Abstract
The kidney plays an essential role in maintaining homeostasis of ion concentrations in the blood. Because the concentration gradient of potassium across the cell membrane is a key determinant of the membrane potential of cells, even small deviations in serum potassium level from the normal setpoint can lead to severe muscle dysfunction, resulting in respiratory failure and cardiac arrest. Less severe hypo- and hyperkalemia are also associated with morbidity and mortality across various patient populations. In addition, deficiencies in potassium intake have been associated with hypertension and adverse cardiovascular and renal outcomes, likely due in part to the interrelated handling of sodium and potassium by the kidney. Here, data on the beneficial effects of potassium on blood pressure and cardiovascular and renal outcomes will be reviewed, along with the physiological basis for these effects. In some patient populations, however, potassium excess is deleterious. Risk factors for the development of hyperkalemia will be reviewed, as well as the risks and benefits of existing and emerging therapies for hyperkalemia.
Similar content being viewed by others
References
Murray CJ, Lopez AD (2013) Measuring the global burden of disease. N Engl J Med 369:448–457
Keith NM, Binger MW (1935) Diuretic action of potassium. J Am Med Assoc 105:1584–1591
Barker M (1932) Edema as influenced by a low ratio of sodium to potassium intake: clinical observations. J Am Med Assoc 98:2193–2197
Aburto NJ, Hanson S, Gutierrez H, Hooper L, Elliott P, Cappuccio FP (2013) Effect of increased potassium intake on cardiovascular risk factors and disease: systematic review and meta-analyses. BMJ 346:f1378
National Academy of Sciences, Institute of Medicine, Food and Nutrition Board (2005) Dietary reference intakes for water, potassium, sodium, chloride, and sulfate. The National Academies Press, Washington, DC
Mente A, O'Donnell MJ, Rangarajan S, McQueen MJ, Poirier P, Wielgosz A, Morrison H, Li W, Wang X, Di C, Mony P, Devanath A, Rosengren A, Oguz A, Zatonska K, Yusufali AH, Lopez-Jaramillo P, Avezum A, Ismail N, Lanas F, Puoane T, Diaz R, Kelishadi R, Iqbal R, Yusuf R, Chifamba J, Khatib R, Teo K, Yusuf S, PURE Investigators (2014) Association of urinary sodium and potassium excretion with blood pressure. N Engl J Med 371:601–611
Cogswell ME, Zhang Z, Carriquiry AL, Gunn JP, Kuklina EV, Saydah SH, Yang Q, Moshfegh AJ (2012) Sodium and potassium intakes among US adults: NHANES 2003–2008. Am J Clin Nutr 96:647–657
O'Donnell M, Mente A, Rangarajan S, McQueen MJ, Wang X, Liu L, Yan H, Lee SF, Mony P, Devanath A, Rosengren A, Lopez-Jaramillo P, Diaz R, Avezum A, Lanas F, Yusoff K, Iqbal R, Ilow R, Mohammadifard N, Gulec S, Yusufali AH, Kruger L, Yusuf R, Chifamba J, Kabali C, Dagenais G, Lear SA, Teo K, Yusuf S, PURE Investigators (2014) Urinary sodium and potassium excretion, mortality, and cardiovascular events. N Engl J Med 371:612–623
Smyth A, Dunkler D, Gao P, Teo KK, Yusuf S, O'Donnell MJ, Mann JF, Clase CM, ONTARGET and TRANSCEND Investigators (2014) The relationship between estimated sodium and potassium excretion and subsequent renal outcomes. Kidney Int 86:1205–1212
Araki S, Haneda M, Koya D, Kondo K, Tanaka S, Arima H, Kume S, Nakazawa J, Chin-Kanasaki M, Ugi S, Kawai H, Araki H, Uzu T, Maegawa H (2015) Urinary potassium excretion and renal and cardiovascular complications in patients with type 2 diabetes and normal renal function. Clin J Am Soc Nephrol 10:2152–2158
He J, Mills KT, Appel LJ, Yang W, Chen J, Lee BT, Rosas SE, Porter A, Makos G, Weir MR, Hamm LL, Kusek JW, Chronic Renal Insufficiency Cohort Study Investigators (2016) Urinary sodium and potassium excretion and CKD progression. J Am Soc Nephrol 27:1202–1212
