GLOMERULAR HEMODYNAMICS AND EICOSANOID SYNTHESIS IN A RAT MODEL OF IGA NEPHROPATHY

We sought to study glomerular pathophysiology in a model of IgA nephropathy (IgAN). Preliminary experiments with oral immunization indicated that Lewis rats had higher IgA levels and IgA/IgG ratios than Wistar, Fischer or Sprague-Dawley rats. Six groups of Lewis rats were studied: four continuously orally immunized for eight weeks with bovine gamma globulin (BGG) in the drinking water, the other two non-immunized controls. Groups of immunized rats were treated with a thromboxane receptor antagonist (SQ 29,485) and/or a thromboxane synthase inhibitor (UK 38,485). After systemic challenge, microscopic hematuria was present in 84% of immunized rats not given anti-thromboxane drugs versus 18% of non-immunized rats (P < 0.01). Immunized rats showed predominantly IgA glomerular deposits with lesser IgG and C3, and produced more glomerular thromboxane than controls, but no significant increase in prostaglandin E2. Immunized rats also had reduced GFR and RPF, but not a reduced filtration fraction, compared to controls. Thromboxane synthase inhibitor diminished glomerular thromboxane and increased prostaglandin E2 in immunized rats. Anti-thromboxane therapy reduced hematuria and apparently re-established the RPF but not the GFR in immunized rats, yielding a reduced filtration fraction. We propose that increased thromboxane, in concert with mesangial contraction that is unaffected by anti-thromboxane drugs, contributes to the pathophysiology in this model of IgAN.