New options for the management of chronic hyperkalemia

Linda Fried, Csaba P Kovesdy, Biff F Palmer, Linda Fried, Csaba P Kovesdy, Biff F Palmer

Abstract

Hyperkalemia is a frequently detected electrolyte abnormality that can cause life-threatening complications. Hyperkalemia is most often the result of intrinsic (decreased glomerular filtration rate; selective reduction in distal tubule secretory function; impaired mineralocorticoid activity; and metabolic disturbances, such as acidemia and hyperglycemia) and extrinsic factors (e.g., drugs, such as renin-angiotensin-aldosterone system inhibitors, and potassium intake). The frequent use of renin-angiotensin-aldosterone system inhibitors in patients who are already susceptible to hyperkalemia (e.g., patients with chronic kidney disease, diabetes mellitus, or congestive heart failure) contributes to the high incidence of hyperkalemia. There is a need to understand the causes of hyperkalemia and to be aware of strategies addressing the disorder in a way that provides the most optimal outcome for affected patients. The recent development of 2 new oral potassium-binding agents has led to the emergence of a new paradigm in the treatment of hyperkalemia.

Keywords: chronic kidney disease; hyperkalemia; potassium; treatment.

References

    1. Coresh J., Selvin E., Stevens L.A. Prevalence of chronic kidney disease in the United States. JAMA. 2007;298:2038–2047.
    1. Kovesdy C.P. Management of hyperkalaemia in chronic kidney disease. Nat Rev Nephrol. 2014;10:653–662.
    1. Einhorn L.M., Zhan M., Hsu V.D. The frequency of hyperkalemia and its significance in chronic kidney disease. Arch Intern Med. 2009;169:1156–1162.
    1. Palmer B.F. Managing hyperkalemia caused by inhibitors of the renin-angiotensin-aldosterone system. N Engl J Med. 2004;351:585–592.
    1. Palmer B.F. Hyperkalemia in predialysis patients. Clin J Am Soc Nephrol. 2012;7:1201–1202.
    1. Palmer B.F., Clegg D.J. Achieving the benefits of a high-potassium, paleolithic diet, without the toxicity. Mayo Clin Proc. 2016;91:496–508.
    1. Kayexalate; Sodium Polystyrene Sulfonate, USP Cation-Exchange Resin [Food and Drug Administration drug label]. Bridgewater, NJ: Sanofi-Aventis U.S. LLC; revised April 2009. Available at: . Accessed June 27, 2017.
    1. Flinn R.B., Merrill J.P., Welzant W.R. Treatment of the oliguric patient with a new sodium-exchange resin and sorbitol; a preliminary report. N Engl J Med. 1961;264:111–115.
    1. Scherr L., Ogden D.A., Mead A.W. Management of hyperkalemia with a cation-exchange resin. N Engl J Med. 1961;264:115–119.
    1. Kovesdy C.P. Management of hyperkalemia: an update for the internist. Am J Med. 2015;128:1281–1287.
    1. Kovesdy C.P. Updates in hyperkalemia: outcomes and therapeutic strategies. Rev Endocr Metab Disord. 2017;18:41–47.
    1. Palmer B.F. Regulation of potassium homeostasis. Clin J Am Soc Nephrol. 2015;10:1050–1060.
    1. Gumz M.L., Rabinowitz L., Wingo C.S. An integrated view of potassium homeostasis. N Engl J Med. 2015;373:60–72.
    1. Mathialahan T., MacLennan K.A., Sandle L.N. Enhanced large intestinal potassium permeability in end-stage renal disease. J Pathol. 2005;206:46–51.
    1. Hayes C.P., Jr., Robinson R.R. Fecal potassium excretion in patients on chronic intermittent hemodialysis. Trans Am Soc Artif Intern Organs. 1965;11:242–246.
    1. Hayes C.P., Jr., McLeod M.E., Robinson R.R. An extrarenal mechanism for the maintenance of potassium balance in severe chronic renal failure. Trans Assoc Am Physicians. 1967;80:207–216.
