Regulation of renal adenosine excretion in humans--role of sodium and fluid homeostasis.
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 (EADO) may therefore provide a sensitive marker of renal functional impairment in allograft rejection and kidney disease. To provide a basis for evaluation of EADO in clinical settings, we investigated, in an intra-individual, crossover clinical trial the physiological variability and regulation of EADO 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. EADO was determined in 24 h urine collections and during clearance investigations.


RESULTS
Mean EADO in humans was 3.2+/-0.2 micromol/ 24 h during euvolaemia and normal sodium intake. A weak correlation was found between sodium load and EADO. In clearance experiments, variation in EADO was <1.3-fold, despite profound alterations in sodium intake. EADO was independent of urinary flow rate. Renal haemodynamics were not significantly altered by dietary regimen or by acute volume load.


CONCLUSIONS
In summary, the physiological variability of EADO is remarkably small in humans. We demonstrate that even profound alterations in sodium and fluid homeostasis do not significantly affect EADO. These data provide a basis for evaluation of elevated EADO as a marker of renal injury in various clinical settings.
Heyne
Nils
N
Department of Internal Medicine III, Section of Nephrology and Hypertension, University of Tübingen, Germany. nils.heyne@med.uni-tuebingen.de
Benöhr
Peter
P
Mühlbauer
Bernd
B
Delabar
Ursula
U
Risler
Teut
T
Osswald
Hartmut
H
D000241:Adenosine / Q000652:urine*; D000328:Adult; D018592:Cross-Over Studies; D005260:Female; D006439:Hemodynamics; D006706:Homeostasis; D006801:Humans; D007444:Inulin / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008297:Male; D009318:Natriuresis / Q000502:physiology*; D012965:Sodium Chloride / Q000008:administration & dosage / Q000378:metabolism; D012982:Sodium, Dietary / Q000008:administration & dosage / Q000378:metabolism; D010130:p-Aminohippuric Acid / Q000378:metabolism
D012982:Sodium, Dietary; D012965:Sodium Chloride; D007444:Inulin; D000241:Adenosine; D010130:p-Aminohippuric Acid