Abstract: TH-PO1184
Quinolinic Acid Reduction May Protect Against AKI-to-CKD Transition
Session Information
- CKD: Mechanisms, AKI, and Beyond - 1
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Saade, Marie Christelle, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Saliba, Afaf, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Clark, Amanda J., The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Alhumaidi, Rahil, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Etzrodt, Valerie, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Vu, Kyle Q., The University of Texas Southwestern Medical Center, Dallas, Texas, United States
- O'Connor, Jason, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Sharma, Kumar, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Parikh, Samir M., The University of Texas Southwestern Medical Center, Dallas, Texas, United States
Background
Acute kidney injury (AKI) is a major clinical problem associated with a high risk of progression to chronic kidney disease (CKD). Emerging evidence delineates the essential role of metabolic reprogramming in the transition from AKI to CKD. Quinolinic acid (Quin), a key metabolite in the de novo NAD+ pathway, may play a pivotal role in this process, with QPRT regulating its production. Understanding the role of Quin in kidney injury could uncover therapeutic targets to slow the AKI to CKD transition.
Methods
Eight-week-old wild-type C57BL/6 male mice (WT), 8-week-old C57BL/6 male mice for QPRT+/-, 72-week-old C57BL/6 male mice for aged models, and 8-week-old C57B6N male mice for KMO and HAAO knockout (KT) models were used. Folic acid (FA) injections (250 mg/kg, i.p.) were used as a model for AKI to CKD transition. WT mice injected with FA were harvested at 0, 36 hrs, 7 and 14 days for metabolomics analysis. Kidney injury was assessed using qPCR, serum BUN and creatinine. Quin (0.5 g/L) was administered to WT mice for 14 days starting on day 14 post-FA injection. Urine samples were collected from children with CKD admitted to Children’s Medical Center Dallas and healthy control presenting to the ER or clinic.
Results
In a FA induced mouse model of AKI to CKD transition, unbiased metabolomic profiling identified Quin as one of the most significantly elevated metabolites one week post-injury. We used genetic and dietary approaches to investigate the consequences of Quin accumulation. FA-injected QPRT+/- mice exhibited increased levels of serum creatinine, BUN, COL3A1, and TGFB at day 14. Aged QPRT+/- mice without injury showed elevated expression of ACTA2, NFKB, TGFB, and PDGF, suggesting a predisposed pro-fibrotic state. Exogenous administration of Quin in the FA model exacerbated kidney injury. FA-injected HAAO or KMO KT mice conferred protection against AKI to CKD transition. Children with CKD exhibited higher urinary Quin levels compared to healthy controls.
Conclusion
Quinolinic acid accumulation plays a pathogenic role in the progression from AKI to CKD. Both genetic and dietary modulation of Quin levels impacted the severity of kidney injury, with Quin reduction conferring protection in experimental models, highlighting its potential as a target for therapeutic intervention in human kidney disease.
Funding
- NIDDK Support