A Randomized Clinical Trial of Kidney Autologous Cell Therapy in Diabetic Kidney Disease

Key Points Bilateral kidney injections with rilparencel was associated with a 78% improvement in the annual eGFR decline in kidney function. There were no serious adverse events related to rilparencel therapy. The interventional procedures were well tolerated and had an acceptable safety profile. Background Despite new treatments to delay disease progression in patients with diabetes and CKD, many patients continue to lose kidney function and progress to kidney failure. Additional therapeutic strategies, perhaps targeting multiple deleterious pathways, are necessary to preserve kidney function in patients with advanced CKD. Methods A multicenter, randomized, phase 2 clinical trial (NCT05018416) assessed rilparencel (an autologous cell therapy composed of cells obtained by kidney biopsy), in participants with diabetes and estimated glomerular filtration rate (eGFR) 20–50 ml/min per 1.73 m 2 . Participants were randomized 1:1 to two cohorts. Cohort 1 received two rilparencel injections percutaneously into the kidney cortex, 3 months apart, one in each kidney. Cohort 2 received one injection and a second injection only upon a sustained decline in eGFR or increase in urinary albumin creatinine ratio. Participants were followed up to 18 months after their last injection. The primary efficacy end point was change in eGFR slope from the preinjection period to the period after the last injection. The primary safety end point was the percentage of participants with procedure or rilparencel-related treatment emergent adverse events (TEAEs). Results Fifty-three participants were randomized and 49 received at least one injection. In Cohort 1, annual eGFR slope (ml/min per 1.73 m 2 /year) in the preinjection period was -5.84 (SEM 1.07) versus −1.27 (SEM 1.36) in the period after the last injection (difference 4.57 [95% confidence interval, 1.95 to 7.18]). In Cohort 2, annual eGFR slope in the pre-injection period was −3.40 (SEM 0.81) versus −1.71 (SEM 1.04) in the period after the last injection (difference 1.70 [95% confidence interval, −0.24 to 3.63]). No interactions were observed across multiple predefined baseline subgroups. Of 87 injections, procedure-related TEAEs occurred in 16 participants and rilparencel-related TEAEs occurred in six participants. No product-related serious adverse events and no procedure-related or product-related deaths were reported. Conclusions Bilateral kidney injection of rilparencel may preserve kidney function with an acceptable safety profile. A multicenter, phase 3, randomized, sham-controlled study is ongoing.