Abstract: FR-PO0391
Guanidinoacetate and Creatine: A Potential Novel Marker in AKI
Session Information
- AKI: Biomarkers, Diagnostics, and Risk Prediction
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 102 AKI: Clinical, Outcomes, and Trials
Authors
- Arroyo Ariza, Daniel Felipe, Washington University in St Louis School of Medicine, St. Louis, Missouri, United States
- Portales Castillo, Ignacio A., Washington University in St Louis School of Medicine, St. Louis, Missouri, United States
Background
The creatine/phosphocreatine buffer system is essential for maintaining ATP homeostasis in high-demand organs like the kidney. The rate-limiting step of creatine synthesis occurs in the proximal tubule via the enzyme L-arginine:glycine amidinotransferase (AGAT), encoded by the GATM gene, which produces the precursor guanidinoacetate (GAA). The clinical significance of this pathway was first highlighted by the P341L GATM mutation in hereditary Fanconi Syndrome. However, data from single-cell transcriptomics in ischemic acute kidney injury (AKI) models reveal a rapid downregulation of GATM within four hours of injury onset. We sought to characterize the creatine synthesis pathway in a clinical cohort to determine if plasma GAA levels could serve as a novel, specific marker for proximal tubular injury in AKI.
Methods
Following IRB approval, plasma samples were collected from seven hospitalized patients with AKI of various etiologies. A control cohort of nine participants (one hospitalized and eight healthy controls) was also sampled. Targeted mass spectrometry was utilized to quantify plasma creatine and GAA levels. Clinical parameters were extracted from electronic medical records.
Results
The AKI cohort (n=7; 71% female; mean age 60.4 years) demonstrated a mean baseline creatinine of 1.07 mg/dL and a peak of 3.04 mg/dL. AKI etiologies were diverse. In the AKI group, mean plasma GAA was significantly lower than in the control group (0.009 mg/dL vs. 0.017 mg/dL, p<0.05). Conversely, plasma creatine was elevated in the AKI cohort (1.25 mg/dL vs. 0.431 mg/dL). The resulting GAA/Creatine ratio was significantly reduced in AKI patients (0.017) compared to controls (0.065), representing a profound 4-fold decrease.
Conclusion
AKI leads to a significant suppression of plasma GAA, likely reflecting the early downregulation of the GATM pathway observed in ischemic AKI models. Because GATM expression is highly localized to the proximal tubule, GAA may serve as a specific marker for tubular injury. These findings generate the hypothesis that monitoring GAA levels and the GAA/Creatine ratio during AKI could assist in determining the timeline of renal recovery. Future longitudinal studies are warranted to validate GAA as a functional biomarker of AKI.
Acknowledgment
The authors want to acknowledge the Mentors in Medicine Grant committee at the Washington University in St. Louis School of Medicine for their thoughtful critiques and comments. Additionally, the authors want to acknowledge the use of Google Gemini to assist in preparation and revision of this abstract.
Funding
- Private Foundation Support