Physiology of the Developing Kidney: Acid-Base Homeostasis and Its Disorders

  • Peter D. Yorgin
  • Elizabeth G. Ingulli
  • Robert H. Mak
Reference work entry


The body is highly dependent on acid–base control by the kidneys, lungs, and buffer systems to provide a cellular environment suitable for normal health, growth, and development. The acid and alkali loads from ingesting food and fluid must be managed so that the extracellular hydrogen ion (H+) concentration is maintained within a very narrow range. There are serious consequences from acid–base perturbations. Patients with severe acidemia, high blood levels of H+, may have problems with hyperkalemia, increased susceptibility to cardiac dysrhythmias, osteopenia, recurrent nephrolithiasis, skeletal muscle atrophy, and growth retardation in children


Chronic Kidney Disease Metabolic Alkalosis Serum Bicarbonate Thick Ascend Limb Serum Bicarbonate Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Mahutte CK. On-line arterial blood gas analysis with optodes: current status. Clin Biochem. 1998;31:119–30.PubMedCrossRefGoogle Scholar
  2. 2.
    J-L H. High performance GdTixOy electrolyte-insulator-semiconductor pH sensor and biosensor. Intl J Electrochem Sci. 2013;8:606–20.Google Scholar
  3. 3.
    Story DA. Bench-to-bedside review: a brief history of clinical acid-base. Crit Care. 2004;8:253–8.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Weiner DI, Verlander JW. Renal acidification mechanisms. In: Brenner & Rector’s the kidney, 9th ed. Philadelphia: Elsevier/Saunders, Ch 9 2012. p. 293–325.Google Scholar
  5. 5.
    Levraut J, Giunti C, Ciebiera JP, et al. Initial effect of sodium bicarbonate on intracellular pH depends on the extracellular nonbicarbonate buffering capacity. Crit Care Med. 2001;29:1033–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Burton RF. The roles of intracellular buffers and bone mineral in the regulation of acid-base balance in mammals. Comp Biochem Physiol Comp Physiol. 1992;102:425–32.PubMedCrossRefGoogle Scholar
  7. 7.
    Rector Jr FC, Carter NW, Seldin DW. The mechanism of bicarbonate reabsorption in the proximal and distal tubules of the kidney. J Clin Invest. 1965;44:278–90.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Bobulescu IA, Moe OW. Na+/H+ exchangers in renal regulation of acid-base balance. Semin Nephrol. 2006;26:334–44.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Ledoussal C, Lorenz JN, Nieman ML, Soleimani M, Schultheis PJ, Shull GE. Renal salt wasting in mice lacking NHE3 Na+/H+ exchanger but not in mice lacking NHE2. Am J Physiol. 2001;281:F718–27.Google Scholar
  10. 10.
    Lorenz JN, Schultheis PJ, Traynor T, Shull GE, Schnermann J. Micropuncture analysis of single-nephron function in NHE3-deficient mice. Am J Physiol. 1999;277:F447–53.PubMedGoogle Scholar
  11. 11.
    Nakamura S, Amlal H, Schultheis PJ, Galla JH, Shull GE, Soleimani M. HCO-3 reabsorption in renal collecting duct of NHE-3-deficient mouse: a compensatory response. Am J Physiol. 1999;276:F914–21.PubMedGoogle Scholar
  12. 12.
    Schultheis PJ, Clarke LL, Meneton P, et al. Renal and intestinal absorptive defects in mice lacking the NHE3 Na+/H+ exchanger. Nat Genet. 1998;19:282–5.PubMedCrossRefGoogle Scholar
  13. 13.
    Kinne-Saffran E, Beauwens R, Kinne R. An ATP-driven proton pump in brush-border membranes from rat renal cortex. J Membr Biol. 1982;64:67–76.PubMedCrossRefGoogle Scholar
  14. 14.
    Wang T, Yang CL, Abbiati T, et al. Mechanism of proximal tubule bicarbonate absorption in NHE3 null mice. Am J Physiol. 1999;277:F298–302.PubMedGoogle Scholar
  15. 15.
    Gluck SL, Lee BS, Wang SP, Underhill D, Nemoto J, Holliday LS. Plasma membrane V-ATPases in proton-transporting cells of the mammalian kidney and osteoclast. Acta Physiol Scand. 1998;643:203–12.Google Scholar
  16. 16.
    Nakhoul NL, Hamm LL. Vacuolar H(+)-ATPase in the kidney. J Nephrol. 2002;15 Suppl 5:S22–31.PubMedGoogle Scholar
  17. 17.
    Stone DK, Crider BP, Xie XS. Structural properties of vacuolar proton pumps. Kidney Int. 1990;38:649–53.PubMedCrossRefGoogle Scholar
  18. 18.
    Shah M, Quigley R, Baum M. Neonatal rabbit proximal tubule basolateral membrane Na+/H+ antiporter and Cl-/base exchange. Am J Physiol. 1999;276:R1792–7.PubMedCentralPubMedGoogle Scholar
  19. 19.
    Baum M. Developmental changes in rabbit juxtamedullary proximal convoluted tubule acidification. Pediatr Res. 1992;31:411–4.PubMedCrossRefGoogle Scholar
  20. 20.
