Background/Aims: Hypokalemia and hyperkalemia are often noted in chronic kidney disease (CKD) patients, but their impact on mortality and end-stage renal disease (ESRD) is less well understood. We aimed at studying the associations between potassium disorders, and mortality and progression to ESRD in a CKD population. Methods: Using our electronic health record-based CKD registry, 36,359 patients with eGFR <60 ml/min/1.73 m2 and potassium levels measured from January 1, 2005 to September 15, 2009 were identified. We examined factors associated with hypokalemia (<3.5 mmol/l) and hyperkalemia (>5.0 mmol/l) using logistic regression models and associations between serum potassium levels (both as continuous and categorical variables) and all-cause mortality or ESRD using Cox-proportional hazards models. Results: Serum potassium <3.5 mmol/l was noted among 3% and >5.0 mmol/l among 11% of the study population. In the multivariable logistic regression analysis, lower eGFR, diabetes and use of ACE inhibitors or Angiotensin-Receptor Blockers were associated with higher odds of having hyperkalemia. Heart failure and African American race were factors associated with higher odds of hypokalemia. After adjustment for covariates including kidney function, serum potassium <4.0 and >5.0 mmol/l were significantly associated with increased mortality risk, but there was no increased risk for progression to ESRD. Time-dependent repeated measures analysis confirmed these findings. When potassium was examined as a continuous variable, there was a U-shaped association between serum potassium levels and mortality. Conclusion: In patients with stage 3-4 CKD, serum potassium levels <4.0 and >5.0 mmol/l are associated with higher mortality but not with ESRD.

1.
Stanton BA: Renal potassium transport: morphological and functional adaptations. Am J Physiol 1989;257(5 pt 2):R989-R997.
2.
Gonick HC, Kleeman CR, Rubini ME, Maxwell MH: Functional impairment in chronic renal disease. 3. Studies of potassium excretion. Am J Med Sci 1971;261:281-290.
3.
Palmer BF: Managing hyperkalemia caused by inhibitors of the renin-angiotensin-aldosterone system. N Engl J Med 2004;351:585-592.
4.
Genovesi S, Valsecchi MG, Rossi E, Pogliani D, Acquistapace I, De Cristofaro V, et al: Sudden death and associated factors in a historical cohort of chronic haemodialysis patients. Nephrol Dial Transplant 2009;24:2529-2536.
5.
Unruh ML, Evans IV, Fink NE, Powe NR, Meyer KB; Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) Study: Skipped treatments, markers of nutritional nonadherence, and survival among incident hemodialysis patients. Am J Kidney Dis 2005;46:1107-1116.
6.
Lowrie EG, Lew NL: 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.
7.
Hayes J, Kalantar-Zadeh K, Lu JL, Turban S, Anderson JE, Kovesdy CP: 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.
8.
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 2010;5:762-769.
9.
Sinha AD, Agarwal R: Chronic renal disease progression: treatment strategies and potassium intake. Semin Nephrol 2013;33:290-299.
10.
Weir MR, Fink JC: Salt intake and progression of chronic kidney disease: an overlooked modifiable exposure? A commentary. Am J Kidney Dis 2005;45:176-188.
11.
Wang W, Soltero L, Zhang P, Huang XR, Lan HY, Adrogue HJ: Renal inflammation is modulated by potassium in chronic kidney disease: possible role of Smad7. Am J Physiol Renal Physiol 2007;293:F1123-F1130.
12.
Reungjui S, Roncal CA, Sato W, Glushakova OY, Croker BP, Suga S, et al: Hypokalemic nephropathy is associated with impaired angiogenesis. J Am Soc Nephrol 2008;19:125-134.
13.
Navaneethan SD, Jolly SE, Schold JD, Arrigain S, Saupe W, Sharp J, et al: Development and validation of an electronic health record-based chronic kidney disease registry. Clin J Am Soc Nephrol 2011;6:40-49.
14.
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al: A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604-612.
15.
Moranne O, Froissart M, Rossert J, Gauci C, Boffa JJ, Haymann JP, et al. Timing of onset of CKD-related metabolic complications. J Am Soc Nephrol 2009;20:164-171.
16.
