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Influence of bowel habits on gut-derived toxins in peritoneal dialysis patients

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Abstract

Background

Gut-derived uremic toxins have been associated with adverse outcomes in chronic kidney disease (CKD). Alterations in bowel habits, including constipation, seem to play an additional role in uremic toxicity. The aim of this study is to investigate the association of bowel habits with gut-derived uremic toxins and intestinal permeability in patients on automated peritoneal dialysis (APD).

Methods

This cross-sectional study enrolled 58 APD patients (age 52.5 ± 15.1 years; dialysis vintage 14.1 (6.0–36.5) months). Constipation was defined according to the Rome IV criteria. Bowel habits were assessed by the Bristol Stool Scale (BSS < 3 characterized by hard consistency of stools and/or low frequency of evacuation, a surrogate of slow intestinal transit time, and BSS ≥ 3, defining regular bowel habit). The total and free serum concentration of p-cresyl sulfate (PCS), indoxyl sulfate (IS) and indole-3-acetic acid (IAA) were dosed by high-performance liquid chromatography. Lipopolysaccharide (LPS) and zonulin were assessed by ELISA and d(–)-lactate by colorimetric method. Dietary intake was assessed by the 3-day food records.

Results

No differences were observed in clinical, demographic, and dietary characteristics between constipated (n = 30) and non-constipated (n = 28) groups. A trend for higher total PCS (p = 0.07) and free PCS (p = 0.06) was found in constipated patients. Patients with BSS < 3 (n = 11) exhibited significantly higher levels of total and free PCS (p < 0.01) and total IAA (p = 0.04). Conversely, No difference was found in IS levels. Except for a lower serum level of d(–)-lactate in patients with BSS < 3 (p = 0.01), zonulin and LPS levels were not different.

Conclusions

Disturbed bowel habits, mainly characterized by slow transit time, may play a role in the accumulation of uremic toxins, particularly PCS, in patients on automatized peritoneal dialysis.

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Acknowledgements

This study was supported by the Oswaldo Ramos Foundation and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2018/12122-7). We thank Danilo Takashi Aoike for the statistical assistance; the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) who provided scholarship and especially all the renal nurses, for their assistance in data collection.

Funding

NBFP received a scholarship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). CIR was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—CAPES, Brazil (88887.352924/2019-00). LC receives a scholarship from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (302765/2017-4). Support for this research was provided by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2018/12122-7).

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Authors and Affiliations

  1. Nutrition Program, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil

    Natalia Barros Ferreira Pereira, Laila Santos de Andrade, Renata Rodrigues Teixeira & Lilian Cuppari

  2. Division of Nephrology, Universidade Federal de São Paulo (UNIFESP), Rua Pedro de Toledo, 282, São Paulo, SP, 04039-000, Brazil

    Christiane Ishikawa Ramos & Lilian Cuppari

  3. Department of Basic Pathology, Universidade Federal do Paraná (UFPR), Curitiba, Brazil

    Lia Sumie Nakao & Silvia Daniéle Rodrigues

  4. Department of Cell Biology, Universidade Federal do Paraná (UFPR), Curitiba, Brazil

    Jordana Dinorá de Lima

  5. Post-graduate Program in Medicine, Universidade Nove de Julho (UNINOVE), São Paulo, Brazil

    Maria Aparecida Dalboni

  6. Hospital do Rim-Fundação Oswaldo Ramos, São Paulo, Brazil

    Lilian Cuppari

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  1. Natalia Barros Ferreira Pereira
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Correspondence to Lilian Cuppari.

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Ethical approval

Approval was obtained from the ethics committee of the Universidade Federal de São Paulo. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

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Pereira, N.B.F., Ramos, C.I., de Andrade, L.S. et al. Influence of bowel habits on gut-derived toxins in peritoneal dialysis patients. J Nephrol 33, 1049–1057 (2020). https://doi.org/10.1007/s40620-020-00819-9

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