Dr. Hricik: This is one of the most problematic areas in kidney transplantation—how to manage the patient with acute or chronic antibody-mediated rejection. Of course, this case is a little more complicated because of the multiple episodes of pyelonephritis—not on the basis of immune injury, but on the basis of scarring from recurrent episodes. But it's also common to see acute humoral rejection emerge in the setting of noncompliance. We're pretty good at treating acute humoral rejection, and the mainstays of therapy now have become plasma exchange and treatment with IVIg, as she received. Now, it's encouraging to note that her creatinine is currently improving, but the DSA [levels], they're still elevated. I think the concern in the long run is that she may lose this kidney from chronic antibody damage.
So what can we do? Repeating plasma exchange and IVIg is a fairly expensive modality, and if her creatinine is improving, I don't think many would accept that. The other therapeutic options that can be considered are the use of rituximab, the anti-CD20 antibody, which has some utility in treating at least acute humoral rejection, but I'm not so sure of a benefit in the chronic picture.1 And of course, the other category of drugs that are being used experimentally are the proteosome inhibitors—the main one being bortezomib. But I believe that the group in Cincinnati has shown pretty convincingly that that class of agents may be helpful in early cases of acute humoral rejection,2 but are not very helpful in patients with late acute humoral rejection or chronic humoral rejection.3
So we are really stumped here, and unfortunately, it remains true that antibody-mediated chronic rejection is now emerging as one of the most common causes of late graft loss. The only other thing I would say about this case is that I've seen some noncompliant patients who improve just by improving adherence,4-7 and in some cases, increasing the maintenance doses of drugs. So, for example, if the patient is on tacrolimus, we would probably increase our target levels for that drug, at least over the short term, in an effort to get some control.
But this is a big problem in the field of kidney transplantation—studies have shown that DSAs emerge in [approximately] 10% to 15% of patients within the first year or two after transplantation.6,8-10 And it's important to know that those de novo DSAs don't always take their toll in terms of an acute event, but most studies have shown that three- and five-year graft survival are poor in patients with de novo DSAs.6,8,10 And they develop even in patients who are completely adherent with their regimens.