Kidney Week

Abstract: FR-PO582

Kidney Medullary Range NaCl Modulates CD8+ T Cell Survival and Function and Associates with Their Accumulation in Kidney Allografts

Session Information

• Fluid, Electrolyte, and Acid-Base Disorders: Basic
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid, Electrolytes, and Acid-Base Disorders

• 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

• Falahat, Peyman, Universitatsklinikum Bonn, Bonn, Nordrhein-Westfalen, Germany

Peyman Falahat, MD

• Goldspink, Adrian, Universitatsklinikum Bonn, Bonn, Nordrhein-Westfalen, Germany

Adrian Goldspink, MS, MSc

• Schmitz, Jessica, Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany

Jessica Schmitz

• Braesen, Jan H., Medizinische Hochschule Hannover, Hannover, Niedersachsen, Germany

Jan H. Braesen, MD, PhD

• Klümper, Niklas, Universitatsklinikum Bonn, Bonn, Nordrhein-Westfalen, Germany

Niklas Klümper, MD

• Toma, Marieta Ioana, Universitatsklinikum Bonn, Bonn, Nordrhein-Westfalen, Germany

Marieta Ioana Toma, DrMed

• Von Vietinghoff, Sibylle, Universitatsklinikum Bonn, Bonn, Nordrhein-Westfalen, Germany

Sibylle Von Vietinghoff, MD

Background

Recent research revealed a significant impact of electrolytes, namely NaCl, on immune responses. The role of the chief renal mobile osmolytes NaCl and urea for CD8⁺ T cell function and accumulation in the kidney has not been systematically explored.

Methods

Human primary kidney and blood CD8⁺ T cell survival and function was studied in elevated NaCl and urea concentrations. Renal T cell and antigen presenting cell densities were quantified in cortex and medulla of allograft biopsies in relation to diuretic therapy in a group of 66 consecutive biopsies obtained in a surveillance program 92.9±2.6 days after transplantation graded according to the Banff classification.

Results

An elevated NaCl but not urea concentration decreased human primary blood CD8⁺ T cell and effector marker KLRG1⁺ cell numbers. Urea inhibited CD8⁺ T cell proliferation. NaCl, but not urea, increased apoptotic CD8⁺ T cell death. In human kidneys in vivo, in tissues obtained during loop diuretic therapy that depletes the concentration gradient, cytotoxic CD8⁺ T cells were significantly more abundant. This observation also was maintained if only tissues without histological rejection were included to the analysis. Ex-vivo primary renal cortical, but not medullary T cell survival and response was impaired by environmental NaCl.

Conclusion

Our data introduce a role of kidney medullary range NaCl and urea concentrations for CD8⁺ T cell proliferation, survival and response. This is amenable to therapeutic interventions, which remain to be studied prospectively.

Funding

• Government Support – Non-U.S.