Constipation in CKD

Abstract

Constipation is one of the most common gastrointestinal disorders among patients with chronic kidney disease (CKD) partly because of their sedentary lifestyle, low fiber and fluid intake, concomitant medications (e.g., phosphate binders), and multiple comorbidities (e.g., diabetes). Although constipation is usually perceived as a benign, often self-limited condition, recent evidence has challenged this most common perception of constipation. The chronic symptoms of constipation negatively affect patients' quality of life and impose a considerable social and economic burden. Furthermore, recent epidemiological studies have revealed that constipation is independently associated with adverse clinical outcomes, such as end-stage renal disease (ESRD), cardiovascular (CV) disease, and mortality, potentially mediated by the alteration of gut microbiota and the increased production of fecal metabolites. Given the importance of the gut in the disposal of uremic toxins and in acid-base and mineral homeostasis with declining kidney function, the presence of constipation in CKD may limit or even preclude these ancillary gastrointestinal roles, potentially contributing to excess morbidity and mortality. With the advent of new drug classes for constipation, some of which showing unique renoprotective properties, the adequate management of constipation in CKD may provide additional therapeutic benefits beyond its conventional defecation control. Nevertheless, the problem of constipation in CKD has long been underrecognized and its management strategies have scarcely been documented. This review outlines the current understanding of the diagnosis, prevalence, etiology, outcome, and treatment of constipation in CKD, and aims to discuss its novel clinical and therapeutic implications.

Keywords: cardiovascular disease; chronic kidney disease; constipation; end-stage renal disease; gut microbiota; laxative.

Figure 1

Visual illustration of Bristol Stool Form Scale. Reprinted with permission from Chumpitazi BP, Self MM, Czyzewski DI, et al. Bristol Stool Form Scale reliability and agreement decreases when determining Rome III stool form designations. Neurogastroenterol Motil. 2016;28:443–448.

Figure 2

Medical conditions associated with constipation in chronic kidney disease. CCB, calcium channel blocker; NSAID, nonsteroidal anti-inflammatory drug.

Figure 3

Schematic representation of potential mechanisms underlying the association between constipation and adverse outcomes in chronic kidney disease (CKD). CVD, cardiovascular disease; TMAO, trimethylamine-N-oxide.

Figure 4

Cumulative probability of (a) incident chronic kidney disease (CKD) and (b) incident end-stage renal disease (ESRD) according to constipation status. Reprinted with permission of the American Society of Nephrology from Constipation and incident CKD, Sumida K, Molnar MZ, Potukuchi PK, et al. J Am Soc Nephrol., volume 28, issue 4, Copyright © 2017; permission conveyed through Copyright Clearance Center, Inc.