Pathophysiology, Evaluation, and Treatment of Hypokalemia
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Tushar Chopra Division of Nephrology, University of Virginia School of Medicine, Charlottesville, Virginia

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Thomas D. DuBose Jr. Wake Forest School of Medicine, Section on General Internal Medicine, Winston-Salem, North Carolina and Division of Nephrology, University of Virginia School of Medicine, Charlottesville, Virginia

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  • 1

    DuBose TD Jr: Regulation of potassium homeostasis in CKD. Adv Chronic Kidney Dis 24: 305314, 2017 PubMed

  • 2

    Youn JH: Gut sensing of potassium intake and its role in potassium homeostasis. Semin Nephrol 33: 248256, 2013 PubMed

  • 3

    McFarlin BE, Chen Y, Priver TS, Ralph DL, Mercado A, Gamba G, et al.: Coordinate adaptations of skeletal muscle and kidney to maintain extracellular [K+] during K+-deficient diet. Am J Physiol Cell Physiol 319: C757C770, 2020 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Rabelink TJ, Koomans HA, Hené RJ, Dorhout Mees EJ: Early and late adjustment to potassium loading in humans. Kidney Int 38: 942947, 1990 PubMed

  • 5

    Wong CS, Pavord ID, Williams J, Britton JR, Tattersfield AE: Bronchodilator, cardiovascular, and hypokalaemic effects of fenoterol, salbutamol, and terbutaline in asthma. Lancet 336: 13961399, 1990 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Clausen T: Hormonal and pharmacological modification of plasma potassium homeostasis. Fundam Clin Pharmacol 24: 595605, 2010 PubMed

  • 7

    Braden GL, von Oeyen PT, Germain MJ, Watson DJ, Haag BL: Ritodrine- and terbutaline-induced hypokalemia in preterm labor: Mechanisms and consequences. Kidney Int 51: 18671875, 1997 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Thomson MN, Cuevas CA, Bewarder TM, Dittmayer C, Miller LN, Si J, et al.: WNK bodies cluster WNK4 and SPAK/OSR1 to promote NCC activation in hypokalemia. Am J Physiol Renal Physiol 318: F216F228, 2020 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Wang MX, Cuevas CA, Su XT, Wu P, Gao ZX, Lin DH, et al.: Potassium intake modulates the thiazide-sensitive sodium-chloride cotransporter (NCC) activity via the Kir4.1 potassium channel. Kidney Int 93: 893902, 2018 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Zhang C, Wang L, Su XT, Zhang J, Lin DH, Wang WH: ENaC and ROMK activity are inhibited in the DCT2/CNT of TgWnk4PHAII mice. Am J Physiol Renal Physiol 312: F682F688, 2017 PubMed

    • PubMed
    • Search Google Scholar
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  • 11

    Malik S, Lambert E, Zhang J, Wang T, Clark HL, Cypress M, et al.: Potassium conservation is impaired in mice with reduced renal expression of Kir4.1. Am J Physiol Renal Physiol 315: F1271F1282, 2018 PubMed

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  • 12

    Codina J, DuBose TD Jr: Molecular regulation and physiology of the H+,K+ -ATPases in kidney. Semin Nephrol 26: 345351, 2006 PubMed

  • 13

    West CA, Welling PA, West DA Jr, Coleman RA, Cheng KY, Chen C, et al.: Renal and colonic potassium transporters in the pregnant rat. Am J Physiol Renal Physiol 314: F251F259, 2018 PubMed

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    • Search Google Scholar
    • Export Citation
  • 14

    Codina J, Delmas-Mata JT, DuBose TD Jr: Expression of HKalpha2 protein is increased selectively in renal medulla by chronic hypokalemia. Am J Physiol 275: F433F440, 1998 PubMed

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  • 15

    Hamm L, DuBose TD Jr: Disorders of acid-base balance. In: Brenner & Rector’s The Kidney, 11th Ed., edited by Yu A, Chertow GM, Luyckx VA, Marsden PA, Skorecki K, and Taal MW, Philadelphia, Elsevier, 2020, pp 559592

