Abstract P147: Changes in Renal Function Precede the Development of Hypertension in Female Mice With Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by inflammation, hypertension, renal injury, and cardiovascular disease. Kidney involvement is common to patients with SLE and renal hemodynamic dysfunction is evident in patients with active renal disease. However, little is known about early changes in renal hemodynamic function that may contribute to the pathogenesis of hypertension during SLE. 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. Female NZBWF1 (SLE) and female NZW (control) mice were instrumented with carotid artery and jugular vein catheters to determine 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. 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 the mice with SLE. GFR is increased in control mice by 28 weeks of age (P = 0.002) and remains unchanged at other time points. Compared with control mice, female mice with SLE have higher MAP by 34 weeks of age (P = <0.0001). These data suggest that changes in renal hemodynamic function occur in female SLE mice prior to changes in MAP suggesting an important mechanistic role for autoimmunity to directly impair renal hemodynamic function and promote the development of hypertension.