Abstract: FR-PO124
Markers for Cell Death and Purine Metabolites in Patients with and without Delayed Graft Function after Kidney Transplantation
Session Information
- AKI: Diagnosis and Outcomes
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 102 AKI: Clinical, Outcomes, and Trials
Authors
- Warncke, Max, Novartis AG, Basel, Basel-Stadt, Switzerland
- Lafont, Armelle, Novartis AG, Basel, Basel-Stadt, Switzerland
- Klein, Laurent, Novartis AG, Basel, Basel-Stadt, Switzerland
- Nakamura, Monica Rika, Hospital do Rim, Goionia, GO, Brazil
- Silva, Helio Tedesco, Hospital do Rim, Goionia, GO, Brazil
- Welzenbach, Karl, Novartis AG, Basel, Basel-Stadt, Switzerland
Background
Delayed graft function (DGF) is defined as the dysfunction of the kidney after transplantation (TX) and manifestation of acute tubular necrosis (ATN). Tubular necrosis is one hallmark of DGF, but there is still an incomplete understanding about the trajectories of biomarkers of tissue injury post transplantation. Markers to identify patients at risk for DGF would support the development of novel therapeutic treatments to ameliorate or reduce DGF in the globally growing number of transplanted patients.
Methods
Plasma and urine samples of 41 patients receiving grafts of living donors (10), or grafts from deceased donors with standard criteria (16) or expanded criteria donors (15) were prospectively collected over 28 days after TX. Markers of tissue injury (plasma LDH, Cystatin C (CycC), AST, ALT, CK), NGAL and urinary purine metabolites (ATP, adenosine) were assessed. The association of markers early post TX with DGF diagnosis was evaluated.
Results
Among the 31 patients who received a deceased donor graft, 19 developed DGF, while the remaining 11 did not experience DGF. The incidence of DGF in patients receiving a cadaveric graft was 61%. The 10 patients with grafts from living donors did not develop DGF. Markers of tissue damage were modulated in plasma of patients following TX. Patients receiving living donor organs showed significantly lower TX-induced modulation of biomarkers suggesting a milder insult on grafts and recipients. Urinary adenosine was significantly lower in the 28 days after transplantation in patients with DGF correlating well with increased plasma CysC and NGAL levels. All markers normalized 3-4 weeks after TX. The relative elevation of LDH and AST at 4h after surgery preceded the development of DGF in ~40% of patients who received a graft of a deceased donor.
Conclusion
This study provides a comprehensive trajectory of established and more recent markers of kidney function, potentially graft quality and the relationship to DGF after kidney transplantation in kidney TX patients. The early induction of tissue damage markers shows the importance to start therapies to protect from DGF as early as possible. The observed decrease of urinary adenosine in patients with DGF point to an important function of the purinergic pathway in this patient population.