    • PubMed
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  • 16

    Cogswell ME, Zhang Z, Carriquiry AL, Gunn JP, Kuklina EV, Saydah SH, et al.: Sodium and potassium intakes among US adults: NHANES 2003-2008. Am J Clin Nutr 96: 647657, 2012 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Mente A, O’Donnell MJ, Rangarajan S, McQueen MJ, Poirier P, Wielgosz A, et al.; PURE Investigators: Association of urinary sodium and potassium excretion with blood pressure. N Engl J Med 371: 601611, 2014 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    O’Donnell M, Mente A, Rangarajan S, McQueen MJ, Wang X, Liu L, et al.; PURE Investigators: Urinary sodium and potassium excretion, mortality, and cardiovascular events. N Engl J Med 371: 612623, 2014 PubMed

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  • 19

    DeSalvo KB, Olson R, Casavale KO: Dietary guidelines for Americans. JAMA 315: 457458, 2016 PubMed

  • 20

    DuBose TD Jr: Inadequate dietary potassium and progression of CKD. Clin J Am Soc Nephrol 14: 319320, 2019 PubMed

  • 21

    Sebastian A, Cordain L, Frassetto L, Banerjee T, Morris RC: Postulating the major environmental condition resulting in the expression of essential hypertension and its associated cardiovascular diseases: Dietary imprudence in daily selection of foods in respect of their potassium and sodium content resulting in oxidative stress-induced dysfunction of the vascular endothelium, vascular smooth muscle, and perivascular tissues. Med Hypotheses 119: 110119, 2018 PubMed

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  • 22

    Kieneker LM, Eisenga MF, Joosten MM, de Boer RA, Gansevoort RT, Kootstra-Ros JE, et al.: Plasma potassium, diuretic use and risk of developing chronic kidney disease in a predominantly White population. PLoS One 12: e0174686, 2017 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Palmer BF: Regulation of potassium homeostasis. Clin J Am Soc Nephrol 10: 10501060, 2015 PubMed

  • 24

    Facchini M, Sala L, Malfatto G, Bragato R, Redaelli G, Invitti C: Low-K+ dependent QT prolongation and risk for ventricular arrhythmia in anorexia nervosa. Int J Cardiol 106: 170176, 2006 PubMed

    • PubMed
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  • 25

    Chen WH, Yin HL, Lin HS, Chen SS, Liu JS: Delayed hypokalemic paralysis following a convulsion due to alcohol abstinence. J Clin Neurosci 13: 453456, 2006 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Centers for Disease Control and Prevention (CDC): Atypical reactions associated with heroin use--five states, January-April 2005. MMWR Morb Mortal Wkly Rep 54: 793796, 2005 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Tricarico D, Servidei S, Tonali P, Jurkat-Rott K, Camerino DC: Impairment of skeletal muscle adenosine triphosphate-sensitive K+ channels in patients with hypokalemic periodic paralysis. J Clin Invest 103: 675682, 1999 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Jiang D, Gamal El-Din TM, Ing C, Lu P, Pomès R, Zheng N, et al.: Structural basis for gating pore current in periodic paralysis. Nature 557: 590594, 2018 PubMed

  • 29

    Statland JM, Fontaine B, Hanna MG, Johnson NE, Kissel JT, Sansone VA, et al.: Review of the diagnosis and treatment of periodic paralysis. Muscle Nerve 57: 522530, 2018 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Kung AW: Clinical review: Thyrotoxic periodic paralysis: A diagnostic challenge. J Clin Endocrinol Metab 91: 24902495, 2006 PubMed

  • 31

    Knochel JP, Dotin LN, Hamburger RJ: Pathophysiology of intense physical conditioning in a hot climate. I. Mechanisms of potassium depletion. J Clin Invest 51: 242255, 1972 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Onozawa M, Fukuhara T, Minoguchi M, Takahata M, Yamamoto Y, Miyake T, et al.: Hypokalemic rhabdomyolysis due to WDHA syndrome caused by VIP-producing composite pheochromocytoma: A case in neurofibromatosis type 1. Jpn J Clin Oncol 35: 559563, 2005 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Lepur D, Klinar I, Mise B, Himbele J, Vranjican Z, Barsić B: McKittrick-Wheelock syndrome: A rare cause of diarrhoea. Eur J Gastroenterol Hepatol 18: 557559, 2006 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34

    van Dinter TG Jr, Fuerst FC, Richardson CT, Ana CA, Polter DE, Fordtran JS, et al.: Stimulated active potassium secretion in a patient with colonic pseudo-obstruction: A new mechanism of secretory diarrhea. Gastroenterology 129: 12681273, 2005 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35

