Pediatric Nephrology

, Volume 32, Issue 11, pp 2037–2049 | Cite as

Potassium regulation in the neonate

  • Melvin Bonilla-FélixEmail author
Educational Review


Potassium, the major cation in intracelluar fluids, is essential for vital biological functions. Neonates maintain a net positive potassium balance, which is fundamental to ensure somatic growth but places these infants, especially those born prematurely, at risk for life-threatening disturbances in potassium concentration [K+] in the extracellular fluid compartment. Potassium conservation is achieved by maximizing gastrointestinal absorption and minimizing renal losses. A markedly low glomerular filtration rate, plus adaptations in tubular transport along the nephron, result in low potassium excretion in the urine of neonates. Careful evaluation of clinical data using reference values that are normal for the neonate’s postmenstrual age is critical to avoid over-treating infants with laboratory results that represent physiologic values for their developmental stage. The treatment should be aimed at correcting the primary cause when possible. Alterations in the levels or sensitivity to aldosterone are common in neonates. In symptomatic patients, the disturbances in [K+] should be corrected promptly, with close electrocardiographic monitoring. Plasma [K+] should be monitored during the first 72 h of life in all premature infants born before 30 weeks of postmenstrual age as these infants are prone to develop non-oliguric hyperkalemia with potential serious complications.


