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

Discussion

In this large national cohort of US veterans transitioning to dialysis, we described the patterns of laxative use during 36 months pre- and post-transition to ESRD and identified clinical factors associated with pre-ESRD laxative use. Laxative use increased as patients progressed to ESRD, peaked at 37.1% in the first 6 months following dialysis initiation and remained fairly stable thereafter throughout the post-ESRD period. While the majority of laxatives were used alone, with stool softeners (~30% of all laxatives), hyperosmotics (~20%) and stimulants (~10%) being most commonly prescribed, there was an increasing trend in combined use of laxatives over time, peaking at ~45% in the 6 months immediately before and after the transition to ESRD. The use of medications, such as anticoagulants, oral iron supplements, non-opioid analgesics, antihistamines and opioid analgesics, was associated with higher odds of pre-ESRD laxative use.

Several studies have examined the prevalence of laxative use and reported its wide variation ranging from 6 to 67% depending on the studied population, including the general population,[35] community-dwelling elderly,[36] hospitalized patients[20] and people living in nursing homes.[37] However, as with the paucity of data on the prevalence of constipation among patients with advanced stages of CKD, information on the prevalence of laxative use in the advanced CKD population is very limited. In a recent study including 21 patients with nondialysis-dependent CKD (NDD-CKD) with eGFR <15 mL/min/1.73 m2, 98 on hemodialysis and 21 on peritoneal dialysis, the prevalence of self-reported laxative use was 23.8, 30.6 and 42.9%, respectively.[38] The study also showed that, among different types of laxatives, docusate (a stool softener) was the most commonly used laxative in all patient groups.[38] In another study investigating the relationship between laxative use and clinical parameters among 136 hemodialysis patients, 66.2% of them used laxatives, and female sex, older age, diabetes and hyperhomocysteinemia were shown to be independently associated with laxative use.[39] These studies, however, were small in size and cross-sectional, focusing separately on NDD-CKD or ESRD populations. In this study, we therefore extended the previous observations to a large and unique cohort of patients with advanced NDD-CKD transitioning to dialysis, and for the first time described temporal changes in laxative use during the ESRD transition period and identified various factors independently associated with pre-ESRD laxative use.

Patients with CKD typically suffer from an immense burden of medications, comorbidities, metabolic abnormalities and altered gut microbiota, particularly in the most advanced stages of CKD,[8,40] all of which are suggested as predisposing factors for constipation.[12] In line with this evidence, our results showed a sustained increase in laxative use as patients progressed to ESRD, with a marked increase seen in the 6 months immediately preceding dialysis initiation. A similar increase observed in the combined use of laxatives might additionally suggest that the severity of constipation symptoms also increased with worsening kidney function during the pre-ESRD period. In this context, our findings regarding the factors associated with pre-ESRD laxative use may be of particular value, with potential clinical and research implications. Among various clinical characteristics, the majority of factors significantly associated with pre-ESRD laxative use were the use of medications, most of which are known to induce constipation as a side effect (e.g. oral iron, opioid analgesics and anticholinergics).[12] Although it is unclear why the use of anticoagulants, which themselves seem unlikely to significantly affect gastrointestinal motility, showed the strongest association with pre-ESRD laxative use, it is possible that patients with anticoagulant use were prescribed laxatives for the purpose of preventing bleeding complications associated with constipation (e.g. lower gastrointestinal bleeding),[41,42] albeit we cannot conclude any causal relationship. It is also possible that patients on warfarin adjust their diet to limit foods high in vitamin K, which could lead to constipation. The identification of these medications may help detect previously under-recognized causes of drug-induced constipation and, perhaps more importantly, can help avoid unnecessary or inappropriate use of laxatives along with their unwanted adverse effects. Specifically, for those taking both iron supplements and laxatives, for example, switching from oral to intravenous iron supplementation might be helpful to ameliorate their symptom of constipation and reduce laxative requirements. These changes in practice habits could also contribute to a lower overall pill burden in this relevant population. Whether the use of laxatives has any beneficial effects beyond conventional defecation management in this unique population (e.g. disposal of uremic toxins, maintaining mineral homeostasis or retaining commensal gut microbiota) may deserve further investigation.

Despite the advantages of this study including its large sample size of patients with advanced CKD, our results must be interpreted in light of some limitations. Most of our patients were male US veterans, and hence results may not apply to women or patients from other geographic areas. Information about over-the-counter use of laxatives was not available; therefore, it is possible that we underestimated the proportion of patients with laxative use and/or misclassified those who used only over-the-counter laxatives as nonlaxative users. It is also important to note that the use of laxatives did not necessarily reflect a person's constipation status, especially given the lack of information about subjective symptoms of constipation and the fact that only a minority of patients with constipation seek medical care.[43] In addition, prescription does not necessarily mean that patients actually took the drugs. Lastly, as with all observational studies, we cannot eliminate the possibility of unmeasured confounders (e.g. diet and lifestyle) that might have potentially affected pre-ESRD laxative use.

In conclusion, laxative use increased considerably as patients progressed to ESRD and remained fairly stable after the transition to ESRD, likely mirroring the increasing burden of drug-induced constipation during the ESRD transition period. Although further studies are needed to identify optimal practice patterns in the use of laxatives, our findings may provide novel insight into better management strategies to alleviate constipation symptoms and reduce medication requirements in patients with advanced CKD, potentially contributing to the improvement of patient-centered care and outcomes in this population.

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