Rethinking Lupus Nephritis: Targeting Immune Dysfunction

Announcer:
This is Living Rheum on ReachMD. On this episode, we’ll hear from Dr. Joan Merrill, who will be sharing insights from her presentation at the 2025 Congress of Clinical Rheumatology West conference on systemic lupus and lupus nephritis. Dr. Merrill is a Professor at the Oklahoma Medical Research Foundation’s Arthritis and Clinical Immunology Research Program in Oklahoma City.

Here she is now.

Dr. Merrill:
I think that there’s a great misunderstanding, because people have a tendency to think of lupus nephritis as a separate disease than systemic lupus. In fact, there’s an overlapping spectrum of what I think we would best call an imbalance in the immune system. And so sometimes, in some patients, you get clinical manifestations that look like it’s attacking the kidney, but in fact, we now know that most lupus patients have some involvement of the kidney, and some of it just isn’t all that severe. So we may not recognize that it’s happening at the time, and maybe you can go your whole life and have a pretty good functioning kidney and never need treatment directed at the kidney, per se.

But in fact, lupus is a disorder of the immune system in which people are born with some genes from their mom, some genes from their dad, and some usually fairly complex combinations of the little proteins that manage the immune system and put you at risk—that when certain stresses happen to the immune system, such as, maybe, an infection or a toxin or something, you’re just a little more likely to go out of balance. And when you go out of balance, it leads to inflammation and/or making antibodies against a substance. And then the process where we usually regulate all of that and hardly notice it’s happening breaks down, so that it’s like a vicious cycle, and the activity of the immune system is a little bit out of whack. 

But it’s an overlapping spectrum of disorder, and we need to start thinking about treating the underlying immune imbalance and not the organ. So there are not the same treatments that are going to work for people with nephritis as for people with other manifestations. Some of them are like each other, and some of them share other features, so not everybody with nephritis is going to respond to the same treatment. But we do have some evidence base now that we didn’t have before, meaning there have been some clinical trials that show more people will get better if they take this regimen than that regimen. But that’s primitive medicine. It’s 20^th century medicine, and we’re in the 21^st century now. So I’m hoping that within the next couple of decades, we can improve our approach and really be able to get from either a kidney biopsy or even better yet, from little clues that have spilt out in the urine—so it’s a non-invasive way to do diagnosis. People are working on that so that we would be able to better select an optimal treatment for an individual patient. But again, this whole idea that there’s this nephritis over here and non-nephritis over there and they don’t overlap is actually wrong. 

Announcer:
That was Dr. Joan Merrill talking about the overlap between systemic lupus and lupus nephritis. To access this and other episodes in our series, visit Living Rheum on ReachMD. com, where you can Be Part of the Knowledge. Thanks for listening!