New treatment modalities for TMA management discussed include Eculizumab and oral C5 inhibitors, showing promise for targeted therapies.
Challenges of conducting RCTs for rare diseases like TMA highlighted due to limited patient population and high treatment costs.
Collaborations and innovative enrollment strategies emphasized for clinical trials in rare diseases like TMA, focusing on multi-center initiatives.
Deep dives
Diversity in Nephrology Expertise and Research Discussions
The podcast episode discusses a panel of nephrology experts sharing insights on research and developments in nephrology, engaging in diverse discussions about primary and secondary thrombotic microangiopathies (TMA). The experts include clinicians, educators, and scientists from various institutions across locations like Boston, Ottawa, and St. Louis.
Innovation in Therapies for TMA Treatment
The podcast explores new treatment modalities for TMA management, such as Eculizumab and upcoming therapies like oral C5 inhibitors and others targeting factor B and C3 for complement-mediated TMA. The discussion highlights the complexities of TMA pathophysiology and the potential advancements in providing more targeted and effective treatments.
Challenges in Conducting Clinical Trials for Rare Diseases
While acknowledging the need for randomized controlled trials (RCTs) to establish treatment efficacy, the episode touches on the challenges of conducting RCTs for rare diseases like TMA due to the limited patient population, high treatment costs, and ethical considerations. The experts express the importance of future studies comparing different therapies to enhance treatment outcomes.
Optimizing Patient Enrollment in Clinical Trials
The panel discusses the significance of collaborations and innovative approaches to enhance patient enrollment in clinical trials for rare diseases like TMA. Considerations include setting up multi-center trials, involving community hospitals, and engaging in specialized initiatives to address the urgency and complexity of TMA treatment and research.
Genetic Testing and Preeclampsia Risk
Research on complement mutations in preeclampsia patients, particularly high-risk cases like preterm or recurrent preeclampsia, is underway. By identifying specific mutations like factor i and C3 in patients with preeclampsia, there is a focus on a subset of patients with genetic implications. Collaboration with OB-GYN specialists and studying African American cohorts sheds light on potential ethnic differences in genetic factors.
Complement Involvement in TMAs and Drug-Induced TMAs
In cases of transplant patients with TMA and identified complement mutations, preemptive use of eculizumab is recommended. Differentiating drug-induced TMAs from those with underlying genetic mutations like factor mutations is crucial for treatment decisions. Factors influencing continuing or refraining from tacrolimus in these patients include genetic implications and risks of rejection, particularly in younger individuals with mutations and TMAs.
Anna Vinakova Associate Professor of Medicine at Virginia Commonwealth University. NephMadness Executive.
Vanuja Java is a transplant nephrologist at Washington University in St. Louis, MO. Her research involves functional characterization of genetic variants in complement-mediated diseases. She co-chairs the ClinGen complement gene curation expert panel.
Early Eculizumab Withdrawal in Patients With Atypical Hemolytic Uremic Syndrome in Native Kidneys Is Safe and Cost-Effective: Results of the CUREiHUS Study. KI reports. This is the Netherlands study. They used home urine dipsticks to monitor for relapses.