    1. Palmer B.F. A physiologic-based approach to the evaluation of a patient with hypokalemia. Am J Kidney Dis. 2010;56:1184–1190.
    1. Hene R.J., Koomans H.A., Boer P. Adaptation to chronic potassium loading in normal man. Miner Electrolyte Metab. 1986;12:165–172.
    1. Jenkins D.J., Kendall C.W., Popovich D.G. Effect of a very-high-fiber vegetable, fruit, and nut diet on serum lipids and colonic function. Metabolism. 2001;50:494–503.
    1. Rabelink T.J., Koomans H.A., Hene R.J. Early and late adjustment to potassium loading in humans. Kidney Int. 1990;38:942–947.
    1. Sebastian A., Harris S.T., Ottaway J.H. Improved mineral balance and skeletal metabolism in postmenopausal women treated with potassium bicarbonate. N Engl J Med. 1994;330:1776–1781.
    1. Witzgall H., Behr J. Effects of potassium loading in normal man on dopaminergic control of mineralocorticoids and renin release. J Hypertens. 1986;4:201–205.
    1. Brandis M., Keyes J., Windhager E.E. Potassium-induced inhibition of proximal tubular fluid reabsorption in rats. Am J Physiol. 1972;222:421–427.
    1. Stokes J.B. 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. 1982;70:219–229.
    1. Sufit C.R., Jamison R.L. Effect of acute potassium load on reabsorption in Henle's loop in the rat. Am J Physiol. 1983;245:F569–F576.
    1. Cheng C.J., Baum M., Huang C.L. Kidney-specific WNK1 regulates sodium reabsorption and potassium secretion in mouse cortical collecting duct. Am J Physiol Renal Physiol. 2013;304:F397–F402.
    1. Hadchouel J., Ellison D.H., Gamba G. Regulation of renal electrolyte transport by WNK and SPAK-OSR1 kinases. Annu Rev Physiol. 2016;78:367–389.
    1. Liu Z., Xie J., Wu T. Downregulation of NCC and NKCC2 cotransporters by kidney-specific WNK1 revealed by gene disruption and transgenic mouse models. Hum Mol Genet. 2011;20:855–866.
    1. Lee F.N., Oh G., McDonough A.A. Evidence for gut factor in K+ homeostasis. Am J Physiol Renal Physiol. 2007;293:F541–F547.
    1. Oh K.S., Oh Y.T., Kim S.W. Gut sensing of dietary K(+) intake increases renal K(+)excretion. Am J Physiol Regul Integr Comp Physiol. 2011;301:R421–R429.
    1. Youn J.H. Gut sensing of potassium intake and its role in potassium homeostasis. Semin Nephrol. 2013;33:248–256.
    1. Preston R.A., Afshartous D., Rodco R. Evidence for a gastrointestinal-renal kaliuretic signaling axis in humans. Kidney Int. 2015;88:1383–1391.
    1. Schultze R.G., Taggart D.D., Shapiro H. On the adaptation in potassium excretion associated with nephron reduction in the dog. J Clin Invest. 1971;50:1061–1068.
    1. Fine L.G., Yanagawa N., Schultze R.G. Functional profile of the isolated uremic nephron: potassium adaptation in the rabbit cortical collecting tubule. J Clin Invest. 1979;64:1033–1043.
    1. Stanton B.A. Renal potassium transport: morphological and functional adaptations. Am J Physiol. 1989;257:R989–R997.
    1. Bourgoignie J.J., Kaplan M., Pincus J. Renal handling of potassium in dogs with chronic renal insufficiency. Kidney Int. 1981;20:482–490.
    1. Mulkerrin E., Epstein F.H., Clark B.A. Aldosterone responses to hyperkalemia in healthy elderly humans. J Am Soc Nephrol. 1995;6:1459–1462.
    1. Bird S.T., Pepe S.R., Etminan M. The association between drospirenone and hyperkalemia: a comparative-safety study. BMC Clin Pharmacol. 2011;11:23.
