Kidney Week

Abstract: FR-PO233

Understanding Gastrointestinal Oxalate Metabolism in Kidney Stone Disease: A Stable Isotope Study

Session Information

• Mineral Bone Disease: Transplant and Kidney Stones
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 502 Bone and Mineral Metabolism: Clinical

Authors

• Deesker, Lisa, Emma Kinderziekenhuis Amsterdam UMC, Amsterdam, Noord-Holland, Netherlands

Lisa Deesker, MD, PhD

• Garrelfs, Sander Frederik, Emma Kinderziekenhuis Amsterdam UMC, Amsterdam, Noord-Holland, Netherlands

Sander Frederik Garrelfs, MD, PhD

• van Harskamp, Dewi, Stable Isotope Research Laboratory, Amsterdam University Medical Centers, Amsterdam, Netherlands

Dewi van Harskamp

• de Meij, Tim, Emma Kinderziekenhuis Amsterdam UMC, Amsterdam, Noord-Holland, Netherlands

Tim de Meij, MD, PhD

• Oosterveld, Michiel Js, Emma Kinderziekenhuis Amsterdam UMC, Amsterdam, Noord-Holland, Netherlands

Michiel Js Oosterveld, MD, PhD

• Groothoff, Jaap, Emma Kinderziekenhuis Amsterdam UMC, Amsterdam, Noord-Holland, Netherlands

Jaap Groothoff, MD, PhD

Background

Intestinal oxalate metabolism plays a significant role in calcium oxalate (CaOx) kidney stone disease. However, the gastrointestinal oxalate metabolism remains insufficiently understood, leading to dietary restrictions for patients based on limited evidence. With this study, we aim to obtain more insight into the gastrointestinal absorption and breakdown of oxalate. Measurement of oxalate absorption will be combined with assessment of the gut microbiome, which has been found to correlate with CaOx stone disease and could be one of the key influences on the gastrointestinal bio-availability of oxalate.

Methods

In this cross-sectional case-control study, we aim to study the influence of dietary oxalate on urinary oxalate levels by quantifying the intestinal oxalate absorption in patients with primary or secondary hyperoxaluria and non-hyperoxaluric CaOx stone formers vs. healthy controls, using an oral stable isotope method described by Von Unruh et al. (1998). After ingesting an oral dose of ¹³C-oxalate, ¹³C-oxalate enrichments will be measured in plasma and urine samples using GC-MS/MS. In breath samples,¹³CO₂ will be analyzed as an indirect measure of intraluminal oxalate degradation. Intestinal oxalate absorption will be calculated and correlated with microbiome diversity and abundance of oxalate-degrading bacteria measured in fecal samples by 16S rRNA sequencing (F1).

Results

The study is currently ongoing. Preliminary data (in healthy controls, n=4) show that plasma oxalate enrichments peaked between 1-3 hours after tracer ingestion and that 75-89% of ¹³C-oxalate is excreted via the urine within 6 hours. Similarly, ¹³CO₂ enrichments in breath samples (n=2) peaked between 1-3 hours, indicating intestinal oxalate degradation. ¹³C-oxalate absorption/degradation rates and microbiome correlations will be presented at the congress based on the final results (n≈45).

Conclusion

This study will be the first to combine oxalate absorption, degradation, and intestinal microbiome analysis. This provides unique insights into gastrointestinal oxalate metabolism, the role of the microbiome, and potential new therapeutic targets for different subgroups of CaOx stone formers.

Funding

• Private Foundation Support