Elevation of intrarenal adenosine by maleic acid decreases GFR and renin release

Maleic acid administration produces a defect in tubular reabsorption resembling that seen in the Fanconi syndrome and also causes a decrease in glomerular filtration rate (GFR). The mechanism by which maleic acid alters renal function is uncertain, though the tubular defect is known to be associated with decreased ATP levels. Because of this alteration in nucleotide metabolism the present study was undertaken to determine the role of elevated endogenous adenosine in mediating the maleic acid-induced changes in renal function. Since the renal effects of exogenous adenosine are enhanced by sodium-depletion and attenuated by sodium-loading, the present study compared the time course of the effects of maleic acid on renal function in 10 dogs maintained on a low sodium diet, and 10 dogs maintained on a high sodium diet. In addition, we examined the effect of maleic acid on adenosine levels in renal venous plasma, on the urinary excretion of adenosine, and the effect of the adenosine antagonist, theophylline, on the maleic acid-induced changes in renal function. After 100 min of the maleic acid, GFR was decreased significantly by 55±4% of control in the sodium-depleted dogs, and by 39±4% of control in the sodium-loaded dogs. In the sodium-depleted dogs, renin release was also significantly depressed (12±8% of control) during the infusion of maleic acid. The fractional excretion of sodium was significantly increased in both groups. The renal venous concentration of adenosine and the urinary excretion of adenosine were both significantly increased during maleic acid. In addition, the infusion of theophylline returned GFR to 78±8% of control in the sodium-depleted dogs and 97±2% of control in the sodium-loaded dogs and returned renin release to 61±10% of control, but did not attenuate the maleic acid-induced increase in fractional sodium excretion. These data suggest that endogenous adenosine may be involved in the decrease in GFR, but not the decrease in tubular transport, seen with maleic acid infusion.