VALIDATION OF THE DIFFERENCE IN URINE AND BLOOD CARBON-DIOXIDE TENSION DURING BICARBONATE LOADING AS AN INDEX OF DISTAL NEPHRON ACIDIFICATION IN EXPERIMENTAL-MODELS OF DISTAL RENAL TUBULAR-ACIDOSIS

Recent classifications of the several pathophysiologic types of distal renal tubular acidosis (secretory, voltage dependent and gradient) have been based on the response of acidification parameters to a series of provocative maneuvers in vivo and in vitro. A reduction in the difference in urine and blood CO2 tension during bicarbonate loading (U-B pCO2 gradient), a widely applied parameter, has been employed as an index of reduced distal nephron proton secretion. This study was designed to test the validity of the U-B pCO2 gradient in a variety of experimental models of distal renal tubular acidosis by measuring and comparing disequilibrium pH (a direct technique to detect H+ secretion in situ) with the pCO2 (blood CO2 tension) in the papillary collecting duct of the rat in vivo during bicarbonate loading. Chronic amiloride, lithium chloride, and amphotericin-B administration, and the post-obstructed kidney models were employed. Amiloride resulted in an acidification defect which did not respond to sulfate infusion (urine pH = 6.15 .+-. 0.08), and was associated with an obliteration of the acid disequilibrium pH (-0.26 .+-. 0.05--0.08 .+-. 0.03) and reduction in papillary pCO2 (116.9 .+-. 3.2-66.9 .+-. 2.5 mm Hg). The defect induced by Li administration responded to Na2SO4 (urine pH = 5.21 .+-. 0.06) but was similar to amiloride with respect to the observed reduction in disequilibrium pH (-0.04 .+-. 0.02) and pCO2 (90.3 .+-. 3.0 mm Hg). The post-obstructed kidney model was characterized by an abnormally alkaline urine pH unresponsive to sulfate (6.59 .+-. 0.06) and a reduction in disequilibrium pH (+0.02 .+-. 0.06) and pCO2 (77.6 .+-. 3.6 mm Hg). Amphotericin-B resulted in a gradient defect as characterized by excretion of an acid urine after infusion of sodium sulfate (5.13 .+-. 0.06). Unlike other models, however, amphotericin-B was associated with a significant acid disequilibrium pH (-0.11 .+-. 0.05) and an appropriately elevated urine pCO2 (119.8 .+-. 6.4 mm Hg) which did not differ from the respective values in control rats. Thus, these findings support the use of the U-B pCO2 as a reliable means of demonstrating impaired distal nephron proton secretion in secretory and voltage-dependent forms of distal renal tubular acidosis (RTA) and supports the view that proton secretion is not impaired in gradient forms of distal RTA.