**4.2 Adrenoceptor-autoantibodies and their impact on kidney function**

The possible clinical implications of adrenoceptor-directed autoimmunity have gained increasing interest in human heart disease. By contrast, the renal effects of functionally active adrenoceptor-aabs have been almost neglected. Previous immuno-histologic studies on the rat kidney strongly suggest that functionally stimulating adrenoceptor aabs are capable of modulating the secretion of renin from the juxtaglomerular cells *via* renal beta1- AR and, also, to increase the sodium-reabsorption in the distal tubulus (Boivin et al., 2001). Thus, through renal beta1-AR-mediated activation of the renin-angiotensin-aldosteronesystem (RAAS) and/or augmentation of the circulating blood volume such aabs might contribute to further worsening of the prognosis of antibody-positive heart failure patients.

To assess the impact of adrenoceptor-aabs on kidney function (and clinical outcome), a number of pre-specified renal functional parameters will be sequentially determined in all ETiCS patients (e.g. serum *versus* urine creatinine/sodium/pH; glomerular filtration rate (GFR), urinary protein excretion). Primary endpoints are the relationship between antibodytitres and renal function at baseline and the "time to first cardiovascular event", adjusted for renal function. Secondary endpoints include the change in renal function dependent on the formation and conversion rates (clearance/persistence) of adrenoceptor-aabs.

These data might furnish a rationale for the development of novel therapeutic strategies to protect the kidney(s) from functional adrenoceptor-aabs in aab-positive heart failure patients.
