilateral percutaneous kidney injections into the kidney cortex with a prescribed dosing schedule versus redosing based on biomarker triggers. METHODS: Eligible participants with type 1 or 2 diabetes and CKD, eGFR 20-50 mL/min/1.73 m2, urine albumin-to-creatinine ratio (UACR) 30-5,000 mg/g, hemoglobin >10 g/dL, and glycosylated hemoglobin <10% were enrolled. After a percutaneous kidney biopsy and bioprocessing ex vivo expansion of selected renal cells, participants were randomized 1:1 into two cohorts determined by the dosing scheme. Cohort 1 receives 2 cell injections, one in each kidney 3 months apart, and cohort 2 receives one injection and the second dose only if there is a sustained eGFR decline of ≥20 mL/min/1.73 m2 and/or UACR increase of ≥30% and ≥30 mg/g, confirmed by re-testing. CONCLUSION: The trial is fully enrolled with fifty-three participants. Cell injections and follow-up clinical visits are ongoing. This multicenter phase 2 RCT is designed to investigate the efficacy and safety of rilparencel with bilateral kidney dosing and compare two injection schedules with the potential of preserving or improving kidney function and delaying kidney disease progression among patients with stages 3a-4 CKD with diabetes.

Comparative observation of microcirculation and tissue healing process in gastrointestinal anastomosis with apposition or inverted suturing / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare microcirculation and tissue healing process in gastrointestinal anastomosis with apposition or inverted suture.</p><p><b>METHODS</b>The study was performed in adult rabbits. Animals were randomly assigned to two groups. In group A, small intestine was transected at 20 cm and 40 cm from duodenojejunal ligament and apposition sutures were performed at 20 cm and inverted sutures at 40 cm. In group B, transaction and anastomosis were at the same location with group A while the suturing method was reversed. Anastomotic microcirculation and number of capillary were observed in vivo with naked eyes to evaluate inflammatory response, collagen proliferation and healing of epithelium and smooth muscle in both groups at postoperative day 3, 7, 14 and 28.</p><p><b>RESULTS</b>In group A, tissue layers at the anastomosis were approximated tight and neat with mild inflammation and primary wound healing. In group B, displacement and poor alignment of layers were seen with severe inflammation and secondary wound healing. Low frequency of microcirculation was detected in group A at day 3, and blood flow velocity significantly increased at day 7. Blood flow velocity was close to normal at day 14 and completely restored to the normal level at day 28. Microcirculation was lower in group A than that in group B at each time point. There were more capillaries, lower number of inflammatory cells, less collagen proliferation, and better healing of anastomotic epithelium and smooth muscle in group A than group B.</p><p><b>CONCLUSION</b>Apposition suturing is better than inverted suturing in restoring local anastomotic microcirculation and healing of intestinal tissues.</p>