Safety and Feasibility of a Novel Percutaneous Locoregional Injection Technique of Renal Cellular Therapy for Chronic Kidney Disease of Diabetes

Yu, Hyeon; Sonntag, Paul D.; Bream, Peter R.; Lazarowicz, Michael; Nowakowski, F.; Woodhead, Gregory; Hennemeyer, Charles; Müller, R; Navuluri, Rakesh; Caoili, Elaine M.; Eifler, Aaron C.; Tominna, Brandon S.; Stavas, Joseph M.

doi:10.1016/j.ekir.2021.06.014

Cited by 3 publications

(4 citation statements)

References 5 publications

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“…The nanoparticle delivery of nanomedicines and gene therapies holds future promise but is still in a nascent phase of development for CKD [20]. Locoregional injections of rilparencel into the kidney cortex with CT image guidance and small-gauge atraumatic needles have demonstrated safety and feasibility while delivering a consistent dose, regardless of asymmetric renal perfusion and size [21,22]. The rilparencel dose is administered by multiple small volume deposits within the cortex layer, each spaced apart to allow cell dispersion and potential migration through Vascular Endothelial Growth Factor signaling factors [3].…”

Section: Discussionmentioning

confidence: 99%

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

Stavas,

Silva,

Wooldridge

et al. 2024

Am J Nephrol

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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.

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Section: Discussionmentioning

confidence: 99%

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

Stavas,

Silva,

Wooldridge

et al. 2024

Am J Nephrol

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“…Despite being a high-risk population, all injection procedures were well tolerated and adverse events commensurate with our previous percutaneous injections of REACT [ 11 ]. Our hypothesis was that the bioactive SRCs in the REACT product would stabilize disease progression in advanced type 2 DKD, based on their presumed mechanism of action.…”

Section: Discussionmentioning

confidence: 99%

“…The REACT dose is 3 × 10 6 cells/g estimated kidney weight, determined by renal volume analysis, with a dose range of 3–8 mL. All injections are performed as outpatient procedures under conscious sedation [ 10 , 11 ]. Post-injection renal ultrasounds, hemoglobin, hematocrit, and chemistry levels are obtained during the recovery period and at 24 h, to detect adverse events.…”

Section: Methodsmentioning

confidence: 99%

“…Findings in our preceding animal studies led to FDA-approved phase I and II clinical trials utilizing an admixture of ex vivo expanded homologous autologous selected renal cells (SRCs) obtained from a percutaneous kidney biopsy, which form the product called Renal Autologous Cell Therapy (REACT) [ 7 , 8 , 9 , 10 ]. Injection procedures have been well tolerated among patients with type 2 diabetes [ 11 ]. Our early trial in diabetic chronic kidney disease (DKD) patients with an eGFR >20 mL/min/1.73 m 2 has demonstrated stabilization of eGFR and UACR levels versus a standard of care comparator group [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Renal Autologous Cell Therapy in Type 2 Diabetes with Late Stage 4 Diabetes-Related Chronic Kidney Disease: Trial Design and Early Analysis

Stavas¹,

Thajudeen

Coca

et al. 2023

Blood Purif

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Introduction: Cell-based therapies potentially delay the trajectory toward end-stage kidney disease (ESKD) in late stage 4 diabetic chronic kidney disease (DKD). We describe the trial design, baseline patient characteristics, and early results of an IRB-approved phase II multicenter clinical trial, utilizing Renal Autologous Cell Therapy (REACT) in adults with pre-ESKD due to type 2 DKD. The trial objectives were safety and tolerability of REACT by assessment of the procedure, product administration, and renal-specific adverse events in addition to evaluate the impact on renal function following injection. Methods: Ten adults with an eGFR of 14–20 mL/min/1.73 m2 were enrolled in a single-arm open-label trial. Following a percutaneous kidney biopsy, an ex vivo expansion of selected renal cells that form the REACT was injected into the cortex of the biopsied kidney with CT image guidance. Each participant received two doses of the REACT product at 6-month intervals. A 6-month observation pre-trial was required to establish patients’ “own” baseline and rate of DKD progression. Results: Five men and 5 women underwent 19 REACT injections (1 participant received only one injection). Their baseline characteristics were as follows: 3 Hispanic/Latino, 7 non-Hispanic, 7 white; mean (SD) age: 58.9 years (5.22), BMI 35.8 (8.2), eGFR (sCR) 15.5 (2.72), eGFR (sCR + Cys-C) 17.7 (3.67) mL/min/1.73 m2, sCr 3.6 mg/mL (0.73), Cys-C 2.6 mg/mL (0.52), and log random UACR 7.9 mg/g (1.01). The pre- and post-injection eGFR slope was −6.5 mL/min/1.73 m2 and −3.9 mL/min/1.73 m2. No cell-related adverse events occurred, and two procedure-related hematomas required observation without transfusion or angiographic interventions. Dialysis was delayed a mean of 16 months (range 6–28 months). At 15 months, 2 patients (20%) have eGFR slope stability and have not commenced renal replacement therapy. Conclusion: Trials that include patients with an eGFR of <20 mL/min/1.73 m2 are uncommon, and none to date involve autologous homologous cell-based treatments. REACT has the potential to stabilize or delay dialysis in high-risk late stage 4 DKD.

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Polyelectrolyte Hydrogels for Tissue Engineering and Regenerative Medicine

Wang

Surat'man

Chang

et al. 2022

Chemistry An Asian Journal

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Polyelectrolyte hydrogels are emerging materials for tissue engineering and regenerative medicine applications due to their tunable biochemical properties, electrical conductivity, biocompatibility and similar network structure to the extracellular matrix in mammalian bodies. In this review, representative polyelectrolyte hydrogels carrying anionic, cationic, ampholytic, zwitterionic and ionic liquid moieties are systemically cataloged to express their chemical structures and preparation strategies. Recent advance of polyelectrolyte hydrogels in tissue engineering and regenerative medicine for drug delivery, skin healing, bone regeneration, cardiac tissue repair and anti-biofouling coating are also highlighted. Eventually, the outlook and challenges of polyelectrolyte hydrogels and their biomedical material applications are also discussed to offer future directions.

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Safety and Feasibility of a Novel Percutaneous Locoregional Injection Technique of Renal Cellular Therapy for Chronic Kidney Disease of Diabetes

Cited by 3 publications

References 5 publications

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

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

Renal Autologous Cell Therapy in Type 2 Diabetes with Late Stage 4 Diabetes-Related Chronic Kidney Disease: Trial Design and Early Analysis

Polyelectrolyte Hydrogels for Tissue Engineering and Regenerative Medicine

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