Transcutaneous auricular vagus nerve stimulation (taVNS) for the treatment of pediatric nephrotic syndrome: a pilot study

Abstract

Background Children with frequently relapsing nephrotic syndrome (FRNS) and steroid resistant nephrotic syndrome (SRNS) are exposed to immunosuppressant medications with adverse side effects and variable efficacy. Transcutaneous auricular vagus nerve stimulation (taVNS) modulates the immune system via the inflammatory reflex and has become a therapy of interest for treating immune-mediated illnesses. Methods An open-label, pilot study of tavNS for five minutes daily for 26 weeks via a TENS 7000 unit was conducted. Results Three FRNS participants and 4 SRNS participants had a mean age of 9.5±4.2 years (range 4 to 17). Those with FRNS remained relapse-free during the study period; two participants continued treatment and remained in remission for 15 and 21 months, respectively. Three SRNS participants experienced a reduction in first morning UPC (mean of 42%, range 25-76%). Although UPC decreased (13.7%) in one SRNS participant with congenital nephrotic syndrome, UPC remained in nephrotic range. All but one participant (non-compliant with treatment) experienced a reduction in TNF (7.33pg/mL vs. 5.46pg/mL, p=0.03). No adverse events or side effects were reported. Conclusions taVNS was associated with clinical remission in FRNS and moderately reduced proteinuria in non-congenital SRNS. Further study of taVNS as a treatment for nephrotic syndrome in children is warranted. ClinicalTrials.gov Identifier: NCT04169776, Registered November 20, 2019, https://clinicaltrials.gov/ct2/show/NCT04169776.

Clinical perspectives on vagus nerve stimulation: present and future

“…In bariatric patients, the NSS-2 BRIDGE Device reduced the OME by 60.2% and pain by 28% at 24 h following laparoscopic Roux-en-Y gastric bypass surgery [ 106 ]. A recent study evaluated the use of a transcutaneous aVNS device in pediatric patients with relapsing nephrotic syndrome (FRNS) and steroid-resistant nephrotic syndrome (SRNS) [ 107 ]. The device used was the transcutaneous electrical nerve stimulation (TENS) unit that was attached to the patients’ ears via an ear clip to left cymba concha.…”

Therapeutic applications of transcutaneous auricular vagus nerve stimulation with potential for application in neurodevelopmental or other pediatric disorders

“…Moreover, frequency (Hz) and pulse width (ms) of stimulation were not correlated with the occurrence of side effects ( 154 ). In addition, taVNS has been used to treat oral feeding dysfunction in premature newborns (≤33 weeks) ( 181 ) and pediatric nephrotic syndrome in young patients ( 183 ) without observing adverse events related to stimulation. These suggest that applying taVNS in pediatric populations should represent little risk of significant side effects, although more future trials are included to assess potential short- or longer-term adverse effects.…”

HMGB1: A Potential Target of Nervus Vagus Stimulation in Pediatric SARS-CoV-2-Induced ALI/ARDS

“…Overall, additional even non-invasive procedures applied in a healthcare environment can be stressful and children, especially smaller ones, can be less compliant compared to adults ( 72 ). Still, vagal stimulation has been successfully used in different pediatric conditions, such as nephrotic syndrome or epilepsy ( 76 – 79 ), showing its potential and opportunities in other pediatric diseases, including SARS-CoV-2-induced ALI. Another consideration should be with regard to voltage and frequency of nervus vagus stimulation.…”

“…Currently, there is no clear duration and frequency for nervus vagus stimulation in acute pediatric conditions. Nevertheless, 2-h stimulation with 2 h off for few days ( 79 ) or once a day for 5 min ( 76 ) has been described, still, it could not be translated to COVID-19. Considering the pathophysiology and immunology of COVID-19, vagal stimulation might be started in a later phase of SARS-CoV-2-induced infection and for few days.…”