Although the definition of renal tubular acidosis (RTA) is simple, understanding the physiologic basis underlying the various types of this clinical entity is much more difficult. The pathophysiology of this disorder is reviewed using the normal acid-base functions of the involved segments of the nephron as a guide to understanding. Clinical and laboratory features of the subtypes of RTA are addressed, and diagnosis and treatment discussed. New developments in the knowledge and understanding of the associated growth disturbances, mineral metabolism, and molecular biology of RTA are also reviewed to provide the most current view of this relatively common pediatric entity.
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References
1.
1. Edelmann CM, Rodriguez-Soriano J, Biochis H, et al. Renal bicarbonate reabsorption and hydrogen ion excretion in infants. J Clin Invest. 1967;46:1309-1317.
2.
2. Svenningsen NW. Renal acid-base titration studies in infants with and without metabolic acidosis in the postneonatal perod. Pediatr Res. 1974;8:659-672.
4. Boron WF, Fong P, Hediger MA, et al. The electrogenic Na/HCO3 cotransporter. Wien Klin Wochenschr. 1997;109:445-456.
5.
5. Soleimani M, Burnham CE. Physiologic and molecular aspects of the Na+:HCO3cotransporter in health and disease processes. Kidney Int.2000;57:371-384.
6.
6. McKinney TD, Burg MB. Bicarbonate absorption by rabbit cortical collecting tubules in vitro. Am J Physiol. 1976;234:F141-F145.
7.
7. Fisher JL, Husted RF, Steinmetz PR. Chloride dependence of the HCO3 exit step in urinary acidification by the turtle bladder. Am J Physiol. 1983;245:F564-F568.
8.
8. Karet FE, Gainza FJ, Gyory AZ, et al. Mutations in the chloride-bicarbonate exchanger gene AE 1 cause autosomal dominant but not autosomal recessive distal renal tubular acidosis. Proc Natl Acad Sci.1998;95:6337-6342.
9.
9. Karet FE, Finberg KE, Nayir A, et al. Localization of a gene for autosomal recessive distal renal tubular acidosis with normal hearing(rdRTA2) to 7q33-34. Am J Hum Genet. 1999;65:1656-1665.
10.
10. Andersson B, Leksel LG, Rundgren M.Regulation of water intake. Annu Rev Nutr1982;2:73-89.
11.
11. Moore EW. Ionized calcium in normal serum, ultrafiltrates and whole blood determined by ion-exchange electrodes. J Clin Invest. 1970;49:318-318.
12.
12. Pedersen KO. Binding of calcium to serum albumin: II. Effect of pH via competitive hydrogen and calcium ion binding to the imidazole groups of albumin. Scand J Clin Lab Invest. 1972;29:75-75.
13.
13. Melnick JZ, Srere PA, Elshourbagy NA, et al. Adenosine triphosphate citrate lyase mediates hypocitraturia in rats.J Clin Invest. 1996;98:2381-2387.
14.
14. Dedmon RE, Wrong O. The excretion of organic anion in renal tubular acidosis with particular reference to citrate. Clin Sci.1962;22:19-32.
15.
15. Strife CF, Clardy CW, Varade WS, et al. Urine-to-blood carbon dioxide tension gradient and maximal depression of urinary pH to distinguish ratedependent from classic distal renal tubular acidosis in children. J Pediatr1993;122:60-65.
17. Hanna JD, Scheinman JI, Chan JCM. The kidney in acid-base balance. Pediatr Clin North Am. 1995;42:1365-1395.
18.
18. Alon U, Hellerstein S, Warady BA. Oral acetazolamide in the assessment of (urine-blood) pC02ø. Pediatr Nephrol. 1991;5:307-311.
19.
19. McSherry E.Renal tubular acidosis in childhood. Kidney Int.1981;20:799-809.
20.
20. Challa A, Krieg RJJr, Thabet MA, et al. Metabolic acidosis inhibits growth hormone secretion in rats: mechanism of growth retardation. Am J Physiol. 1993;265:E547-E553.
21.
21. Guillery EN, Karniski LP, Mathews MS, Robillard JE. Maturation of proximal tubule Na+/H+ antiporter activity in sheep from fetus to newborn. Am J Physiol. 1994;267:F537-F545.
22.
22. Baum M, Moe OW, Gentry DL, Alpern RJ. Effect of glucocorticoids on renal cortical NHE-3 and NHE-1 mRNA. Am J Physiol. 1994;267:F437-F442.
23.
23. Rutherford PA. Expression of Na+-H+ exchanger isoforms in the kidneyimplications for renal function and disease. Nephrol Dial Transplant. 1996;11:1711-1713.
24.
24. Romero MF, Boron WF. Electrogenic Na+/HCO3cotransporters: cloning and physiology. Annu Rev Physiol. 1999;61:699-723.
25.
25. Foreman JW, Roth KS. The human renal Fanconi syndrome-then and now. Nephrology. 1989;51:301-306.
26.
26. Rodriguez-Soriano J.New insights into the pathogenesis of renal tubular acidosis-from functional to molecular studies. Pediatr Nephrol. 2000;14:1121-1136.
27.
27. Roth DE, Venta PJ, Tashian RE, Sly WS. Molecular basis of human carbonic anhydrase II deficiency. Proc Natl Acad Sci USA. 1992;89:1804-1808.
28.
28. Lai LW, Chan DM, Erickson RP, et al. Correction of renal tubular acidosis in carbonic anhydrase 1I-deficient mice with gene therapy. J Clin Invest. 1998;101:1320-1325.
29.
29. Jarolim P, Shayakul C, Prabakaran D, et al. Autosomal dominant distal renal tubular acidosis is associated in three families with heterozygosity for the R589H mutation in the AE1 (band 3) Cl-/HCO3exchanger. J Biol Chem. 1998;273:6380-6388.
30.
30. Norman ME, Feldman NI, Cohn RM, et al. Urinary citrate excretion in the diagnosis of distal renal tubular acidosis. J Pediatx1978;92:394-400.
32. Brenner RJ, Spring DB, Sebastian A, et al. Incidence of radiologically evident bone disease, nephrocalcinosis, and nephrolithiasis in various types of renal tubular acidosis. N Engl J Med. 1982:217-221.
33.
33. Santos F, Chan JCM. Renal tubular acidosis in children: diagnosis, treatment and prognosis. Am J Nephrol. 1986;6:289-295.