Potassium Neonate Potassium channels Renal development Hyperkalemia Hypokalemia 


Compliance with ethical standards

Conflict of interest statement

None to declare


  1. 1.
    Lorenz JM, Kleinman LI, Markarian K (1997) Potassium metabolism in extremely low birth weight infants in the first week of life. J Pediatr 131:8–86CrossRefGoogle Scholar
  2. 2.
    Youn JH, McDonough AA (2009) Recent advances in understanding integrative control of potassium homeostasis. Annu Rev Physiol 71:381–401CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Agarwal R, Afzalpurkar R, Fordtran JS (1994) Pathophysiology of potassium absorption and secretion by the human intestine. Gastroenterology 107:548–571CrossRefPubMedGoogle Scholar
  4. 4.
    Codina J, Pressley TA, DuBose TD Jr (1997) Effect of chronic hypokalemia on H-K-ATPase expression in rat colon. Am J Physiol 272:F22–F30PubMedGoogle Scholar
  5. 5.
    Rabelink TJ, Koomans HA, Hené RJ, Dorhout Mees EJ (1990) Early and late adjustment to potassium loading in humans. Kidney Int 38:942–947CrossRefPubMedGoogle Scholar
  6. 6.
    Giebisch G, Krapf R, Wagner C (2007) Renal and extrarenal regulation of potassium. Kidney Int 72:397–410CrossRefPubMedGoogle Scholar
  7. 7.
    Youn JH (2013) Gut sensing of potassium intake and its role in potassium homeostasis. Semin Nephrol 33:248–256CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Rabinowitz L (1996) Aldosterone and potassium homeostasis. Kidney Int 49:1738–1742CrossRefPubMedGoogle Scholar
  9. 9.
    Morita H, Fujiki N, Miyahara T, Lee K, Tanaka K (2000) Hepatoportal bumetanide-sensitive K-sensor mechanism controls urinary K excretion. Am J Physiol 278:R1134–R1139Google Scholar
  10. 10.
    Tsuchiya Y, Nakashima S, Banno Y, Suzuki Y, Morita H (2004) Effect of high-NaCl or high-KCl diet on hepatic Na+- and K+-receptor sensitivity and NKCC1 expression in rats. Am J Physiol 286:R591–R596Google Scholar
  11. 11.
    Chen P, Guzman JP, Leong PK, Yang LE, Perianayagam A, Babilonia E, Ho JS, Youn JH, Wang WH, McDonough AA (2006) Modest dietary K restriction provokes insulin resistance of cellular K uptake and phosphorylation of renal outer medulla K channel without fall in plasma K+ concentration. Am J Physiol 290:C1355–C1363Google Scholar
  12. 12.
    Aizman R, Grahnquist L, Celsi G (1998) Potassium homeostasis: ontogenic aspects. Acta Paediatr 87:609–617CrossRefPubMedGoogle Scholar
  13. 13.
    Aizman R, Celsi G, Grahnquist L, Wang Z, Finkel Y, Aperia A (1996) Ontogeny of K+ transport in rat distal colon. Am J Physiol 271:G268–G274Google Scholar
  14. 14.
    Stefano JL, Norman ME, Morales MC, Goplerud JM, Mishra OP, Delivoria-Papadopoulos M (1993) Decreased erythrocyte Na+, K(+)-ATPase activity associated with cellular potassium loss in extremely low birth weight infants with nonoliguric hyperkalemia. J Pediatr 122:276–284Google Scholar
  15. 15.
    Omar SE, DeCristofaro JD, Agarwal BI, LaGamma EF (2000) Effect of prenatal steroids on potassium balance in extremely low birth weight neonates. Pediatrics 106:561–567CrossRefPubMedGoogle Scholar
  16. 16.
    Sato K, Kondo T, Iwao H, Honda S, Ueda K (1995) Internal potassium shift in premature infants: cause of nonoliguric hyperkalemia. J Pediatr 126:109–113CrossRefPubMedGoogle Scholar
  17. 17.
    Palmer BF (2015) Regulation of potassium homeostasis. Clin J Am Soc Nephrol 10:1050–1060CrossRefPubMedGoogle Scholar
  18. 18.
    Vieux R, Hascoet JM, Merdariu D, Fresson J, Guillemin F (2010) Glomerular filtration rate reference values in very preterm infants. Pediatrics 125:e1186–e1192CrossRefPubMedGoogle Scholar
  19. 19.
    Schmidt U, Horster M (1977) Na-K-activated ATPase: activity maturation in rabbit nephron segments dissected in vitro. Am J Physiol 233:F55–F60PubMedGoogle Scholar