    Baum M, Quigley R. Maturation of proximal tubular acidification. Pediatr Nephrol. 1993;7:785–91.PubMedCrossRefGoogle Scholar
  21. 21.
    Schwartz GJ, Evan AP. Development of solute transport in rabbit proximal tubule. I. HCO-3 and glucose absorption. Am J Physiol. 1983;245:F382–90.PubMedGoogle Scholar
  22. 22.
    Shah M, Gupta N, Dwarakanath V, Moe OW, Baum M. Ontogeny of Na+/H+ antiporter activity in rat proximal convoluted tubules. Pediatr Res. 2000;48:206–10.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Fukuda Y, Aperia A. Differentiation of Na + -K+ pump in rat proximal tubule is modulated by Na + -H+ exchanger. Am J Physiol. 1988;255:F552–7.PubMedGoogle Scholar
  24. 24.
    Larsson SH, Rane S, Fukuda Y, Aperia A, Lechene C. Changes in Na influx precede post-natal increase in Na, K-ATPase activity in rat renal proximal tubular cells. Acta Physiol Scand. 1990;138:99–100.PubMedCrossRefGoogle Scholar
  25. 25.
    Wong PS, Johns EJ. The action of angiotensin II on the intracellular sodium content of suspensions of rat proximal tubules. J Physiol. 1996;497(Pt 1):219–27.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Purkerson JM, Schwartz GJ. The role of carbonic anhydrases in renal physiology. Kidney Int. 2007;71:103–15.PubMedCrossRefGoogle Scholar
  27. 27.
    Pushkin A, Abuladze N, Gross E, et al. Molecular mechanism of kNBC1-carbonic anhydrase II interaction in proximal tubule cells. J Physiol. 2004;559:55–65.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Gross E, Kurtz I. Structural determinants and significance of regulation of electrogenic Na(+)-HCO(3)(-) cotransporter stoichiometry. Am J Physiol. 2002;283:F876–87.Google Scholar
  29. 29.
    Soleimani M, Grassi SM, Aronson PS. Stoichiometry of Na + -HCO-3 cotransport in basolateral membrane vesicles isolated from rabbit renal cortex. J Clin Invest. 1987;79:1276–80.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Kondo Y, Fromter E. Axial heterogeneity of sodium-bicarbonate cotransport in proximal straight tubule of rabbit kidney. Pflugers Arch. 1987;410:481–6.PubMedCrossRefGoogle Scholar
  31. 31.
    Kondo Y, Fromter E. Evidence of chloride/bicarbonate exchange mediating bicarbonate efflux from S3 segments of rabbit renal proximal tubule. Pflugers Arch. 1990;415:726–33.PubMedCrossRefGoogle Scholar
  32. 32.
    Seki G, Fromter E. The chloride/base exchanger in the basolateral cell membrane of rabbit renal proximal tubule S3 segment requires bicarbonate to operate. Pflugers Arch. 1990;417:37–41.PubMedCrossRefGoogle Scholar
  33. 33.
    Steinmetz PR. Cellular organization of urinary acidification. Am J Physiol. 1986;251:F173–87.PubMedGoogle Scholar
  34. 34.
    Breton S, Brown D. New insights into the regulation of V-ATPase-dependent proton secretion. Am J Physiol. 2007;292:F1–10.Google Scholar
  35. 35.
    Wang T, Hropot M, Aronson PS, Giebisch G. Role of NHE isoforms in mediating bicarbonate reabsorption along the nephron. Am J Physiol. 2001;281:F1117–22.Google Scholar
  36. 36.
    Wang T, Malnic G, Giebisch G, Chan YL. Renal bicarbonate reabsorption in the rat. IV. Bicarbonate transport mechanisms in the early and late distal tubule. J Clin Invest. 1993;91:2776–84.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Stuart-Tilley AK, Shmukler BE, Brown D, Alper SL. Immunolocalization and tissue-specific splicing of AE2 anion exchanger in mouse kidney. J Am Soc Nephrol. 1998;9:946–59.PubMedGoogle Scholar
  38. 38.
    Alper SL, Stuart-Tilley AK, Biemesderfer D, Shmukler BE, Brown D. Immunolocalization of AE2 anion exchanger in rat kidney. Am J Physiol. 1997;273:F601–14.PubMedGoogle Scholar
  39. 39.
    Ko SB, Luo X, Hager H, et al. AE4 is a DIDS-sensitive Cl(-)/HCO(-)(3) exchanger in the basolateral membrane of the renal CCD and the SMG duct. Am J Physiol Cell Physiol. 2002;283:C1206–18.PubMedCrossRefGoogle Scholar
  40. 40.
    Xu J, Worrell RT, Li HC, et al. Chloride/bicarbonate exchanger SLC26A7 is localized in endosomes in medullary collecting duct cells and is targeted to the basolateral membrane in hypertonicity and potassium depletion. J Am Soc Nephrol. 2006;17:956–67.PubMedCrossRefGoogle Scholar
  41. 41.
