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The gut and healthy ageing in kidney transplant recipients: focus on chronic use of proton-pump inhibitors and the microbiome

PhD ceremony:R.M. Douwes
When:December 14, 2022
Supervisor:prof. dr. S.J.L. (Stephan) Bakker
Co-supervisor:dr. J. Blokzijl
Where:Academy building RUG
Faculty:Medical Sciences / UMCG

Many factors negatively affect healthy ageing after kidney transplantation. Among these are the unavoidable use of immunosuppressive medication and proton-pump inhibitors, which are often accompanied by side effects. With the aim to improve the long-term outcomes after solid organ transplantation and to identify factors that affect healthy ageing, TransplantLines was set up in the UMCG. The TransplantLines study is one of the biggest cohort and biobank studies in solid organ transplant recipients, including patients with kidney-, liver-, lung-, heart- and small bowel transplantation. 

Using data from this study, Douwes shows that the use of proton-pump inhibitors not only increases the risk of hypomagnesaemia and iron deficiency, but is also associated with premature mortality in kidney transplant recipients. In collaboration with the University of Leuven, this finding was replicated in an independent transplant cohort. Future research should identify whether a causal relationship exists and by what mechanism. These findings could lead to the inclusion in transplantation guidelines of the advice to reduce the use of proton-pump inhibitors as soon as the phase with an increased risk of gastrointestinal bleeding is over.

In addition, she has shown that the gut microbiome of kidney transplant recipients is strongly influenced by the use of immunosuppressants and proton-pump inhibitors. For example, the microbiome of kidney transplant recipients was found to have a lower diversity than the microbiome of healthy controls, also known as dysbiosis. The health implications of dysbiosis and effects on long-term outcomes in kidney transplant recipient will be explored in the near future.