Geleijnse JM, Grobbee DE, Hofman A (1990) Sodium and potassium intake and blood pressure change in childhood. BMJ 300:899–902
Buendia JR, Bradlee ML, Daniels SR, Singer MR, Moore LL (2015) Longitudinal effects of dietary sodium and potassium on blood pressure in adolescent girls. JAMA Pediatr 169:560–568
Womersley RA, Darragh JH (1955) Potassium and sodium restriction in the normal human. J Clin Invest 34:456–461
Krishna GG, Miller E, Kapoor S (1989) Increased blood-pressure during potassium-depletion in normotensive men. N Engl J Med 320:1177–1182
Malnic G, Giebisch G, Muto S, Wang W, Bailey MA, Satlin LM (2013) Chapter 49 - regulation of K+ excretion. In: Caplan RJAWM (ed) Seldin and Giebisch’s the kidney, 5th edn. Academic Press, Cambridge, pp 1659–1715
Welling PA (2013) Regulation of renal potassium secretion: molecular mechanisms. Semin Nephrol 33:215–228
Satlin LM (2004) Developmental regulation of expression of renal potassium secretory channels. Curr Opin Nephrol Hypertens 13:445–450
Brandis M, Keyes J, Windhager EE (1972) Potassium-induced inhibition of proximal tubular fluid reabsorption in rats. Am J Physiol 222:421–427
Stokes JB (1982) Consequences of potassium recycling in the renal medulla. Effects of ion transport by the medullary thick ascending limb of Henle’s loop. J Clin Invest 70:219–229
Battilana CA, Dobyan DC, Lacy FB, Bhattacharya J, Johnston PA, Jamison RL (1978) Effect of chronic potassium loading on potassium secretion by the pars recta or descending limb of the juxtamedullary nephron in the rat. J Clin Invest 62:1093–1103
Higashihara E, Kokko JP (1985) Effects of aldosterone on potassium recycling in the kidney of adrenalectomized rats. Am J Physiol 248:F219–F227
Cheng CJ, Truong T, Baum M, Huang CL (2012) Kidney-specific WNK1 inhibits sodium reabsorption in the cortical thick ascending limb. Am J Physiol Renal Physiol 303:F667–F673
Pacheco-Alvarez D, Cristobal PS, Meade P, Moreno E, Vazquez N, Munoz E, Diaz A, Juarez ME, Gimenez I, Gamba G (2006) The Na+:Cl- cotransporter is activated and phosphorylated at the amino-terminal domain upon intracellular chloride depletion. J Biol Chem 281:28755–28763
Richardson C, Rafiqi FH, Karlsson HK, Moleleki N, Vandewalle A, Campbell DG, Morrice NA, Alessi DR (2008) Activation of the thiazide-sensitive Na+−Cl- cotransporter by the WNK-regulated kinases SPAK and OSR1. J Cell Sci 121:675–684
Wade JB, Fang L, Coleman RA, Liu J, Grimm PR, Wang T, Welling PA (2011) Differential regulation of ROMK (Kir1.1) in distal nephron segments by dietary potassium. Am J Physiol Renal Physiol 300:F1385–F1393
van der Lubbe N, Moes AD, Rosenbaek LL, Schoep S, Meima ME, Danser AH, Fenton RA, Zietse R, Hoorn EJ (2013) K + −induced natriuresis is preserved during Na+ depletion and accompanied by inhibition of the Na+−Cl-cotransporter. Am J Physiol Renal Physiol 305:F1177–F1188
Rengarajan S, Lee DH, Oh YT, Delpire E, Youn JH, McDonough AA (2014) Increasing plasma [K+] by intravenous potassium infusion reduces NCC phosphorylation and drives kaliuresis and natriuresis. Am J Physiol Renal Physiol 306:F1059–F1068
Castaneda-Bueno M, Cervantes-Perez LG, Rojas-Vega L, Arroyo-Garza I, Vazquez N, Moreno E, Gamba G (2014) Modulation of NCC activity by low and high K(+) intake: insights into the signaling pathways involved. Am J Physiol Renal Physiol 306:F1507–F1519
Vallon V, Schroth J, Lang F, Kuhl D, Uchida S (2009) Expression and phosphorylation of the Na+−Cl-cotransporter NCC in vivo is regulated by dietary salt, potassium, and SGK1. Am J Physiol Renal Physiol 297:F704–F712
