Regulation of renal adenosine excretion in humans--role of sodium and fluid homeostasis

Abstract

Background. Adenosine is a vasoactive metabolite of ATP hydrolysis that is involved in the regulation of renal haemodynamics, tubular reabsorption and renin release. Elevated tissue levels are found under conditions of increased metabolic load, ischaemia or renal injury. Urinary adenosine excretion (E ADO ) may therefore provide a sensitive marker of renal functional impairment in allograft rejection and kidney disease. To provide a basis for evaluation of E ADO in clinical settings, we investigated, in an intra-individual, crossover clinical trial the physiological variability and regulation of E ADO in response to altered sodium and fluid balance. Methods. Twelve healthy volunteers were randomized to normal (ad libitum), low (<5 g/day) or high (supplementation of 100 mg/kg/day) sodium chloride diets for 8 days prior to assessment of renal haemodynamics and tubular function in standard clearance investigations. Following baseline periods, fluid homeostasis was altered independently by acute oral water load. E ADO was determined in 24 h urine collections and during clearance investigations. Results. Mean E ADO in humans was 3.2±0.2 mmol/ 24 h during euvolaemia and normal sodium intake. A weak correlation was found between sodium load and E ADO . In clearance experiments, variation in E ADO was <1.3-fold, despite profound alterations in sodium intake. E ADO was independent of urinary flow rate. Renal haemodynamics were not significantly altered by dietary regimen or by acute volume load. Conclusion. In summary, the physiological variability of E ADO is remarkably small in humans. We demonstrate that even profound alterations in sodium and fluid homeostasis do not significantly affect E ADO . These data provide a basis for evaluation of elevated E ADO as a marker of renal injury in various clinical settings.

The Extracellular cAMP-Adenosine Pathway Significantly Contributes to the in Vivo Production of Adenosine

“…In addition, the fact that DPSPX did not significantly affect cAMP excretion but did reduce the ratio of adenosine to cAMP excretion argues strongly that the effects of DPSPX were not merely secondary to changes in urine volume or renal excretory function. Consistent with this conclusion, Heyne et al (2004) report that urine volume and sodium excretion have little if any effect on the urinary excretion of adenosine.…”

“…We used urinary adenosine as a marker for total body adenosine production for two reasons. First, under normal physiological conditions, urinary adenosine is derived in part from filtered adenosine that escapes uptake and metabolism by tubular epithelial cells and in part from renal tubular production of adenosine (Thompson et al, 1985;Heyne et al, 2004). Second, plasma, but not urinary, adenosine measurements are fraught with technical problems that give rise to misleading results because of rapid uptake and metabolism by cells in whole blood and because of rapid synthesis of adenosine in whole blood.…”

Early Renal Injury Induced by Caffeine Consumption in Obese, Diabetic ZSF1Rats

“…Currently, the physiological and pathophysiological significance of renal adenosine excretion is not clear. However, it seems that urinary adenosine excretion (normalized by GFR) is quite constant both under basal conditions and salt loading, [37,38] and, therefore, augmented urinary adenosine excretion might reflect increased renal adenosine production. In this regard, enhanced renal adenosine excretion occurs during acute renal injury, [39] and kidneys from diabetic rats are not only more sensitive to renal vascular and growth inhibitory effects of adenosine, but also have a greater capacity to produce and maintain higher extracellular concentrations of adenosine.…”

A metabolomics approach using juvenile cystic mice to identify urinary biomarkers and altered pathways in polycystic kidney disease

“…7) has been proposed as a possible marker of renal injury (15), although it has not been reported in PKD. However, cAMP has been thoroughly implicated in PKD cyst progression in human disease as well as in animal models, and there are novel therapeutic approaches based on attenuating the increased levels of cAMP, which can occur primarily as a result of low intracellular calcium due to calcium channel defects seen in ADPKD.…”