    Petrovic S, Barone S, Xu J, et al. SLC26A7: a basolateral Cl-/HCO3- exchanger specific to intercalated cells of the outer medullary collecting duct. Am J Physiol. 2004;286:F161–9.Google Scholar
  42. 42.
    McKinney TD, Burg MB. Bicarbonate absorption by rabbit cortical collecting tubules in vitro. Am J Physiol. 1978;234:F141–5.PubMedGoogle Scholar
  43. 43.
    Good DW, Burg MB. Ammonia production by individual segments of the rat nephron. J Clin Invest. 1984;73:602–10.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    Curthoys NP, Lowry OH. The distribution of glutaminase isoenzymes in the various structures of the nephron in normal, acidotic, and alkalotic rat kidney. J Biol Chem. 1973;248:162–8.PubMedGoogle Scholar
  45. 45.
    Tannen RL, Sahai A. Biochemical pathways and modulators of renal ammoniagenesis. Miner Electrolyte Metab. 1990;16:249–58.PubMedGoogle Scholar
  46. 46.
    Hamm LL, Simon EE. Ammonia transport in the proximal tubule in vivo. Am J Kidney Dis. 1989;14:253–7.PubMedCrossRefGoogle Scholar
  47. 47.
    Flessner MF, Mejia R, Knepper MA. Ammonium and bicarbonate transport in isolated perfused rodent long-loop thin descending limbs. Am J Physiol. 1993;264:F388–96.PubMedGoogle Scholar
  48. 48.
    Strnad Z. Numerical calculation of basic indicators of blood acid-base balance using an equilibration method. Vet Med. 1986;31:557–64.Google Scholar
  49. 49.
    Edelmann CM, Soriano JR, Boichis H, Gruskin AB, Acosta MI. Renal bicarbonate reabsorption and hydrogen ion excretion in normal infants. J Clin Invest. 1967;46:1309–17.PubMedCentralPubMedCrossRefGoogle Scholar
  50. 50.
    Swan RC, Axelrod DR, Seip M, Pitts RF. Distribution of sodium bicarbonate infused into nephrectomized dogs. J Clin Invest. 1955;34:1795–801.PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Gunn VL, Barone MA. Johns hopkins hospital. Children’s medical and surgical center. The Harriet Lane handbook : a manual for pediatric house officers. 16th ed. Philadelphia: Mosby; 2002.Google Scholar
  52. 52.
    Story DA, Morimatsu H, Bellomo R. Strong ions, weak acids and base excess: a simplified Fencl-Stewart approach to clinical acid-base disorders. Br J Anaesth. 2004;92:54–60.PubMedCrossRefGoogle Scholar
  53. 53.
    Andersen OS. Blood acid-base alignment nomogram. Scales for pH, pCO2 base excess of whole blood of different hemoglobin concentrations, plasma bicarbonate, and plasma total-CO2. Scand J Clin Lab Invest. 1963;15:211–7.PubMedCrossRefGoogle Scholar
  54. 54.
    Emmett M, Narins RG. Clinical use of the anion gap. Medicine (Baltimore). 1977;56:38–54.CrossRefGoogle Scholar
  55. 55.
    Kraut JA, Madias NE. Approach to patients with acid-base disorders. Respir Care. 2001;46:392–403.PubMedGoogle Scholar
  56. 56.
    Figge J, Jabor A, Kazda A, Fencl V. Anion gap and hypoalbuminemia. Crit Care Med. 1998;26:1807–10.PubMedCrossRefGoogle Scholar
  57. 57.
    Weizman Z, Houri S, Ben-Ezer GD. Type of acidosis and clinical outcome in infantile gastroenteritis. J Pediatr Gastroenterol Nutr. 1992;14:187–91.PubMedCrossRefGoogle Scholar
  58. 58.
    Garella S, Chang BS, Kahn SI. Dilution acidosis and contraction alkalosis: review of a concept. Kidney Int. 1975;8:279–83.PubMedCrossRefGoogle Scholar
  59. 59.
    Moe OW, Fuster D. Clinical acid-base pathophysiology: disorders of plasma anion gap. Best Pract Res Clin Endocrinol Metab. 2003;17:559–74.PubMedCrossRefGoogle Scholar
  60. 60.
    Schwartz WB, Orning KJ, Porter R. The internal distribution of hydrogen ions with varying degrees of metabolic acidosis. J Clin Invest. 1957;36:373–82.PubMedCentralPubMedCrossRefGoogle Scholar
  61. 61.
    Burnell JM. Changes in bone sodium and carbonate in metabolic acidosis and alkalosis in the dog. J Clin Invest. 1971;50:327–31.PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Kurtzman NA. Relationship of extracellular volume and CO2 tension to renal bicarbonate reabsorption. Am J Physiol. 1970;219:1299–304.PubMedGoogle Scholar
  63. 63.
    Hoste EA, Colpaert K, Vanholder RC, et al. Sodium bicarbonate versus THAM in ICU patients with mild metabolic acidosis. J Nephrol. 2005;18:303–7.PubMedGoogle Scholar
  64. 64.