Frindt G, Houde V, Palmer LG (2011) Conservation of Na+ vs. K+ by the rat cortical collecting duct. Am J Physiol Renal Physiol 301:F14–F20
Wade JB, Liu J, Coleman R, Grimm PR, Delpire E, Welling PA (2015) SPAK-mediated NCC regulation in response to low-K+ diet. Am J Physiol Renal Physiol 308:F923–F931
Sorensen MV, Grossmann S, Roesinger M, Gresko N, Todkar AP, Barmettler G, Ziegler U, Odermatt A, Loffing-Cueni D, Loffing J (2013) Rapid dephosphorylation of the renal sodium chloride cotransporter in response to oral potassium intake in mice. Kidney Int 83:811–824
Chiga M, Rai T, Yang SS, Ohta A, Takizawa T, Sasaki S, Uchida S (2008) Dietary salt regulates the phosphorylation of OSR1/SPAK kinases and the sodium chloride cotransporter through aldosterone. Kidney Int 74:1403–1409
Turban S, Thompson CB, Parekh RS, Appel LJ (2013) Effects of sodium intake and diet on racial differences in urinary potassium excretion: results from the dietary approaches to stop hypertension (DASH)-sodium trial. Am J Kidney Dis 61:88–95
Vitzthum H, Seniuk A, Schulte LH, Muller ML, Hetz H, Ehmke H (2014) Functional coupling of renal K+ and Na+ handling causes high blood pressure in Na + replete mice. J Physiol 592:1139–1157
Terker AS, Zhang C, McCormick JA, Lazelle RA, Zhang C, Meermeier NP, Siler DA, Park HJ, Fu Y, Cohen DM, Weinstein AM, Wang WH, Yang CL, Ellison DH (2015) Potassium modulates electrolyte balance and blood pressure through effects on distal cell voltage and chloride. Cell Metab 21:39–50
Hou J, Renigunta A, Yang J, Waldegger S (2010) Claudin-4 forms paracellular chloride channel in the kidney and requires claudin-8 for tight junction localization. Proc Natl Acad Sci USA 107:18010–18015
Gong Y, Wang J, Yang J, Gonzales E, Perez R, Hou J (2015) KLHL3 regulates paracellular chloride transport in the kidney by ubiquitination of claudin-8. Proc Natl Acad Sci USA 112:4340–4345
Gong Y, Yu M, Yang J, Gonzales E, Perez R, Hou M, Tripathi P, Hering-Smith KS, Hamm LL, Hou J (2014) The Cap1-claudin-4 regulatory pathway is important for renal chloride reabsorption and blood pressure regulation. Proc Natl Acad Sci USA 111:E3766–E3774
Terada Y, Knepper MA (1990) Thiazide-sensitive NaCl absorption in rat cortical collecting duct. Am J Physiol 259:F519–F528
Gueutin V, Vallet M, Jayat M, Peti-Peterdi J, Corniere N, Leviel F, Sohet F, Wagner CA, Eladari D, Chambrey R (2013) Renal beta-intercalated cells maintain body fluid and electrolyte balance. J Clin Invest 123:4219–4231
Chambrey R, Kurth I, Peti-Peterdi J, Houillier P, Purkerson JM, Leviel F, Hentschke M, Zdebik AA, Schwartz GJ, Hubner CA, Eladari D (2013) Renal intercalated cells are rather energized by a proton than a sodium pump. Proc Natl Acad Sci USA 110:7928–7933
Leviel F, Hubner CA, Houillier P, Morla L, El Moghrabi S, Brideau G, Hassan H, Parker MD, Kurth I, Kougioumtzes A, Sinning A, Pech V, Riemondy KA, Miller RL, Hummler E, Shull GE, Aronson PS, Doucet A, Wall SM, Chambrey R, Eladari D (2010) The Na+-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na + reabsorption process in the renal cortical collecting ducts of mice. J Clin Invest 120:1627–1635
Ellison DH, Velazquez H, Wright FS (1989) Adaptation of the distal convoluted tubule of the rat. Structural and functional effects of dietary salt intake and chronic diuretic infusion. J Clin Invest 83:113–126
Nesterov V, Dahlmann A, Krueger B, Bertog M, Loffing J, Korbmacher C (2012) Aldosterone-dependent and -independent regulation of the epithelial sodium channel (ENaC) in mouse distal nephron. Am J Physiol Renal Physiol 303:F1289–F1299
