Abstract: SA-PO717
Direct and Indirect Effects of Macrophage Compartmental Localization and Salt Concentration in the Kidney Graft
Session Information
- Pathology and Lab Medicine: Clinical
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pathology and Lab Medicine
- 1602 Pathology and Lab Medicine: Clinical
Authors
- Casper, Janis, Hannover Medical School, Hannover, Germany
- Schmitz, Jessica, Hannover Medical School, Hannover, Germany
- Braesen, Jan H., Medizinische Hochschule Hannover, Hannover, Germany
- Khalifa, Abedalrazag Ahmad, Medizinische Hochschule Hannover, Hannover, Germany
- Schmidt, Bernhard M.W., Hannover Medical School, Hannover, Germany
- Haller, Hermann G., Hannover Medical School, Hannover, Germany
- Von Vietinghoff, Sibylle, Hannover Medical School, Hannover, Germany
Background
Recent data have delineated a role for sodium chloride in immune regulation. The kidney is characterized by a marked cortico-medullary salt gradient. A better understanding of local immunoregulatory mechanisms is especially relevant in the transplanted kidney, where the balance between detrimental inflammation in rejection and beneficial inflammation for host response is frequently lost.
Methods
Primary human macrophage and tubular cell culture single and co-cultures was performed in defined sodium chloride and urea concentrations serving as osmolarity control with an without therapeutic dose calcineurin inhibitors and analyzed by flow cytometry, qPCR and microscopy. In a cohort of 112 adult renal allograft recipients, renal cortical and medullary macrophage polarization markers and MCP-1 chemokine production were analyzed by digitally assisted immunohistology of surveillance biopsies. Incidence of urinary tract infection during five years after transplantation was extracted from the records.
Results
Under defined conditions in vitro, an elevated sodium chloride concentration dose-dependently increased chemotactic cytokine MCP-1 production in human renal tubular epithelial cells and also in monocyte derived macrophages. Patients who received loop diuretic therapy, which depletes the renal cortico-medullary salt gradient, had significantly lower MCP-1 serum levels and no gradient between renal medullary and cortical MCP-1 protein, in contrast to patients without diuretic therapy, where it was significant. The renal medullary M1/M2 macrophage marker ratio decreased with increasing loop diuretic dose. Clinically, diuretic therapy significantly correlated with urinary tract infection rate in uni- and multivariable regression analysis in this cohort of renal allograft recipients.
Conclusion
Renal medullary M1/M2 macrophage marker ratio and MCP-1 gradient significantly associated with loop diuretic therapy as did urinary tract infection rate. Modulation of the renal salt gradient should be considered and further investigated in patients at a high risk of urinary tract infections.
Funding
- Government Support - Non-U.S.