    White BC, Tintinalli JE. Effects of sodium bicarbonate administration during cardiopulmonary resuscitation. J Am Collage Emerg Phys. 1977;6:187–90.CrossRefGoogle Scholar
  65. 65.
    Nahas GG, Sutin KM, Fermon C, et al. Guidelines for the treatment of acidaemia with THAM. Drugs. 1998;55:191–224.PubMedCrossRefGoogle Scholar
  66. 66.
    Jacobson HR. Medullary collecting duct acidification. Effects of potassium, HCO3 concentration, and pCO2. J Clin Invest. 1984;74:2107–14.PubMedCentralPubMedCrossRefGoogle Scholar
  67. 67.
    Schwartz GJ. Na+-dependent H+ efflux from proximal tubule: evidence for reversible Na+-H+ exchange. Am J Physiol. 1981;241:F380–5.PubMedGoogle Scholar
  68. 68.
    Madias NE, Adrogue HJ. Cross-talk between two organs: how the kidney responds to disruption of acid-base balance by the lung. Nephron Physiol. 2003;93:p61–6.PubMedCrossRefGoogle Scholar
  69. 69.
    Schwartz GJ, Al-Awqati Q. Carbon dioxide causes exocytosis of vesicles containing H+ pumps in isolated perfused proximal and collecting tubules. J Clin Invest. 1985;75:1638–44.PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    Brackett Jr NC, Cohen JJ, Schwartz WB. Carbon dioxide titration curve of normal man. Effect of increasing degrees of acute hypercapnia on acid-base equilibrium. N Engl J Med. 1965;272:6–12.PubMedCrossRefGoogle Scholar
  71. 71.
    Schwartz WB, Cohen JJ. The nature of the renal response to chronic disorders of acid-base equilibrium. Am J Med. 1978;64:417–28.PubMedCrossRefGoogle Scholar
  72. 72.
    Krapf R, Beeler I, Hertner D, Hulter HN. Chronic respiratory alkalosis. The effect of sustained hyperventilation on renal regulation of acid-base equilibrium. N Engl J Med. 1991;324:1394–401.PubMedCrossRefGoogle Scholar
  73. 73.
    Wong HR, Chundu KR. Metabolic alkalosis in children undergoing cardiac surgery. Crit Care Med. 1993;21:884–7.PubMedCrossRefGoogle Scholar
  74. 74.
    Mauri S, Pedroli G, Rudeberg A, Laux-End R, Monotti R, Bianchetti MG. Acute metabolic alkalosis in cystic fibrosis: prospective study and review of the literature. Miner Electrolyte Metab. 1997;23:33–7.PubMedGoogle Scholar
  75. 75.
    Fustik S, Pop-Jordanova N, Slaveska N, Koceva S, Efremov G. Metabolic alkalosis with hypoelectrolytemia in infants with cystic fibrosis. Pediatr Int. 2002;44:289–92.PubMedCrossRefGoogle Scholar
  76. 76.
    Hebert SC. Bartter syndrome. Curr Opin Nephrol Hypertens. 2003;12:527–32.PubMedCrossRefGoogle Scholar
  77. 77.
    Naesens M, Steels P, Verberckmoes R, Vanrenterghem Y, Kuypers D. Bartter’s and Gitelman’s syndromes: from gene to clinic. Nephron Physiol. 2004;96:p65–78.PubMedCrossRefGoogle Scholar
  78. 78.
    Schmidt H, Kabesch M, Schwarz HP, Kiess W. Clinical, biochemical and molecular genetic data in five children with Gitelman’s syndrome. Horm Metab Res. 2001;33:354–7.PubMedCrossRefGoogle Scholar
  79. 79.
    Perez GO, Oster JR, Rogers A. Acid-base disturbances in gastrointestinal disease. Dig Dis Sci. 1987;32:1033–43.PubMedCrossRefGoogle Scholar
  80. 80.
    Bosch JP, Goldstein MH, Levitt MF, Kahn T. Effect of chronic furosemide administration on hydrogen and sodium excretion in the dog. Am J Physiol. 1977;232:F397–404.PubMedGoogle Scholar
  81. 81.
    van Buren M, Rabelink TJ, van Rijn HJ, Koomans HA. Effects of acute NaCl, KCl and KHCO3 loads on renal electrolyte excretion in humans. Clin Sci (Lond). 1992;83:567–74.CrossRefGoogle Scholar
  82. 82.
    Schwartz GJ. Physiology and molecular biology of renal carbonic anhydrase. J Nephrol. 2002;15 Suppl 5:S61–74.PubMedGoogle Scholar
  83. 83.
    Khanna A, Kurtzman NA. Metabolic alkalosis. Respir Care. 2001;46:354–65.PubMedGoogle Scholar
  84. 84.
    Arruda JA, Kurtzman NA. Mechanisms and classification of deranged distal urinary acidification. Am J Physiol. 1980;239:F515–23.PubMedGoogle Scholar
  85. 85.
    Wagner CA, Kovacikova J, Stehberger PA, Winter C, Benabbas C, Mohebbi N. Renal acid-base transport: old and new players. Nephron Physiol. 2006;103:p1–6.PubMedCrossRefGoogle Scholar
  86. 86.
