Early Sympathetic Activation in the Initial Clinical Stages of Chronic Renal Failure

Abstract

Abstract-Direct and indirect indices of neuroadrenergic function have shown that end-stage renal disease is characterized by a marked sympathetic overdrive. It is unknown, however, whether this phenomenon represents a peculiar feature of end-stage renal disease or whether it is also detectable in the early clinical phases of the disease. The study has been performed in 73 hypertensive patients, of which there were 42 (age: 60.7Ϯ1.8 years, meanϮSEM) with a stable moderate chronic renal failure (mean estimated glomerular filtration rate: 40.7 mL/min per 1.73 m 2 , MDRD formula) and 31 age-matched controls with a preserved renal function. Measurements included anthropometric variables, sphygmomanometric and beat-to-beat blood pressure, heart rate (ECG), venous plasma norepinephrine (highperformance liquid chromatography), and efferent postganglionic muscle sympathetic nerve activity (microneurography, peroneal nerve). For similar anthropometric and hemodynamic values, renal failure patients displayed muscle sympathetic nerve activity values significantly and markedly greater than controls (60.0Ϯ2.1 versus 45.7Ϯ2.0 bursts per 100 heartbeats; PϽ0.001). Muscle sympathetic nerve activity showed a progressive and significant increase from the first to the fourth quartile of the estimated glomerular filtration rate values (first: 41.0Ϯ2.7; second: 51.9Ϯ1.7; third: 59.8Ϯ3.0; fourth: 61.9Ϯ3.3 bursts per 100 heartbeats), the statistical significance (PϽ0.05) between groups being maintained after adjustment for confounders. In the population as a whole, muscle sympathetic nerve activity was significantly and inversely correlated with the estimated glomerular filtration rate (rϭϪ0.59; PϽ0.0001). Thus, adrenergic activation is a phenomenon not confined to advanced renal failure but already detectable in the initial phases of the disease. The sympathetic overdrive parallels the severity of the renal failure, state and, thus, it might participate, in conjunction with other factors, at the disease progression. (Hypertension. 2011;57:846-851.) Key Words: chronic renal failure Ⅲ microneurography Ⅲ sympathetic nervous system A dvanced renal failure is accompanied by a marked activation of sympathetic cardiovascular influences, as documented by the increase in the circulating plasma levels of norepinephrine, the elevated number of sympathetic neural bursts recorded in the peroneal nerve via the microneurographic technique, and the augmented oscillations in the high-frequency band of the heart rate power spectra. [1][2][3][4][5][6][7][8][9][10][11][12][13] Whether the sympathetic activation also characterizes the earlier clinical phases of the renal failure state is not clear, however. This is because in the few studies performed so far in patients with mild renal disease, the population sample was small, and the plasma levels of norepinephrine showed inconsistent changes. 11,12 Furthermore, in the 2 previously published studies that assessed sympathetic nerve traffic via microneurography, approximately half of the patients evaluated ...

Sympathetic Activation in Chronic Kidney Disease

“…8 In addition to the reduction in sympathetic nerve activity, there is evidence for a blood pressure-independent renoprotective effect of the drug as demonstrated by a reduced decline of eGFR in CKD patients when compared with an equipotent dose of a calcium channel blocker 8 and by a favorable effect on microalbuminuria in the absence of blood pressure changes in patients with type 1 diabetes mellitus and optimal blood pressure control. 9 Importantly and consistent with the data presented by Grassi et al 6 in this issue, a previous study also found that sympathetic activity remains elevated in CKD patients despite adequate The kidneys are strategically positioned to be both origin and target of increased sympathetic activation. Various forms of renal injury can stimulate afferent sensory nerve fiber signaling to central integrative structures in the brain (1).…”

Renal Denervation in Moderate to Severe CKD

“…Sympathetic activity is already elevated in early phases of chronic renal failure, and the magnitude of sympathetic overdrive increases with disease progression. 22 Evidence also suggests that the afferent sensory renal nerves in response to intra-renal injury have an excitatory influence on central sympathetic outflow. 10 Consequently, renal sympathetic efferent and afferent nerves exert a powerful influence on initiation, development, and maintenance of elevated systemic BP commonly present in patients with renal failure.…”

Vascular and Renal Hemodynamic Changes after Renal Denervation

“…A meta-analysis of long-term trials has shown a linear correlation between deterioration in renal function over time and BP (24). Moreover, muscle sympathetic nerve activity (assessed by microneurography) was significantly and inversely correlated with eGFR in hypertensive patients (25). In the Symplicity HTN-2 trial renal function (assessed by serum creatinine, eGFR [MDRD], and cystatin C concentrations) did not change from baseline to 6 months of RDN (13).…”