Constipation in chronic kidney disease: it is time to reconsider

Abstract

Constipation is highly prevalent in patients with chronic kidney disease (CKD) and is primarily characterized by decreased intestinal motility. This chronic disorder affects the quality of life of patients. However, nephrologist and dialysis clinicians have long had a disproportionately limited understanding of constipation. Accumulating evidence has revealed a relationship between constipation and cardiovascular disease and CKD. The pathogenesis of constipation in CKD patients is multifactorial: decreased physical activity, comorbidities affecting bowel movement, such as diabetes mellitus, cerebrovascular disease, and hyperparathyroidism, a restricted dietary intake of plantbased fiber-rich foods, and multiple medications, including phosphate binders and potassium-binding resins, have all been implicated. CKD is associated with alterations in the composition and function of the gut microbiota, socalled gut dysbiosis. Recent studies showed that CKD-related gut dysbiosis decreased intestinal motility via intestinal inflammation or the increased generation of gut-derived uremic toxins, such as indoxyl sulfate and pcresyl sulfate. Furthermore, the gastrointestinal secretion of mucin was found to be decreased in CKD animal models, which may delay colonic transit by diminished lubrication in the alimentary tract. Thus, CKD-related gut dysbiosis may play a role in constipation, but limited information is currently available. Since constipation is often intractable, particularly in CKD patients, every available means needs to be employed in its treatment. The effects of probiotics, prebiotics, and synbiotics on the composition of the gut microbiota and gut-derived uremic toxins have been increasingly reported. However, their effects on stool consistency or frequency in CKD patients remain unclear. Some laxatives may be beneficial for improving not only bowel habits but also gut dysbiosis. Further studies are required to elucidate the CKD-specific pathogenesis of constipation and develop novel effective treatment options.

Associations between constipation symptoms and the sleep quality in non-dialysis chronic kidney disease patients: a cross-sectional study

“…It is in agreement with recent studies that have shown that both drug groups are associated with nocturia [35][36][37] and decreased gastrointestinal motility [19,[38][39][40]. Recent review articles comprehensively analyzed possible pathogenic mechanisms of CKD-related constipation [41,42].…”

Survey of defecation habits in apparently healthy and chronic kidney disease cats

“…Recognizing abnormalities in these frequencies may assist in disease recognition, optimized patient management and improved outcomes as seen in human medicine. 7…”

“…1,4,8,9 Gut dysbiosis and the gut–kidney axis is an emerging area of focus in both human and veterinary medicine. 7,10 Dysbiosis in kidney disease is noted early in the course of disease and has been implicated in altered metabolism of dietary components, altered metabolome, production of uremic toxins and precursors, oxidative stress, chronic inflammation, as well as changes in gut epithelium integrity. 7,11 More recently, experimental models of CKD and clinical studies in uremic patients have started to link gut dysbiosis, uremic metabolites and motility to constipation.…”

Gastrointestinal symptom burden and dietary intake in patients with chronic kidney disease

“…Furthermore, the use of fibre supplements, stool softeners and probiotics which are confounders when examining stool consistency and frequency, were very low in this cohort. These findings were surprising as both constipation and diarrhoea have been reported as being problematic in this population (Higashihara et al, 2018; Ikee et al, 2019). Our results showing 20% of those on PD reporting constipation and 16% of those on HD is consistent with other studies (Zuvela et al, 2018).…”

“…There is a lack of studies examining whether the prevalence of constipation or diarrhoea increases with the progression of CKD (Ikee et al, 2019). Results from this study suggest that the prevalence is similar for CKD‐ND, HD and PD.…”