DAMPs Released From Injured Renal Tubular Epithelial Cells Activate Innate Immune Signals in Healthy Renal Tubular Epithelial Cells.

BACKGROUND: Renal ischemia-reperfusion injury (IRI) predictably causes acute kidney injury after shock and major cardiovascular procedures in all kidneys procured for transplantation. The earliest events of IRI are triggered by molecules released from injured cells, damage-associated molecular patterns (DAMPs), that bind pattern recognition receptors (PRRs) constitutively expressed on many cells within the kidney. Activation of PRR signaling leads to production of proinflammatory molecules, which incite a cascade of inflammatory events leading to acute kidney injury. Renal tubular epithelial cells (RTECs) are particularly susceptible to ischemic injury, and proximal RTEC injury is pathognomonic of renal IRI. To better understand how injured RTECs contribute to the cycle of deleterious inflammation in the setting of renal IRI, this study asked whether DAMPs released from injured RTECs induced PRR signals in healthy RTECs. METHODS: Human RTECs were necrosed ex vivo to release intracellular DAMPs and resulting necrotic supernatant used to stimulate healthy RTECs, T lymphocytes, and monocytes. RESULTS: DAMPs released from necrosed RTECs upregulated PRRs known to be associated with renal IRI and activated mitogen-activated protein kinase signaling pathways. Proinflammatory cytokines were upregulated in response to necrotic supernatant, and this upregulation was abrogated by MEK-1 inhibition. The RTEC-derived DAMPs were also potent inducers of T-cell activation/proliferation and monocyte migration. CONCLUSIONS: This is the first study to our knowledge to show that endogenous DAMPs released from injured RTECs directly activate PRR signaling in healthy RTECs. These findings provide new insights directed to therapeutics for renal IRI.

An Adapted Process and Organ Procurement Perspective on Heart Retransplantation for a Healthy Heart's Third Life.

As organ procurement organizations nationwide see an increased opportunity to retransplant already transplanted hearts, we would like to share the overview and process of our 2 successful cases. Heart retransplantation increased our cardiac placement rates by 2.64% and 2% in 2015 and 2019, respectively. Spread across a nation that sees over 3500 heart placements annually, a 2% increase would be substantial. Since 2009, our cases stand as the only documented heart retransplantations in the United States. However, United Network for Organ Sharing data shows that potential exists. From a facilitation perspective, we have developed a protocol to ease the matching process. From a surgical perspective, these cases had no complications and saved 2 lives, with each heart now beating in a third person. We hope that by sharing our process and success, we can familiarize fellow organ procurement organizations and transplant communities with this viable opportunity.