BACKGROUND Sympathetic hyperactivity has been associated with adverse clinical outcome and is common in patients with chronic kidney disease (CKD). Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) have been shown to reduce sympathetic activity in CKD patients. The present study was performed to investigate whether sympathetic hyperactivity was related to clinical outcome in CKD patients treated with ACEi or ARB. METHODS Muscle sympathetic nerve activity (MSNA) was measured in 66 nondiabetic patients (70% men) with CKD, median age 47 years (range 21-65) and mean estimated glomerular filtration rate (eGFR) 39+/-29 ml/min per 1.73 m2. Patients were followed up for a median 78 months (range 6-123), and subsequent clinical events were recorded. RESULTS During follow-up, average blood pressure was 131+/-11 mm Hg systolic and 83+/-6 mm Hg diastolic. Twenty-one events (4 deaths and 17 nonfatal cardiovascular events) occurred in 16 patients. MSNA among the group with events was 40+/-18 bursts/min, compared with 30+/-11 bursts/min in those with no events (p=0.009). An increase of MSNA of 10 bursts/min was related to an increased risk of an event (hazard ratio=1.6; 95% confidence interval, 1.0-2.8; p=0.08), independent of GFR and blood pressure. Age attenuated this relation. CONCLUSION Sympathetic hyperactivity was associated with the composite of all-cause mortality and nonfatal cardiovascular events in CKD patients, despite treatment with ACEi or ARB. Further studies to investigate potential effects of additional sympatholytic therapy in these patients are warrented.