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Nephro Flash 2016 › Nephro Flash Vol-2, No-3, 2016

The Importance of Potassium Balance in Maintenance Hemodialysis

Introduction

The primary goal of maintenance hemodialysis is to balance the extracellular fluid volume (ECV) by preserving the electrolyte equilibrium via interdialytic electrolyte intake and removal during the therapy.1Lee SW. Sodium Balance in Maintenance Hemodialysis. Electrolytes & Blood Pressure : E & BP. 2012;10(1):1-6.  Although the advent of hemodialysis has enabled nephrologists to enhance the quality of life of the individuals, potassium balance is one of the dangers that accompanies end-stage renal disease (ESRD) cases.2Sanghavi S, Whiting S, Uribarri J. Potassium balance in dialysis patients. Semin Dial. 2013 Sep-Oct;26(5):597-603.  3Musso CG. Potassium metabolism in patients with chronic kidney disease (CKD), Part I: patients not on dialysis (stages 3-4). Int Urol Nephrol. 2004;36(3):465-8.  Dyskalemia is a prevalent electrolyte imbalance observed amongst maintenance hemodialysis patients.4Choi HY, Ha SK. Potassium Balances in Maintenance Hemodialysis. Electrolytes & Blood Pressure : E & BP. 2013;11(1):9-16.  This can result either in hyperkalemia or hypokalemia. Hypokalemia, in contrast to its counterpart, is responsible for several complications and is believed as an independent prognostic factor of hemodialysis. Altered potassium intake or inadequate dialysis are accused as preliminary causes of the potassium-imbalance in more than half of ESRD patients; however other contributory factors including certain therapeutic agents and miscellaneous causes are still to be demystified.5Kim H-J. Pathogenesis and Treatment of Dyskalemia in Maintenance Hemodialysis and CAPD. Electrolytes & Blood Pressure : E & BP. 2006;4(1):47- 52.  

Pathophysiology of Hypokalemia

The kidneys, in their steady state, play a central role in the regulation of potassium (Figure 1).6Hughes J, Jefferson JA. Clinical Chemistry Made Easy. Elsevier Health Sciences; 2008. Chapter 2, Disorders of potassium balance; 21-37.  During an imbalance, the ability of the kidneys to excrete potassium is hampered proportionally to the loss of glomerular filtration. The main factors of hyperkalemia include: use of ACEIs, ARBs, NSAIDs, aldosterone antagonists, nonselective beta-blockers, heparin, trimetoprim, calcineurin inhibitors.7Arroyo AR. Electrolyte and acid-base balance disorders in advanced chronic kidney disease. Nefrologia. 2008;28 Suppl 3:87-93.  Cellular uptake i.e. the shift of potassium in the extracellular to intracellular compartments, and bowel loss are also considered as potential players in the pathogenesis.4Choi HY, Ha SK. Potassium Balances in Maintenance Hemodialysis. Electrolytes & Blood Pressure : E & BP. 2013;11(1):9-16.  8Kim H-W, Chang JH, Park SY, et al. Factors associated with Hypokalemia in Continuous Ambulatory Peritoneal Dialysis Patients. Electrolytes & Blood Pressure : E & BP. 2007;5(2):102-110.  Furthermore, amongst hemodialysis patients, hypokalemia is induced by a plethora of factors affecting internal and external potassium balance. The internal potassium balance involves diminished potassium uptake by cells because of uremia, acidosis, drugs, and hormonal alterations, which in turn affect the potassium movement and its redistribution between the intracellular and the extracellular compartments. On the other hand, the external balance includes retarded renal excretion, lower dietary intake, and high stool fractional excretion of potassium. To evaluate this, a study8Kim H-W, Chang JH, Park SY, et al. Factors associated with Hypokalemia in Continuous Ambulatory Peritoneal Dialysis Patients. Electrolytes & Blood Pressure : E & BP. 2007;5(2):102-110.  assessed the underlying driving forces of hypokalemia in maintenance dialysis patients by calculating the amount of potassium-intake minus that of urinary and peritoneal potassium excretion, and considering stool potassium losses of around 6-50 mEq/day. The results revealed that not just external factors but also certain internal ones were responsible for the development of hypokalemia.

