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. 1974 Mar;53(3):669–677. doi: 10.1172/JCI107604

Studies on the Pathogenesis of Type I (Distal) Renal Tubular Acidosis as Revealed by the Urinary Pco2 Tensions

M L Halperin 1,2, M B Goldstein 1,2, A Haig 1,2, M D Johnson 1,2, B J Stinebaugh 1,2
PMCID: PMC333046  PMID: 4812435

Abstract

This study was designed to investigate the pathogenesis of type I (distal) renal tubular acidosis.

Urinary and blood Pco2 tensions were determined when the pH of the urine was equal to or exceeded the corresponding blood pH. This provided an indication of net hydrogen ion secretion in the distal nephron. In 16 normal subjects, the Pco2 of the urine exceeded blood values (U-B Pco2) by 32.7±3.1 mm Hg. In contrast, the urinary Pco2 tensions in 10 patients with type I (distal) renal tubular acidosis were not significantly greater than blood values (U-B Pco2 = 2.0±2.2 mm Hg). These results indicate that type I (distal) renal tubular acidosis is caused by failure of the cells of the distal nephron to secrete hydrogen ions rather than to gradient-limited hydrogen ion addition to the urine. This is suggested by the fact that urinary Pco2 levels should be higher than blood Pco2 levels when hydrogen ions are secreted into urine containing bicarbonate in the distal nephron and they were not in this study despite the presence of a favorable hydrogen ion gradient (tubular fluid pH exceeded blood pH).