    Roberts KE, Randall HT, Sanders HL, Hood M. Effects of potassium on renal tubular reabsorption of bicarbonate. J Clin Invest. 1955;34:666–72.PubMedCentralPubMedCrossRefGoogle Scholar
  87. 87.
    Korosi A, Kahn T, Kalb T, Uribarri J. Marked hyperlactatemia associated with severe alkalemia in a patient with thrombotic thrombocytopenic purpura. Am J Kidney Dis. 2000;36:E6.PubMedCrossRefGoogle Scholar
  88. 88.
    Jacobson HR, Seldin DW. On the generation, maintenance, and correction of metabolic alkalosis. Am J Physiol. 1983;245:F425–32.PubMedGoogle Scholar
  89. 89.
    Mazur JE, Devlin JW, Peters MJ, Jankowski MA, Iannuzzi MC, Zarowitz BJ. Single versus multiple doses of acetazolamide for metabolic alkalosis in critically ill medical patients: a randomized, double-blind trial. Crit Care Med. 1999;27:1257–61.PubMedCrossRefGoogle Scholar
  90. 90.
    Marik PE, Kussman BD, Lipman J, Kraus P. Acetazolamide in the treatment of metabolic alkalosis in critically ill patients. Heart Lung. 1991;20:455–9.PubMedGoogle Scholar
  91. 91.
    Amlal H, Habo K, Soleimani M. Potassium deprivation upregulates expression of renal basolateral Na(+)-HCO(3)(-) cotransporter (NBC-1). Am J Physiol Renal Physiol. 2000;279:F532–43.PubMedGoogle Scholar
  92. 92.
    Dave-Sharma S, Wilson RC, Harbison MD, et al. Examination of genotype and phenotype relationships in 14 patients with apparent mineralocorticoid excess. J Clin Endocrinol Metab. 1998;83:2244–54.PubMedGoogle Scholar
  93. 93.
    Colussi G, Rombola G, De Ferrari ME, Macaluso M, Minetti L. Correction of hypokalemia with antialdosterone therapy in Gitelman’s syndrome. Am J Nephrol. 1994;14:127–35.PubMedCrossRefGoogle Scholar
  94. 94.
    Ramsay LE, Hettiarachchi J, Fraser R, Morton JJ. Amiloride, spironolactone, and potassium chloride in thiazide-treated hypertensive patients. Clin Pharmacol Ther. 1980;27:533–43.PubMedCrossRefGoogle Scholar
  95. 95.
    Vania A, Tucciarone L, Mazzeo D, Capodaglio PF, Cugini P. Liddle’s syndrome: a 14-year follow-up of the youngest diagnosed case. Pediatr Nephrol. 1997;11:7–11.PubMedCrossRefGoogle Scholar
  96. 96.
    Korkmaz A, Yildirim E, Aras N, Ercan F. Hydrochloric acid for treating metabolic alkalosis. Jpn J Surg. 1989;19:519–23.PubMedCrossRefGoogle Scholar
  97. 97.
    McLaughlin ML, Kassirer JP. Rational treatment of acid-base disorders. Drugs. 1990;39:841–55.PubMedCrossRefGoogle Scholar
  98. 98.
    Nasimi A, Cardona J, Berthier M, Oriot D. Hydrochloric acid infusion for treatment of severe metabolic alkalosis in a neonate. Clin Pediatr (Phila). 1996;35:271–2.CrossRefGoogle Scholar
  99. 99.
    Giebisch G, Berger L, Pitts RF. The extrarenal response to acute acid-base disturbances of respiratory origin. J Clin Invest. 1955;34:231–45.PubMedCentralPubMedCrossRefGoogle Scholar
  100. 100.
    Arbus GS, Herbert LA, Levesque PR, Etsten BE, Schwartz WB. Characterization and clinical application of the “significance band” for acute respiratory alkalosis. N Engl J Med. 1969;280:117–23.PubMedCrossRefGoogle Scholar
  101. 101.
    Gledhill N, Beirne GJ, Dempsey JA. Renal response to short-term hypocapnia in man. Kidney Int. 1975;8:376–84.PubMedCrossRefGoogle Scholar
  102. 102.
    Gennari FJ, Goldstein MB, Schwartz WB. The nature of the renal adaptation to chronic hypocapnia. J Clin Invest. 1972;51:1722–30.PubMedCentralPubMedCrossRefGoogle Scholar
  103. 103.
    Cohen JJ, Madias NE, Wolf CJ, Schwartz WB. Regulation of acid-base equilibrium in chronic hypocapnia. Evidence that the response of the kidney is not geared to the defense of extracellular (H+). J Clin Invest. 1976;57:1483–9.PubMedCentralPubMedCrossRefGoogle Scholar
  104. 104.
    Schwartz WB, Brackett Jr NC, Cohen JJ. The response of extracellular hydrogen ion concentration to graded degrees of chronic hypercapnia: the physiologic limits of the defense of Ph. J Clin Invest. 1965;44:291–301.PubMedCentralPubMedCrossRefGoogle Scholar
  105. 105.