    1. Epstein F.H. Signs and symptoms of electrolyte disorders. In: Maxwell M.H., Kleeman C.R., editors. Clinical Disorders of Fluid and Electrolyte Metabolism. 3rd ed. McGraw-Hill; New York: 1980. pp. 499–516.
    1. Fisch C. Electrolytes and the heart. In: Hurst J.W., editor. The Heart. McGraw-Hill; New York: 1982. p. 1599.
    1. US Dept of Health and Human Services, Agency for HealthCare Research and Quality. Web site. Available at: . Accessed December 21, 2015.
    1. Hayes J., Kalantar-Zadeh K., Lu J.L. Association of hypo- and hyperkalemia with disease progression and mortality in males with chronic kidney disease: the role of race. Nephron Clin Pract. 2012;120:c8–c16.
    1. Korgaonkar S., Tilea A., Gillespie B.W. Serum potassium and outcomes in CKD: insights from the RRI-CKD cohort study. Clin J Am Soc Nephrol. 2010;5:762–769.
    1. Collins A.J., Pitt B., Reaven N. Association of serum potassium with all-cause mortality in patients with and without heart failure, chronic kidney disease, and/or diabetes. Am J Nephrol. 2017;46:213–221.
    1. Lowrie E.G., Lew N.L. Death risk in hemodialysis patients: the predictive value of commonly measured variables and an evaluation of death rate differences between facilities. Am J Kidney Dis. 1990;15:458–482.
    1. Iseki K., Uehara H., Nishime K. Impact of the initial levels of laboratory variables on survival in chronic dialysis patients. Am J Kidney Dis. 1996;28:541–548.
    1. Kovesdy C.P., Regidor D.L., Mehrotra R. Serum and dialysate potassium concentrations and survival in hemodialysis patients. Clin J Am Soc Nephrol. 2007;2:999–1007.
    1. Goyal A., Spertus J.A., Gosch K. Serum potassium levels and mortality in acute myocardial infarction. JAMA. 2012;307:157–164.
    1. Yetkin E., Ileri M., Tandogan I. Increased QT interval dispersion after hemodialysis: role of peridialytic electrolyte gradients. Angiology. 2000;51:499–504.
    1. Nappi S.E., Virtanen V.K., Saha H.H. QTc dispersion increases during hemodialysis with low-calcium dialysate. Kidney Int. 2000;57:2117–2122.
    1. Burton J.O., Korsheed S., Grundy B.J. Hemodialysis-induced left ventricular dysfunction is associated with an increase in ventricular arrhythmias. Ren Fail. 2008;30:701–709.
    1. Voroneanu L., Covic A. Arrhythmias in hemodialysis patients. J Nephrol. 2009;22:716–725.
    1. Selby N.M., McIntyre C.W. The acute cardiac effects of dialysis. Semin Dial. 2007;20:220–228.
    1. Fordjour K.N., Walton T., Doran J.J. Management of hyperkalemia in hospitalized patients. Am J Med Sci. 2014;347:93–100.
    1. Dubose T.D., Jr. Hyperkalemic hyperchloremic metabolic acidosis: pathophysiologic insights. Kidney Int. 1997;51:591–602.
    1. Kovesdy C.P. Metabolic acidosis and kidney disease: does bicarbonate therapy slow the progression of CKD? Nephrol Dial Transplant. 2012;27:3056–3062.
    1. de Brito-Ashurst I., Varagunam M., Raftery M.J. Bicarbonate supplementation slows progression of CKD and improves nutritional status. J Am Soc Nephrol. 2009;20:2075–2084.
    1. Goraya N., Simoni J., Jo C. Dietary acid reduction with fruits and vegetables or bicarbonate attenuates kidney injury in patients with a moderately reduced glomerular filtration rate due to hypertensive nephropathy. Kidney Int. 2012;81:86–93.
