• 1.

    Leonberg-Yoo AK, et al. Urine potassium excretion, kidney failure, and mortality in CKD. Am J Kidney Dis 2017; 69:341349. doi: 10.1053/j.ajkd.2016.03.431

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Gritter M, et al. Effects of short-term potassium chloride supplementation in patients with chronic kidney disease. J Am Soc Nephrol, published online ahead of print May 24, 2022. doi: 10.1681/asn.2022020147; https://jasn.asnjournals.org/content/33/9/1779

    • Search Google Scholar
    • Export Citation
  • 3.

    Terker AS, et al. Unique chloride-sensing properties of WNK4 permit the distal nephron to modulate potassium homeostasis. Kidney Int 2016; 89:127134. doi: 10.1038/ki.2015.289

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Grimm PR, et al. Regulated dephosphorylation of NCC shapes the renal potassium switch pathway. FASEB J 2018; 32(S1):620.12. doi: 10.1096/fasebj.2018.32.1_supplement.620.12; https://faseb.onlinelibrary.wiley.com/doi/10.1096/fasebj.2018.32.1_supplement.620.12

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Kovesdy CP, et al. Serum potassium and adverse outcomes across the range of kidney function: A CKD Prognosis Consortium meta-analysis. Eur Heart J 2018; 39:15351542. doi: 10.1093/eurheartj/ehy100

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Neal B, et al. Effect of salt substitution on cardiovascular events and death. N Engl J Med 2021; 385:10671077. doi: 10.1056/NEJMoa2105675

  • 7.

    Morris Jr. RC, et al. Differing effects of supplemental KCl and KHCO3: Pathophysiological and clinical implications. Semin Nephrol 1999; 19:487493. PMID: 10511388; https://www.researchgate.net/publication/12789862_Differing_effects_of_supplemental_KCl_and_KHCO3_Pathophysiological_and_clinical_implications

    • Search Google Scholar
    • Export Citation
  • 8.

    Boyd-Shiwarski CR, et al. Effects of extreme potassium stress on blood pressure and renal tubular sodium transport. Am J Physiol Renal Physiol 2020; 318:F1341F1356. doi: 10.1152/ajprenal.00527.2019

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Appel LJ, et al. A clinical trial of the effects of dietary patterns on blood pressure. N Engl J Med 1997; 336:11171124. doi: 10.1056/NEJM199704173361601

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Verma A, et al. Aldosterone in chronic kidney disease and renal outcomes. Eur Heart J 2022;00:111. https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehac352/6652163?login=false

    • Search Google Scholar
    • Export Citation
  • 11.

    Oberleithner H, et al. Endothelial cells as vascular salt sensors. Kidney Int 2010; 77:490494. doi: 10.1038/ki.2009.490

  • 12.

    Bakris GL, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med 2020; 383:22192229. doi: 10.1056/nejmoa2025845

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Pitt B, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med 2021; 385:22522263. doi: 10.1056/nejmoa2110956

    • Crossref
    • Search Google Scholar
    • Export Citation

Potassium Supplementation in Chronic Kidney Disease

Carmen CajinaCarmen Cajina, MD, and Vivek Bhalla, MD, are with the Division of Nephrology and the Stanford Hypertension Center, Department of Medicine, Stanford University School of Medicine, Stanford, CA.

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Vivek BhallaCarmen Cajina, MD, and Vivek Bhalla, MD, are with the Division of Nephrology and the Stanford Hypertension Center, Department of Medicine, Stanford University School of Medicine, Stanford, CA.

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Cardiovascular disease represents the leading cause of mortality in chronic kidney disease (CKD), and higher odds of cardiovascular events are associated with lower dietary potassium intake in the general population (1). However, due to the intrinsic risk of hyperkalemia, the effects and applicability of supplementation in patients with CKD are poorly studied.

A new study was published in JASN (2) based on a prespecified analysis of an ongoing randomized controlled trial, which includes 191 patients with CKD stage G3b-4. Thirty-eight percent of patients have diabetes mellitus, and 83% were prescribed renin-angiotensin system inhibitors. During the run-in phase, patients received 40 mmol/day of potassium chloride for 2 weeks. This intervention resulted in the following: an increase in serum potassium of 0.4 mmol/L; no significant effect on blood pressure, estimated glomerular filtration rate, albuminuria, or urinary sodium excretion; and hyperkalemia (plasma potassium, 5.9 ± 0.4 mmol/L) in 21 participants (11%). Multivariable analysis demonstrated that older age and higher baseline plasma potassium were independently associated with the risk of hyperkalemia after supplementation.

