Background: Activation of the sympathetic nervous system during progressive deterioration of kidney function contributes to cardiac and renal damage. Renal denervation (RDN) can reduce blood pressure and sympathetic nervous system activity. 

Objective: This study aimed to investigate whether the beneficial effects of RDN on neuroendocrine function and kidney and cardiac function differ in the presence of glomerular or tubular renal damage. 

Methods We compared rats with renal insufficiency primarily driven by glomerular damage (obese spontaneous hypertensive rats; GloD; n=15) or chronic tubulo-interstitial disease (Sprague Dawley rats with adenine-induced chronic kidney disease; TubD; n=6). In both groups, RDN or sham operations were performed (GloD+RDN (n=15), TubD+RDN (n=6)).  Mean arterial blood pressure (MAP) was measured by radiotelemetry. Renal and left ventricular tissue was histologically analysed for sympathetic innervation using tyrosine hydroxylase staining. Fibrosis was determined using Picro-Sirius Red staining. 

Results: In GloD rats, MAP, plasma renin activity, aldosterone concentration, and creatinine were significantly increased and associated with enhanced LV interstitial fibrosis. RDN in these rats significantly reduced MAP (p=0.006), PRA (p=0.005), aldosterone (p=0.02), and creatinine levels (p=0.039), accompanied by reversal of left ventricular fibrosis (p=0.03). These beneficial effects of RDN, however, were not observed in rats with adenine-induced tubular damage. 

Conclusions: RDN prevents cardiac and kidney dysfunction in the presence of glomerular renal injury, but not in the presence of adenine-induced tubular damage. These data suggest, that glomerular renal damage, as present in patients with hypertension and diabetes, represent the most promising target for RDN in chronic kidney disease.