Therapeutic and mechanistic insights on mitochondrial transplantation in kidney disease.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are major contributors to global morbidity and mortality, with limited treatment options beyond supportive care. Mitochondrial dysfunction is a shared feature of both conditions, driving impaired energy production, oxidative stress and cell death. Owing to its reliance on oxidative phosphorylation, the kidney is especially vulnerable to ischaemia-reperfusion injury, a leading cause of AKI and a risk factor for long-term loss of kidney function. Persistent mitochondrial damage contributes to the transition from AKI to CKD, and strategies aimed at restoring mitochondrial health, therefore, have therapeutic potential. Here, we focus on mitochondrial transplantation, a therapeutic approach that delivers viable, respiratory-competent mitochondria to injured tissue to support recovery. Mitochondria for transplantation can be isolated from a variety of sources (autologous or allogeneic) without triggering an immune, autoimmune or inflammatory response, or a reaction to damage-associated molecular patterns. Isolated mitochondria can be delivered by intra-arterial injection, and, once in the target organ, they are rapidly integrated into the cells through endocytosis. Mitochondrial transplantation supports the restoration of mitochondrial function and associated signalling pathways, promoting enhanced organ function and cellular viability. Several preclinical studies have demonstrated improved kidney function, reduced inflammation and preserved mitochondrial structure following mitochondrial therapy in models of ischaemia.