In patients with severe aortic valve stenosis (valve area <or= 1 cm(2), AS), the prevalence and the prognostic impact of comorbidities is unknown. Fifty-eight patients with severe AS (mean aortic valve area 0.8 +/- 0.2 cm(2)), who underwent cardiac catheterization and 2-D/Doppler echocardiography, were prospectively enrolled. The glomerular filtration rate (eGFR) was estimated using the abbreviated Modification of Diet in Renal Disease Study equation. Death from a cardiac cause was defined as study end point. Coronary artery disease was present in 33 patients (57%). Subsequently, 43 patients (77%) underwent aortic valve replacement. During a follow-up of 485 +/- 336 days, 11 patients suffered a cardiac death. Survivors and non-survivors did not differ with respect the prevalence of coronary artery disease, invasive hemodynamic measurements or echocardiographic variables of systolic/diastolic function. Non-survivors were in a poorer NYHA functional class (3.2 +/- 0.3 vs 2.4+/-0.8, p = 0.002), had a lower eGFR (33.4 +/- 15.5 ml/min/1.73 m(2) vs 49.1 +/- 15.6 ml/min/1.73m(2), p = 0.004), a higher prevalence of diabetes mellitus (73% vs. 22%, p = 0.0001) and a lower serum hemoglobin level (11.6 +/- 2.1 vs 13.0 +/- 1.5 g/dL, p = 0.017). By multivariate Cox analysis, NYHA class (hazard ratio: 6.17, p = 0.013) and eGFR (hazard ratio 0.95, p = 0.04) were independent prognostic predictors. In patients with eGFR < 41.8 ml/min/1.73 m(2) (cut-off value derived from ROC analysis, area under the curve: 0.78 +/- 0.08), outcome was markedly poorer as compared to patients with eGFR > 41.8 ml/min/1.73 m(2) (event-free survival rate of 38% vs 93%, p = 0.004). Thus, in patients with severe AS, comorbidities are frequent, and particularly kidney disease significantly impacts longterm outcome.