Frindt G, Sackin H, Palmer LG (1990) Whole-cell currents in rat cortical collecting tubule: low-Na diet increases amiloride-sensitive conductance. Am J Physiol 258:F562–F567
Shibata S, Rinehart J, Zhang J, Moeckel G, Castaneda-Bueno M, Stiegler AL, Boggon TJ, Gamba G, Lifton RP (2013) Mineralocorticoid receptor phosphorylation regulates ligand binding and renal response to volume depletion and hyperkalemia. Cell Metab 18:660–671
Grimm PR, Lazo-Fernandez Y, Delpire E, Wall SM, Dorsey SG, Weinman EJ, Coleman R, Wade JB, Welling PA (2015) Integrated compensatory network is activated in the absence of NCC phosphorylation. J Clin Invest 125:2136–2150
Yang SS, Lo YF, Wu CC, Lin SW, Yeh CJ, Chu P, Sytwu HK, Uchida S, Sasaki S, Lin SH (2010) SPAK-knockout mice manifest Gitelman syndrome and impaired vasoconstriction. J Am Soc Nephrol 21:1868–1877
Grimm PR, Taneja TK, Liu J, Coleman R, Chen YY, Delpire E, Wade JB, Welling PA (2012) SPAK isoforms and OSR1 regulate sodium-chloride co-transporters in a nephron-specific manner. J Biol Chem 287:37673–37690
Tokonami N, Morla L, Centeno G, Mordasini D, Ramakrishnan SK, Nikolaeva S, Wagner CA, Bonny O, Houillier P, Doucet A, Firsov D (2013) alpha-Ketoglutarate regulates acid–base balance through an intrarenal paracrine mechanism. J Clin Invest 123:3166–3171
Soleimani M, Barone S, Xu J, Shull GE, Siddiqui F, Zahedi K, Amlal H (2012) Double knockout of pendrin and Na-Cl cotransporter (NCC) causes severe salt wasting, volume depletion, and renal failure. Proc Natl Acad Sci USA 109:13368–13373
Pela I, Bigozzi M, Bianchi B (2008) Profound hypokalemia and hypochloremic metabolic alkalosis during thiazide therapy in a child with Pendred syndrome. Clin Nephrol 69:450–453
Xu B, English JM, Wilsbacher JL, Stippec S, Goldsmith EJ, Cobb MH (2000) WNK1, a novel mammalian serine/threonine protein kinase lacking the catalytic lysine in subdomain II. J Biol Chem 275:16795–16801
Wilson FH, Disse-Nicodeme S, Choate KA, Ishikawa K, Nelson-Williams C, Desitter I, Gunel M, Milford DV, Lipkin GW, Achard JM, Feely MP, Dussol B, Berland Y, Unwin RJ, Mayan H, Simon DB, Farfel Z, Jeunemaitre X, Lifton RP (2001) Human hypertension caused by mutations in WNK kinases. Science 293:1107–1112
Hadchouel J, Ellison DH, Gamba G (2016) Regulation of renal electrolyte transport by WNK and SPAK-OSR1 kinases. Annu Rev Physiol 78:367–389
Rodan AR, Baum M, Huang CL (2012) The drosophila NKCC Ncc69 is required for normal renal tubule function. Am J Physiol Cell Physiol 303:C883–C894
Wu Y, Schellinger JN, Huang CL, Rodan AR (2014) Hypotonicity stimulates potassium flux through the WNK-SPAK/OSR1 kinase cascade and the Ncc69 sodium-potassium-2-chloride cotransporter in the drosophila renal tubule. J Biol Chem 289:26131–26142
Dbouk HA, Huang CL, Cobb MH (2016) Hypertension: the missing WNKs. Am J Physiol Renal Physiol. doi:10.1152/ajprenal.00358.2015
Piala AT, Moon TM, Akella R, He H, Cobb MH, Goldsmith EJ (2014) Chloride sensing by WNK1 involves inhibition of autophosphorylation. Sci Signal 7:ra41
Terker AS, Zhang C, Erspamer KJ, Gamba G, Yang CL, Ellison DH (2015) Unique chloride-sensing properties of WNK4 permit the distal nephron to modulate potassium homeostasis. Kidney Int. doi:10.1038/ki.2015.289
Petrov DB (2012) Images in clinical medicine. An electrocardiographic sine wave in hyperkalemia. N Engl J Med 366:1824
Cheng CJ, Kuo E, Huang CL (2013) Extracellular potassium homeostasis: insights from hypokalemic periodic paralysis. Semin Nephrol 33:237–247
Palmer BF (2010) A physiologic-based approach to the evaluation of a patient with hyperkalemia. Am J Kidney Dis 56:387–393