  20. 20.
    Schwartz GJ, Evan AP (1984) Development of solute transport in rabbit proximal tubule. III. Na-K-ATPase activity. Am J Physiol 246:F845–F852PubMedGoogle Scholar
  21. 21.
    Wareing M, Wilson RW, Kibble JD, Green R (1995) Estimated potassium reflection coefficient in perfused proximal convoluted tubules of the anaesthetized rat in vivo. J Physiol 488:153–161CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Kibble JD, Wareing M, Wilson RW, Green R (1995) Effect of barium on potassium diffusion across the proximal convoluted tubule of the anaesthetized rat. Am J Physiol 268:F778–F783PubMedGoogle Scholar
  23. 23.
    Quigley R, Baum M (2005) Developmental changes in rabbit proximal straight tubule paracellular permeability. Am J Physiol 283:F525–F531Google Scholar
  24. 24.
    Baum M, Quigley R (2005) Maturation of rat proximal tubule chloride permeability. Am J Physiol 289:R1659–R1664Google Scholar
  25. 25.
    Haddad M, Lin F, Dwarakanath V, Cordes K, Baum M (2005) Developmental changes in proximal tubule tight junction membrane proteins. Pediatr Res 57:453–457CrossRefPubMedGoogle Scholar
  26. 26.
    Lelievre-Pegorier M, Merlet-Benichou C, Roinel N, de Rouffignac C (1983) Developmental pattern of water and electrolyte transport in rat superficial nephrons. Am J Physiol 245:F15–F21PubMedGoogle Scholar
  27. 27.
    Palmer LG, Schnermann J (2015) Integrated control of Na transport along the nephron. Clin J Am Soc Nephrol 10:676–687CrossRefPubMedGoogle Scholar
  28. 28.
    Mount DB (2014) Thick ascending limb of the loop of Henle. Clin J Am Soc Nephrol 9:1974–1986CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Welling PA, Ho K (2009) A comprehensive guide to the ROMK potassium channel: form and function in health and disease. Am J Physiol 29:F849–F863Google Scholar
  30. 30.
    Igarashi P, Vanden-Heuvel GB, Payne JA, Forbush B III (1995) Cloning, embryonic expression, and alternative splicing of a murine kidney-specific Na-K-Cl cotransporter. Am J Physiol 269:F405–F418PubMedGoogle Scholar
  31. 31.
    Gurkan S, Estilo GK, Wei Y, Satlin LM (2007) Potassium transport in the maturing kidney. Pediatr Nephrol 22:915–925CrossRefPubMedGoogle Scholar
  32. 32.
    Martinerie L, Pussard E, Foix-L’hélias L, Petit F, Cosson C, Boileau P, Lombès M (2009) Physiological partial aldosterone resistance in human newborns. Pediatr Res 66:323–328CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Aperia A, Broberger O, Herin P, Zetterström R (1979) Sodium excretion in relation to sodium intake and aldosterone excretion in newborn pre-term and full-term infants. Acta Paediatr Scand 68:813–817CrossRefPubMedGoogle Scholar
  34. 34.
    Vehaskari VM (1994) Ontogeny of cortical collecting duct sodium transport. Am J Physiol 267:F49–F54PubMedGoogle Scholar
  35. 35.
    Martinerie L, Viengchareun S, Delezoide AL, Jaubert F, Sinico M, Prevot S, Boileau P, Meduri G, Lombe M (2009) Low renal mineralocorticoid receptor expression at birth contributes to partial aldosterone resistance in neonates. Endocrinology 150:4414–4424CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Kunau RT Jr, Webb HL, Borman SC (1974) Characteristics of the relationship between the flow rate of tubular fluid and potassium transport in the distal tubule of the rat. J Clin Invest 54:1488–1495CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Engbretson BG, Stoner LC (1987) Flow-dependent potassium secretion by rabbit cortical collecting tubule in vitro. Am J Physiol 253:F896–F903PubMedGoogle Scholar
  38. 38.
