Renalase is a recently described enzyme secreted by the kidney into both plasma and urine, where it was suggested to degrade catecholamines contributing to blood pressure control. While there is a controversy regarding the relationship between renal function and plasma renalase levels, there is virtually no data in humans on plasma renalase activity as well as on both urine renalase levels and activity. We prospectively examined the time course of plasma and urine renalase levels and activity in 26 end-stage renal disease (ESRD) patients receiving a cadaver kidney transplant (cadaver kidney recipients [CKR]) before surgery and during the recovery of renal function up to day 90 post transplant. The relationship with sympathetic and renal dopaminergic activities was also evaluated. The recovery of renal function in CKR closely predicted decreases in plasma renalase levels ( r = 0.88; P < 0.0001), urine renalase levels ( r = 0.75; P < 0.0001) and urine renalase activity ( r = 0.56; P < 0.03), but did not predict changes in plasma renalase activity ( r = −0.02; NS). Plasma norepinephrine levels positively correlated with plasma renalase levels ( r = 0.64, P < 0.002) as well as with urine renalase levels and activity ( r = 0.47 P < 0.02; r = 0.71, P < 0.0005, respectively) and negatively correlated with plasma renalase activity ( r = −0.57, P < 0.002). By contrast, plasma epinephrine levels positively correlated with plasma renalase activity ( r = 0.67, P < 0.0001) and negatively correlated with plasma renalase levels ( r = −0.62, P < 0.003). A significant negative relationship was observed between urine dopamine output and urine renalase levels ( r = −0.48; P < 0.03) but not with urine renalase activity ( r = −0.33, NS). We conclude that plasma and urine renalase levels closely depend on renal function and sympathetic nervous system activity. It is suggested that epinephrine-mediated activation of circulating renalase may occur in renal transplant recipients with good recovery of renal function. The increase in plasma renalase activity observed in ESRD patients and renal transplant recipients can be explained on the basis of reduced inhibition of the circulating enzyme.