    1. Rossignol P., Legrand M., Kosiborod M. Emergency management of severe hyperkalemia: guideline for best practice and opportunities for the future. Pharmacol Res. 2016;113:585–591.
    1. Allon M., Copkney C. Albuterol and insulin for treatment of hyperkalemia in hemodialysis patients. Kidney Int. 1990;38:869–872.
    1. Blumberg A., Weidmann P., Shaw S. Effect of various therapeutic approaches on plasma potassium and major regulating factors in terminal renal failure. Am J Med. 1988;85:507–512.
    1. Fried L.F., Emanuele N., Zhang J.H. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med. 2013;369:1892–1903.
    1. Marques J.S., Diogo A.N. Dead man walking: an extreme case of sinusoidal wave pattern in severe hyperkalemia. J Am Coll Cardiol. 2012;59:2118.
    1. Petrov D.B. Images in clinical medicine. An electrocardiographic sine wave in hyperkalemia. N Engl J Med. 2012;366:1824.
    1. Siniorakis E., Arvanitakis S., Psatheris G. Hyperkalaemia, pseudohyperkalaemia and electrocardiographic correlates. Int J Cardiol. 2011;148:242–243.
    1. Jadoul M., Thumma J., Fuller D.S. Modifiable practices associated with sudden death among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study. Clin J Am Soc Nephrol. 2012;7:765–774.
    1. Karaboyas A., Zee J., Brunelli S.M. Dialysate potassium, serum potassium, mortality, and arrhythmia events in hemodialysis: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS) Am J Kidney Dis. 2017;69:266–277.
    1. Lepage L., Dufour A.C., Doiron J. Randomized clinical trial of sodium polystyrene sulfonate for the treatment of mild hyperkalemia in CKD. Clin J Am Soc Nephrol. 2015;10:2136–2142.
    1. Chelcun J.L., Sable R.A., Friedman K. Colonic ulceration in a patient with renal disease and hyperkalemia. JAAPA. 2012;25 34, 37–34, 38.
    1. Gorospe E.C., Lewis J.T., Bruining D.H. Kayexalate-induced esophageal ulcer in a patient with gastroparesis. Clin Gastroenterol Hepatol. 2012;10:A28.
    1. Joo M., Bae W.K., Kim N.H. Colonic mucosal necrosis following administration of calcium polystryrene sulfonate (Kalimate) in a uremic patient. J Korean Med Sci. 2009;24:1207–1211.
    1. Takeuchi N., Nomura Y., Meda T. Development of colonic perforation during calcium polystyrene sulfonate administration: a case report. Case Rep Med. 2013;2013:102614.
    1. Harel Z., Harel S., Shah P.S. Gastrointestinal adverse events with sodium polystyrene sulfonate (Kayexalate) use: a systematic review. Am J Med. 2013;126 264.e9–e24.
    1. Gerstman B.B., Kirkman R., Platt R. Intestinal necrosis associated with postoperative orally administered sodium polystyrene sulfonate in sorbitol. Am J Kidney Dis. 1992;20:159–161.
    1. Sterns R.H., Rojas M., Bernstein P. Ion-exchange resins for the treatment of hyperkalemia: are they safe and effective? J Am Soc Nephrol. 2010;21:733–735.
    1. Chaitman M., Dixit D., Bridgeman M.B. Potassium-binding agents for the clinical management of hyperkalemia. P T. 2016;41:43–50.
    1. Weir M.R., Bakris G.L., Bushinsky D.A. Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med. 2015;372:211–221.
    1. Bakris G.L., Pitt B., Weir M.R. Effect of patiromer on serum potassium level in patients with hyperkalemia and diabetic kidney disease: the AMETHYST-DN Randomized Clinical Trial. JAMA. 2015;314:151–161.
    1. Packham D.K., Rasmussen H.S., Lavin P.T. Sodium zirconium cyclosilicate in hyperkalemia. N Engl J Med. 2015;372:222–231.
    1. Kosiborod M., Rasmussen H.S., Lavin P. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical trial. JAMA. 2014;312:2223–2233.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe