Since heart rate (HR) is a cardiovascular risk factor and a marker of sympathetic activity, we tested the predictive value of HR for progression to kidney failure in a well characterized cohort of 759 patients with stage 2-5 CKD followed up for 29 ± 11 months. Overall, a total of 244 patients had renal events. In an unadjusted analysis by age tertiles the predictive value of HR for renal events was apparent only in patients in the third age tertile (older than 68 years) but not in those in the first two tertiles indicating effect modification by age of the HR--progression to kidney failure relationship. In a multiple Cox regression model adjusting for potential confounders, a 5 beats/min increase in HR entailed a 16% risk excess (Hazard Ratio = 1.16, P = .004) for renal events in patients in the third age tertile but no excess risk for the same events in patients in the first two tertiles. A statistically significant interaction (P<.001) was also found between age and the risk for renal events associated with proteinuria. Heart rate is an independent age-dependent effect modifier for progression to kidney failure in CKD patients. This observation generates the hypothesis that high sympathetic activity is a relevant risk factor for adverse renal outcomes in elderly patients with CKD.