Screening Methods to Evaluate for Lupus

Fotios Koumpouras, MD, FACR: In your patients with standard lupus, are you measuring urinalysis as a screen, and are you following up if there’s mild hematuria or pyuria? I’m curious. What’s the threshold to take the next step to investigate potential smoldering lupus nephritis for you?

Ronald van Vollenhoven, Prof. PhD: Oh, gosh, that’s tough, right?

Fotios Koumpouras, MD, FACR: Yes.

Ronald van Vollenhoven, Prof. PhD: The thing to know is in lupus, for many things that can happen, the patient will tell you. If they have a skin rash, they will tell you. If they have pleurisy, they will tell you. But there are 2 things that can happen that the patient won’t realize, and one is the cytopenias, people can have dangerously low levels of thrombocytes or leukocytes without realizing it. The other thing is, of course, the nephritis, which can be clinically totally silent. I think it is very good practice to monitor for those things at fairly frequent intervals, of course depending a bit on what kind of severity the patient has previously shown.

At the initial evaluation of lupus, of course we always check those things, and I think it is a bit up for discussion how often you want to repeat, but it should certainly be done with some regularity, don’t you think?

Fotios Koumpouras, MD, FACR: Yes, I agree, and I’m glad we’re practicing similarly so many miles away, because these are potentially silent serious manifestations of SLE [systemic lupus erythematosus]. I can think of 2 particular cases where I found a platelet count of 2000 on a routine CBC [complete blood count]. In fact, one lady had had COVID-19, and we were worried she might have a lupus flare, and it was my junior colleague who just checked her CBC because she’d had a problem with….. Asymptomatic.

Ronald van Vollenhoven, Prof. PhD: Just to underscore the international nature of this broadcast, when you said 2000, in Amsterdam that would have been 2, because we use different units. For my colleagues here in Amsterdam, this is a patient who is at a very high risk for bleeding. But if they heard you say 2000, they might have felt this patient has thrombocytosis. That’s how tricky it gets sometimes.

Fotios Koumpouras, MD, FACR: If we say 2, the surgeons would get upset because it’s usually 2000 per microliter.

Ronald van Vollenhoven, Prof. PhD: Yes, it’s different, right? We use different units, and that’s just part of the things that will never completely go away. I think we understand this to be a very severe thrombocytopenia in any case.

Fotios Koumpouras, MD, FACR: For rheumatologists, if I could just interrupt, and in terms of the nephritis part of it, I’m a program director and I work with trainees, and they usually look for a rise in the creatinine. Do you think a rise in the creatinine is when you should intervene and some of them might have lupus nephritis?

Ronald van Vollenhoven, Prof. PhD: Yes, so back to that question. Obviously, you need to check the urine and the creatinine, but the question is when do you act? Certainly, an increase in the creatinine, my goodness, yes, of course you have to investigate. The question is at what level of proteinuria or sediment changes do you have to investigate? It’s a tricky question because mild lupus nephritis, it turns out to be class 2 on the biopsy, if you did a biopsy. That sounds very dangerous, but that is something you can leave be. But it’s hard to tell without investigating further. In practicality, it’s really not one level where we decide to go to the next step, which usually is a biopsy. You can obviously let it depend a little on the patient’s preceding history, other risks, did you find another explanation for either the creatinine, or the proteinuria is obviously a different story. I would say that any time you get to, say, 350 mg per day of proteinuria or even higher, 500 mg, it gets to the point where you don’t want to just sit back and wait. But it’s an open discussion. I don’t know, do you have actual guidelines for that, like a certain level?

Fotios Koumpouras, MD, FACR: We don’t. The point I make to my trainees is if the creatinine is rising, they’re in trouble, because by the time the creatinine increases, you’ve lost 50% of your nephron unit, or 50% of your glomerular filtration rate. So that creatinine rise is the last stage of really bad damage. It’s looking at proteinuria, looking at mild hematuria, and something like cystatin C, which sometimes we use in the clinical trials, to see if there’s activity in renal disease for patients with SLE. For the general rheumatologist who might not be aware, you can have significant renal inflammation, though the creatinine could look quite normal.

Ronald van Vollenhoven, Prof. PhD: Yes, I totally agree. But that was interesting because you mentioned cystatin C. Is that available to the clinician?

Fotios Koumpouras, MD, FACR: Not yet.

Ronald van Vollenhoven, Prof. PhD: Only on a research level maybe.

Fotios Koumpouras, MD, FACR: It’s on a research level.

Ronald van Vollenhoven, Prof. PhD: Because sometimes, particularly in the United States, for measuring or gauging lupus activity, you do have a few tools that we don’t yet have in Europe. I think there is the erythrocyte-bound complement test?

Fotios Koumpouras, MD, FACR: Correct, the EC4d. Fortunately, that was my mentors’ work, who had discovered EC4d. It was Sue Manzi, MD, MPH, and Joe Ahearn, MD, who discovered that EC4d, a byproduct of complement activation, forms a covalent linkage on erythrocytes it turns out. That’s C3b and C4a. The idea is that the erythrocyte can bind these products of complement activation and serve as these 3-month time capsules. Yes, that is commercially available, although it’s not widely incorporated in many academic centers because it’s slightly difficult to get those specimens to the specialty laboratory. But you’re right, it also brings to light the fact that we need additional methods to help understand if there’s ongoing inflammation aside from our very crude measurements of complement, blood counts, and the like.

Transcript Edited for Clarity