Laxative use found safe for patients with advanced CKD transitioning to dialysis
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A retrospective cohort study of U.S. veterans with advanced chronic kidney disease demonstrated that laxative use within the 2-year period before dialysis initiation did not significantly impact eGFR decline.
Moreover, due to the observed safety profile, researchers contended that laxatives show promise for treating constipation — recently found to increase risk for adverse kidney outcomes — and, therefore, may be utilized in active interventions for this purpose.
Constipation in patients with kidney disease
“Constipation is highly prevalent in patients with chronic kidney disease (CKD), especially in its advanced stages, due in part to their dietary restrictions (eg, limited fiber and/or fluid intake), high prevalence of comorbidities (eg, diabetes mellitus), concomitant medication use (eg, phosphate binders and diuretics) and altered gut microbiota,” Keiichi Sumida, MD, MPH, PhD, of the University of Tennessee Health Science Center, and colleagues wrote. “ ... [To] the best of our knowledge no previous studies have investigated the effect of laxative use on longitudinal change in kidney function among patients with advance stages of CKD.
Our aim was to examine the association of laxative use with change in estimated glomerular filtration rate (eGFR) during the last 2 years before transition to ESRD using a large nationally representative cohort of U.S. veterans with advanced non-dialysis-dependent CKD transitioning to dialysis.”
For the study, Sumida and colleagues identified 43,622 veterans who had at least 2 outpatient eGFR measurements during the 2-year period before end-stage kidney disease and who had documented prescription information (mean time-averaged outpatient eGFR was 26.1 mL/min/ 1.73 m2).
The cohort primarily consisted of men, who made up 98% of the study population, with a large proportion also having diabetes (76.1%). Most patients were taking loop diuretics, calcium channel blockers, renin-angiotensin system inhibitor and/or opioid analgesics.
“Given the time-varying nature of laxative use (due in part to symptom improvement and/or adverse events such as diarrhea) and its potential influence on the change in eGFR over time, laxative use was treated as a time-varying exposure in this study,” Sumida and colleagues wrote of the study methods, explaining that time-varying use was based on whether the day of eGFR measurement was covered by any prescribed laxative (eg, stool softeners, hyperosmotics, stimulants, bulk formers, chloride channel activator and lubricants).
Among the entire cohort, 22.5% had a diagnosis of constipation and 49.8% were prescribed laxatives.
Impact of laxatives on eGFR decline
Researchers found a “clinically negligible” association between laxative use and eGFR change, with results showing a modest association between laxative use and a more progressive eGFR decline compared with non-use (27.1 mL/min/1.73 m2 vs. 26.8 mL/min/1.73 m2), and a “minimal” between-group difference in GFR slope (-8.8 mL/min/1.73 m2 per year compared with -8.6 mL/min/1.73 m2 per year).
“Although some of the associations between laxative use and eGFR slope described in our study were statistically significant, their magnitude was negligibly small and hence the biological significance of these findings is questionable,” the researchers wrote.
When treating laxative use as a fixed exposure, Sumida and colleagues found a “more evident” association between laxatives and eGFR decline, with hyperosmotics use leading to faster eGFR decline and stool softeners appearing to slow eGFR decline compared with non-use.
“The results of the present study suggest the renal safety profile of laxatives in patients with advanced CKD, whose constipation management relying largely on pharmacological interventions due to their severe dietary restrictions,” the researchers concluded. “Furthermore, given the recent evidence on the greater risk of adverse kidney outcomes associated with constipation, our results may also support active interventions with laxatives to treat constipation in advanced CKD patients.”
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