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.

Abstract

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 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 mmHg). The defect induced by lithium 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 mmHg). 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 mmHg). Amphotericin

Effect of selective aldosterone deficiency on acidification in nephron segments of the rat inner medulla.

“…Second, in the latter study (36) systemic respiratory alkalosis (Paco2 = 27 mmHg) was present. Third, urinary Pco2, even in sham controls receiving bicarbonate, was much lower in the previous study (53 mmHg) than that routinely observed in bicarbonate loaded control rats in our laboratory (100-120 mmHg) (14) (27). Compatible with our data, however, Robson et al (37) have reported that mineralocorticoid (9-afluorohydrocortisone) administration to adrenal intact rabbits increased the U-B Pco2 relative to controls undergoing a similar bicarbonate diuresis.…”

“…Based on these previous findings we would predict that disequilibrium pH would also be reduced or obliterated in rats with aldosterone deficiency, although, such data are not available at present. In the defects associated with the postobstructed kidney and amiloride, a minimal urine pH cannot be achieved either with an acute acid load alone, or after superimposed sodium sulfate infusion (27). Since a normal minimal urine pH can be achieved in SAD in association with low buffer excretion, this finding in conjunction with the findings in the present study implies that a direct effect of aldosterone on H+ secretion may be quantitatively more important than indirect effects mediated through voltage changes.…”

“…In these latter experimental models of defective acidification in the "distal" nephron, disequilibrium pH (a direct measure of H+ secretion) was also shown to be reduced in the papillary collecting duct (27). Based on these previous findings we would predict that disequilibrium pH would also be reduced or obliterated in rats with aldosterone deficiency, although, such data are not available at present.…”

“…A reduction in papillary Pco2 relative to controls during bicarbonate loading has also been observed after chronic administration ofeither amiloride or lithium, and after unilateral ureteral obstruction (27). In these latter experimental models of defective acidification in the "distal" nephron, disequilibrium pH (a direct measure of H+ secretion) was also shown to be reduced in the papillary collecting duct (27).…”

Regulation of nephron acidification by corticosteroids

“…Urine pCO 2 may have a number of origins, including delayed dehydration of carbonic acid, trapping of CO 2 in the countercurrent system, mixture of urines at different pH values from different nephrons, and ampholyte properties of bicarbonate buffer, among others (16). However, U-B pCO 2 has also been considered to represent the magnitude of distal nephron (mostly collecting duct) H + -ion secretion at high urinary bicarbonate concentrations (17,18). In these experiments, corticosterone (B), aldosterone (A) or 18-OH corticosterone (18-OH-B) was given to ADX rats in order to investigate the role of each of them in supporting the normal rate of renal tubule H + secretion.…”