Kidney Week

Abstract: FR-PO0350

Perifusate Metabolomics of Kidney Tubules Reveals Nutrient-Dependent Modulation of Stress Response

Session Information

• AKI: Mechanisms - Metabolism and Repair
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Wulfmeyer, Vera Christine, Aarhus Universitet, Aarhus, Central Denmark Region , Denmark

Vera Christine Wulfmeyer, DrMed

• Gernemann, Marlon, Aarhus Universitet, Aarhus, Central Denmark Region , Denmark

Marlon Gernemann

• de la Rosa Siles, Xaiver, Aarhus Universitet, Aarhus, Central Denmark Region , Denmark

Xaiver de la Rosa Siles

• Kristensen, Anders Meldgaard, Aarhus Universitet, Aarhus, Central Denmark Region , Denmark

Anders Meldgaard Kristensen, MS, PhD

• Berg, Peder, Aarhus Universitet, Aarhus, Central Denmark Region , Denmark

Peder Berg, MD, PhD

• Xiong, Lingyun, University of California Los Angeles, Los Angeles, California, United States

Lingyun Xiong, PhD

• Kretz, Oliver, Universitatsklinikum Hamburg-Eppendorf, Hamburg, HH, Germany

Oliver Kretz, MD, DrMed, MBA

• Fiedler, Imke A. K., Universitatsklinikum Hamburg-Eppendorf, Hamburg, HH, Germany

Imke A. K. Fiedler, PhD

• Jaegers, Johannes, Aarhus Universitet, Aarhus, Central Denmark Region , Denmark

Johannes Jaegers, PhD

• Billing, Anja M., Aarhus Universitet, Aarhus, Central Denmark Region , Denmark

Anja M. Billing, PhD

• Bøgh, Nikolaj, Aarhus Universitet, Aarhus, Central Denmark Region , Denmark

Nikolaj Bøgh, MD, PhD

• Hoyer-Allo, Karla Johanna Ruth, Universitatsklinikum Koln, Cologne, NRW, Germany

Karla Johanna Ruth Hoyer-Allo, MD

• Grundmann, Franziska, Universitatsklinikum Koln, Cologne, NRW, Germany

Franziska Grundmann, MD, DrMed

• Burst, Volker Rolf, Universitatsklinikum Koln, Cologne, NRW, Germany

Volker Rolf Burst, MD

• Laustsen, Christoffer, Aarhus Universitet, Aarhus, Central Denmark Region , Denmark

Christoffer Laustsen, MSc, PhD

• Schiessl, Ina M., Aarhus Universitet, Aarhus, Central Denmark Region , Denmark

Ina M. Schiessl, MD, PharmD, PhD

• Mueller, Roman-Ulrich, Universitatsklinikum Koln, Cologne, NRW, Germany

Roman-Ulrich Mueller, MD

• Demir, Fatih, Aarhus Universitet, Aarhus, Central Denmark Region , Denmark

Fatih Demir

• Rinschen, Markus M., Aarhus Universitet, Aarhus, Central Denmark Region , Denmark

Markus M. Rinschen, MD

Background

Measuring renal metabolism at the organ level is challenging, as metabolite signals in tissues are transient and reflect transport, metabolism, and interorgan communication. To adress this, we engineered a fluidic platform that, for the first time, enables precise metabolic perturbation and time-resolved metabolomic readouts from living kidney tissues. Here, we apply fluidic-coupled metabolomics to tubules and glomeruli to resolve their time-dependent metabolic responses under basal, nutrient-defined, and stress conditions.

Methods

Tubules and glomeruli were isolated from mice (C57BL/6NTac) and rats (SD/Janvier) using established protocols. Tissues were exposed to control buffer (electrolytes, hydrogen phosphates, α-ketoglutarate, gluconate, acetate, and glycine) or amino acid- and/or hydrogen peroxide - containing buffers. Outputs were collected at 4°C, extracted, and analyzed using high-sensitivity targeted metabolomics, yielding more than 45,000 time-resolved metabolite measurements.

Results

Fluidic-coupled metabolomics revealed distinct metabolic signatures of renal tubules versus glomeruli. Tubules secreted tricarboxylic acid (TCA) cycle intermediates and acetylated amino acids, whereas glomeruli released purine-related metabolites. Amino acid application rapidly modulated tubular metabolism. Pronounced sex differences in tubular metabolism were uncovered under baseline, amino acid, and hydrogen peroxide application.
¹³C₂-acetate tracing revealed impaired TCA cycle flux under oxidative stress, accompanied by progressive ultrastructural mitochondrial damage. Oxidative stress triggered rapid lactate release, followed by fumarate and malate during prolonged exposure, while impairing glucose release, putatively from gluconeogenesis. These changes were partially rescued by amino acid application, which moreover ameliorated tubular damage.
Lysine oxidation to hydroxylysine emerged as a conserved stress-response pathway associated with oxidative stress and AKI severity across humans and pigs.

Conclusion

Fluidic-coupled metabolomics of native kidney tissues enables precise, time-resolved interrogation of renal metabolism, i.e., core physiological functions such as nutrient processing and stress responses. This approach provides mechanistic insight into acute kidney injury. Further efforts will be made to apply the system to translational questions in health and disease.