Role of renal sympathetic nerve activity in volatile anesthesia's effect on renal excretory function

Regulation of fluid balance is pivotal during surgery and anesthesia and affects patient morbidity, mortality, and hospital length of stay. Retention of sodium and water is known to occur during surgery but the mechanisms are poorly defined. In this study, we explore how the volatile anesthetic sevoflurane influences renal function by affecting renal sympathetic nerve activity (RSNA). Our results demonstrate that sevoflurane induces renal sodium and water retention during pediatric anesthesia in association with elevated plasma concentration of renin but not arginine–vasopressin. The mechanisms are further explored in conscious and anesthetized ewes where we show that RSNA is increased by sevoflurane compared with when conscious. This is accompanied by renal sodium and water retention and decreased renal blood flow (RBF). Finally, we demonstrate that renal denervation normalizes renal excretory function and improves RBF during sevoflurane anesthesia in sheep. Taken together, this study describes a novel role of the renal sympathetic nerves in regulating renal function and blood flow during sevoflurane anesthesia

Pathophysiology of renal tubular obstruction: Therapeutic role of synthetic RGD peptides in acute renal failure

In his famous work On the Natural Faculties, Galen of Pergamum introduced the idea of “attraction” [δλκηζ] as the principal mode of kidney function: the attraction of blood to the kidney, he claimed, results in the production of urine [1]. Though unproven in Galen's ancient times and entirely rejected by the later generations as a mechanistic explanation of renal function, the concept of attraction has not only survived, albeit in a modified form, but has become one of the cornerstone principles of modern physiology and our current understanding of the pathophysiology of processes as diverse as platelet aggregation, metastases, immune recognition and wound healing, to name a few, all of which are governed by adhesion molecules. Here we review the role of adhesion molecules in the pathophysiology of tubular obstruction, focusing on the integrins and their newly recognized function in it.The importance of renal tubular obstruction in the pathogenesis of acute renal failure (ARF) was brought to center stage by a series of elegant microdissection studies by Oliver, MacDowell and Tracy [2]. Using servo-null pressure monitoring of the proximal tubular pressure in diverse models of ARF, investigators have provided solid evidence for the elevation in hydrostatic intratubular pressure concomitant with the unchanged stop-flow and estimated glomerular capillary pressures, further confirming the tubulo-obstructive component of this syndrome [3–5]. It has been concluded, therefore, that tubular obstruction and elevated proximal tubular pressure equilibrate glomerular filtration pressure, thus leading to the persisting oliguria. Necrotic epithelial cells have been postulated to provide the matrix for casts obstructing the tubular lumen. Recent findings of viable epithelial cells in the urine of patients and experimental animals with ARF, however, cast doubt on the postulated schema and suggest the possibility of epithelial cell detachment as an important contributor to the development of tubular obstruction [6–8].In the following discussion we develop this theme, providing data on the possible mechanism(s) of tubular obstruction in ischemic ARF, and on the therapeutic strategies in and benefits of inhibiting tubular obstruction, and suggest some future directions of this fledgling field of investigations

Renal Denervation Update From the International Sympathetic Nervous System Summit:JACC State-of-the-Art Review

Three recent renal denervation studies in both drug-naïve and drug-treated hypertensive patients demonstrated a significant reduction of ambulatory blood pressure compared with respective sham control groups. Improved trial design, selection of relevant patient cohorts, and optimized interventional procedures have likely contributed to these positive findings. However, substantial variability in the blood pressure response to renal denervation can still be observed and remains a challenging and important problem. The International Sympathetic Nervous System Summit was convened to bring together experts in both experimental and clinical medicine to discuss the current evidence base, novel developments in our understanding of neural interplay, procedural aspects, monitoring of technical success, and others. Identification of relevant trends in the field and initiation of tailored and combined experimental and clinical research efforts will help to address remaining questions and provide much-needed evidence to guide clinical use of renal denervation for hypertension treatment and other potential indications