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. CLAPP J. R., RECTOR F. C., Jr, SELDIN D. W. Effect of unreabsorbed anions on proximal and distal transtubular potentials in rats. Am J Physiol. 1962 Apr;202:781–786. doi: 10.1152/ajplegacy.1962.202.4.781. [DOI] [PubMed] [Google Scholar]
  2. FLEISHMAN S. J., SENIOR B., SUZMAN M. M. Renal tubular acidosis. The role of defective renal tubular sodium reabsorption and secondary hyperaldosteronism in its pathogenesis. Arch Intern Med. 1959 Oct;104:613–618. [PubMed] [Google Scholar]
  3. GOTTSCHALK C. W., LASSITER W. E., MYLLE M. Localization of urine acidification in the mammalian kidney. Am J Physiol. 1960 Mar;198:581–585. doi: 10.1152/ajplegacy.1960.198.3.581. [DOI] [PubMed] [Google Scholar]
  4. Gill J. R., Jr, Bell N. H., Bartter F. C. Impaired conservation of sodium and potassium in renal tubular acidosis and its correction by buffer anions. Clin Sci. 1967 Dec;33(3):577–592. [PubMed] [Google Scholar]
  5. Györy A. Z., Edwards K. D. Renal tubular acidosis. A family with an autosomal dominant genetic defect in renal hydrogen ion transport, with proximal tubular and collecting duct dysfunction and increased metabolism of citrate and ammonia. Am J Med. 1968 Jul;45(1):43–62. doi: 10.1016/0002-9343(68)90006-5. [DOI] [PubMed] [Google Scholar]
  6. Hills A. G., Reid E. L. PCO2 and PNH3 in mammalian kidney and urinary tract related to urine pH and flow. Am J Physiol. 1970 Aug;219(2):423–434. doi: 10.1152/ajplegacy.1970.219.2.423. [DOI] [PubMed] [Google Scholar]
  7. KENNEDY T. J., Jr, ORLOFF J., BERLINER R. W. Significance of carbon dioxide tension in urine. Am J Physiol. 1952 Jun;169(3):596–608. doi: 10.1152/ajplegacy.1952.169.3.596. [DOI] [PubMed] [Google Scholar]
  8. Kurtzman N. A., White M. G., Rogers P. W. Aldosterone deficiency and renal bicarbonate reabsorption. J Lab Clin Med. 1971 Jun;77(6):931–940. [PubMed] [Google Scholar]
  9. Malnic G., De Mello Aires M., Giebisch G. Micropuncture study of renal tubular hydrogen ion transport in the rat. Am J Physiol. 1972 Jan;222(1):147–158. doi: 10.1152/ajplegacy.1972.222.1.147. [DOI] [PubMed] [Google Scholar]
  10. Malnic G., Giebisch G. Symposium on acid-base homeostasis. Mechanism of renal hydrogenion secretion. Kidney Int. 1972 May;1(5):280–296. doi: 10.1038/ki.1972.41. [DOI] [PubMed] [Google Scholar]
  11. Maren T. H. Carbonic anhydrase: chemistry, physiology, and inhibition. Physiol Rev. 1967 Oct;47(4):595–781. doi: 10.1152/physrev.1967.47.4.595. [DOI] [PubMed] [Google Scholar]
  12. McSherry E., Sebastian A., Morris R. C., Jr Renal tubular acidosis in infants: the several kinds, including bicarbonate-wasting, classic renal tubular acidosis. J Clin Invest. 1972 Mar;51(3):499–514. doi: 10.1172/JCI106838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Morris R. C., Jr, McSherry E. Symposium on acid-base homeostasis. Renal acidosis. Kidney Int. 1972 May;1(5):322–340. doi: 10.1038/ki.1972.44. [DOI] [PubMed] [Google Scholar]
  14. Morris R. C., Jr Renal tubular acidosis. Mechanisms, classification and implications. N Engl J Med. 1969 Dec 18;281(25):1405–1413. doi: 10.1056/NEJM196912182812508. [DOI] [PubMed] [Google Scholar]
  15. Morris R. C., Piel C. F., Audioun E. Renal tubular acidosis. Effects of sodium phosphate and sulfate on renal acidification in two patients with renal tubular acidosis. Pediatrics. 1965 Dec;36(6):899–904. [PubMed] [Google Scholar]
  16. OCHWADT B. K., PITTS R. F. Effects of intravenous infusion of carbonic anhydrase on carbon dioxide tension of alkaline urine. Am J Physiol. 1956 May;185(2):426–429. doi: 10.1152/ajplegacy.1956.185.2.426. [DOI] [PubMed] [Google Scholar]
  17. PORTWOOD R. M., SELDIN D. W., RECTOR F. C., Jr, CADE R. The relation of urinary CO2 tension to bicarbonate excretion. J Clin Invest. 1959 May;38(5):770–776. doi: 10.1172/JCI103858. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. POY R. K., WRONG O. The urinary pCO2 in renal disease. Clin Sci. 1960 Nov;19:631–639. [PubMed] [Google Scholar]
  19. Pitts R. F., Lotspeich W. D., Schiess W. A., Ayer J. L., Miner P. THE RENAL REGULATION OF ACID-BASE BALANCE IN MAN. I. THE NATURE OF THE MECHANISM FOR ACIDIFYING THE URINE. J Clin Invest. 1948 Jan;27(1):48–56. doi: 10.1172/JCI101923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. RECTOR F. C., Jr, CARTER N. W., SELDIN D. W. THE MECHANISM OF BICARBONATE REABSORPTION IN THE PROXIMAL AND DISTAL TUBULES OF THE KIDNEY. J Clin Invest. 1965 Feb;44:278–290. doi: 10.1172/JCI105142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. RECTOR F. C., Jr, PORTWOOD R. M., SELDIN D. W. Examination of the mixing hypothesis as an explanation for elevated urinary carbon dioxide tensions. Am J Physiol. 1959 Oct;197:861–864. doi: 10.1152/ajplegacy.1959.197.4.861. [DOI] [PubMed] [Google Scholar]
  22. RECTOR F. C., Jr, SELDIN D. W., ROBERTS A. D., Jr, SMITH J. S. The role of plasma CO2 tension and carbonic anhydrase activity in the renal reabsorption of bicarbonate. J Clin Invest. 1960 Nov;39:1706–1721. doi: 10.1172/JCI104193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. REID E. L., HILLS A. G. DIFFUSION OF CARBON DIOXIDE OUT OF THE DISTAL NEPHRON IN MAN DURING ANTIDIURESIS. Clin Sci. 1965 Feb;28:15–28. [PubMed] [Google Scholar]
  24. REYNOLDS T. B. Observations on the pathogenesis of renal tubular acidosis. Am J Med. 1958 Oct;25(4):503–515. doi: 10.1016/0002-9343(58)90040-8. [DOI] [PubMed] [Google Scholar]
  25. Reid E. L., Hills A. G. The effect of delayed dehydration of carbonic acid on renal bicarbonate clearance, and its significance for acid-base balance. Clin Sci. 1969 Oct;37(2):381–393. [PubMed] [Google Scholar]
  26. Rodriguez-Soriano J., Edelmann C. M., Jr Renal tubular acidosis. Annu Rev Med. 1969;20:363–382. doi: 10.1146/annurev.me.20.020169.002051. [DOI] [PubMed] [Google Scholar]
  27. SKEGGS L. T., Jr An automatic method for the determination of carbon dioxide in blood plasma. Am J Clin Pathol. 1960 Feb;33:181–185. doi: 10.1093/ajcp/33.2_ts.181. [DOI] [PubMed] [Google Scholar]
  28. SMITH L. H., Jr, SCHREINER G. E. Studies on renal hyperchloremic acidosis. J Lab Clin Med. 1954 Mar;43(3):347–358. [PubMed] [Google Scholar]
  29. Sebastian A., McSherry E., Morris R. C., Jr On the mechanism of renal potassium wasting in renal tubular acidosis associated with the Fanconi syndrome (type 2 RTA). J Clin Invest. 1971 Jan;50(1):231–243. doi: 10.1172/JCI106479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Vieira F. L., Malnic G. Hydrogen ion secretion by rat renal cortical tubules as studied by an antimony microelectrode. Am J Physiol. 1968 Apr;214(4):710–718. doi: 10.1152/ajplegacy.1968.214.4.710. [DOI] [PubMed] [Google Scholar]
  31. WRONG O., DAVIES H. E. The excretion of acid in renal disease. Q J Med. 1959 Apr;28(110):259–313. [PubMed] [Google Scholar]

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