Expert insights on Lupus Nephritis

[00:05]
Sparing nephrons for lupus nephritis patients is key — it’s what we should aim for. That’s why I advocate for combination therapy from the beginning.
We have to contextualize things: we’re dealing with a young population — young women, often in the early years of adulthood. We have nothing to spare here. The only thing we do need to spare is nephrons.
So we have to act quickly — with the tools we have — to fight inflammation early, spare nephrons, and
[00:50]
preserve renal function long-term for these patients.
We know that the loss of nephrons can happen quickly. When a flare occurs, a large number of nephrons can be lost in a short period of time.
So we need to act fast — and we need to act effectively.

[00:05]
I think one of the changes already happening — despite the talk we heard yesterday — is that we’re heading toward much lower doses of steroids. What I’d really like to see on the horizon in five years is, perhaps similar to what we’ve seen in vasculitis, the possibility of steroid-free regimens becoming the norm. And also, therapies that are intermittent — biological therapies that can be given intermittently — allowing patients to have a much lower tablet burden while still achieving very good long-term control of their disease.

[00:05]
So hi, B.R. — what do you think about kidney-related outcomes? Which is the most important one in clinical practice?

For me, the most important outcome is preserving kidney function — so, some measure of GFR. That could be creatinine, eGFR, or ideally a real GFR measurement. We tend to get wound up in proteinuria as a surrogate marker, but as you all know, that’s a marker that comes with a lot of difficulties in interpretation. Proper interpretation of proteinuria — at least currently — requires histology to understand where it's coming from.

So bottom line: all treatments should be working toward preserving kidney function for the patient, for the future.
[00:47]
But that takes a lot of time.

So what about aiming for a short-term outcome? What’s a good one to go for — histology, eGFR slope, remission as we define it now?

Yeah, so I think that if we can define remission precisely — and as you and I both know, we have several different definitions of remission from all the different trials and what we use clinically — but if we really have a sustained, complete remission, then I think that’s a good long-term predictor of how the kidney is going to do over time — and how the patient will do over time.

Now, the trick is defining that, of course.
[01:30]
Yeah — and maybe we can move our trials toward using eGFR slope over one or two years.

I do like eGFR slope, and certainly we are using it now in other types of diseases — certainly FSGS and IgA nephropathy. What’s interesting about lupus is that we haven’t really taken that on yet. And the caution — or caveat — is: how do you measure slope?

[02:13]
Okay, this is a really difficult issue, and there’s a lot of input needed from our biostatistical colleagues. Do you measure total slope if the drug affects the slope or the GFR acutely? Do you measure just the chronic slope? Or how do you account for the acute changes?

But I do think we’re figuring this out. And I do think we’ve done secondary analyses now on GFR slope in at least one phase 2 and one phase 3 clinical trial — and they’ve been quite useful in informing what the drug
[02:53]
possibilities can do.
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