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Sequelae of Hypokalemia

Amongst individuals with ESRD on maintenance hemodialysis, regulating the levels of serum potassium and other electrolytes within a normal range remains a challenge.9Hung AM, Hakim RM. Dialysate and serum potassium in hemodialysis. Am J Kidney Dis. 2015 Jul;66(1):125-32.  Below mentioned are a few commonly noted manifestations in this patient population.

Potential Cardiac Manifestations

Several studies show very prominent ECG changes in cases with hypokalemia.10Marti G, Schwarz C, Leichtle AB, Fiedler GM, Arampatzis S, Exadaktylos AK, Lindner G. Etiology and symptoms of severe hypokalemia in emergency department patients. Eur J Emerg Med. 2014 Feb;21(1):46-51.  A distinctive decrease in the T-wave amplitude is commonly observed. As potassium levels decline further, ST-segment depression and T-wave inversions are visualized, while the PR interval usually gets prolonged along with an increase in the amplitude of the P wave. In cases of severe hypokalemia, T- and U-wave merge showing giant U-waves masking the smaller preceding T waves. In addition, a pseudo-prolonged QT interval is also observed in some ECGs, which is actually the QU interval with an absent T wave. Frequent incidence of tachyarrhythmias, ventricular tachycardia/fibrillation, and occasional atrioventricular block are observed in individuals with severe hypokalemia.11Levis JT. ECG Diagnosis: Hypokalemia. The Permanente Journal. 2012;16(2):57.    12Diercks DB, Shumaik GM, Harrigan RA, Brady WJ, Chan TC. Electrocardiographic manifestations: electrolyte abnormalities. J Emerg Med. 2004;27(2):153-60.   13El-Sherif N, Turitto G. Electrolyte disorders and arrythmogenesis. Cardiol J. 2011;18(3):233-45.    14Glancy DL, Wiklow FE, Rochon BJ. Electrocardiogram after 2 weeks of diarrhea. Proc (Bayl Univ Med Cent) 2010;23(2):173-4.  

Medication-Induced Hypokalemia

Medication-induced hypokalemia is much prevalent. Certain ongoing therapies (Table 1) are responsible in making the patient vulnerable to a variety of mechanical alterations, including intracellular potassium shifting, increased renal loss, and/or stool loss of potassium, thereby resulting in hypokalemia.15Veltri KT, Mason C. Medication-Induced Hypokalemia. Pharmacy and Therapeutics. 2015;40(3):185-190.  Therefore, considering the entangled pathophysiological mechanisms and multifaceted consequences associated with hypokalemia, early initiation of the management strategies, involving the continuous regulation of potassium levels, are highly necessitated.

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Management of Hypokalemia in Hemodialysis Patients

The cornerstone treatment strategy for hypokalemia in maintenance hemodialysis patients is to balance the levels of potassium and also to ameliorate the risk of associated comorbidities. Potassium supplementation is the key to the therapy and is usually achieved with the oral administration of potassium preparations.4Choi HY, Ha SK. Potassium Balances in Maintenance Hemodialysis. Electrolytes & Blood Pressure : E & BP. 2013;11(1):9-16.   The four vital goals in managing hypokalemia include16Glover P. Hypokalemia. Crit Care Resusc. 1999 Sep;1(3):239-51.  :

  • To minimize the potassium losses
  • To replenish the potassium stores
  • To evaluate potential toxicities
  • To determine the underlying cause to prevent recurrences.

Moreover, as it is mentioned that hypokalemia is associated with the use of certain medications (Table 1), especially diuretics (the common causative agents for hypokalemia), it may be prudent to discontinue using or, if deemed necessary, switch over to potassium sparing diuretics like triamterene, amiloride, spironolactone, etc.16Glover P. Hypokalemia. Crit Care Resusc. 1999 Sep;1(3):239-51.  17Mahmood MM, John K. Hypokalemia: common but not always benign. Severe,persistent hypokalemia secondary to ectopic ACTH from a carcinoid tumour. BMJ Case Rep. 2012;2012. pii: bcr-2012-007193.  The treatment of hypokalemia invariably involves replenishing the potassium levels. Increasing potassium intake should therefore be considered when serum potassium levels are between 3.5 and 4.0 mmol.18Lederer E, Alsauskas ZC, Mackelaite L, et al. Hypokalemia Treatment & Management. Available at: http://emedicine. medscape.com/article/242008- treatment [Accessed on 8/8/2013].  Focusing on patients with hypokalemia undergoing maintenance hemodialysis therapy, the role of potassium chloride and potassium citrate has been observed valuable.4Choi HY, Ha SK. Potassium Balances in Maintenance Hemodialysis. Electrolytes & Blood Pressure : E & BP. 2013;11(1):9-16.  