    DuBose T. Acid-base disorders. In: Brenner BM, editor. The kidney. 7th ed. Philadelphia: Saunders/Elsevier; 2004. p. 2870.Google Scholar
  106. 106.
    Temple AR. Pathophysiology of aspirin overdosage toxicity, with implications for management. Pediatrics. 1978;62:873–6.PubMedGoogle Scholar
  107. 107.
    Rennke H DB. Acid-base physiology and metabolic alkalosis. In: Renal pathophysiology: the essentials. 2nd ed. Boston: Lippincott Williams & Wilkins 2007. p. 127–156.Google Scholar
  108. 108.
    Vormann J, Remer T. Dietary, metabolic, physiologic, and disease-related aspects of acid-base balance: foreword to the contributions of the second International acid-base symposium. J Nutr. 2008;138:413S–4.PubMedGoogle Scholar
  109. 109.
    Remer T, Manz F. Estimation of the renal net acid excretion by adults consuming diets containing variable amounts of protein. Am J Clin Nutr. 1994;59:1356–61.PubMedGoogle Scholar
  110. 110.
    Kalhoff H, Manz F. Nutrition, acid-base status and growth in early childhood. Eur J Nutr. 2001;40:221–30.PubMedCrossRefGoogle Scholar
  111. 111.
    Alexy U, Kersting M, Remer T. Potential renal acid load in the diet of children and adolescents: impact of food groups, age and time trends. Public Health Nutr. 2008;11:300–6.PubMedCrossRefGoogle Scholar
  112. 112.
    Prynne CJ, Ginty F, Paul AA, et al. Dietary acid-base balance and intake of bone-related nutrients in Cambridge teenagers. Eur J Clin Nutr. 2004;58:1462–71.PubMedCrossRefGoogle Scholar
  113. 113.
    Remer T, Dimitriou T, Manz F. Dietary potential renal acid load and renal net acid excretion in healthy, free-living children and adolescents. Am J Clin Nutr. 2003;77:1255–60.PubMedGoogle Scholar
  114. 114.
    Frassetto LA, Morris Jr RC, Sebastian A. Effect of age on blood acid-base composition in adult humans: role of age-related renal functional decline. Am J Physiol. 1996;271:F1114–22.PubMedGoogle Scholar
  115. 115.
    Goodman AD, Lemann Jr J, Lennon EJ, Relman AS. Production, excretion, and net balance of fixed acid in patients with renal acidosis. J Clin Invest. 1965;44:495–506.PubMedCentralPubMedCrossRefGoogle Scholar
  116. 116.
    Manz F, Kalhoff H, Remer T. Renal acid excretion in early infancy. Pediatr Nephrol. 1997;11:231–43.PubMedCrossRefGoogle Scholar
  117. 117.
    Rector Jr FC. Sodium, bicarbonate, and chloride absorption by the proximal tubule. Am J Physiol. 1983;244:F461–71.PubMedGoogle Scholar
  118. 118.
    Twombley K, Gattineni J, Bobulescu IA, Dwarakanath V, Baum M. Effect of metabolic acidosis on neonatal proximal tubule acidification. Am J Physiol Regul Integr Comp Physiol. 2010;299:18.CrossRefGoogle Scholar
  119. 119.
    Joseph C, Twombley K, Gattineni J, Zhang Q, Dwarakanath V, Baum M. Acid increases NHE8 surface expression and activity in NRK cells. Am J Physiol Renal Physiol. 2012;302:16.CrossRefGoogle Scholar
  120. 120.
    Baum M. Neonatal rabbit juxtamedullary proximal convoluted tubule acidification. J Clin Invest. 1990;85:499–506.PubMedCentralPubMedCrossRefGoogle Scholar
  121. 121.
    Schwartz GJ, Evan AP. Development of solute transport in rabbit proximal tubule. III. Na-K-ATPase activity. Am J Physiol. 1984;246:F845–52.PubMedGoogle Scholar
  122. 122.
    Karashima S, Hattori S, Ushijima T, Furuse A, Nakazato H, Matsuda I. Developmental changes in carbonic anhydrase II in the rat kidney. Pediatr Nephrol. 1998;12:263–8.PubMedCrossRefGoogle Scholar
  123. 123.
    Winkler CA, Kittelberger AM, Watkins RH, Maniscalco WM, Schwartz GJ. Maturation of carbonic anhydrase IV expression in rabbit kidney. Am J Physiol Renal Physiol. 2001;280:F895–903.PubMedGoogle Scholar
  124. 124.
    Schwartz GJ, Olson J, Kittelberger AM, Matsumoto T, Waheed A, Sly WS. Postnatal development of carbonic anhydrase IV expression in rabbit kidney. Am J Physiol. 1999;276:F510–20.PubMedGoogle Scholar
  125. 125.
    Lonnerholm G, Wistrand PJ. Carbonic anhydrase in the human fetal kidney. Pediatr Res. 1983;17:390–7.PubMedCrossRefGoogle Scholar
  126. 126.
    Goldstein L. Renal ammonia and acid excretion in infant rats. Am J Physiol. 1970;218:1394–8.PubMedGoogle Scholar
  127. 127.
