Understanding the interplay between the gut-kidney axis in patients with chronic kidney disease

Abstract

People with kidney failure on dialysis, or have kidney transplant, experience severe and debilitating gastrointestinal (GI) symptoms reported in up to 88% of patients receiving maintenance dialysis and up to 50% in kidney transplant recipients. These are associated with significantly reduced quality of life, morbidity burden, increased risk of allograft complications, and increased use of healthcare resources.

The cause of GI symptoms in kidney failure include: medications, dialysis, retention of uremic toxin molecules that are produced by microbial metabolism within the GI tract. Microorganisms associated with uraemia can present in higher concentrations within the GI tract due to alterations in gut microbiota and colonic flora. This is described as the gut-kidney axis.

This program of work defines the burden of GI symptoms in patients with kidney failure, identifies the gaps to synthesise the evidence for current therapeutic options, and aims to understand patient experiences of GI symptoms.

The first part of this thesis provides an introduction to: kidney failure, GI symptoms in kidney failure, the gut-kidney axis.

The second part of this thesis synthesises current evidence of biotic supplementary interventions for improving GI and kidney outcomes in CKD.

The third part of this thesis describes observational evidence generated from a patient-centred perspective: a cross-sectional cohort, semi-structured qualitative interviews, and a discrete choice experiment survey.

The final CH 9 summarises the key findings and recommendations to inform and develop the best study design with a patient-centred approach in a clinical trial setting.

In conclusion, this thesis has confirmed that GI symptoms are highly prevalent in patients receiving maintenance dialysis and who have had a kidney transplant. The findings highlight a strong demand for treatment options via a patient-centred approach, to improve the quality of life and daily living of these already comorbid patients.