Palmer BF (2004) Managing hyperkalemia caused by inhibitors of the renin-angiotensin-aldosterone system. N Engl J Med 351:585–592
Einhorn LM, Zhan M, Hsu VD, Walker LD, Moen MF, Seliger SL, Weir MR, Fink JC (2009) The frequency of hyperkalemia and its significance in chronic kidney disease. Arch Intern Med 169:1156–1162
Jain N, Kotla S, Little BB, Weideman RA, Brilakis ES, Reilly RF, Banerjee S (2012) Predictors of hyperkalemia and death in patients with cardiac and renal disease. Am J Cardiol 109:1510–1513
Michel A, Martin-Perez M, Ruigomez A, Garcia Rodriguez LA (2015) Risk factors for hyperkalaemia in a cohort of patients with newly diagnosed heart failure: a nested case–control study in UK general practice. Eur J Heart Fail 17:205–213
Korgaonkar S, Tilea A, Gillespie BW, Kiser M, Eisele G, Finkelstein F, Kotanko P, Pitt B, Saran R (2010) Serum potassium and outcomes in CKD: insights from the RRI-CKD cohort study. Clin J Am Soc Nephrol 5:762–769
Gwoo S, Kim YN, Shin HS, Jung YS, Rim H (2014) Predictors of hyperkalemia risk after hypertension control with aldosterone blockade according to the presence or absence of chronic kidney disease. Nephron Clin Pract 128:381–386
Weinberg JM, Appel LJ, Bakris G, Gassman JJ, Greene T, Kendrick CA, Wang X, Lash J, Lewis JA, Pogue V, Thornley-Brown D, Phillips RA, African American Study of Hypertension and Kidney Disease Collaborative Research Group (2009) Risk of hyperkalemia in nondiabetic patients with chronic kidney disease receiving antihypertensive therapy. Arch Intern Med 169:1587–1594
Alappan R, Buller GK, Perazella MA (1999) Trimethoprim-sulfamethoxazole therapy in outpatients: is hyperkalemia a significant problem? Am J Nephrol 19:389–394
Antoniou T, Gomes T, Juurlink DN, Loutfy MR, Glazier RH, Mamdani MM (2010) Trimethoprim-sulfamethoxazole-induced hyperkalemia in patients receiving inhibitors of the renin-angiotensin system: a population-based study. Arch Intern Med 170:1045–1049
Antoniou T, Gomes T, Mamdani MM, Yao Z, Hellings C, Garg AX, Weir MA, Juurlink DN (2011) Trimethoprim-sulfamethoxazole induced hyperkalaemia in elderly patients receiving spironolactone: nested case–control study. BMJ 343:d5228
Antoniou T, Hollands S, MacDonald EM, Gomes T, Mamdani MM, Juurlink DN, Canadian Drug Safety and Effectiveness Research Network (2015) Trimethoprim-sulfamethoxazole and risk of sudden death among patients taking spironolactone. CMAJ 187:E138–E143
Fralick M, MacDonald EM, Gomes T, Antoniou T, Hollands S, Mamdani MM, Juurlink DN, Canadian Drug Safety and Effectiveness ResearchNetwork (2014) Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population based study. BMJ 349:g6196
Muschart X, Boulouffe C, Jamart J, Nougon G, Gerard V, de Canniere L, Vanpee D (2014) A determination of the current causes of hyperkalaemia and whether they have changed over the past 25 years. Acta Clin Belg 69:280–284
Weir MR, Rolfe M (2010) Potassium homeostasis and renin-angiotensin-aldosterone system inhibitors. Clin J Am Soc Nephrol 5:531–548
Juurlink DN, Mamdani MM, Lee DS, Kopp A, Austin PC, Laupacis A, Redelmeier DA (2004) Rates of hyperkalemia after publication of the randomized aldactone evaluation study. N Engl J Med 351:543–551
Moore C, Lin J, McGinn T, Halm E (2007) Factors associated with time to follow-up of severe hyperkalemia in the ambulatory setting. Am J Med Qual 22:428–437
Moore CR, Lin JJ, O'Connor N, Halm EA (2006) Follow-up of markedly elevated serum potassium results in the ambulatory setting: implications for patient safety. Am J Med Qual 21:115–124
Field MJ, Stanton BA, Giebisch GH (1984) Differential acute effects of aldosterone, dexamethasone, and hyperkalemia on distal tubular potassium secretion in the rat kidney. J Clin Invest 74:1792–1802