    Codina J, Pressley TA, DuBose TD Jr: Effect of chronic hypokalemia on H(+)-K(+)-ATPase expression in rat colon. Am J Physiol 272: F22F30, 1997 PubMed

  • 36

    Sausbier M, Matos JE, Sausbier U, Beranek G, Arntz C, Neuhuber W, et al.: Distal colonic K(+) secretion occurs via BK channels. J Am Soc Nephrol 17: 12751282, 2006 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37

    del Castillo JR, Burguillos L: Pathways for K+ efflux in isolated surface and crypt colonic cells. Activation by calcium. J Membr Biol 205: 3747, 2005 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38

    Cohen EP, Bastani B, Cohen MR, Kolner S, Hemken P, Gluck SL: Absence of H(+)-ATPase in cortical collecting tubules of a patient with Sjogren’s syndrome and distal renal tubular acidosis. J Am Soc Nephrol 3: 264271, 1992 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39

    Simpson AM, Schwartz GJ: Distal renal tubular acidosis with severe hypokalaemia, probably caused by colonic H(+)-K(+)-ATPase deficiency. Arch Dis Child 84: 504507, 2001 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40

    Tran KM, Hinther K, Bueti J, Karpinski M, Hingwala J: Toluene toxicity: A case report of transdermal exposure causing hypokalemic paralysis. Can J Kidney Health Dis 6: 2054358119871594, 2019 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41

    Raphael KL, Gilligan S, Ix JH: Urine anion gap to predict urine ammonium and related outcomes in kidney disease. Clin J Am Soc Nephrol 13: 205212, 2018 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42

    Raphael KL, Yee J: It is really time for ammonium measurement. Adv Chronic Kidney Dis 25: 297300, 2018 PubMed

  • 43

    Kirschbaum B, Sica D, Anderson FP: Urine electrolytes and the urine anion and osmolar gaps. J Lab Clin Med 133: 597604, 1999 PubMed

  • 44

    Pela I, Materassi M, Seracini D, Lavoratti G, Bettinelli A: Hypokalemic rhabdomyolysis in a child with Bartter’s syndrome. Pediatr Nephrol 20: 11891191, 2005 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45

    Duman O, Koyun M, Akman S, Güven AG, Haspolat S: Case of Bartter syndrome presenting with hypokalemic periodic paralysis. J Child Neurol 21: 255256, 2006 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 46

    Bailey MA, Cantone A, Yan Q, MacGregor GG, Leng Q, Amorim JB, et al.: Maxi-K channels contribute to urinary potassium excretion in the ROMK-deficient mouse model of Type II Bartter’s syndrome and in adaptation to a high-K diet. Kidney Int 70: 5159, 2006 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 47

    Jang HR, Lee JW, Oh YK, Na KY, Joo KW, Jeon US, et al.: From bench to bedside: Diagnosis of Gitelman’s syndrome -- defect of sodium-chloride cotransporter in renal tissue. Kidney Int 70: 813817, 2006 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 48

    Pachulski RT, Lopez F, Sharaf R: Gitelman’s not-so-benign syndrome. N Engl J Med 353: 850851, 2005 PubMed

  • 49

    Morita R, Takeuchi K, Nakamura A, Tajima T, Kuroda Y: Gitelman’s syndrome with mental retardation. Intern Med 45: 211213, 2006 PubMed

  • 50

    Blanchard A, Bockenhauer D, Bolignano D, Calò LA, Cosyns E, Devuyst O, et al.: Gitelman syndrome: Consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int 91: 2433, 2017 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 51

    Lin SH, Lin YF, Chen DT, Chu P, Hsu CW, Halperin ML: Laboratory tests to determine the cause of hypokalemia and paralysis. Arch Intern Med 164: 15611566, 2004 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 52

    Crop MJ, Hoorn EJ, Lindemans J, Zietse R: Hypokalaemia and subsequent hyperkalaemia in hospitalized patients. Nephrol Dial Transplant 22: 34713477, 2007 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 53