Potassium Chloride

Potassium chloride is the preferred potassium supplement in treating mild or moderate hypokalemia in hemodialysis patients as it demonstrates a unique effectiveness against the most common causes of potassium depletion.19Cohn JN, Kowey PR, Whelton PK, Prisant LM. New Guidelines for Potassium eplacement in Clinical Practice. A Contemporary Review by the National Council on Potassium in Clinical Practice. Arch Intern Med. 2000;160:2429-2436.  Usually a dose of 50 to 100 mmol of potassium chloride is required per day in order to maintain serum potassium concentration within the normal range in patients with increased potassium loss (such as those receiving a diuretic). Moreover, potassium chloride may also be used in a pre-operative setting as a prophylactic measure for hypokalemia. It has been observed that oral potassium chloride with oral rehydration solution supplement for sodium phosphate bowel preparation regimen can prevent hypokalemia prior to surgery.20Kamolpornwijit W, Phupong V. Oral potassium chloride and oral rehydration solution supplement to prevent hypokalemia in sodium phosphate regimen for bowel preparation prior to gynecological laparoscopic surgery. J Med Assoc Thai. 2008 May;91(5):615-8.  This agent is available in liquid or tablet formulations19Cohn JN, Kowey PR, Whelton PK, Prisant LM. New Guidelines for Potassium eplacement in Clinical Practice. A Contemporary Review by the National Council on Potassium in Clinical Practice. Arch Intern Med. 2000;160:2429-2436.  ; however, while tablets have a number of attributes, such as the size of medication, ease of swallowing, and rate of disintegration, which might limit their use, liquid formulation has immediate effect with few erosions.

A study21Amirmokri P, Morgan P, Bastani B. Intra-peritoneal administration of potassium and magnesium: a practical method to supplement these electrolytes in peritoneal dialysis patients. Ren Fail. 2007;29(5):603-5.  assessed the effects of administration of potassium chloride in patients with hypokalemia due to various reasons (malnutrition and gastrointestinal losses) during dialysis. Overall, 27 individuals on continuous cyclic maintenance dialysis were recommended oral potassium supplements. The outcomes divulged that 60-80 mEq of potassium chloride (KCl) when added to a 2 liter, 2.5% dialysis solution bag, the mean serum potassium concentration increased from a baseline of 3.2 mEq/L to 4.1, 4.2, 4.1, and 4.2 mEq/L at 2, 4, 6-8, and 20-24 hours post-administration of KCl, correspondingly (Figure 2). In addition, the therapy was well-tolerated with trivial adverse events. Serum potassium concentration was normalized in all patients deducing that potassium chloride supplementation in patients with hypokalemia is a valuable, practical, and efficient method to regulate the level of potassium in maintenance dialysis patients.

