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

Kumail Merchant,Timir Datta-Chaudhuri,Clifford S Deutschman,Stavros Zanos,Christine B Sethna

doi:10.1186/s42234-021-00084-6

Abstract

BackgroundChildren 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.MethodsAn open-label, pilot study of tavNS for five minutes daily for 26 weeks via a TENS 7000 unit was conducted.ResultsThree 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.ConclusionstaVNS 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.

Highlights

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
Children aged 3-17 years diagnosed with minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS) who were classified as either FRNS or SRNS and who had an estimated glomerular filtration rate ≥30 ml/min/1.73 m2were eligible to participate
The demonstrated decrease in TNF with Transcutaneous auricular vagus nerve stimulation (taVNS) in this study suggests a possible immunemediated mechanism, the mechanisms by which taVNS interacts with the kidney in nephrotic syndrome are not known

Summary

Introduction

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. The most common glomerular disease affecting children, is characterized by damage to podocytes in the kidney resulting in protein loss, edema and dyslipidemia. Most children respond to steroid therapy, up to 50% develop frequently relapsing nephrotic syndrome (FRNS). 1020% develop steroid resistant nephrotic syndrome (SRNS) and 36-50% of these children progress to kidney failure (Chapter 2011). Children with FRNS and SRNS are exposed to prolonged courses of immunosuppressant medications. Given the adverse side effects and variable efficacy of these medications (Zhang et al 2016); (Alfakeekh et al 2019), novel and safe therapies to treat nephrotic syndrome are needed. It has been suggested that podocyte damage may be mediated by cytokines, T regulatory cells and/or circulating factors (i.e. autoantibodies)

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