Keiichi Sumida1, Ankur A Dashputre1,2, Praveen K Potukuchi1, Fridtjof Thomas3, Yoshitsugu Obi1, Miklos Z Molnar4, Justin D Gatwood5, Elani Streja6, Kamyar Kalantar-Zadeh6, Csaba P Kovesdy7,8. 1. Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee. 2. Institute for Health Outcomes and Policy, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, Tennessee. 3. Division of Biostatistics, Department of Preventive Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee. 4. Division of Nephrology & Hypertension, Department of Medicine, University of Utah, Salt Lake City, UT, USA. 5. Department of Clinical Pharmacy and Translational Science, College of Pharmacy, University of Tennessee Health Science Center, Nashville, Tennessee. 6. Harold Simmons Center for Chronic Disease Research and Epidemiology, Division of Nephrology and Hypertension, University of California, Irvine, Orange, California. 7. Division of Nephrology, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee ckovesdy@uthsc.edu. 8. Nephrology Section, Memphis Veterans Affairs Medical Center, Memphis, Tennessee.
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.
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.
Authors: Kathleen A McGinnis; Cynthia A Brandt; Melissa Skanderson; Amy C Justice; Shahida Shahrir; Adeel A Butt; Sheldon T Brown; Matthew S Freiberg; Cynthia L Gibert; Matthew Bidwell Goetz; Joon Woo Kim; Margaret A Pisani; David Rimland; Maria C Rodriguez-Barradas; Jason J Sico; Hilary A Tindle; Kristina Crothers Journal: Nicotine Tob Res Date: 2011-09-12 Impact factor: 4.244
Authors: Csaba P Kovesdy; Kunihiro Matsushita; Yingying Sang; Nigel J Brunskill; Juan J Carrero; Gabriel Chodick; Takeshi Hasegawa; Hiddo L Heerspink; Atsushi Hirayama; Gijs W D Landman; Adeera Levin; Dorothea Nitsch; David C Wheeler; Josef Coresh; Stein I Hallan; Varda Shalev; Morgan E Grams Journal: Eur Heart J Date: 2018-05-01 Impact factor: 29.983
Authors: Elani Streja; Csaba Pal Kovesdy; Melissa Soohoo; Yoshitsugu Obi; Connie M Rhee; Christina Park; Joline L T Chen; Tracy Nakata; Danh V Nguyen; Alpesh N Amin; Steven J Jacobsen; John J Sim; Kamyar Kalantar-Zadeh Journal: Clin J Am Soc Nephrol Date: 2018-06-14 Impact factor: 8.237