    Matsumoto T, Fejes-Toth G, Schwartz GJ. Postnatal differentiation of rabbit collecting duct intercalated cells. Pediatr Res. 1996;39:1–12.PubMedCrossRefGoogle Scholar
  128. 128.
    Benyajati S, Goldstein L. Renal glutaminase adaptation and ammonia excretion in infant rats. Am J Physiol. 1975;228:693–8.PubMedGoogle Scholar
  129. 129.
    Chan JC. Acid-base disorders and the kidney. Adv Pediatr. 1983;30:401–71.PubMedGoogle Scholar
  130. 130.
    McSherry E, Morris Jr RC. Attainment and maintenance of normal stature with alkali therapy in infants and children with classic renal tubular acidosis. J Clin Invest. 1978;61:509–27.PubMedCentralPubMedCrossRefGoogle Scholar
  131. 131.
    Challa A, Krieg Jr RJ, Thabet MA, Veldhuis JD, Chan JC. Metabolic acidosis inhibits growth hormone secretion in rats: mechanism of growth retardation. Am J Physiol. 1993;265:E547–53.PubMedGoogle Scholar
  132. 132.
    Hanna JDCA, Chan JCM, Han VKM. Insulin-like growth factor-1 gene expression in the tibial epiphyseal growth plate of the acidotic and with nutritional limited rats. Pediatr Res. 1995;37:363A.CrossRefGoogle Scholar
  133. 133.
    Krieger NS, Frick KK, Bushinsky DA. Mechanism of acid-induced bone resorption. Curr Opin Nephrol Hypertens. 2004;13:423–36.PubMedCrossRefGoogle Scholar
  134. 134.
    Lemann Jr J, Lennon EJ, Goodman AD, Litzow JR, Relman AS. The net balance of acid in subjects given large loads of acid or alkali. J Clin Invest. 1965;44:507–17.PubMedCentralPubMedCrossRefGoogle Scholar
  135. 135.
    Lemann Jr J, Litzow JR, Lennon EJ. The effects of chronic acid loads in normal man: further evidence for the participation of bone mineral in the defense against chronic metabolic acidosis. J Clin Invest. 1966;45:1608–14.PubMedCentralPubMedCrossRefGoogle Scholar
  136. 136.
    Litzow JR, Lemann Jr J, Lennon EJ. The effect of treatment of acidosis on calcium balance in patients with chronic azotemic renal disease. J Clin Invest. 1967;46:280–6.PubMedCentralPubMedCrossRefGoogle Scholar
  137. 137.
    Cochran M, Wilkinson R. Effect of correction of metabolic acidosis on bone mineralisation rates in patients with renal osteomalacia. Nephron. 1975;15:98–110.PubMedCrossRefGoogle Scholar
  138. 138.
    Bleich HL, Moore MJ, Lemann Jr J, Adams ND, Gray RW. Urinary calcium excretion in human beings. N Engl J Med. 1979;301:535–41.PubMedCrossRefGoogle Scholar
  139. 139.
    Lefebvre A, de Vernejoul MC, Gueris J, Goldfarb B, Graulet AM, Morieux C. Optimal correction of acidosis changes progression of dialysis osteodystrophy. Kidney Int. 1989;36:1112–8.PubMedCrossRefGoogle Scholar
  140. 140.
    Lemann Jr J, Bushinsky DA, Hamm LL. Bone buffering of acid and base in humans. Am J Physiol Renal Physiol. 2003;285:F811–32.PubMedCrossRefGoogle Scholar
  141. 141.
    Rodriguez-Soriano J, Vallo A. Renal tubular acidosis. Pediatr Nephrol. 1990;4:268–75.PubMedCrossRefGoogle Scholar
  142. 142.
    Halperin ML, Jungas RL. Metabolic production and renal disposal of hydrogen ions. Kidney Int. 1983;24:709–13.PubMedCrossRefGoogle Scholar
  143. 143.
    Warnock DG. Uremic acidosis. Kidney Int. 1988;34:278–87.PubMedCrossRefGoogle Scholar
  144. 144.
    Hakim RM, Lazarus JM. Biochemical parameters in chronic renal failure. Am J Kidney Dis. 1988;11:238–47.PubMedCrossRefGoogle Scholar
  145. 145.
    Bailey JL. Metabolic acidosis: an unrecognized cause of morbidity in the patient with chronic kidney disease. Kidney Int Suppl. 2005;96:S15–23.PubMedCrossRefGoogle Scholar
  146. 146.
    Kraut JA, Kurtz I. Metabolic acidosis of CKD: diagnosis, clinical characteristics, and treatment. Am J Kidney Dis. 2005;45:978–93.PubMedCrossRefGoogle Scholar
  147. 147.
    Uribarri J, Douyon H, Oh MS. A re-evaluation of the urinary parameters of acid production and excretion in patients with chronic renal acidosis. Kidney Int. 1995;47:624–7.PubMedCrossRefGoogle Scholar
  148. 148.
    Welbourne T, Weber M, Bank N. The effect of glutamine administration on urinary ammonium excretion in normal subjects and patients with renal disease. J Clin Invest. 1972;51:1852–60.PubMedCentralPubMedCrossRefGoogle Scholar
  149. 149.
