The Journal of Heart and Lung Transplantation · Nov 10, 2026

Harnessing Lung-Kidney Crosstalk: A Novel Ex Vivo Platform for Donor Lung Rehabilitation

By Gao FY, Garza G, Wang A et al.

Background The lack of perfusate metabolic homeostasis during ex vivo lung perfusion (EVLP) may impair lung physiology or stability and limit the application of advanced donor lung therapies. There is evidence that additional organ support during EVLP can improve graft preservation and transplant outcomes. We hypothesized that incorporation of a kidney into an EVLP circuit would maintain perfusate homeostasis and improve lung preservation and metabolic activity. Methods A novel circuit was developed to allow simultaneous normothermic perfusion of lungs and kidney in parallel. Donor pig lungs underwent 12 hours of cellular EVLP (EVLP, n=5) or combined cellular ex vivo lung-kidney perfusion (EVLKP, n=5). Lung function was assessed hourly and inflammatory cytokines, edema formation, hemolysis, histologic injury, and kidney performance were evaluated. Results Simultaneous lung and kidney perfusion achieved target pulmonary and renal perfusion parameters with stable hemodynamics. EVLKP demonstrated trends of higher compliance, lower inspiratory pressure and pulmonary vascular resistance. Perfusate lactate concentration in EVLKP was markedly lower (P<0.0001), glucose concentrations were higher (P=0.0102), and pH shifted towards physiologic levels (P=0.0009) compared to EVLP. Oxygenation capacity was comparable between groups. Kidney perfusion remained stable throughout EVLKP. Conclusions Combined ex vivo lung-kidney perfusion is safe and feasible in a large-animal model for prolonged lung perfusion. EVLKP improved perfusate homeostasis compared with EVLP alone, which is associated with trends of improvement in lung physiologic parameters. These findings suggest that kidney-derived metabolic and biological support may provide benefits beyond perfusate filtration and highlight the potential importance of organ-organ crosstalk during ex vivo perfusion.

doi.org/10.1016/j.healun.2026.11.004PubMed 43009110Interventions