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Kidney Week

Abstract: FR-PO391

Adipose Tissue Macrophage Infiltration in CKD

Session Information

  • CKD: Mechanisms - II
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Katz-Greenberg, Goni, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States
  • Lin, Zhao, Thomas Jefferson University, Philadelphia, Pennsylvania, United States
  • Martos-Rus, Cristina, Thomas Jefferson University, Philadelphia, Pennsylvania, United States
  • Martinez Cantarin, Maria P., Thomas Jefferson University, Philadelphia, Pennsylvania, United States
Background

Patients with advanced chronic kidney disease (CKD) present higher levels of inflammatory markers, associated with significant morbidity and mortality. Increased adipose tissue macrophages (ATM) may play an important role in a state of chronic inflammation seen in CKD patients. Historically, macrophages were divided into two main phenotypes, M1 or pro-inflammatory, and M2 associated with tissue repair. The aim of this study is to examine the degree of macrophage infiltration and macrophage characteristics of adipose tissue in patients and mice models with CKD.

Methods

We studied adipose tissue from 4 pairs of control-advanced CKD patients undergoing kidney donation or transplantation the same day. Stromal vascular fractions (SVF) were isolated from subcutaneous (SCF) and visceral (VF) adipose tissue. Macrophage populations were studied by flow cytometry. In a model of advanced CKD mice, macrophage populations were studied in adipose tissue SVF and peripheral blood. The same experiment was replicated in a model of advanced CKD in IL-6 knock-out (KO) mice.

Results

Patients with CKD had higher number of macrophages in adipose tissue compared to controls [fold change 1.9 for SCF and 2.7 for VF p<0.01]. In CKD mice, there was an increase in total number of macrophages in SCF versus control [42.24% vs 5.96%; P<0.01]. SCF of CKD mice also had lower CD301-/CD11c+ macrophages [1.5% vs 16.15%; P=0.005] and higher CD301+/CD11c-macrophages versus controls [96.6% vs 71.4%; P<0.001]. No difference was seen between the CKD and controls in VF. When SVF were studied in an IL-6 KO mice CKD model, there were no differences in ATM numbers in SCF or VF. In peripheral blood and despite lower total number of leukocytes [CD45+ 10.5% vs 16%; P<0.05], CD163+, CD11c+ and CD206+ macrophages were significantly increased in CKD mice compared to controls [47% vs 27%, 4.3% vs 2.6%, and 2% vs 1.3% respectably; P<0.05 for all]. There was also a higher number of T-cell sub-populations seen in CKD mice compared to controls [CD4+ 13.6% vs 11.4% and CD8+ 7.5% vs 5.4%; p <0.001 for both].

Conclusion

In humans, there was higher macrophage infiltration in adipose tissue. This was reproduced in a mice model of CKD. The lack of increased ATM numbers in the IL-6 KO mice model, suggest IL-6 may play a role in the recruitment of macrophages to adipose tissue in advanced CKD.