1. Chronically increased sympathetic nerve activity is present during chronic kidney disease (CKD); however, its role in contributing to hypertension or the progression of CKD remains poorly understood. The aim of the present study was to determine whether neonatal sympathectomy attenuates hypertension in 5/6 nephrectomized rats and affects renal structure and function in a blood pressure-independent manner. 2. We performed 5/6 nephrectomy (referred to as CKD) in both sympathetically intact and sympathectomized (injected neonatally with guanethidine; referred to as CKD + Sympath) male Sprague-Dawley rats. Sham-operated sympathetically intact and sympathectomized rats (Sham and Sham + Sympath, respectively) were used as controls. Radiotelemetry was used to monitor blood pressure throughout the 6 week duration of the study, after which renal function and histology were assessed. 3. Overall average systolic arterial pressure and final urinary protein excretion were significantly lower in CKD + Sympath compared with CKD rats (168 +/- 7 mmHg and 33 +/- 5 mg/24 h vs. 184 +/- 6 mmHg and 66 +/- 7 mg/24 h, respectively). However, the level of proteinuria in the CKD + Sympath group was reduced to a greater extent than what would be expected solely on the basis of lower blood pressure. All other indices of renal function and histology were comparable between both CKD groups. All measurements were comparable between Sham and Sham + Sympath groups. 4. In conclusion, sympathectomy attenuated hypertension by approximately one-third in 5/6 nephrectomized rats. Furthermore, sympathetic nerves to the kidney during 5/6 nephrectomy may contribute to proteinuria in a blood pressure-independent manner.