Kidney Week

Abstract: FR-PO1071

Levels of the Endogenous Nephrotoxin Adenine in Healthy Humans and Effects of Diet

Session Information

• Kidney Nutrition and Metabolism
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Health Maintenance, Nutrition, and Metabolism

• 1500 Health Maintenance, Nutrition, and Metabolism

Authors

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

Subrata Debnath, MBBS, PhD

• Du, Yan, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States

Yan Du, PhD, MPH

• Meireles, Christiane Lumachi, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States

Christiane Lumachi Meireles, PhD, RD, RDN

• Matta, Shane, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States

Shane Matta, MS

• Montellano, Richard, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States

Richard Montellano

• Saliba, Afaf, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States

Afaf Saliba, MS, PhD

• Lorenzo, Carlos, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States

Carlos Lorenzo, MD, PhD

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

Kumar Sharma, MD, FASN

Background

Recent publications indicate that endogenous adenine is likely in the causative pathway for kidney disease in humans and urine adenine/creatinine ratio (UAdCR) is a mechanistic biomarker for ESKD in prospective studies of patients with DKD. However, adenine level in urine of healthy individuals has not been well studied. It is also not known if adenine levels vary according to age, gender, and body mass index (BMI). To shed light on these we conducted two separate studies.

Methods

In one study (Healthy Study), we determined adenine concentrations using validated HPLC-MS/MS analysis in random urine samples collected from apparently healthy individuals (n=122, age 18-89 yrs) without diabetes and hypertension and with eGFR >90 mL/min/1.73m². We also performed a post-hoc analysis of the KETO Study (NCT05071287) data that randomized 60 individuals (age 25-82 yrs) with eGFR of >60 mL/min/1.73m² to either low-fat or keto diet for 6 months with primary outcome of weight change.

Results

In the Healthy Study, mean±SD urine adenine/creatinine ratio (µM/mM) in females (n=60; 0.052 ± 0.065) was significantly higher compared to males (n=62; 0.010 ± 0.012, P = 0.0016). Similar significant difference was noted in the KETO Study. Urine adenine level did not correlate with age in either study. In the KETO Study, BMI declined in both males and females at 3-Mon and 6-Mon compared to Baseline values (P for all <0.01) but did not correlate with UAdCR. Compared to Baseline, UAdCR level declined significantly only in females at 6-Mon (0.06 ± 0.01 vs 0.03 ± 0.05, P=0.04). There was no correlation of eGFR or UACR with the UAdCR.

Conclusion

Reduction in urine adenine/creatinine ratio observed in females was similar with both type of diets, suggesting that weight reduction by diet may be reno-protective. Further work is warranted to explore mechanistic pathway for higher urine adenine/creatinine ratio in females and clinical implications of these novel findings.