Abstract: TH-PO748
Autoimmunity and Altered Renal Function Precede the Development of Hypertension in Female Mice with Lupus
Session Information
- Women's Health and Kidney Diseases
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Women’s Health and Kidney Diseases
- 2000 Women’s Health and Kidney Diseases
Authors
- Dent, Elena L., University of Mississippi Medical Center, Jackson, Mississippi, United States
- Ryan, Michael J., University of Mississippi Medical Center, Jackson, Mississippi, United States
Background
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by circulating autoantibodies, hypertension, and renal injury. Kidney involvement is common in SLE and renal dysfunction is evident in patients with active renal disease, yet little is known about early changes in renal function that may contribute to the pathogenesis of hypertension. We hypothesize that the loss of immunological tolerance and subsequent production of autoantibodies in SLE leads to impaired renal hemodynamic function that precedes the development hypertension.
Methods
Female NZBWF1 mice, an established experimental model of SLE, and female NZW (control) mice were instrumented with carotid artery and jugular vein catheters to determine mean arterial pressure (MAP) and glomerular filtration rate (GFR) respectively at ages 15, 20, 24, 28, 31, and 34 weeks. MAP was measured in conscious, freely-moving mice. GFR was measured by the clearance of fluorescein isothiocyanate-inulin (FITC-inulin) after achieving steady state through continuous infusion for five hours.
Results
Circulating autoantibodies are signifcantly increased by 28 weeks of age in mice with SLE (P = 0.0135), whereas autoantibodies are unchanged in control mice (Figure 1). GFR increases at 28 weeks of age followed by a significant decline by 34 weeks of age (P = 0.0127, P = <0.0001) compared to 34 and 15 weeks of age respectively, in SLE mice. GFR is increased in control mice by 28 weeks of age (P = 0.002) and remains unchanged at other time points (Figure 2).
Conclusion
These data suggest that changes in renal hemodynamic function occur in female SLE mice prior to changes in MAP suggesting a mechanistic role for autoimmunity to directly impair renal hemodynamic function and promote the development of hypertension.
Funding
- Veterans Affairs Support