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Potassium Citrate

The above mentioned data proves that potassium chloride supplementation is an effective treatment option in up-regulating the levels of serum potassium levels in maintenance hemodialysis patients. On similar grounds, the potency of potassium citrate is also well-established in the literature.4Choi HY, Ha SK. Potassium Balances in Maintenance Hemodialysis. Electrolytes & Blood Pressure : E & BP. 2013;11(1):9-16.   Potassium citrate, while being an effective urinary alkalinizer, also displays an acceptable tolerability profile as well.22Zuckerman JM, Assimos DG. Hypocitraturia: Pathophysiology and Medical Management. Rev Urol. 2009;11(3):134-144.  23Whitmore KE. Complementary and Alternative Therapies as Treatment Approaches for Interstitial Cystitis. Rev Urol. 2002;4(Suppl 1):S28-S35.  It neither neutralizes the gastric juice nor alters the digestion.24Sweetman S. Martindale: The Complete Drug Reference. Edition 37;London:pharmaceutical press; 2011.  Other advantages of potassium citrate include high palatability, pleasant taste, and tolerable even on prolonged use, which make it suitable to be considered as a first line urine alkalizing agent.25Sakhaee K, Nicar M, Hill K, Pak CY. Contrasting effects of potassium citrate and sodium citrate therapies on urinary chemistries and crystallization of stoneforming salts. Kidney International. 1983;24:348-352.  The effect of one tablet of potassium citrate lasts for around 12 hours. It has been observed that multiple doses of this agent can be administered for up to 3 days.26Drugs. Com. Available at: http://www.drugs.com/mmx/potassium-citrateandsodium-citrate.html. Accessed on: 23.3.2016.  Further, it is preferred over sodium containing salts, such as sodium bicarbonate or sodium citrate, as the latter may result in excessive sodium load and thus has to be carefully used in patients with hypertension, heart failure, edema, renal impairment, eclampsia, or hyperaldosteronism.24Sweetman S. Martindale: The Complete Drug Reference. Edition 37;London:pharmaceutical press; 2011.  25Sakhaee K, Nicar M, Hill K, Pak CY. Contrasting effects of potassium citrate and sodium citrate therapies on urinary chemistries and crystallization of stoneforming salts. Kidney International. 1983;24:348-352.  

Ruml et al27Singh N, Gandhi S, McArthur E, et al. Kidney function and the use of nitrofurantoin to treat urinary tract infections in older women. CMAJ : Canadian Medical Association Journal. 2015;187(9):648-656.  assessed the efficacy of potassium magnesium citrate, magnesium citrate, and potassium citrate in overcoming thiazide-induced hypokalemia and magnesium loss. Overall, 62 healthy patients were first given hydrochlorothiazide, 50 mg/d. After 3 weeks of thiazide treatment (or earlier for potassium level

  • All the three agents amplified the serum potassium concentration compared with that resulting from thiazide alone
  • Potassium magnesium citrate increased serum potassium levels from 3.3 +/- 0.2 to 3.8 +/- 0.3 mEq/L
  • Additionally, potassium citrate escalated the serum potassium levels from 3.4 +/- 0.4 to 3.9 +/-0.3 mEq/L, and magnesium citrate from 3.4 +/- 0.4 to 3.7 +/- 0.3 mEq/L

Therefore, it was inferred that potassium magnesium citrate and potassium citrate significantly increase the urinary pH and citrate values in patients with hypokalemia.

Conclusion

Hypokalemia remains one of the most common complications in maintenance hemodialysis patients as potassium balance is one of the dangers that accompany ESRD patients. Hypokalemia, in contrast to hyperkalemia, is responsible for several complications and is believed to be an independent prognostic factor of hemodialysis. If left untreated, hypokalemia present with a number of consequences namely, cardiovascular complications with initial dramatic ECG changes, and certain neuromuscular disorders such as hypokalemia quadriparesis. Investigators have also ruled out a number of medications which significantly make the patient vulnerable to drastic potassium imbalances, divulging in hypokalemia. A multifaceted therapeutic approach focuses on the use of certain potassium substitutes which up-regulate the levels of this electrolyte, thereby improving the condition in hemodialysis cases. A plethora of studies show that potassium chloride and potassium citrate are one of the most valuable as well as well-tolerated agents which significantly normalize the potassium levels.

