7. Abstract
Nearly half (47%) of people with end-stage kidney disease (ESKD) whose kidney function is restored after kidney
transplantation experience chronic pain compared to 19% of adults in the US general population. Pain is
associated with comorbid fatigue, depression and anxiety, and withdrawal from usual physical and social
activities; resulting in an inability to participate in and enjoy life. Severe pain can result in nonadherence to
immunosuppression and treatment protocols and result in an increased risk of rejection, graft loss, and mortality.
The role of symbiotic microbes (microbiota) in the gastrointestinal tract, and their functional genes (microbiome),
is well established in diseases involving pain. Diet and stress play a major role in synthesis of signaling molecules
critical to immunologic, metabolic, and endocrine pathways regulating chronic pain. Dietary patterns change
dramatically after transplantation, as recipients move from a restricted “renal” diet to a regular diet, often resulting
in increased consumption of foods high in sugars and fat. Moreover, psychological stress significantly impairs
the function of the microbiome, initiating biological pathways involved in pain, leading to a disproportionate pain
burden. Because the microbiome, serum metabolites, and pain are dynamic, our novel investigation will employ
a prospective repeated measures design to interrogate the dynamic temporal relationships between the
microbiome, metabolites associated with pathways regulating pain, transplantation factors (e.g.
immunosuppression, kidney function), changing dietary patterns, and perceived stress, on pain scores before
and after kidney transplantation. We posit the gut microbiome, and its byproducts, may partially explain the
underlying biological mechanisms of pain Interference in kidney disease. We will address three aims: 1) To
determine differential dynamic temporal relationships between microbial composition/functional genes and
circulating serum metabolites in KTRs with pain vs no pain, 2) To determine the moderation effects of diet and
perceived stress on dynamic temporal relationships between microbiome features, serum metabolites, and pain
scores among KTRs, and 3) To use machine learning algorithms to identify host-microbial interactions that are
causally linked to pain interference among KTRs. Because kidney function is restored, the kidney transplant
model is powerful to study the longitudinal relationships between the microbiome, circulating metabolites and
chronic pain in people with ESKD to develop patient-centered interventions to treat pain across the spectrum of
CKD.
