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Clinical Epidemiology
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Laxative Use and Risk of Dyskalemia in Patients with Advanced CKD Transitioning to Dialysis

Keiichi Sumida, Ankur A. Dashputre, Praveen K. Potukuchi, Fridtjof Thomas, Yoshitsugu Obi, Miklos Z. Molnar, Justin D. Gatwood, Elani Streja, Kamyar Kalantar-Zadeh and Csaba P. Kovesdy
JASN February 2021, ASN.2020081120; DOI: https://doi.org/10.1681/ASN.2020081120
Keiichi Sumida
1Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
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Ankur A. Dashputre
1Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
2Institute for Health Outcomes and Policy, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, Tennessee
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Praveen K. Potukuchi
1Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
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Fridtjof Thomas
3Division of Biostatistics, Department of Preventive Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
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Yoshitsugu Obi
1Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
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Miklos Z. Molnar
4Division of Nephrology & Hypertension, Department of Medicine, University of Utah, Salt Lake City, UT, USA
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Justin D. Gatwood
5Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Nashville, Tennessee
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Elani Streja
6Harold Simmons Center for Chronic Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California, Irvine, Orange, California
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Kamyar Kalantar-Zadeh
6Harold Simmons Center for Chronic Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California, Irvine, Orange, California
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Csaba P. Kovesdy
1Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee
7Nephrology Section, Memphis Veterans Affairs Medical Center, Memphis, Tennessee
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Significance Statement

Intestinal potassium excretion is increased in patients with advanced CKD. It is possible that this compensatory mechanism is enhanced by laxative use, but little is known about the association of laxative use with risk of dyskalemias in advanced CKD. In a cohort of 36,116 United States military veterans who transitioned to ESKD, the authors found that time-varying laxative use was significantly associated with lower risk of hyperkalemia (potassium >5.5 mEq/L) but was not associated with risk of hypokalemia (potassium <3.5 mEq/L) during the last year prior to ESKD. These findings suggest a putative role of constipation in potassium disarrays and also support (with a careful consideration for risks and benefits) the therapeutic potential of laxatives for hyperkalemia management in advanced CKD.

Abstract

Background Patients with advanced CKD experience increased intestinal potassium excretion. This compensatory mechanism may be enhanced by laxative use; however, little is known about the association of laxative use with risk of dyskalemia in advanced CKD.

Methods Our study population encompassed 36,116 United States veterans transitioning to ESKD from 2007 to 2015 with greater than or equal to one plasma potassium measurement during the last 1-year period before ESKD transition. Using generalized estimating equations with adjustment for potential confounders, we examined the association of time-varying laxative use with risk of dyskalemia (i.e., hypokalemia [potassium <3.5 mEq/L] or hyperkalemia [>5.5 mEq/L]) versus normokalemia (3.5–5.5 mEq/L) over the 1-year pre-ESKD period. To avoid potential overestimation of dyskalemia risk, potassium measurements within 7 days following a dyskalemia event were disregarded in the analyses.

Results Over the last 1-year pre-ESKD period, there were 319,219 repeated potassium measurements in the cohort. Of these, 12,787 (4.0%) represented hypokalemia, and 15,842 (5.0%) represented hyperkalemia; the time-averaged potassium measurement was 4.5 mEq/L. After multivariable adjustment, time-varying laxative use (compared with nonuse) was significantly associated with lower risk of hyperkalemia (adjusted odds ratio [aOR], 0.79; 95% confidence interval [95% CI], 0.76 to 0.84) but was not associated with risk of hypokalemia (aOR, 1.01; 95% CI, 0.95 to 1.07). The results were robust to several sensitivity analyses.

Conclusions Laxative use was independently associated with lower risk of hyperkalemia during the last 1-year pre-ESKD period. Our findings support a putative role of constipation in potassium disarrays and also support (with a careful consideration for the risk-benefit profiles) the therapeutic potential of laxatives in hyperkalemia management in advanced CKD.

  • chronic kidney disease
  • gastrointestinal medications
  • end-stage renal disease
  • electrolytes
  • hypokalemia
  • Copyright © 2021 by the American Society of Nephrology
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Journal of the American Society of Nephrology: 32 (3)
Journal of the American Society of Nephrology
Vol. 32, Issue 3
March 2021
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Laxative Use and Risk of Dyskalemia in Patients with Advanced CKD Transitioning to Dialysis
Keiichi Sumida, Ankur A. Dashputre, Praveen K. Potukuchi, Fridtjof Thomas, Yoshitsugu Obi, Miklos Z. Molnar, Justin D. Gatwood, Elani Streja, Kamyar Kalantar-Zadeh, Csaba P. Kovesdy
JASN Feb 2021, ASN.2020081120; DOI: 10.1681/ASN.2020081120

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Laxative Use and Risk of Dyskalemia in Patients with Advanced CKD Transitioning to Dialysis
Keiichi Sumida, Ankur A. Dashputre, Praveen K. Potukuchi, Fridtjof Thomas, Yoshitsugu Obi, Miklos Z. Molnar, Justin D. Gatwood, Elani Streja, Kamyar Kalantar-Zadeh, Csaba P. Kovesdy
JASN Feb 2021, ASN.2020081120; DOI: 10.1681/ASN.2020081120
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  • Subtyping CKD Patients by Consensus Clustering: The Chronic Renal Insufficiency Cohort (CRIC) Study
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Keywords

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