References

  1. Lee SW. Sodium Balance in Maintenance Hemodialysis. Electrolytes & Blood Pressure : E & BP. 2012;10(1):1-6.
  2. Sanghavi S, Whiting S, Uribarri J. Potassium balance in dialysis patients. Semin Dial. 2013 Sep-Oct;26(5):597-603.
  3. Musso CG. Potassium metabolism in patients with chronic kidney disease (CKD), Part I: patients not on dialysis (stages 3-4). Int Urol Nephrol. 2004;36(3):465-8.
  4. Choi HY, Ha SK. Potassium Balances in Maintenance Hemodialysis. Electrolytes & Blood Pressure : E & BP. 2013;11(1):9-16.
  5. Kim H-J. Pathogenesis and Treatment of Dyskalemia in Maintenance Hemodialysis and CAPD. Electrolytes & Blood Pressure : E & BP. 2006;4(1):47- 52.
  6. Hughes J, Jefferson JA. Clinical Chemistry Made Easy. Elsevier Health Sciences; 2008. Chapter 2, Disorders of potassium balance; 21-37.
  7. Arroyo AR. Electrolyte and acid-base balance disorders in advanced chronic kidney disease. Nefrologia. 2008;28 Suppl 3:87-93.
  8. Kim H-W, Chang JH, Park SY, et al. Factors associated with Hypokalemia in Continuous Ambulatory Peritoneal Dialysis Patients. Electrolytes & Blood Pressure : E & BP. 2007;5(2):102-110.
  9. Hung AM, Hakim RM. Dialysate and serum potassium in hemodialysis. Am J Kidney Dis. 2015 Jul;66(1):125-32.
  10. Marti G, Schwarz C, Leichtle AB, Fiedler GM, Arampatzis S, Exadaktylos AK, Lindner G. Etiology and symptoms of severe hypokalemia in emergency department patients. Eur J Emerg Med. 2014 Feb;21(1):46-51.
  11. Levis JT. ECG Diagnosis: Hypokalemia. The Permanente Journal. 2012;16(2):57.
  12. Diercks DB, Shumaik GM, Harrigan RA, Brady WJ, Chan TC. Electrocardiographic manifestations: electrolyte abnormalities. J Emerg Med. 2004;27(2):153-60.
  13. El-Sherif N, Turitto G. Electrolyte disorders and arrythmogenesis. Cardiol J. 2011;18(3):233-45.
  14. Glancy DL, Wiklow FE, Rochon BJ. Electrocardiogram after 2 weeks of diarrhea. Proc (Bayl Univ Med Cent) 2010;23(2):173-4.
  15. Veltri KT, Mason C. Medication-Induced Hypokalemia. Pharmacy and Therapeutics. 2015;40(3):185-190.
  16. Glover P. Hypokalemia. Crit Care Resusc. 1999 Sep;1(3):239-51.
  17. Mahmood MM, John K. Hypokalemia: common but not always benign. Severe,persistent hypokalemia secondary to ectopic ACTH from a carcinoid tumour. BMJ Case Rep. 2012;2012. pii: bcr-2012-007193.
  18. Lederer E, Alsauskas ZC, Mackelaite L, et al. Hypokalemia Treatment & Management. Available at: http://emedicine. medscape.com/article/242008- treatment [Accessed on 8/8/2013].
  19. Cohn JN, Kowey PR, Whelton PK, Prisant LM. New Guidelines for Potassium eplacement in Clinical Practice. A Contemporary Review by the National Council on Potassium in Clinical Practice. Arch Intern Med. 2000;160:2429-2436.
  20. Kamolpornwijit W, Phupong V. Oral potassium chloride and oral rehydration solution supplement to prevent hypokalemia in sodium phosphate regimen for bowel preparation prior to gynecological laparoscopic surgery. J Med Assoc Thai. 2008 May;91(5):615-8.
  21. Amirmokri P, Morgan P, Bastani B. Intra-peritoneal administration of potassium and magnesium: a practical method to supplement these electrolytes in peritoneal dialysis patients. Ren Fail. 2007;29(5):603-5.
  22. Zuckerman JM, Assimos DG. Hypocitraturia: Pathophysiology and Medical Management. Rev Urol. 2009;11(3):134-144.
  23. Whitmore KE. Complementary and Alternative Therapies as Treatment Approaches for Interstitial Cystitis. Rev Urol. 2002;4(Suppl 1):S28-S35.
  24. Sweetman S. Martindale: The Complete Drug Reference. Edition 37;London:pharmaceutical press; 2011.
  25. Sakhaee K, Nicar M, Hill K, Pak CY. Contrasting effects of potassium citrate and sodium citrate therapies on urinary chemistries and crystallization of stoneforming salts. Kidney International. 1983;24:348-352.
  26. Drugs. Com. Available at: http://www.drugs.com/mmx/potassium-citrateandsodium-citrate.html. Accessed on: 23.3.2016.
  27. Ruml LA, Pak CY. Effect of potassium magnesium citrate on thiazide-induced hypokalemia and magnesium loss. Am J Kidney Dis. 1999 Jul;34(1):107-13.
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