    DuBose TD Jr: A 42-year-old woman with flaccid paralysis. Am J Kidney Dis 54: 965969, 2009 PubMed

  • 54

    Weiss JN, Qu Z, Shivkumar K: Electrophysiology of hypokalemia and hyperkalemia. Circ Arrhythm Electrophysiol 10: e004667, 2017 PubMed

  • 55

    Harada K, Akai Y, Iwano M, Nakatani K, Nishino T, Fujimoto T, et al.: Tubulointerstitial macrophage infiltration in a patient with hypokalemic nephropathy and primary Sjögren’s syndrome. Clin Nephrol 64: 387390, 2005 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 56

    Zillich AJ, Garg J, Basu S, Bakris GL, Carter BL: Thiazide diuretics, potassium, and the development of diabetes: A quantitative review. Hypertension 48: 219224, 2006 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 57

    Palmer BF: Metabolic complications associated with use of diuretics. Semin Nephrol 31: 542552, 2011 PubMed

  • 58

    Brown MJ, Williams B, Morant SV, Webb DJ, Caulfield MJ, Cruickshank JK, et al.; British Hypertension Society’s Prevention and Treatment of Hypertension with Algorithm-based Therapy (PATHWAY) Studies Group: Effect of amiloride, or amiloride plus hydrochlorothiazide, versus hydrochlorothiazide on glucose tolerance and blood pressure (PATHWAY-3): A parallel-group, double-blind randomised phase 4 trial. Lancet Diabetes Endocrinol 4: 136147, 2016 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 59

    Koster JC, Remedi MS, Masia R, Patton B, Tong A, Nichols CG: Expression of ATP-insensitive KATP channels in pancreatic beta-cells underlies a spectrum of diabetic phenotypes. Diabetes 55: 29572964, 2006 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 60

    Chen Y, Chang AR, McAdams DeMarco MA, Inker LA, Matsushita K, Ballew SH, et al.: Serum potassium, mortality, and kidney outcomes in the Atherosclerosis Risk in Communities Study. Mayo Clin Proc 91: 14031412, 2016 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 61

    Collins AJ, Pitt B, Reaven N, Funk S, McGaughey K, Wilson D, et al.: Association of serum potassium with all-cause mortality in patients with and without heart failure, chronic kidney disease, and/or diabetes. Am J Nephrol 46: 213221, 2017 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 62

    Crews DC, Kuczmarski MF, Miller ER 3rd, Zonderman AB, Evans MK, Powe NR: Dietary habits, poverty, and chronic kidney disease in an urban population. J Ren Nutr 25: 103110, 2015 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 63

    Liu Y, Kuczmarski MF, Miller ER 3rd, Nava MB, Zonderman AB, Evans MK, et al.: Dietary habits and risk of kidney function decline in an urban population. J Ren Nutr 27: 1625, 2017

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 64

    Kim HW, Park JT, Yoo TH, Lee J, Chung W, Lee KB, et al.; KNOW-CKD Study Investigators: Urinary potassium excretion and progression of CKD. Clin J Am Soc Nephrol 14: 330340, 2019 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 65

    Kieneker LM, Bakker SJ, de Boer RA, Navis GJ, Gansevoort RT, Joosten MM: Low potassium excretion but not high sodium excretion is associated with increased risk of developing chronic kidney disease. Kidney Int 90: 888896, 2016 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 66

    Korgaonkar S, Tilea A, Gillespie BW, Kiser M, Eisele G, Finkelstein F, et al.: Serum potassium and outcomes in CKD: Insights from the RRI-CKD cohort study. Clin J Am Soc Nephrol 5: 762769, 2010 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 67

    Leonberg-Yoo AK, Tighiouart H, Levey AS, Beck GJ, Sarnak MJ: Urine potassium excretion, kidney failure, and mortality in CKD. Am J Kidney Dis 69: 341349, 2017 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 68

    He J, Mills KT, Appel LJ, Yang W, Chen J, Lee BT, et al.; Chronic Renal Insufficiency Cohort Study Investigators: Urinary sodium and potassium excretion and CKD progression. J Am Soc Nephrol 27: 12021212, 2016 PubMed

    • PubMed
    • Search Google Scholar
    • Export Citation

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