Question

Explain how impaired or reduced renal function has the potential to impact the functionality of the cardiovascular system?

Answer 1

kidney functions as a sensory organ that is richly innervated with chemoreceptors and baroreceptors .These renal afferent nerves connect with centers in the brain that regulate blood pressure and central sympathetic outflow. Animal studies have highlighted the importance of the renal afferent nerves in the pathogenesis of SNS overactivity and high blood pressure in renal failure. In 5/6th nephrectomized rats, the increase in blood pressure was accompanied by increased NE turnover in the areas of the brain responsible for sympathetic regulation, including the posterior, anterior, and lateral hypothalamic nuclei and the locus ceruleus . In animal models, selective renal afferent nerve denervation can be performed with a dorsal rhizotomy, in which the dorsal roots from T10-L2 are severed, selectively denervating the renal afferent nerves while leaving the efferent nerves intact. Dorsal rhizotomy in 5/6 nephrectomized rats prevented the increase in BP and NE turnover in the posterior and lateral hypothalamic nuclei and the locus ceruleus, suggesting that renal afferent nerve activation by the diseased kidneys modulates central SNS activity in rats with chronic renal failure . Furthermore, in the phenol renal injury model of minimal renal damage without a reduction in renal function, the elevation in blood pressure is concomitant with increased NE turnover in sympathetic brain centers, and increase in renal sympathetic nerve activity A. renal afferent denervation by dorsal rhizotomy normalized blood pressure, NE turnover in the brain, and renal sympathetic nerve activity, in the phenol renal injury model. Thus, renal injury, independent of renal function, activates central SNS outflow via renal afferent nerve activation.

Human studies using direct recordings of MSNA via microneurography corroborate the findings from experimental studies. In hemodialysis patients with intact kidneys, MSNA was significantly elevated when compared to controls . However, after bilateral nephrectomies, dialysis patients had a significant reduction in MSNA to the level of controls, suggesting a role for the diseased kidneys in chronic SNS overactivation in ESRD. Similarly, restoration of renal function through kidney transplantation resulted in no change in MSNA in transplant recipients with intact native kidneys, independent of treatment with calcineurin inhibitors.However, after undergoing bilateral nephrectomies, MSNA was reduced significantly in transplant recipients to the same levels as controls, suggesting that the diseased kidneys themselves, independent of renal function, contribute to sympathetic overactivity in ESRD.

The specific factors that bind and activate the renal nerves are unknown and largely unstudied. Purported ligands include urea, and adenosine, a product of renal ischemia. Chemoreceptor activation via ischemic metabolites may cause reflex increases in SNS outflow in order to attempt to redirect blood flow away from other areas of the body, to the ischemic tissues. In a study of uninephrectomized dogs, changes in blood pressure and renal sympathetic nerve activity were measured during intrarenal infusion of adenosine, before and after renal denervation .There was a concomitant increase in blood pressure, efferent renal sympathetic nerve activity, and renal NE spillover during adenosine infusion, that was eliminated after renal afferent denervation, implicating a role for adenosine in renal nerve stimulation.