Abstract: FR-PO104
Uridine Diphosphate (UDP) Sugars Predict AKI in Cardiac Surgery Patients
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
- Legare, Christine, Centre Hospitalier Universitaire de Quebec-Universite Laval, Quebec, Quebec, Canada
- Caron, Patrick, Centre Hospitalier Universitaire de Quebec-Universite Laval, Quebec, Quebec, Canada
- Guillemette, Chantal, Centre Hospitalier Universitaire de Quebec-Universite Laval, Quebec, Quebec, Canada
- Mohammadi, Siamak, Institut Universitaire de Cardiologie et de Pneumologie de Quebec - Universite Laval, Quebec, Quebec, Canada
- Breton, Sylvie, Centre Hospitalier Universitaire de Quebec-Universite Laval, Quebec, Quebec, Canada
Background
UDP-sugars including UDP-glucose (UDP-Glc), UDP-galactose (UDP-Gal), UDP-N-acetylgalactosamine (UDP-GalNAc), UDP-N-acetylglucosamine (UDP-GlcNAc), and UDP-glucuronic acid (UDP-GlcA) activate the pro-inflammatory P2Y14 receptor. Previously, we showed elevated urine UDP-Glc in intensive care unit patients with AKI compared to those without AKI. In addition, renal ischemia reperfusion injury in mice led to an increase in UDP-Glc urine concentration, followed by activation of P2Y14 in intercalated cells (ICs), initiating an inflammatory cascade that worsened AKI. Ischemic-AKI is prevalent among cardiac surgery patients. Here we investigated whether UDP-sugars serve as early markers of AKI in these patients.
Methods
Urine and plasma samples were collected from 53 cardiac surgery patients: prior to initiation of cardio-pulmonary bypass (CPB), at the end of CPB, and 4h, 12h, 24h, 48h, and 72h post-CPB. The concentration of UDP-sugars was quantified using mass spectrometry. The ROC-AUC was used to evaluate the association between urinary and plasma UDP-sugars and AKI. Correlation analysis was performed with urinary kidney injury molecule -1 (KIM-1), measured by electroluminescence.
Results
Compared to patients without AKI, urinary concentration of UDP-Glc (P=0.002), UDP-Gal (P=0.001) and UDP-GalNAc/GlcNAc (P= 0.0001) increased 12h post-CPB, followed by a return to reference levels in patients diagnosed with AKI 24h after surgery. Urinary UDP-GlcA and plasma UDP-sugars did not vary with AKI. Optimal threshold values of UDP-Glc, UDP-Gal, UDP-GalNAc/GlcNAc, and their sum, predicted AKI with AUC values of 0.71, 0.72, 0.75 and 0.76, respectively. Urinary levels of UDP-Glc and UDP-Gal correlated with KIM-1 at 12h post-CPB (R > 0.43).
Conclusion
Our findings indicate that UDP-Glc, UDP-Gal and UDP-GalNAc/GlcNAc measured in urine are predictors of AKI. Given the correlation observed between KIM-1 - a marker indicative of proximal tubule (PT) injury - and UDP-Glc and UDP-Gal, we suggest that these UDP-sugars are actively released by damaged PT during CPB. Following their release, they are eliminated in the urine, where they trigger the activation of the P2Y14 receptor in ICs. This study, thus, identifies P2Y14 as a key driver in AKI.
Funding
- Government Support – Non-U.S.