Jonathan Barratt, PhD, FRCP: Moving to you Anuja, in terms of your clinical practice, does it ring through the comments that Gerald has made in terms of the typical presentation and the heterogeneity in the disease?

Anuja Java, MD: Absolutely. And in fact, just following up on that conversation, I want to add since I'm a transplant nephrologist, I get to see these patients after they've had end-stage kidney disease and they're looking for renal replacement therapy and they come to us to get evaluated for a kidney transplant. At that time, it is challenging for us because we know that the disease will record after a transplant, but which patients are going to record? What is going to be their course after a transplant? It's hard to predict that. Because we do see that one-third of patients may have a very aggressive course right after transplant. They may develop proteinuria and the IgAN may come back very aggressively early on. And there is another subset of patients where we may not even identify that the recurrences happened unless we've done a biopsy for another etiology. Say that we are worried about a rejection, we biopsy them and then we find, oh, by the way, they also have recurrence of the disease. That kind of heterogeneity is something that we see in our transplant population. And it's interesting to think about it because these patients are already on immunosuppression to start out with, and despite that, the recurrence is high. The transplant aspects adds on to what Dr Appel just mentioned about the heterogeneity and so many unknowns about these patients.

Jonathan Barratt, PhD, FRCP: What you've described actually mirrors the native disease, doesn't it?

Anuja Java, MD: Exactly.

Jonathan Barratt, PhD, FRCP: We see patients by chance often, by making a diagnosis because something else has happened and we've been pointed to a potential diagnosis because someone's picked up blood and protein in the urine, like you say, making a diagnosis of recurrent disease when you're looking in a transplant for something else. All those patients who are obviously progressing. I do think that that raises interesting questions, which we'll come onto about how we identify those patients. Because in most countries in the world, we don't have a screening program, do we? It's very much by chance.

Anuja Java, MD: Right. And we don't have a way to tell which of these will have an aggressive course, which of these will go without recognizing. And that's an unmet need too.

Jonathan Barratt, PhD, FRCP: It's a massive unmet need. One of the common things I'm consulted about now is actually those poor people who know what end-stage kidney disease is like. They have the precious gift of a kidney transplant and then they have this ticking time bomb of wondering whether they're going to get recurrent disease. And if they have recurrent disease, what can we do to stop them from developing kidney failure again?

Transcript Edited for Clarity