In basic science studies, a primary mechanism by which high potassium intake reduces blood pressure is by lower phosphorylation or dephosphorylation of the sodium chloride co-transporter, located along the distal convoluted tubule (3, 4). The majority of mechanisms that are associated with dietary changes are ascribed to subsequent changes in the plasma potassium. On the other hand, studies have demonstrated a higher number of cardiovascular and kidney events with very low or very high serum potassium (5). Thus, it remains unclear if benefits of potassium supplementation, which are not accompanied by a rise in plasma potassium, would be beneficial overall.

Potassium supplementation comes in different forms. Importantly, this study will compare the effects between potassium chloride and potassium citrate in CKD. Specifically, the type of potassium salt may be critical to determine the risk:benefit ratio. Although potassium chloride reduces blood pressure and cardiovascular disease compared with sodium chloride (6), potassium citrate might lower blood pressure—and therefore, cardiovascular risk—more than potassium chloride (79). Moreover, fewer acidic therapies may ameliorate the anticipated hyperchloremic acidosis.

One potential adverse effect of a higher potassium diet on CKD progression is the accompanying rise in aldosterone secretion. Independent of changes in blood pressure, aldosterone levels directly correlate with CKD progression (10) and vascular disease (11). Moreover, mineralocorticoid receptor blockade in patients with diabetes reduces major cardiovascular and kidney events (12, 13). This concern prompts a significant question: Does potassium supplementation benefit patients despite the increase in aldosterone levels?

In conclusion, this prespecified analysis demonstrates the feasibility of the authors’ intended, longer-term study, which is already an important step forward. Nevertheless, the high rate of hyperkalemia with more immediate and long-term sequelae must be weighed against potential beneficial outcomes of potassium chloride or potassium citrate.

References

  • 1.

    Leonberg-Yoo AK, et al. Urine potassium excretion, kidney failure, and mortality in CKD. Am J Kidney Dis 2017; 69:341349. doi: 10.1053/j.ajkd.2016.03.431

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Gritter M, et al. Effects of short-term potassium chloride supplementation in patients with chronic kidney disease. J Am Soc Nephrol, published online ahead of print May 24, 2022. doi: 10.1681/asn.2022020147; https://jasn.asnjournals.org/content/33/9/1779

    • Search Google Scholar
    • Export Citation
  • 3.

    Terker AS, et al. Unique chloride-sensing properties of WNK4 permit the distal nephron to modulate potassium homeostasis. Kidney Int 2016; 89:127134. doi: 10.1038/ki.2015.289

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Grimm PR, et al. Regulated dephosphorylation of NCC shapes the renal potassium switch pathway. FASEB J 2018; 32(S1):620.12. doi: 10.1096/fasebj.2018.32.1_supplement.620.12; https://faseb.onlinelibrary.wiley.com/doi/10.1096/fasebj.2018.32.1_supplement.620.12

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Kovesdy CP, et al. Serum potassium and adverse outcomes across the range of kidney function: A CKD Prognosis Consortium meta-analysis. Eur Heart J 2018; 39:15351542. doi: 10.1093/eurheartj/ehy100

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Neal B, et al. Effect of salt substitution on cardiovascular events and death. N Engl J Med 2021; 385:10671077. doi: 10.1056/NEJMoa2105675

  • 7.

    Morris Jr. RC, et al. Differing effects of supplemental KCl and KHCO3: Pathophysiological and clinical implications. Semin Nephrol 1999; 19:487493. PMID: 10511388; https://www.researchgate.net/publication/12789862_Differing_effects_of_supplemental_KCl_and_KHCO3_Pathophysiological_and_clinical_implications

    • Search Google Scholar
    • Export Citation
  • 8.

    Boyd-Shiwarski CR, et al. Effects of extreme potassium stress on blood pressure and renal tubular sodium transport. Am J Physiol Renal Physiol 2020; 318:F1341F1356. doi: 10.1152/ajprenal.00527.2019

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Appel LJ, et al. A clinical trial of the effects of dietary patterns on blood pressure. N Engl J Med 1997; 336:11171124. doi: 10.1056/NEJM199704173361601

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Verma A, et al. Aldosterone in chronic kidney disease and renal outcomes. Eur Heart J 2022;00:111. https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehac352/6652163?login=false

    • Search Google Scholar
    • Export Citation
  • 11.

    Oberleithner H, et al. Endothelial cells as vascular salt sensors. Kidney Int 2010; 77:490494. doi: 10.1038/ki.2009.490

  • 12.

    Bakris GL, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med 2020; 383:22192229. doi: 10.1056/nejmoa2025845

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Pitt B, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med 2021; 385:22522263. doi: 10.1056/nejmoa2110956

    • Crossref
    • Search Google Scholar
    • Export Citation
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