    Carrisoza-Gaytan R, Carattino MD, Kleyman TR, Satlin LM (2016) An unexpected journey: conceptual evolution of mechanoregulated potassium transport in the distal nephron. Am J Physiol 310:C243–C259CrossRefGoogle Scholar
  39. 39.
    Wang WH, Giebisch G (2009) Regulation of potassium (K) handling in the renal collecting duct. Pflugers Arch 458:157–168CrossRefPubMedGoogle Scholar
  40. 40.
    Woda CB, Bragin A, Kleyman TR, Satlin LM (2001) Flow-dependent K+ secretion in the cortical collecting duct is mediated by a maxi-K channel. Am J Physiol 280:F786–F793Google Scholar
  41. 41.
    Satlin LM (2004) Developmental regulation of expression of renal potassium secretory channels. Curr Opin Nephrol Hypertens 13:445–450CrossRefPubMedGoogle Scholar
  42. 42.
    Pácha J, Frindt G, Sackin H, Palmer LG (1991) Apical maxi K channels in intercalated cells of CCT. Am J Physiol 261:F696–F705PubMedGoogle Scholar
  43. 43.
    Nüsing RM, Pantalone F, Gröne HJ, Seyberth HW, Wegmann M (2005) Expression of the potassium channel ROMK in adult and fetal human kidney. Histochem Cell Biol 123:553–559CrossRefPubMedGoogle Scholar
  44. 44.
    Velázquez H, Ellison DH, Wright FS (1987) Chloride dependent potassium secretion in early and late renal distal tubules. Am J Physiol 253:F555–F562PubMedGoogle Scholar
  45. 45.
    Simon DB, Nelson-Williams C, Bia MJ, Ellison D, Karet FE, Molina AM, Vaara I, Iwata F, Cushner HM, Koolen M, Gainza FJ, Gitleman HJ, Lifton RP (1996) Gitelman’s variant of Bartter’s syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide sensitive Na-Cl cotransporter. Nat Genet 12:24–30CrossRefPubMedGoogle Scholar
  46. 46.
    Ellison DH, Terker AS, Gamba G (2016) Potassium and its discontents: new insight, new treatments. J Am Soc Nephrol 27:981–989CrossRefPubMedGoogle Scholar
  47. 47.
    Kahle KT, Wilson FH, Leng Q, Lalioti MD, O’Connell AD, Dong K, Rapson AK, MacGregor GG, Giebisch G, Hebert SC, Lifton RP (2003) WNK4 regulates the balance between renal NaCl reabsorption and K+ secretion. Nat Genet 35:372–376Google Scholar
  48. 48.
    O’Shaughnessy KM (2015) Gordon Syndrome: a continuing story. Pediatr Nephrol 30:1903–1908CrossRefPubMedGoogle Scholar
  49. 49.
    Schmitt R, Ellison DH, Farman N, Rossier BC, Reilly RF, Reeves WB, Oberbäumer I, Tapp R, Bachmann S (1999) Developmental expression of sodium entry pathways in rat nephron. Am J Physiol 276:F367–F381PubMedGoogle Scholar
  50. 50.
    Shekarabi M, Lafrenière RG, Gaudet R, Laganière J, Marcinkiewicz MM, Dion PA, Rouleau GA (2013) Comparative analysis of the expression profile of Wnk1 and Wnk1/Hsn2 splice variants in developing and adult mouse tissues. PLoS One 8:e57807CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Nako Y, Ohki Y, Harigaya A, Tomomasa T, Morikawa A (1999) Transtubular potassium concentration gradient in preterm neonates. Pediatr Nephrol 13:880–885CrossRefPubMedGoogle Scholar
  52. 52.
    Satlin LM (1994) Postnatal maturation of potassium transport in rabbit cortical collecting duct. Am J Physiol 266:F57–F65PubMedGoogle Scholar
  53. 53.
    Satlin LM, Palmer LG (1997) Apical K+ conductance in maturing rabbit principal cell. Am J Physiol 272:F397–F404Google Scholar
  54. 54.
    Woda CB, Miyawaki N, Ramalakshmi S, Ramkumar M, Rojas R, Zavilowitz B, Kleyman TR, Satlin LM (2003) Ontogeny of flow-stimulated potassium secretion in rabbit cortical collecting duct: functional and molecular aspects. Am J Physiol 285:F629–F639Google Scholar
  55. 55.
    Delgado MM, Rohatgi R, Khan S, Holzman IR, Satlin LM (2003) Sodium and potassium clearances by the maturing kidney: Clinical-molecular correlates. Pediatr Nephrol 18:759–767CrossRefPubMedGoogle Scholar
  56. 56.
