To determine the prognosis and risk factors for ischemic heart disease in chronic uremia, a cohort of 432 dialysis patients were followed prospectively from start of dialysis therapy until death or renal transplantation. Baseline demographic, clinical and echocardiographic data were obtained. After the initiation of dialysis laboratory data were collected at monthly intervals, and clinical and echocardiographic data at yearly intervals. Twenty-two percent of patients (N = 95) had either a history of angina pectoris or myocardial infarction on starting dialysis therapy. Median time to onset of heart failure was 24 months in those with ischemic heart disease on initiation of dialysis, compared to 55 months in those without (P < 0.0001). This effect was independent of age, diabetes and underlying cardiomyopathy. Median survival was 44 months in those with ischemic disease compared to 56 months in those without (P = 0.0001). This adverse impact was independent of age and diabetes mellitus but, when cardiac failure was added to the Cox's model, ischemic heart disease was no longer an independent predictor of survival. De novo ischemic heart disease, not evident on starting dialysis therapy, occurred in 41 (9%) patients. When compared to patients who never developed ischemic disease (N = 296; 69%), significant and independent predictors of de novo disease were older age (P = 0.0007), diabetes mellitus (P = 0.0001), high blood pressure during follow up on dialysis (P = 0.02) and hypoalbuminemia (P = 0.03), whereas anemia was not an independent predictor. LV mass index was 174 +/- 7 g/m2 in those who developed de novo ischemic disease compared to 155 +/- 3 g/m2 (P < 0.001) in those who did not. Concentric LV hypertrophy, LV dilation and systolic dysfunction were independent risk factors for de novo ischemic heart disease. We conclude that ischemic heart disease occurs frequently in dialysis patients, that its adverse impact is mediated through the development of heart failure, and that the most important, potentially reversible risk factors are hypertension, hypoalbuminemia, and underlying cardiomyopathy.