Mitochondrial transplantation for kidney disease: evidence, delivery constraints, and translational priorities

Mitochondrial dysfunction underlies multiple forms of renal injury, prompting strategies to restore organellar function rather than target discrete signaling pathways. Mitochondrial transplantation (MTx) has produced short-term functional, histological, or cellular benefits in preclinical models of renal ischemia-reperfusion, toxic and complex acute kidney injury, focal diabetic tubular injury, ex vivo kidney perfusion, and direct renal-cell stress. Interpretation remains difficult because routes, preparations, and follow-up differ, and few studies connect organ benefit to recipient-cell delivery and donor-organelle fate. We posit that renal MTx is most plausible when reversible mitochondrial lesions, viable recipient renal cells, and accessible delivery routes coexist. Acute reperfusion-associated injury currently aligns these conditions most clearly, whereas diffuse chronic disease is less clearly suited to intact-organelle therapy. The immediate task is to determine whether a defined product can reproducibly reach an accessible renal target and alter its trajectory.