Anuja Java, MD, Associate Professor of Medicine, Director, Kidney Transplant John Cochran VA Medical Center, Division of Nephrology, Washington University School of Medicine recently had two articles published in Science Direct.
Thrombotic Microangiopathies and the Kidney
Both articles delve into defining current understanding of the pathophysiological mechanisms underlying Thrombotic Microangiopathies (TMAs). TMA is a multisystem disease characterized by thrombosis of small blood vessels due to endothelial injury. Endothelium is the inner lining of blood vessels. This kind of injury leads to low blood counts and decreased blood supply to organs and can lead to multiorgan failure, with kidneys being the predominant organ involved. Other manifestations can include stroke and cardiovascular complications. It is imperative to diagnose and treat a TMA timely, to prevent kidney or other organ failure.
Java shares, “Identifying the etiology of a TMA can be challenging because there can be multiple etiologies/triggers for TMA development (for example, infections, medications, pregnancy, autoimmune diseases)”.
One core mechanism revolves around overactivation of the complement system. Complement system is part of our innate immune system and protects us from infections but if the complement system gets overactive or dysregulated, it starts attacking healthy host cells. In a TMA, an overactive complement system can attack endothelial cells and cause injury. Dysregulation or overactivation of the complement system occurs commonly due to genetic mutations in proteins that normally keep the complement system in check, so called complement regulatory proteins.
These mutations lead to loss of function of these regulatory proteins which results in complement system “going out of hand” and causing injury to self. Over the past few years, there has been a lot of development around understanding the role of complement system in TMAs and there are many new drugs in trials to treat complement-mediated diseases.
The 1st review briefly goes over the basics and evolution of the complement system and then goes into details about the various etiologies for a TMA and how an overactive complement system is involved in causing disease associated with different etiologies. It also describes how to diagnose these conditions and what lab testing (particularly related to complement system) should be conducted in these patients. We have also given an overview of the new and upcoming drug trials for TMA.
The 2nd article is more focused on TMA associated with pregnancy and aims to help the reader understand how to differentiate between the various etiologies of a TMA in pregnancy and in the postpartum setting since the treatment for each etiology is different and needs to be diagnosed and initiated timely for safer maternal and fetal outcomes.
The goal of these reviews is to provide the readers and clinicians a better understanding of TMAs, diagnostic algorithms, interpretation of testing as well as available and upcoming treatments.