Laxative Use in Patients With Advanced Chronic Kidney Disease 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

Disclosures

Nephrol Dial Transplant. 2021;36(11):2018-2026. 

In This Article

Abstract and Introduction

Abstract

Background: Constipation is highly prevalent in patients with chronic kidney disease (CKD), particularly among those with end-stage renal disease (ESRD), partly due to their dietary restrictions, comorbidities and medications. Laxatives are typically used for constipation management; however, little is known about laxative use and its associated factors in patients with advanced CKD transitioning to ESRD.

Methods: In a retrospective cohort of 102 477 US veterans transitioning to dialysis between October 2007 and March 2015, we examined the proportion of patients who filled a prescription for any type of laxative within each 6-month period over 36 months pre- and post-transition to ESRD. Factors associated with laxative use during the last 1-year pre-ESRD period were identified by multivariable logistic regression.

Results: The proportion of patients prescribed laxatives increased as patients progressed to ESRD, peaking at 37.1% in the 6 months immediately following ESRD transition, then remaining fairly stable throughout the post-ESRD transition period. Among laxative users, stool softeners were the most commonly prescribed (~30%), followed by hyperosmotics (~20%), stimulants (~10%), bulk formers (~3%), chloride channel activator (<1%) and several combinations of these. The use of anticoagulants, oral iron supplements, non-opioid analgesics, antihistamines and opioid analgesics were among the factors independently associated with pre-ESRD laxative use.

Conclusion: The use of laxatives increased considerably as patients neared transition to ESRD, likely mirroring the increasing burden of drug-induced constipation during the ESRD transition period. Findings may provide novel insight into better management strategies to alleviate constipation symptoms and reduce medication requirements in patients with advanced CKD.

Introduction

Constipation is the prototype of functional gastrointestinal disorders and one of the most prevalent conditions encountered in daily clinical practice.[1] Approximately 30% of the general population experiences problems with constipation during their lifetime, with women and elderly people being most affected.[2] In patients with chronic kidney disease (CKD), especially in its advanced stages, the prevalence of constipation is reported to be higher than in the general population,[3–5] presumably due in part to their dietary restrictions (e.g. limited fiber and/or fluid intake), comorbidities, concomitant medications and altered gut microbiota.[6–11] Because of these predisposing factors, nonpharmacological treatments such as increased fiber supplements and physical activity may not always be practical and effective, and pharmacological interventions are often required for the management of constipation in this particular population.[12]

Currently, a wide range of pharmacological agents are available, including commonly used laxative compounds (e.g. bulk formers, hyperosmotics, stimulants, stool softeners and lubricants) and relatively new laxatives with more physiological mechanisms of action (e.g. chloride channel activators, guanylate cyclase C-receptor agonists, selective serotonin 5-HT4 receptor agonists and ileal bile acid transporter inhibitors),[13,14] some of which have been shown to have unique renoprotective properties.[15–17] Despite these therapeutic advances, no practice guidelines currently exist for constipation management in CKD; thus physicians may supposedly base their treatments largely on their clinical experience or habitual practice, which can sometimes be wasteful and harmful to patients.[18] Furthermore, the costs related to laxative administration (e.g. drug cost, pharmacy management and downstream investigations for laxative-induced adverse effects) are estimated to be strikingly high, contributing substantially to healthcare financial burden.[19–21]

Given these problems with laxative use and the exceptionally high health and economic burden in patients with advanced CKD transitioning to end-stage renal disease (ESRD),[22] it is vital to better understand the real-world practice patterns of laxative use during this critical transition period toward efforts to improve patient-centered care and outcomes. However, information is scarce on the prevalence and patterns of laxative use in patients with advanced CKD. We therefore aimed to describe the prevalence and patterns of laxative use during the 36-month pre- and post-ESRD transition periods, and further examined the clinical factors independently associated with pre-ESRD laxative use.

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