    Widmer B, Gerhardt RE, Harrington JT, Cohen JJ. Serum electrolyte and acid base composition. The influence of graded degrees of chronic renal failure. Arch Intern Med. 1979;139:1099–102.PubMedCrossRefGoogle Scholar
  150. 150.
    Hsu CY, Chertow GM. Elevations of serum phosphorus and potassium in mild to moderate chronic renal insufficiency. Nephrol Dial Transplant. 2002;17:1419–25.PubMedCrossRefGoogle Scholar
  151. 151.
    Schambelan M, Sebastian A, Biglieri EG. Prevalence, pathogenesis, and functional significance of aldosterone deficiency in hyperkalemic patients with chronic renal insufficiency. Kidney Int. 1980;17:89–101.PubMedCrossRefGoogle Scholar
  152. 152.
    Jr E. Hydrogen ion turnover in health and disease. Ann Intern Med. 1962;57:660–84.CrossRefGoogle Scholar
  153. 153.
    Wallia R, Greenberg A, Piraino B, Mitro R, Puschett JB. Serum electrolyte patterns in end-stage renal disease. Am J Kidney Dis. 1986;8:98–104.PubMedCrossRefGoogle Scholar
  154. 154.
    Kraut JA. Disturbances of acid-base balance and bone disease in end-stage renal disease. Semin Dial. 2000;13:261–6.PubMedCrossRefGoogle Scholar
  155. 155.
    Uribarri J, Zia M, Mahmood J, Marcus RA, Oh MS. Acid production in chronic hemodialysis patients. J Am Soc Nephrol. 1998;9:114–20.PubMedGoogle Scholar
  156. 156.
    Sebastian A, Schambelan M, Lindenfeld S, Morris Jr RC. Amelioration of metabolic acidosis with fludrocortisone therapy in hyporeninemic hypoaldosteronism. N Engl J Med. 1977;297:576–83.PubMedCrossRefGoogle Scholar
  157. 157.
    Kurtz I, Maher T, Hulter HN, Schambelan M, Sebastian A. Effect of diet on plasma acid-base composition in normal humans. Kidney Int. 1983;24:670–80.PubMedCrossRefGoogle Scholar
  158. 158.
    Uribarri J, Levin NW, Delmez J, et al. Association of acidosis and nutritional parameters in hemodialysis patients. Am J Kidney Dis. 1999;34:493–9.PubMedCrossRefGoogle Scholar
  159. 159.
    Kopple JD, Kalantar-Zadeh K, Mehrotra R. Risks of chronic metabolic acidosis in patients with chronic kidney disease. Kidney Int Suppl. 2005;95:S21–7.PubMedCrossRefGoogle Scholar
  160. 160.
    Kovesdy CP, Anderson JE, Kalantar-Zadeh K. Association of serum bicarbonate levels with mortality in patients with non-dialysis-dependent CKD. Nephrol Dial Transplant. 2009;24:1232–7.PubMedCentralPubMedCrossRefGoogle Scholar
  161. 161.
    Oh MS, Uribarri J, Weinstein J, et al. What unique acid-base considerations exist in dialysis patients? Semin Dial. 2004;17:351–64.PubMedCrossRefGoogle Scholar
  162. 162.
    Kovacic V, Roguljic L, Kovacic V. Metabolic acidosis of chronically hemodialyzed patients. Am J Nephrol. 2003;23:158–64.PubMedCrossRefGoogle Scholar
  163. 163.
    Frassetto LA, Hsu CY. Metabolic acidosis and progression of chronic kidney disease. J Am Soc Nephrol. 2009;20(9):1869–70. doi:10.1681/ASN.2009070710. Epub 2009 Aug 20.PubMedCrossRefGoogle Scholar
  164. 164.
    KDIGO. Chapter 3: Management of progression and complications of CKD. Kidney Int Suppl. 2013;3:73–90.Google Scholar
  165. 165.
    Ambuhl PM. Posttransplant metabolic acidosis: a neglected factor in renal transplantation? Curr Opin Nephrol Hypertens. 2007;16:379–87.PubMedCrossRefGoogle Scholar
  166. 166.
    Yakupoglu HY, Corsenca A, Wahl P, Wuthrich RP, Ambuhl PM. Posttransplant acidosis and associated disorders of mineral metabolism in patients with a renal graft. Transplantation. 2007;84:1151–7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Peter D. Yorgin
    • 1
    • 2
  • Elizabeth G. Ingulli
    • 3
    • 4
    • 5
  • Robert H. Mak
    • 1
    • 2
  1. 1.Pediatric NephrologyUniversity of CaliforniaSan DiegoUSA
  2. 2.Pediatric Nephrology DivisionRady Children’s HospitalSan DiegoUSA
  3. 3.Department of PediatricsUniversity of CaliforniaSan DiegoUSA
  4. 4.Division of NephrologyRady Children’s Hospital San DiegoSan DiegoUSA
  5. 5.Kidney Transplant ProgramRady Children’s HospitalSan DiegoUSA

Personalised recommendations