    Hansen GP, Tisher CC, Robinson RR (1980) Response of the collecting duct to disturbances of acid-base and potassium balance. Kidney Int 17:326–337CrossRefPubMedGoogle Scholar
  57. 57.
    Codina J, DuBose TD Jr (2006) Molecular regulation and physiology of the H+, K+-ATPases in kidney. Semin Nephrol 26:345–351Google Scholar
  58. 58.
    Suarez-Rivera M, Bonilla-Felix M (2014) Fluid and electrolyte disorders in the newborn: sodium and potassium. Curr Pediatr Rev 10:115–122CrossRefPubMedGoogle Scholar
  59. 59.
    Auron A, Auron-Gomez M, Raina R, Viswanathan S, Mhanna MJ (2009) Effect of amphotericin B lipid complex (ABLC) in very low birth weight infants. Pediatr Nephrol 24:295–299CrossRefPubMedGoogle Scholar
  60. 60.
    Seyberth HW, Schlingmann KP (2011) Bartter- and Gitelman-like syndromes: salt-losing tubulopathies with loop or DCT defects. Pediatr Nephrol 26:1789–1802CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Laghmani K, Beck BB, Yang SS, Seaayfan E, Wenzel A, Reusch B, Vitzthum H, Priem D, Demaretz S, Bergmann K, Duin LK, Göbel H, Mache C, Thiele H, Bartram MP, Dombret C, Altmüller J, Nürnberg P, Benzing T, Levtchenko E, Seyberth HW, Klaus G, Yigit G, Lin SH, Timmer A, de Koning TJ, Scherjon SA, Schlingmann KP, Bertrand MJ, Rinschen MM, de Backer O, Konrad M, Kömhoff M (2016) Polyhydramnios, transient antenatal Bartter’s syndrome, and MAGED2 mutations. N Engl J Med 374:1853–1863CrossRefPubMedGoogle Scholar
  62. 62.
    Tammaro F, Bettinelli A, Cattarelli D, Cavazza A, Colombo C, Syrén ML, Tedeschi S, Bianchetti MG (2010) Early appearance of hypokalemia in Gitelman syndrome. Pediatr Nephrol 25:2179–2182CrossRefPubMedGoogle Scholar
  63. 63.
    Greco M, Brugnara M, Zaffanello M, Taranta A, Pastore A, Emma F (2010) Long-term outcome of nephropathic cystinosis: a 20-year single-center experience. Pediatr Nephrol 25:2459–2467CrossRefPubMedGoogle Scholar
  64. 64.
    Vehaskari VM (2009) Heritable forms of hypertension. Pediatr Nephrol 24:1929–1937CrossRefPubMedGoogle Scholar
  65. 65.
    Dluhy RGMD, Anderson B, Harlin B, Ingelfinger J, Lifton R (2001) Glucocorticoid-remediable aldosteronism is associated with severe hypertension in early childhood. J Pediatr 138:715–720CrossRefPubMedGoogle Scholar
  66. 66.
    Rodriguez-Soriano J, Ubetagoyena M, Vallo A (1990) Transtubular potassium concentration gradient: a useful test to estimate renal aldosterone bio-activity in infants and children. Pediatr Nephrol 4:105–110CrossRefPubMedGoogle Scholar
  67. 67.
    Kamel KS, Halperin ML (2011) Intrarenal urea recycling leads to a higher rate of renal excretion of potassium: an hypothesis with clinical implications. Curr Opin Nephrol Hypertens 20:547–554CrossRefPubMedGoogle Scholar
  68. 68.
    Huang CL, Kuo E (2007) Mechanism of hypokalemia in magnesium deficiency. J Am Soc Nephrol 18:2649–2652CrossRefPubMedGoogle Scholar
  69. 69.
    Luke RG, Galla JH (2012) It is chloride depletion alkalosis, not contraction alkalosis. J Am Soc Nephrol 23:204–207CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Welfare W, Sasi P, English M (2002) Challenges in managing profound hypokalaemia. BMJ 324:269–270CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Rodriguez-Soriano J (1995) Potassium homeostasis and its disturbances in children. Pediatr Nephrol 9:364–374CrossRefPubMedGoogle Scholar
  72. 72.
    Chevalier RL (1998) What are normal potassium concentrations in the neonate? What is a reasonable approach to hyperkalemia in the newborn with normal renal function? Sem Nephrol 18:360–361Google Scholar
  73. 73.
    Ong YL, Deore R, El-Agnaf M (2010) Pseudohyperkalaemia is a common finding in myeloproliferative disorders that may lead to inappropriate management of patients. Int J Lab Hematol 32:151–157CrossRefGoogle Scholar