Hirsch D, Kashgarian M, Boulpaep EL, Hayslett JP (1984) Role of aldosterone in the mechanism of potassium adaptation in the initial collecting tubule. Kidney Int 26:798–807
Stanton B, Pan L, Deetjen H, Guckian V, Giebisch G (1987) Independent effects of aldosterone and potassium on induction of potassium adaptation in rat kidney. J Clin Invest 79:198–206
Wingo CS, Seldin DW, Kokko JP, Jacobson HR (1982) Dietary modulation of active potassium secretion in the cortical collecting tubule of adrenalectomized rabbits. J Clin Invest 70:579–586
Young DB (1988) Quantitative analysis of aldosterone’s role in potassium regulation. Am J Physiol 255:F811–F822
Frindt G, Palmer LG (2009) K+ secretion in the rat kidney: Na+ channel-dependent and -independent mechanisms. Am J Physiol Renal Physiol 297:F389–F396
Todkar A, Picard N, Loffing-Cueni D, Sorensen MV, Mihailova M, Nesterov V, Makhanova N, Korbmacher C, Wagner CA, Loffing J (2015) Mechanisms of renal control of potassium homeostasis in complete aldosterone deficiency. J Am Soc Nephrol 26:425–438
Van Buren PN, Adams-Huet B, Nguyen M, Molina C, Toto RD (2014) Potassium handling with dual renin-angiotensin system inhibition in diabetic nephropathy. Clin J Am Soc Nephrol 9:295–301
Walsh M, Manns B, Garg AX, Bueti J, Rabbat C, Smyth A, Tyrwhitt J, Bosch J, Gao P, Devereaux PJ, Wald R (2015) The safety of eplerenone in hemodialysis patients: a noninferiority randomized controlled trial. Clin J Am Soc Nephrol 10:1602–1608
Bowling CB, Pitt B, Ahmed MI, Aban IB, Sanders PW, Mujib M, Campbell RC, Love TE, Aronow WS, Allman RM, Bakris GL, Ahmed A (2010) Hypokalemia and outcomes in patients with chronic heart failure and chronic kidney disease: findings from propensity-matched studies. Circ Heart Fail 3:253–260
Luo J, Brunelli SM, Jensen DE, Yang A (2016) Association between serum potassium and outcomes in patients with reduced kidney function. Clin J Am Soc Nephrol 11:90–100
Kovesdy CP (2014) Management of hyperkalaemia in chronic kidney disease. Nat Rev Nephrol 10:653–662
Nguyen TQ, Maalouf NM, Sakhaee K, Moe OW (2011) Comparison of insulin action on glucose versus potassium uptake in humans. Clin J Am Soc Nephrol 6:1533–1539
Sterns RH, Rojas M, Bernstein P, Chennupati S (2010) Ion-exchange resins for the treatment of hyperkalemia: are they safe and effective? J Am Soc Nephrol 21:733–735
Food and Drug Administration (2011) Kayexelate (sodium polystyrene sulfonate) powder. Detailed view: safety labeling changes approved by FDA Center for Drug Evaluation and Research (CDER). Food and Drug Administration, Washington DC. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm186845.htm
Watson MA, Baker TP, Nguyen A, Sebastianelli ME, Stewart HL, Oliver DK, Abbott KC, Yuan CM (2012) Association of prescription of oral sodium polystyrene sulfonate with sorbitol in an inpatient setting with colonic necrosis: a retrospective cohort study. Am J Kidney Dis 60:409–416
Lepage L, Dufour AC, Doiron J, Handfield K, Desforges K, Bell R, Vallee M, Savoie M, Perreault S, Laurin LP, Pichette V, Lafrance JP (2015) Randomized clinical trial of sodium polystyrene sulfonate for the treatment of mild hyperkalemia in CKD. Clin J Am Soc Nephrol 10:2136–2142
Kessler C, Ng J, Valdez K, Xie H, Geiger B (2011) The use of sodium polystyrene sulfonate in the inpatient management of hyperkalemia. J Hosp Med 6:136–140
Fordjour KN, Walton T, Doran JJ (2014) Management of hyperkalemia in hospitalized patients. Am J Med Sci 347:93–100
Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S, RENAAL Study Investigators (2001) Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 345:861–869
