ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on X

Kidney Week

Please note that you are viewing an archived section from 2023 and some content may be unavailable. To unlock all content for 2023, please visit the archives.

Abstract: SA-PO415

Blocking LFA-1 Reduces Diabetic Kidney Disease in a Mouse Model of Type 2 Diabetes

Session Information

Category: Diabetic Kidney Disease

  • 701 Diabetic Kidney Disease: Basic


  • Cervantes, Jocelyn, University of Washington, Seattle, Washington, United States
  • Kramer, Farah, University of Washington, Seattle, Washington, United States
  • Kanter, Jenny E., University of Washington, Seattle, Washington, United States

Diabetic dyslipidemia, characterized by elevated triglyceride-rich lipoproteins (TRLs), is a known risk factor for renal function decline. At the same time, macrophage accumulation has been observed in kidney biopsies in individuals with diabetic kidney disease (DKD). Thus, we wanted to test the role of monocyte infiltration in the progression of diabetic kidney disease.


BTBR wildtype (WT) and leptin-deficient (OB; diabetic) mice with LDL receptor deficiency were maintained on a high-fat diet to promote human-like dyslipidemia.


OB diabetic mice with human-like dyslipidemia have a dramatic increase in DKD (glomerular size: 4164 ± 385 μm2 in WT mice and 8299 ± 622 in OB mice, albuminuria to creatinine ratio: 374.3 ± 71.0 μg/mg in WT mice and 4648 ± 1021 in OB mice). This was associated with increased monocyte recruitment, glomerular macrophage accumulation, and glomerular foam cells, suggesting a pathogenic role for macrophages in DKD progression (Mac-2 positive cells per glomerulus in WT mice was 1.0 ± 0.2 and 6.8 ± 0.6 in OB mice). Notably, diabetes increased the expression of the adhesion molecule ICAM-1 in the glomerulus and in isolated kidney endothelial cells (ICAM-1 μm2 per glomerulus in WT mice was 11.2 ± 3.1 and 54.7 ± 15.0 in OB mice) with a concomitant increase in monocyte binding partner, LFA-1. To test if LFA-1 facilitates monocyte infiltration into the kidney glomerulus and exacerbates DKD injury, we treated WT and OB mice with a control blocking antibody or an anti-LFA-1 blocking antibody (900 μg/week) for 4 weeks. Blocking LFA-1 did not affect blood glucose or lipid levels but resulted in a reduction in glomerular hypertrophy and urinary albuminuria in OB mice (glomerular hypertrophy: 6209 ± 346 μm2 in control antibody-treated OB mice compared to LFA-1 treated OB mice 4844 ± 251, albumin to creatinine ratio: 1084 ± 157 μg/mg in control-treated OB mice compared to anti-LFA-1 treated OB mice 546 ± 164.0).


Together, these data suggest that diabetes promotes monocyte infiltration into the glomerulus, which in turn contributes to DKD.


  • NIDDK Support