  74. 74.
    Lehnhardt A, Marcus J, Kemper MJ (2011) Pathogenesis, diagnosis and management of hyperkalemia. Pediatr Nephrol 26:377–384CrossRefPubMedGoogle Scholar
  75. 75.
    Perazella MA (2000) Trimethoprim-induced hyperkalaemia: clinical data, mechanism, prevention and management. Drug Saf 22:227–236CrossRefPubMedGoogle Scholar
  76. 76.
    White PC (1997) Abnormalities of aldosterone synthesis and action in children. Curr Opin Pediatr 9:424–430CrossRefPubMedGoogle Scholar
  77. 77.
    White PC (2004) Aldosterone synthase deficiency and related disorders. Mol Cell Endocrinol 217:81–87CrossRefPubMedGoogle Scholar
  78. 78.
    Sudeep K, Rajpoot SK, Maggi C, Bhangoo A (2014) Pseudohypoaldosteronism in a neonate presenting as life-threatening arrhythmia. Endocrinol Diabetes Metab Case Rep 2014:130077Google Scholar
  79. 79.
    Gereda JE, Bonilla-Felix M, Kalil B, Dewitt SJ (1996) Neonatal presentation of Gordon syndrome. J Pediatr 129:615–617CrossRefPubMedGoogle Scholar
  80. 80.
    Shortland D, Trounce JQ, Levene MI (1987) Hyperkalaemia, cardiac arrhythmias, and cerebral lesions in high risk neonates. Arch Dis Child 62:1139–1143CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Yaseen H (2009) Nonoliguric hyperkalemia in neonates: a case-controlled study. Am J Perinatol 26:185–189CrossRefPubMedGoogle Scholar
  82. 82.
    Masilamani K, van der Voort J (2012) The management of acute hyperkalaemia in neonates and children. Arch Dis Child 97:376–380CrossRefPubMedGoogle Scholar
  83. 83.
    Ditzenberger GR, Collins SD, Binder N (1999) Continuous insulin intravenous infusion therapy for VLBW infants. J Perinat Neonatal Nurs 13:70–82CrossRefPubMedGoogle Scholar
  84. 84.
    Singh BS, Sadiq HF, Noguchi A, Keenan WJ (2002) Efficacy of albuterol inhalation in treatment of hyperkalemia in premature neonates. J Pediatr 141:16–20CrossRefPubMedGoogle Scholar
  85. 85.
    Helfrich E, de Vries TW, van Roon EN (2001) Salbutamol for hyperkalaemia in children. Acta Paediatr 90:1213–1216CrossRefPubMedGoogle Scholar
  86. 86.
    Yaseen H, Khalaf M, Dana A, Yaseen N, Darwich M (2008) Salbutamol versus cation-exchange resin (kayexalate) for the treatment of nonoliguric hyperkalemia in preterm infants. Am J Perinatol 25:193–197CrossRefPubMedGoogle Scholar
  87. 87.
    Wigglesworth JS, Keith IH, Girling DJ, Slade SA (1976) Hyaline membrane disease, alkali, and intraventricular haemorrhage. Arch Dis Child 51:755–762CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Papile LA, Burstein J, Burstein R, Koffier H, Koops B (1978) Relationship of intravenous sodium bicarbonate in fusions and cerebral intraventricular hemorrhage. J Pediatr 93:834–836CrossRefPubMedGoogle Scholar
  89. 89.
    Szpecht D, Szymankiewicz M, Nowak I, Gadzinowski J (2016) Intraventricular hemorrhage in neonates born before 32 weeks of gestation-retrospective analysis of risk factors. Childs Nerv Syst 32:1399–1404CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Vemgal P, Ohlsson A (2012) Interventions for non-oliguric hyperkalaemia in preterm neonates. Cochrane Database Syst Rev 5:CD005257Google Scholar
  91. 91.
    Ohlsson A, Hosking M (1987) Complications following oral administration of exchange resins in extremely low-birth-weight infants. Eur J Pediatr 146:571–574CrossRefPubMedGoogle Scholar
  92. 92.
    Bennett LN, Myers TF, Lambert GH (1996) Cecal perforation associated with sodium polystyrene sulfonate-sorbitol enemas in a 650 grams infant with hyperkalemia. Am J Perinatol 13:167–170CrossRefPubMedGoogle Scholar

Copyright information

© IPNA 2017

Authors and Affiliations

  1. 1.Department of PediatricsUniversity of Puerto RicoSan JuanPuerto Rico

Personalised recommendations