Journal of the American Society of Nephrology : JASN · 26 authors, 13 centres
This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.
A single intravenous infusion of 80×10^6 ORBCEL-M cells was safe and well-tolerated in patients with type 2 diabetes and progressive diabetic kidney disease over 18 months. Although measured GFR decline was numerically slower in the cell-treated group, estimated GFR decline was significantly slower (eGFR CKD-EPI: −2.6 vs −8.7 ml/min/1.73m²/year, p=0.034). These findings support further investigation of ORBCEL-M in a larger phase 2b trial.
**Background:** Diabetic kidney disease (DKD) affects 30–40% of adults with type 2 diabetes and is a leading cause of end-stage kidney failure. Despite advances in glycemic and blood pressure control, and newer agents like SGLT2 inhibitors, residual risk remains high. Mesenchymal stromal cells (MSCs) have shown renoprotective effects in preclinical models by targeting inflammation, oxidative stress, and fibrosis. The NEPHSTROM trial investigated a next-generation, CD362-selected allogeneic MSC product (ORBCEL-M) in patients with progressive DKD.
**Methods:** This phase 1b/2a multicenter, randomized, double-blind, placebo-controlled trial enrolled 16 participants (12 ORBCEL-M, 4 placebo) with type 2 diabetes and progressive DKD (eGFR 25–55 ml/min/1.73m², UACR ≥88 mg/g, and documented eGFR decline). Participants received a single intravenous infusion of 80×10^6 ORBCEL-M cells or placebo and were followed for 18 months. Primary outcome was safety (adverse events). Secondary outcomes included changes in measured GFR (mGFR by iohexol clearance), eGFR (CKD-EPI and MDRD), UACR, metabolic parameters, blood pressure, immune cell subsets, and inflammatory biomarkers.
**Key Results:** ORBCEL-M infusion was well-tolerated with no acute infusion reactions. Over 18 months, 11 serious adverse events occurred in 4 ORBCEL-M recipients (none deemed treatment-related) and 1 in a placebo recipient (bronchospasm, treatment-related). Two deaths occurred in the ORBCEL-M group (congestive heart failure and multiple myeloma), both considered unrelated to treatment. mGFR decline was numerically slower in the ORBCEL-M group (−3.8 vs −7.5 ml/min/1.73m²/year, p=0.467). eGFR decline was significantly slower in the ORBCEL-M group (CKD-EPI: −2.6 vs −8.7 ml/min/1.73m²/year, p=0.034; MDRD: −2.4 vs −8.1 ml/min/1.73m²/year, p=0.034). UACR did not differ between groups. Immune profiling showed that ORBCEL-M recipients had stable proportions of memory regulatory T cells and lower proportions of proinflammatory intermediate monocytes compared to placebo. Anti-HLA antibodies developed in only one ORBCEL-M recipient (low-level, class I).
**Clinical Implications:** This first-in-human trial demonstrates that a single infusion of 80×10^6 ORBCEL-M cells is safe and well-tolerated in patients with progressive DKD. The preliminary efficacy signals, particularly the significant slowing of eGFR decline and favorable immune modulation, support further investigation in a larger, adequately powered phase 2b trial. The low immunogenicity of ORBCEL-M is advantageous for potential future kidney transplantation. Limitations include small sample size, all-male cohort, and lack of SGLT2 inhibitor use in most participants.