Understanding Nephrotic Syndrome in Children

Oct 17, 2024

Lecture Notes on Multi-Trakulosis Dengue-Phobic Syndrome by Marina Livanovi

Speaker Background

  • Marina Livanovi
    • Trained in PEDS at the University of Pavia, Italy.
    • Research fellowship at Harvard, Children's Hospital in Boston focused on neural reseal function.
    • Since 2006, she has been with the Division of Pediatric Podiatry at the University of Pavia, Rome.
    • Works in the Department of Sensational Research in Pediatric and Immunomediated Venal diseases.

Introduction

  • Gratitude for the invitation to speak at the meeting.
  • Shift from monogenic diseases to those with unknown pathophysiology.

Nephrotic Syndrome in Children

Overview

  • Idiopathic Nephrotic Syndrome is extremely heterogeneous.
  • Patients can be steroid-sensitive or steroid-resistant (10-25% resistant).
  • Steroid-resistant patients often respond to second-line immunosuppression (e.g., calcineurin inhibitors).
  • Some patients progress to end-stage renal disease (ESRD).

Patient Groups

  1. Steroid-Sensitive Nephrotic Syndrome:
    • Often experiences multiple relapses over decades.
    • Some progress to adulthood.
  2. Multi-Drug Resistant Nephrotic Syndrome:
    • Those not responding to steroids or second-line treatment.
    • Immune-mediated pathophysiology, often recurring post-transplant.
    • Genetic forms do not respond to immunosuppression and lead to ESRD.
  3. Clinical Scenarios:
    • Scenario 1: Primary multi-drug resistant child with late-onset nephrotic syndrome who doesn't respond to treatment.
    • Scenario 2: Steroid-sensitive child with multiple relapses and significant morbidity despite treatment.
    • Scenario 3: Secondary steroid-resistant nephrotic syndrome - challenges with relapse and treatment.

Pathophysiology and Immune System Role

  • Lack of clear understanding of the immune dysregulation causing nephrotic syndrome.
  • Genome-wide association studies (GWAS) identified genetic variants, particularly in the HLA locus, related to steroid-sensitive nephrotic syndrome.
  • Identified SNPs include those impacting T-cell responses.

Treatment Approaches

  1. Rituximab:
    • Anti-CD20 antibody effective in some patients.
    • Can lead to remission and decreased relapses.
    • Memory B-cell levels may predict relapse.
  2. Potential for Other Treatments:
    • Mesenchymal stromal cells (MSC) studied for their immunomodulatory properties.
    • Innovative approaches such as combining therapies (e.g., anti-CD20 with other immunosuppressants).

Conclusion

  • Progress made, but significant challenges remain in treating nephrotic syndrome.
  • Need for a better understanding of pathophysiology and tailored treatment approaches.
  • Collaborative efforts and innovative studies are crucial for the future.

Q&A Highlights

  • Memory B-cells and Treatment:
    • Importance of understanding B-cell dynamics in treatment response.
  • Antigen-Dependent and Independent Effects:
    • Discussion on the role of BAF and antibodies in immune responses.
  • Gene Therapy Potential:
    • Exciting prospects for targeting podocyte functions, gene therapy advancements, and ongoing studies.

These notes summarize key points from Marina Livanovi's lecture on multi-trakulosis dengue-phobic syndrome, focusing on nephrotic syndrome in children, treatment strategies, and implications for future research.