Kidney Week

Abstract: TH-PO0627

Urinary Adenine-to-5'-Methylthioadenosine Ratio Cut Points for Predicting Composite Kidney Outcomes in Patients with Diabetic Kidney Disease

Session Information

• CKD: Clinical - Guidelines, Biomarkers, Progression, Procedures, Outcomes, and More
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2202 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Ragi, Nagarjunachary, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States

Nagarjunachary Ragi, PhD

• Buti, Prince A., The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States

Prince A. Buti, PhD

• Debnath, Subrata, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States

Subrata Debnath, MBBS, PhD, MPH

• Liu, Jian-Jun, Khoo Teck Puat Hospital, Singapore, Singapore

Jian-Jun Liu, DrMed

• Lim, Su Chi, Lee Kong Chian School of Medicine, Singapore, Singapore

Su Chi Lim, MD, PhD

• Sharma, Kumar, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States

Kumar Sharma, MD, FASN

Background

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease, yet early biomarkers reflecting metabolic dysfunction remain limited. Adenine, a purine metabolite, has been associated with kidney injury. In contrast, 5'-Methylthioadenosine (MTA), a precursor of adenine and key intermediate in the methionine salvage pathway regulated by methylthioadenosine phosphorylase (MTAP), may reflect protective methylation pathways. Because MTAP converts MTA to adenine, the adenine-to-MTA ratio (AMR) may serve as an indirect index of MTAP activity and altered purine metabolism. This study evaluated urinary AMR as a biomarker for DKD progression.

Methods

Random urine samples were collected from the Chronic Renal Insufficiency Cohort study, (n = 652) and Singapore Study of Macro-Angiopathy and microvascular Reactivity in Type 2 Diabetes (SMART2D) study, (n = 309) participants. Targeted metabolomics was performed to quantify adenine and MTA. Participants had baseline eGFR 20-70 mL/min/1.73 m². The composite renal endpoint included rapid eGFR decline, kidney replacement therapy. AMR values were natural log transformed. Cox proportional hazards models were applied using both continuous and survival based binary approaches, overall and stratified by sex. Optimal cut points were identified using maximally selected rank statistics, with cohort specific derivation and ongoing cross cohort validation.

Results

High urinary AMR was associated with adverse renal outcomes across both cohorts. In CRIC, continuous log-AMR showed a strong unadjusted association (HR 1.34, 95% CI 1.22-1.48, p<0.001) that attenuated after adjustment (HR 1.10, 95% CI 0.99-1.24, p=0.088). Binary AMR improved risk discrimination in both unadjusted (HR 1.71, 95% CI 1.38-2.12, p<0.001) and adjusted models (HR 1.36, 95% CI 1.06-1.73, p=0.015). In SMART2D, findings were directionally consistent, with continuous log-AMR associated with renal risk in both unadjusted (HR 1.58, 95% CI 1.23-2.02, p<0.001) and adjusted analyses (HR 1.48, 95% CI 1.15-1.91, p=0.0025). Binary AMR showed stronger effects, with unadjusted HR 3.58 (95% CI 1.94-6.63, p<0.001) and adjusted HR 3.49 (95% CI 1.72-7.09, p=0.001). Despite cohort-specific thresholds, elevated AMR consistently identified a high-risk subgroup.

Conclusion

Urinary AMR is a biologically plausible and clinically promising biomarker for predicting DKD progression.

Acknowledgment

Funding for the CRIC study was obtained under a cooperative agreement from the NIDDK.

Funding

• Veterans Affairs Support