Perez GO, Pelleya R, Oster JR, Kem DC, Vaamonde CA: Blunted kaliuresis after an acute potassium load in patients with chronic renal failure. Kidney Int 1983;24:656-662.
17.
Kraft MD, Btaiche IF, Sacks GS, Kudsk KA: Treatment of electrolyte disorders in adult patients in the intensive care unit. Am J Health Syst Pharm 2005;62:1663-1682.
18.
Williams ME: Endocrine crises. Hyperkalemia. Crit Care Clin 1991;7:155-174.
19.
Seliger SL, Zhan M, Hsu VD, Walker LD, Fink JC: Chronic kidney disease adversely influences patient safety. J Am Soc Nephrol 2008;19:2414-2419.
20.
Reardon LC, Macpherson DS: Hyperkalemia in outpatients using angiotensin-converting enzyme inhibitors. How much should we worry? Arch Intern Med 1998;158:26-32.
21.
Tannen RL: Diuretic-induced hypokalemia. Kidney Int 1985;28:988-1000.
22.
Berenson GS, Voors AW, Dalferes ER Jr, Webber LS, Shuler SE: Creatinine clearance, electrolytes, and plasma renin activity related to the blood pressure of white and black children - the Bogalusa heart study. J Lab Clin Med 1979;93:535-548.
23.
Lasker N, Hopp L, Grossman S, Bamforth R, Aviv A: Race and sex differences in erythrocyte Na+, K+, and Na+-K+-adenosine triphosphatase. J Clin Invest 1985;75:1813-1820.
24.
Gallen IW, Rosa RM, Esparaz DY, Young JB, Robertson GL, Batlle D, et al: On the mechanism of the effects of potassium restriction on blood pressure and renal sodium retention. Am J Kidney Dis 1998;31:19-27.
25.
Voors AW, Dalferes ER Jr, Frank GC, Aristimuno GG, Berenson GS: Relation between ingested potassium and sodium balance in young blacks and whites. Am J Clin Nutr 1983;37:583-594.
26.
Ahmed A, Zannad F, Love TE, Tallaj J, Gheorghiade M, Ekundayo OJ, et al: A propensity-matched study of the association of low serum potassium levels and mortality in chronic heart failure. Eur Heart J 2007;28:1334-1343.
27.
Hunt SA; American College of Cardiology; American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol 2005;46:e1-e82.
28.
Bowling CB, Pitt B, Ahmed MI, Aban IB, Sanders PW, Mujib M, et al: Hypokalemia and outcomes in patients with chronic heart failure and chronic kidney disease: findings from propensity-matched studies. Circ Heart Fail 2010;3:253-260.
29.
Schulman M, Narins RG: Hypokalemia and cardiovascular disease. Am J Cardiol 1990;65:4E-9E; discussion 22E-23E.
30.
Erlinger TP, Tarver-Carr ME, Powe NR, Appel LJ, Coresh J, Eberhardt MS, et al: Leukocytosis, hypoalbuminemia, and the risk for chronic kidney disease in US adults. Am J Kidney Dis 2003;42:256-263.
31.
Einhorn LM, Zhan M, Hsu VD, Walker LD, Moen MF, Seliger SL, et al: The frequency of hyperkalemia and its significance in chronic kidney disease. Arch Intern Med 2009;169:1156-1162.
32.
Surawicz B, Chlebus H, Mazzoleni A: Hemodynamic and electrocardiographic effects of hyperpotassemia. Differences in response to slow and rapid increases in concentration of plasma K. Am Heart J 1967;73:647-664.
33.
Elger M, Bankir L, Kriz W: Morphometric analysis of kidney hypertrophy in rats after chronic potassium depletion. Am J Physiol 1992;262(4 pt 2):F656-F667.
34.
Ray PE, Suga S, Liu XH, Huang X, Johnson RJ: Chronic potassium depletion induces renal injury, salt sensitivity, and hypertension in young rats. Kidney Int 2001;59:1850-1858.
35.
Drawz PE, Goswami P, Azem R, Babineau DC, Rahman M: A simple tool to predict end-stage renal disease within 1 year in elderly adults with advanced chronic kidney disease. J Am Geriatr Soc 2013;61:762-768.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.