Lewis EJ, Hunsicker LG, Bain RP, Rohde RD (1993) The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 329:1456–1462
Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R, Raz I, Collaborative Study Group (2001) Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 345:851–860
Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R, Hurley S, Kleiman J, Gatlin M, Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators (2003) Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med 348:1309–1321
Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J (1999) The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med 341:709–717
Pitt B, Anker SD, Bushinsky DA, Kitzman DW, Zannad F, Huang IZ, PEARL-HF Investigators (2011) Evaluation of the efficacy and safety of RLY5016, a polymeric potassium binder, in a double-blind, placebo-controlled study in patients with chronic heart failure (the PEARL-HF) trial. Eur Heart J 32:820–828
Weir MR, Bakris GL, Bushinsky DA, Mayo MR, Garza D, Stasiv Y, Wittes J, Christ-Schmidt H, Berman L, Pitt B, OPAL-HK Investigators (2015) Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med 372:211–221
Bakris GL, Pitt B, Weir MR, Freeman MW, Mayo MR, Garza D, Stasiv Y, Zawadzki R, Berman L, Bushinsky DA, AMETHYST-DN Investigators (2015) Effect of patiromer on serum potassium level in patients with hyperkalemia and diabetic kidney disease: the AMETHYST-DN randomized clinical trial. JAMA 314:151–161
Federal Drug Administration (2015) FDA approves new drug to treat hyperkalemia. Federal Drug Administration, Washington DC. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm468546.htm. Accessed 27 Feb 2016
Federal Drug Administration (2015) FDA drug safety communication: FDA requires drug interaction studies with potassium-lowering drug Kayexelate (sodium polystyrene sulfonate). Federal Drug Administration, Washington, DC. Available at: http://www.fda.gov/Drugs/DrugSafety/ucm468035.htm. Accessed 27 Feb 2016
Stavros F, Yang A, Leon A, Nuttall M, Rasmussen HS (2014) Characterization of structure and function of ZS-9, a K+ selective ion trap. PLoS One 9:e114686
Ash SR, Singh B, Lavin PT, Stavros F, Rasmussen HS (2015) A phase 2 study on the treatment of hyperkalemia in patients with chronic kidney disease suggests that the selective potassium trap, ZS-9, is safe and efficient. Kidney Int 88:404–411
Packham DK, Rasmussen HS, Lavin PT, El-Shahawy MA, Roger SD, Block G, Qunibi W, Pergola P, Singh B (2015) Sodium zirconium cyclosilicate in hyperkalemia. N Engl J Med 372:222–231
Kosiborod M, Rasmussen HS, Lavin P, Qunibi WY, Spinowitz B, Packham D, Roger SD, Yang A, Lerma E, Singh B (2014) Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical trial. JAMA 312:2223–2233
Kosiborod M, Peacock WF, Packham DK (2015) Sodium zirconium cyclosilicate for urgent therapy of severe hyperkalemia. N Engl J Med 372:1577–1578
Bushinsky DA, Williams GH, Pitt B, Weir MR, Freeman MW, Garza D, Stasiv Y, Li E, Berman L, Bakris GL (2015) Patiromer induces rapid and sustained potassium lowering in patients with chronic kidney disease and hyperkalemia. Kidney Int 88:1427–1433
Acknowledgments
The author would like to thank Dr. Jyothsna Gattineni for helpful discussion. ARR is supported by NIH grants DK091316 and DK106350.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The author declares no conflict of interest.
Rights and permissions
About this article
Cite this article
Rodan, A.R. Potassium: friend or foe?. Pediatr Nephrol 32, 1109–1121 (2017). https://doi.org/10.1007/s00467-016-3411-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-016-3411-8