The cholinergic anti-inflammatory pathway in chronic kidney disease—review and vagus nerve stimulation clinical pilot study

Abstract

Inflammation and autonomic dysfunction are common findings in chronic and end-stage kidney disease and contribute to a markedly increased risk of mortality in this patient population. The cholinergic anti-inflammatory pathway (CAP) is a vagal neuro-immune circuit that upholds the homoeostatic balance of inflammatory activity in response to cell injury and pathogens. CAP models have been examined in preclinical studies to investigate its significance in a range of clinical inflammatory conditions and diseases. More recently, cervical vagus nerve stimulation (VNS) implants have been shown to be of potential benefit for patients with chronic autoimmune diseases such as rheumatoid arthritis and inflammatory bowel disease. We have previously shown that dialysis patients have a functional CAP ex vivo. Here we review the field and the potential role of the CAP in acute kidney injury and chronic kidney disease (CKD) as well as in hypertension. We also present a VNS pilot study in haemodialysis patients. Controlling inflammation by neuroimmune modulation may lead to new therapeutic modalities for improved treatment, outcome, prognosis and quality of life for patients with CKD.

Clinical perspectives on vagus nerve stimulation: present and future

“…Recently, Hilderman and Bruchfeld conducted a pilot clinical trial involving VNS treatment in hemodialysis patients [ 87 ]. The authors hypothesized that VNS would suppress inflammation and alter HRV in hemodialysis patients.…”

Kynurenine pathway in kidney diseases

“…CKD is one of the most common health care problems, affecting more than 10% of the general population [ 15 ]. The incidence of CKD is increasing due to population ageing and higher rate of concomitant disorders.…”

“…The mortality of patients with CKD receiving dialysis is comparable to that of patients with some solid organ cancers [ 17 ] and is predicted to increase in the coming years [ 18 ]. Among the mechanisms involved in CKD pathogenesis, chronic inflammation and autonomic dysfunction are of special importance [ 15 ]. Overall, decreased excretion of waste products and impaired metabolic kidney function contribute to inflammatory conditions during the CKD course [ 19 ].…”

Medicinal nicotine in COVID-19 acute respiratory distress syndrome, the new corticosteroid

“…Direct electrical stimulation of the vagus nerve aims to trigger an action potential that consequently activate this pathway downstream. Vagal nerve stimulation has been shown to suppress inflammation and decrease serum levels of TNF, IL-1β and IL-6[ 28 - 32 ]. Pharmacological modalities to increase the activity of CAP have also yielded similar results.…”